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Fluoroquinolone No Match for Traveler's Diarrhea
Major Finding: Fluoroquinolone resistance has increased among pathogens that cause traveler's diarrhea.
Data Source: A study of stool samples from 434 travelers to India and Latin America.
Disclosures: Dr. Ouyang-Latimer stated that she has no conflicts of interest. The principal investigator, Dr. Herbert L. DuPont, has received speaking honoraria and/or research grants from several companies, including Salix Pharmaceuticals Ltd., Merck Vaccine Division, IOMAI Corp., Intercell Corp., Optimer Pharmaceuticals Inc., and Santarus Inc.
BETHESDA, MD. — The level of fluoroquinolone resistance in enteric pathogens has increased considerably over the last decade among travelers to Mexico, Guatemala, and India, based on an analysis of stool samples from more than 400 adult travelers to those countries.
Susceptibility, however, has remained fairly stable for the poorly absorbed agent rifaximin as well as for azithromycin, suggesting that those agents may represent more suitable options for self-initiated treatment and prophylaxis of traveler's diarrhea, Dr. Jeanette Ouyang-Latimer said at the annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.
“It's important to monitor susceptibility patterns of enteropathogens causing traveler's diarrhea over time, especially when we've seen more liberal use of antibiotics for self-initiated therapy and also prophylaxis. The further increase in fluoroquinolone resistance may make it less ideal for those uses,” said Dr. Ouyang-Latimer of Baylor College of Medicine, Houston.
The stool samples were taken during 2006–2008 and were tested for enterotoxigenic Escherichia coli (ETEC), Salmonella, Vibrio, Shigella, Aeromonas, and Plesiomonas. The minimum inhibitory concentration (MIC) was determined for the antibiotics ampicillin; tetracyclines, including doxycycline, nalidixic acid, ceftriaxone, and trimethoprim-sulfamethoxazole (TMP/SMX); fluoroquinolones, including ciprofloxacin and levofloxacin; and azithromycin and rifaximin.
The most common agent in all regions was ETEC, with 270 samples isolated from the total 291 travelers to Mexico/Guatemala (grouped together as “Latin America”) and 98 of 143 travelers to India. Campylobacter was more common in samples from travelers to India (17) than to Latin America (6).
From all the regions combined, the proportion of ETEC-resistant strains was 24% to levofloxacin, 20% to ciprofloxacin, 18% to azithromycin, 17% to rifaximin, and 5% to ceftriaxone. Resistance was much higher—around 50% each—to the older, less-used agents: ampicillin, nalidixic acid, and TMP/SMX.
Contrary to reports from Southeast Asia, campylobacter isolates did not demonstrate significant fluoroquinolone resistance, but 22% did show resistance to rifaximin, Dr. Ouyang-Latimer reported.
By location, ETEC resistance to levo-floxacin was far greater in India, compared with Latin America (41% vs. 20%, respectively). Azithromycin resistance also was higher in India than in Latin America (24.5% vs. 16%). All of the resistant campylobacter strains were seen in India, with 29% of the total showing rifaximin resistance.
The MIC at which 90% of the strains tested were inhibited (MIC90) from these samples was compared with MIC90 values previously reported from travelers to the same regions in 1997 (Antimicrob. Agents Chemother. 2001;45:212–6).
For ETEC, MIC90 levels had increased by twofold or greater for all the commonly used antibiotics. For ciprofloxacin, ETEC strains demonstrated a ninefold increase in resistance, from 3% in 1997 to 20% in 2006–2008. Levofloxacin resistance also increased dramatically among ETEC, from 3% to 24%.
These findings reflect the fact that fluoroquinolones and azithromycin often can be obtained without prescriptions in these regions, she noted.
Major Finding: Fluoroquinolone resistance has increased among pathogens that cause traveler's diarrhea.
Data Source: A study of stool samples from 434 travelers to India and Latin America.
Disclosures: Dr. Ouyang-Latimer stated that she has no conflicts of interest. The principal investigator, Dr. Herbert L. DuPont, has received speaking honoraria and/or research grants from several companies, including Salix Pharmaceuticals Ltd., Merck Vaccine Division, IOMAI Corp., Intercell Corp., Optimer Pharmaceuticals Inc., and Santarus Inc.
BETHESDA, MD. — The level of fluoroquinolone resistance in enteric pathogens has increased considerably over the last decade among travelers to Mexico, Guatemala, and India, based on an analysis of stool samples from more than 400 adult travelers to those countries.
Susceptibility, however, has remained fairly stable for the poorly absorbed agent rifaximin as well as for azithromycin, suggesting that those agents may represent more suitable options for self-initiated treatment and prophylaxis of traveler's diarrhea, Dr. Jeanette Ouyang-Latimer said at the annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.
“It's important to monitor susceptibility patterns of enteropathogens causing traveler's diarrhea over time, especially when we've seen more liberal use of antibiotics for self-initiated therapy and also prophylaxis. The further increase in fluoroquinolone resistance may make it less ideal for those uses,” said Dr. Ouyang-Latimer of Baylor College of Medicine, Houston.
The stool samples were taken during 2006–2008 and were tested for enterotoxigenic Escherichia coli (ETEC), Salmonella, Vibrio, Shigella, Aeromonas, and Plesiomonas. The minimum inhibitory concentration (MIC) was determined for the antibiotics ampicillin; tetracyclines, including doxycycline, nalidixic acid, ceftriaxone, and trimethoprim-sulfamethoxazole (TMP/SMX); fluoroquinolones, including ciprofloxacin and levofloxacin; and azithromycin and rifaximin.
The most common agent in all regions was ETEC, with 270 samples isolated from the total 291 travelers to Mexico/Guatemala (grouped together as “Latin America”) and 98 of 143 travelers to India. Campylobacter was more common in samples from travelers to India (17) than to Latin America (6).
From all the regions combined, the proportion of ETEC-resistant strains was 24% to levofloxacin, 20% to ciprofloxacin, 18% to azithromycin, 17% to rifaximin, and 5% to ceftriaxone. Resistance was much higher—around 50% each—to the older, less-used agents: ampicillin, nalidixic acid, and TMP/SMX.
Contrary to reports from Southeast Asia, campylobacter isolates did not demonstrate significant fluoroquinolone resistance, but 22% did show resistance to rifaximin, Dr. Ouyang-Latimer reported.
By location, ETEC resistance to levo-floxacin was far greater in India, compared with Latin America (41% vs. 20%, respectively). Azithromycin resistance also was higher in India than in Latin America (24.5% vs. 16%). All of the resistant campylobacter strains were seen in India, with 29% of the total showing rifaximin resistance.
The MIC at which 90% of the strains tested were inhibited (MIC90) from these samples was compared with MIC90 values previously reported from travelers to the same regions in 1997 (Antimicrob. Agents Chemother. 2001;45:212–6).
For ETEC, MIC90 levels had increased by twofold or greater for all the commonly used antibiotics. For ciprofloxacin, ETEC strains demonstrated a ninefold increase in resistance, from 3% in 1997 to 20% in 2006–2008. Levofloxacin resistance also increased dramatically among ETEC, from 3% to 24%.
These findings reflect the fact that fluoroquinolones and azithromycin often can be obtained without prescriptions in these regions, she noted.
Major Finding: Fluoroquinolone resistance has increased among pathogens that cause traveler's diarrhea.
Data Source: A study of stool samples from 434 travelers to India and Latin America.
Disclosures: Dr. Ouyang-Latimer stated that she has no conflicts of interest. The principal investigator, Dr. Herbert L. DuPont, has received speaking honoraria and/or research grants from several companies, including Salix Pharmaceuticals Ltd., Merck Vaccine Division, IOMAI Corp., Intercell Corp., Optimer Pharmaceuticals Inc., and Santarus Inc.
BETHESDA, MD. — The level of fluoroquinolone resistance in enteric pathogens has increased considerably over the last decade among travelers to Mexico, Guatemala, and India, based on an analysis of stool samples from more than 400 adult travelers to those countries.
Susceptibility, however, has remained fairly stable for the poorly absorbed agent rifaximin as well as for azithromycin, suggesting that those agents may represent more suitable options for self-initiated treatment and prophylaxis of traveler's diarrhea, Dr. Jeanette Ouyang-Latimer said at the annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.
“It's important to monitor susceptibility patterns of enteropathogens causing traveler's diarrhea over time, especially when we've seen more liberal use of antibiotics for self-initiated therapy and also prophylaxis. The further increase in fluoroquinolone resistance may make it less ideal for those uses,” said Dr. Ouyang-Latimer of Baylor College of Medicine, Houston.
The stool samples were taken during 2006–2008 and were tested for enterotoxigenic Escherichia coli (ETEC), Salmonella, Vibrio, Shigella, Aeromonas, and Plesiomonas. The minimum inhibitory concentration (MIC) was determined for the antibiotics ampicillin; tetracyclines, including doxycycline, nalidixic acid, ceftriaxone, and trimethoprim-sulfamethoxazole (TMP/SMX); fluoroquinolones, including ciprofloxacin and levofloxacin; and azithromycin and rifaximin.
The most common agent in all regions was ETEC, with 270 samples isolated from the total 291 travelers to Mexico/Guatemala (grouped together as “Latin America”) and 98 of 143 travelers to India. Campylobacter was more common in samples from travelers to India (17) than to Latin America (6).
From all the regions combined, the proportion of ETEC-resistant strains was 24% to levofloxacin, 20% to ciprofloxacin, 18% to azithromycin, 17% to rifaximin, and 5% to ceftriaxone. Resistance was much higher—around 50% each—to the older, less-used agents: ampicillin, nalidixic acid, and TMP/SMX.
Contrary to reports from Southeast Asia, campylobacter isolates did not demonstrate significant fluoroquinolone resistance, but 22% did show resistance to rifaximin, Dr. Ouyang-Latimer reported.
By location, ETEC resistance to levo-floxacin was far greater in India, compared with Latin America (41% vs. 20%, respectively). Azithromycin resistance also was higher in India than in Latin America (24.5% vs. 16%). All of the resistant campylobacter strains were seen in India, with 29% of the total showing rifaximin resistance.
The MIC at which 90% of the strains tested were inhibited (MIC90) from these samples was compared with MIC90 values previously reported from travelers to the same regions in 1997 (Antimicrob. Agents Chemother. 2001;45:212–6).
For ETEC, MIC90 levels had increased by twofold or greater for all the commonly used antibiotics. For ciprofloxacin, ETEC strains demonstrated a ninefold increase in resistance, from 3% in 1997 to 20% in 2006–2008. Levofloxacin resistance also increased dramatically among ETEC, from 3% to 24%.
These findings reflect the fact that fluoroquinolones and azithromycin often can be obtained without prescriptions in these regions, she noted.
High-Dose Influenza Vaccine Helpful for Older Adults
ATLANTA — Fluzone High-Dose vaccine was significantly more immunogenic than standard-dose influenza vaccine in a study of 3,876 individuals aged 65 years or older.
Sanofi-Pasteur's Fluzone High-Dose was licensed last December for use in that age group. In the phase III, multicenter, double-blind study, participants were randomizedito receive either high-dose (HD) vaccine containing 60 mcg hemagglutinin per strain or standard dose (SD) with 15 mcg hemagglutinin per strain. Blood specimens were obtained before vaccination and on day 28 for evaluation of influenza antibodies. Safety data were collectedbyor up to 6 months after vaccination, Dr. David Greenberg said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.
Reported injection site reactions within 7 days of vaccination were more common with HD. Pain was reported by 36% of the 2,573 participants who were assessed after receiving the HD vaccine and in 24% of the 1,260 in the SD group. Grade III pain was uncommon in both groups (0.3% with HD and 0.2% with SD). Erythema occurred in 15% with HD and 11% with SD, and swelling in 9% and 6%, respectively. Grade III erythema and swelling occurred in less than 2% of both groups. Most injection site reactions were mild to moderate and resolved within 3 days, said Dr. Greenberg, Sanofi-Pasteur's senior director of scientific and medical affairs.
Rates of systemic reactions were similar between the HD and SD groups, including myalgia (21% HD, 18% SD), malaise (18%, 14%), headache (17%, 14%), and fever (0%, 0.1%). Adverse events in the 30 minutes following vaccination were comparable (about 0.3% in both groups), as were rates of unsolicited adverse events within 28 days post vaccination (22% of both groups) (J. Infect. Dis. 2009;200:172–80).
Only two serious adverse events were reported by investigators as being vaccine-related: an exacerbation of Crohn's disease 2 days after receipt of HD vaccine, and a new diagnosis of myasthenia gravis 1 month after SD vaccination.
To satisfy requirements of the Food and Drug Administration, Fluzone was required to demonstrate superiority to SD vaccine for at least two of the three vaccine influenza strains, without inferiority for any strain. Fluzone achieved superiority—as determined by significantly greater geometric mean antibody titers—for the H1N1 and H3N2 strains and noninferiority for the B strain, Dr. Greenberg reported.
ATLANTA — Fluzone High-Dose vaccine was significantly more immunogenic than standard-dose influenza vaccine in a study of 3,876 individuals aged 65 years or older.
Sanofi-Pasteur's Fluzone High-Dose was licensed last December for use in that age group. In the phase III, multicenter, double-blind study, participants were randomizedito receive either high-dose (HD) vaccine containing 60 mcg hemagglutinin per strain or standard dose (SD) with 15 mcg hemagglutinin per strain. Blood specimens were obtained before vaccination and on day 28 for evaluation of influenza antibodies. Safety data were collectedbyor up to 6 months after vaccination, Dr. David Greenberg said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.
Reported injection site reactions within 7 days of vaccination were more common with HD. Pain was reported by 36% of the 2,573 participants who were assessed after receiving the HD vaccine and in 24% of the 1,260 in the SD group. Grade III pain was uncommon in both groups (0.3% with HD and 0.2% with SD). Erythema occurred in 15% with HD and 11% with SD, and swelling in 9% and 6%, respectively. Grade III erythema and swelling occurred in less than 2% of both groups. Most injection site reactions were mild to moderate and resolved within 3 days, said Dr. Greenberg, Sanofi-Pasteur's senior director of scientific and medical affairs.
Rates of systemic reactions were similar between the HD and SD groups, including myalgia (21% HD, 18% SD), malaise (18%, 14%), headache (17%, 14%), and fever (0%, 0.1%). Adverse events in the 30 minutes following vaccination were comparable (about 0.3% in both groups), as were rates of unsolicited adverse events within 28 days post vaccination (22% of both groups) (J. Infect. Dis. 2009;200:172–80).
Only two serious adverse events were reported by investigators as being vaccine-related: an exacerbation of Crohn's disease 2 days after receipt of HD vaccine, and a new diagnosis of myasthenia gravis 1 month after SD vaccination.
To satisfy requirements of the Food and Drug Administration, Fluzone was required to demonstrate superiority to SD vaccine for at least two of the three vaccine influenza strains, without inferiority for any strain. Fluzone achieved superiority—as determined by significantly greater geometric mean antibody titers—for the H1N1 and H3N2 strains and noninferiority for the B strain, Dr. Greenberg reported.
ATLANTA — Fluzone High-Dose vaccine was significantly more immunogenic than standard-dose influenza vaccine in a study of 3,876 individuals aged 65 years or older.
Sanofi-Pasteur's Fluzone High-Dose was licensed last December for use in that age group. In the phase III, multicenter, double-blind study, participants were randomizedito receive either high-dose (HD) vaccine containing 60 mcg hemagglutinin per strain or standard dose (SD) with 15 mcg hemagglutinin per strain. Blood specimens were obtained before vaccination and on day 28 for evaluation of influenza antibodies. Safety data were collectedbyor up to 6 months after vaccination, Dr. David Greenberg said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.
Reported injection site reactions within 7 days of vaccination were more common with HD. Pain was reported by 36% of the 2,573 participants who were assessed after receiving the HD vaccine and in 24% of the 1,260 in the SD group. Grade III pain was uncommon in both groups (0.3% with HD and 0.2% with SD). Erythema occurred in 15% with HD and 11% with SD, and swelling in 9% and 6%, respectively. Grade III erythema and swelling occurred in less than 2% of both groups. Most injection site reactions were mild to moderate and resolved within 3 days, said Dr. Greenberg, Sanofi-Pasteur's senior director of scientific and medical affairs.
Rates of systemic reactions were similar between the HD and SD groups, including myalgia (21% HD, 18% SD), malaise (18%, 14%), headache (17%, 14%), and fever (0%, 0.1%). Adverse events in the 30 minutes following vaccination were comparable (about 0.3% in both groups), as were rates of unsolicited adverse events within 28 days post vaccination (22% of both groups) (J. Infect. Dis. 2009;200:172–80).
Only two serious adverse events were reported by investigators as being vaccine-related: an exacerbation of Crohn's disease 2 days after receipt of HD vaccine, and a new diagnosis of myasthenia gravis 1 month after SD vaccination.
To satisfy requirements of the Food and Drug Administration, Fluzone was required to demonstrate superiority to SD vaccine for at least two of the three vaccine influenza strains, without inferiority for any strain. Fluzone achieved superiority—as determined by significantly greater geometric mean antibody titers—for the H1N1 and H3N2 strains and noninferiority for the B strain, Dr. Greenberg reported.
ACIP Recommends Newly Licensed PCV13
ATLANTA — Recommendations for routine use of the newly licensed 13-valent pneumococcal conjugate vaccine in children should provide a smooth transition from the current 7-valent vaccine.
Licensure of the 13-valent pneumococcal conjugate vaccine (PCV13), Pfizer's Prevnar 13, was announced by a representative from the Food and Drug Administration at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices. The vaccine was approved for use in children aged 6 weeks through 5 years of age and is indicated for the prevention of invasive pneumococcal disease caused by all of its 13 serotypes and for prevention of otitis media caused by the serotypes in the 7-valent vaccine (the FDA's Dr. Wellington Sun said.
Following the announcement, the committee then voted on recommendations for routine use of the 13-valent vaccine in previously unvaccinated children aged 2–59 months of age—with the routine primary series given at 2, 4, 6, and 12–15 months of age—and in high-risk children aged 60–71 months, as well as on guidelines for transitioning to PCV13 in children who previously received one or more doses of PCV7.
Children who previously received one or more doses of PCV7 should complete the series with PCV13. Children aged 14–59 months who were completely vaccinated with four doses of PCV7 should receive a single “supplemental” dose of PCV13, but this can occur at the next regularly scheduled office visit, said Dr. Pekka Nuorti of the CDC's respiratory diseases branch.
A supplemental PCV13 dose should also be given to children with underlying medical conditions through 71 months of age, including those who previously received the 23-valent pneumococcal polysaccharide vaccine. Vaccination with a single dose of PCV13 also may be considered for high-risk children aged 6 through 18 years, although such use would be off label, Dr. Nuorti said.
When published in the CDC's Morbidity and Mortality Weekly Report, the guidelines will contain detailed charts for transitioning children from PCV7 to PCV13 based on age and how many doses of PCV7 they have already received. Dosage intervals also will be included, Dr. Nuorti noted.
Dr. Joseph A. Bocchini, the liaison to ACIP from the American Academy of Pediatrics, said that the academy is likely to support the ACIP recommendations. “The recommendations line up with what we consider appropriate use of the vaccine. … I think it will be easy for people to make the [PCV7 to PCV13] transition,” Dr. Bocchini of Louisiana State University, Shreveport, said in an interview at the meeting.
Disclosures: Dr. Nuorti and Dr. Bocchini said they had no conflicts of interest.
'The [committee's] recommendations line up with what we consider appropriate use of the vaccine.'
Source DR. BOCCHINI
My Take
Transition Should be 'Pretty Smooth'
I don't think the American Academy of Family Physicians will have any trouble with these recommendations, and I don't think family physicians will have any trouble implementing them, because they're already doing pretty well with PCV7 and this is just going to substitute.
It's a good move for Pfizer Inc. to issue credit to providers for unused doses of PCV7. There was a lingering question about what we were going to do with the current PCV7 supplies. If they weren't going to buy them back, the tendency would be to continue to use them. Now that they're going to buy back, the transition should be pretty smooth.
ATLANTA — Recommendations for routine use of the newly licensed 13-valent pneumococcal conjugate vaccine in children should provide a smooth transition from the current 7-valent vaccine.
Licensure of the 13-valent pneumococcal conjugate vaccine (PCV13), Pfizer's Prevnar 13, was announced by a representative from the Food and Drug Administration at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices. The vaccine was approved for use in children aged 6 weeks through 5 years of age and is indicated for the prevention of invasive pneumococcal disease caused by all of its 13 serotypes and for prevention of otitis media caused by the serotypes in the 7-valent vaccine (the FDA's Dr. Wellington Sun said.
Following the announcement, the committee then voted on recommendations for routine use of the 13-valent vaccine in previously unvaccinated children aged 2–59 months of age—with the routine primary series given at 2, 4, 6, and 12–15 months of age—and in high-risk children aged 60–71 months, as well as on guidelines for transitioning to PCV13 in children who previously received one or more doses of PCV7.
Children who previously received one or more doses of PCV7 should complete the series with PCV13. Children aged 14–59 months who were completely vaccinated with four doses of PCV7 should receive a single “supplemental” dose of PCV13, but this can occur at the next regularly scheduled office visit, said Dr. Pekka Nuorti of the CDC's respiratory diseases branch.
A supplemental PCV13 dose should also be given to children with underlying medical conditions through 71 months of age, including those who previously received the 23-valent pneumococcal polysaccharide vaccine. Vaccination with a single dose of PCV13 also may be considered for high-risk children aged 6 through 18 years, although such use would be off label, Dr. Nuorti said.
When published in the CDC's Morbidity and Mortality Weekly Report, the guidelines will contain detailed charts for transitioning children from PCV7 to PCV13 based on age and how many doses of PCV7 they have already received. Dosage intervals also will be included, Dr. Nuorti noted.
Dr. Joseph A. Bocchini, the liaison to ACIP from the American Academy of Pediatrics, said that the academy is likely to support the ACIP recommendations. “The recommendations line up with what we consider appropriate use of the vaccine. … I think it will be easy for people to make the [PCV7 to PCV13] transition,” Dr. Bocchini of Louisiana State University, Shreveport, said in an interview at the meeting.
Disclosures: Dr. Nuorti and Dr. Bocchini said they had no conflicts of interest.
'The [committee's] recommendations line up with what we consider appropriate use of the vaccine.'
Source DR. BOCCHINI
My Take
Transition Should be 'Pretty Smooth'
I don't think the American Academy of Family Physicians will have any trouble with these recommendations, and I don't think family physicians will have any trouble implementing them, because they're already doing pretty well with PCV7 and this is just going to substitute.
It's a good move for Pfizer Inc. to issue credit to providers for unused doses of PCV7. There was a lingering question about what we were going to do with the current PCV7 supplies. If they weren't going to buy them back, the tendency would be to continue to use them. Now that they're going to buy back, the transition should be pretty smooth.
ATLANTA — Recommendations for routine use of the newly licensed 13-valent pneumococcal conjugate vaccine in children should provide a smooth transition from the current 7-valent vaccine.
Licensure of the 13-valent pneumococcal conjugate vaccine (PCV13), Pfizer's Prevnar 13, was announced by a representative from the Food and Drug Administration at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices. The vaccine was approved for use in children aged 6 weeks through 5 years of age and is indicated for the prevention of invasive pneumococcal disease caused by all of its 13 serotypes and for prevention of otitis media caused by the serotypes in the 7-valent vaccine (the FDA's Dr. Wellington Sun said.
Following the announcement, the committee then voted on recommendations for routine use of the 13-valent vaccine in previously unvaccinated children aged 2–59 months of age—with the routine primary series given at 2, 4, 6, and 12–15 months of age—and in high-risk children aged 60–71 months, as well as on guidelines for transitioning to PCV13 in children who previously received one or more doses of PCV7.
Children who previously received one or more doses of PCV7 should complete the series with PCV13. Children aged 14–59 months who were completely vaccinated with four doses of PCV7 should receive a single “supplemental” dose of PCV13, but this can occur at the next regularly scheduled office visit, said Dr. Pekka Nuorti of the CDC's respiratory diseases branch.
A supplemental PCV13 dose should also be given to children with underlying medical conditions through 71 months of age, including those who previously received the 23-valent pneumococcal polysaccharide vaccine. Vaccination with a single dose of PCV13 also may be considered for high-risk children aged 6 through 18 years, although such use would be off label, Dr. Nuorti said.
When published in the CDC's Morbidity and Mortality Weekly Report, the guidelines will contain detailed charts for transitioning children from PCV7 to PCV13 based on age and how many doses of PCV7 they have already received. Dosage intervals also will be included, Dr. Nuorti noted.
Dr. Joseph A. Bocchini, the liaison to ACIP from the American Academy of Pediatrics, said that the academy is likely to support the ACIP recommendations. “The recommendations line up with what we consider appropriate use of the vaccine. … I think it will be easy for people to make the [PCV7 to PCV13] transition,” Dr. Bocchini of Louisiana State University, Shreveport, said in an interview at the meeting.
Disclosures: Dr. Nuorti and Dr. Bocchini said they had no conflicts of interest.
'The [committee's] recommendations line up with what we consider appropriate use of the vaccine.'
Source DR. BOCCHINI
My Take
Transition Should be 'Pretty Smooth'
I don't think the American Academy of Family Physicians will have any trouble with these recommendations, and I don't think family physicians will have any trouble implementing them, because they're already doing pretty well with PCV7 and this is just going to substitute.
It's a good move for Pfizer Inc. to issue credit to providers for unused doses of PCV7. There was a lingering question about what we were going to do with the current PCV7 supplies. If they weren't going to buy them back, the tendency would be to continue to use them. Now that they're going to buy back, the transition should be pretty smooth.
Cost of Antibiotic Resistance Hits Private Payers
Major Finding: The overall cost of antimicrobial resistance is rising, but because patients now are younger and living longer, the burden has shifted from Medicare to private insurance.
Data Source: Two studies assessing hospital database data and one Internet survey.
Disclosures: Supported by unrestricted educational grant from bioMérieux.
BETHESDA, MD. — The overall cost burden of antimicrobial resistance—as high as $38 billion in one 2009 hospital estimate—has shifted sharply from Medicare to private payers over the last decade.
Medicare still pays the majority of the costs for excess length of stay, increased use of more expensive drugs, and poorer health attributable to treatment-resistant infections. However, the rise in infections caused by methicillin-resistant Staphylococcus aureus (MRSA), which largely affects younger, healthier individuals, has meant that the overall cost per patient has declined but more is being borne by private HMOs and PPOs, Susan D. Foster, Ph.D., said at the 2010 Conference on Antimicrobial Resistance sponsored by the National Foundation for Infectious Diseases.
“There's been a major shift in who's actually paying. I don't think the insurance companies are quite aware of this,” said Dr. Foster, professor of international health at Boston University and director of public policy and education for the Alliance for the Prudent Use of Antibiotics at Tufts University, Boston.
Dr. Foster analyzed data from three studies. In an unpublished study, she and her associates reviewed Massachusetts hospital discharge data from 2000 to 2007 to look for ICD-9 “VO9” codes, which are specific for drug-resistant infections. Although these codes are difficult to use and therefore represent a study limitation, they do allow for analysis of trends over time, she explained.
Overall, the number of hospital discharges reporting antibiotic resistance in Massachusetts increased from 3,861 in 2000 to 11,218 in 2007. The inflation-adjusted total cost more than doubled over the 7 years, from $135 to $285 million. However, the length of stay (LOS) per patient for drug-resistant infections dropped by 4.5 days, and the cost per patient fell by nearly $10,000.
In contrast, the length of stay for drug-susceptible infections didn't change during the study period (just under 5 days), while the cost per patient with susceptible infections rose only slightly.
The drop in LOS and cost per patient with drug-resistant infections is largely explained by the dramatic shift in patient age, particularly among 19- to 64-year-olds: In 2000, that age group accounted for 30% of drug-resistant infection discharges, whereas in 2007 the proportion had risen to 45.5%. At the same time, the 65- to 80-year-old group dropped from 38% to 25%. While the proportion of infections due to drug-resistant organisms rose in all age groups, the greatest rise was among working-age adults, Dr. Foster noted.
Not surprisingly, then, was the concurrent payer shift: Medicare's proportion of the cost dropped from 73% in 2000 to 58% in 2007, while Medicaid's rose from 6% to 15%. The proportion paid by “other,” including private insurance, rose from 20.5% to 28%, she said.
There were also declines in inpatient mortality due to drug-resistant infections (from 11% to 5%) and in discharge of patients to nursing homes (32% to 28%), with a concomitant increase in patients returning home from the hospital (33% to 48%).
The second study, conducted by Dr. Rebecca Roberts and her associates for the Chicago Antimicrobial Resistance Project, analyzed discharge data at Cook County Hospital for a random sample of 1,391 high-risk (more than five ICD-9 codes, excluding trauma, burn, or obstetric care) adult patients, of whom 13.5% (188) had an antibiotic-resistant infection (ARI). Societal costs for the study year 2000 were estimated at $10.7-$15 million, or $13.35 million in 2008 dollars (Clin. Infect. Dis. 2009;49:1175-84).
In that study, LOS was three times longer for the patients with ARIs (24 vs. 8 days) and mortality 6 times higher (18% vs. 3%). Total inpatient costs were $58,029, compared with $13,210 for non-ARI patients. Even the daily cost was $517 greater for the ARI group, she noted.
The most common type of ARI was MRSA (43%), followed by vancomycin-resistant enterococci (VRE, 31%), Escherichia coli/Klebsiella species (16%), and multiple infections (6%). By cost, however, VRE accounted for the greatest proportion (36%), followed by MRSA (34%), and multiple infections (16%).
After publication of the study, Dr. Foster collaborated with Dr. Roberts in extrapolating the Chicago data to the entire United States: In 2000, there were 900,000 admissions with the same criteria the study used. Applying the costs found in that study gives $16.6-$26 billion in additional health care costs (the range reflects different inflation adjustments). Updating the figure to 2009 costs using the Consumer Price Index gives an estimated $21-$34 billion, while using medical inflation rates boosts the figures to as high as $24-$38 billion.
The third study, also unpublished work by Dr. Foster and her associates, was an Internet-based survey of more than 300 respondents recruited from MRSA chat rooms, listservs, and Google Adwords. Acknowledging the limitations of such surveys—particularly the bias toward younger, healthier Internet users with strong opinions—she described “some heart-rending responses,” including one from parents who felt they had to send their children away to prevent transmission.
Respondents reported a mean out-of-pocket expenditure of $2,251, including copays for office visits, prescription drugs, and hospital stays. Nearly 70% reported having private insurance (HMO or PPO), and 14% said they were uninsured, which approximately reflects the national average, Dr. Foster said.
“Individuals and households affected by drug resistance bear a large uncompensated burden in terms of out-of-pocket expenses and lost wages,” she concluded.
A related video is at www.youtube.com/InternalMedicineNews
Major Finding: The overall cost of antimicrobial resistance is rising, but because patients now are younger and living longer, the burden has shifted from Medicare to private insurance.
Data Source: Two studies assessing hospital database data and one Internet survey.
Disclosures: Supported by unrestricted educational grant from bioMérieux.
BETHESDA, MD. — The overall cost burden of antimicrobial resistance—as high as $38 billion in one 2009 hospital estimate—has shifted sharply from Medicare to private payers over the last decade.
Medicare still pays the majority of the costs for excess length of stay, increased use of more expensive drugs, and poorer health attributable to treatment-resistant infections. However, the rise in infections caused by methicillin-resistant Staphylococcus aureus (MRSA), which largely affects younger, healthier individuals, has meant that the overall cost per patient has declined but more is being borne by private HMOs and PPOs, Susan D. Foster, Ph.D., said at the 2010 Conference on Antimicrobial Resistance sponsored by the National Foundation for Infectious Diseases.
“There's been a major shift in who's actually paying. I don't think the insurance companies are quite aware of this,” said Dr. Foster, professor of international health at Boston University and director of public policy and education for the Alliance for the Prudent Use of Antibiotics at Tufts University, Boston.
Dr. Foster analyzed data from three studies. In an unpublished study, she and her associates reviewed Massachusetts hospital discharge data from 2000 to 2007 to look for ICD-9 “VO9” codes, which are specific for drug-resistant infections. Although these codes are difficult to use and therefore represent a study limitation, they do allow for analysis of trends over time, she explained.
Overall, the number of hospital discharges reporting antibiotic resistance in Massachusetts increased from 3,861 in 2000 to 11,218 in 2007. The inflation-adjusted total cost more than doubled over the 7 years, from $135 to $285 million. However, the length of stay (LOS) per patient for drug-resistant infections dropped by 4.5 days, and the cost per patient fell by nearly $10,000.
In contrast, the length of stay for drug-susceptible infections didn't change during the study period (just under 5 days), while the cost per patient with susceptible infections rose only slightly.
The drop in LOS and cost per patient with drug-resistant infections is largely explained by the dramatic shift in patient age, particularly among 19- to 64-year-olds: In 2000, that age group accounted for 30% of drug-resistant infection discharges, whereas in 2007 the proportion had risen to 45.5%. At the same time, the 65- to 80-year-old group dropped from 38% to 25%. While the proportion of infections due to drug-resistant organisms rose in all age groups, the greatest rise was among working-age adults, Dr. Foster noted.
Not surprisingly, then, was the concurrent payer shift: Medicare's proportion of the cost dropped from 73% in 2000 to 58% in 2007, while Medicaid's rose from 6% to 15%. The proportion paid by “other,” including private insurance, rose from 20.5% to 28%, she said.
There were also declines in inpatient mortality due to drug-resistant infections (from 11% to 5%) and in discharge of patients to nursing homes (32% to 28%), with a concomitant increase in patients returning home from the hospital (33% to 48%).
The second study, conducted by Dr. Rebecca Roberts and her associates for the Chicago Antimicrobial Resistance Project, analyzed discharge data at Cook County Hospital for a random sample of 1,391 high-risk (more than five ICD-9 codes, excluding trauma, burn, or obstetric care) adult patients, of whom 13.5% (188) had an antibiotic-resistant infection (ARI). Societal costs for the study year 2000 were estimated at $10.7-$15 million, or $13.35 million in 2008 dollars (Clin. Infect. Dis. 2009;49:1175-84).
In that study, LOS was three times longer for the patients with ARIs (24 vs. 8 days) and mortality 6 times higher (18% vs. 3%). Total inpatient costs were $58,029, compared with $13,210 for non-ARI patients. Even the daily cost was $517 greater for the ARI group, she noted.
The most common type of ARI was MRSA (43%), followed by vancomycin-resistant enterococci (VRE, 31%), Escherichia coli/Klebsiella species (16%), and multiple infections (6%). By cost, however, VRE accounted for the greatest proportion (36%), followed by MRSA (34%), and multiple infections (16%).
After publication of the study, Dr. Foster collaborated with Dr. Roberts in extrapolating the Chicago data to the entire United States: In 2000, there were 900,000 admissions with the same criteria the study used. Applying the costs found in that study gives $16.6-$26 billion in additional health care costs (the range reflects different inflation adjustments). Updating the figure to 2009 costs using the Consumer Price Index gives an estimated $21-$34 billion, while using medical inflation rates boosts the figures to as high as $24-$38 billion.
The third study, also unpublished work by Dr. Foster and her associates, was an Internet-based survey of more than 300 respondents recruited from MRSA chat rooms, listservs, and Google Adwords. Acknowledging the limitations of such surveys—particularly the bias toward younger, healthier Internet users with strong opinions—she described “some heart-rending responses,” including one from parents who felt they had to send their children away to prevent transmission.
Respondents reported a mean out-of-pocket expenditure of $2,251, including copays for office visits, prescription drugs, and hospital stays. Nearly 70% reported having private insurance (HMO or PPO), and 14% said they were uninsured, which approximately reflects the national average, Dr. Foster said.
“Individuals and households affected by drug resistance bear a large uncompensated burden in terms of out-of-pocket expenses and lost wages,” she concluded.
A related video is at www.youtube.com/InternalMedicineNews
Major Finding: The overall cost of antimicrobial resistance is rising, but because patients now are younger and living longer, the burden has shifted from Medicare to private insurance.
Data Source: Two studies assessing hospital database data and one Internet survey.
Disclosures: Supported by unrestricted educational grant from bioMérieux.
BETHESDA, MD. — The overall cost burden of antimicrobial resistance—as high as $38 billion in one 2009 hospital estimate—has shifted sharply from Medicare to private payers over the last decade.
Medicare still pays the majority of the costs for excess length of stay, increased use of more expensive drugs, and poorer health attributable to treatment-resistant infections. However, the rise in infections caused by methicillin-resistant Staphylococcus aureus (MRSA), which largely affects younger, healthier individuals, has meant that the overall cost per patient has declined but more is being borne by private HMOs and PPOs, Susan D. Foster, Ph.D., said at the 2010 Conference on Antimicrobial Resistance sponsored by the National Foundation for Infectious Diseases.
“There's been a major shift in who's actually paying. I don't think the insurance companies are quite aware of this,” said Dr. Foster, professor of international health at Boston University and director of public policy and education for the Alliance for the Prudent Use of Antibiotics at Tufts University, Boston.
Dr. Foster analyzed data from three studies. In an unpublished study, she and her associates reviewed Massachusetts hospital discharge data from 2000 to 2007 to look for ICD-9 “VO9” codes, which are specific for drug-resistant infections. Although these codes are difficult to use and therefore represent a study limitation, they do allow for analysis of trends over time, she explained.
Overall, the number of hospital discharges reporting antibiotic resistance in Massachusetts increased from 3,861 in 2000 to 11,218 in 2007. The inflation-adjusted total cost more than doubled over the 7 years, from $135 to $285 million. However, the length of stay (LOS) per patient for drug-resistant infections dropped by 4.5 days, and the cost per patient fell by nearly $10,000.
In contrast, the length of stay for drug-susceptible infections didn't change during the study period (just under 5 days), while the cost per patient with susceptible infections rose only slightly.
The drop in LOS and cost per patient with drug-resistant infections is largely explained by the dramatic shift in patient age, particularly among 19- to 64-year-olds: In 2000, that age group accounted for 30% of drug-resistant infection discharges, whereas in 2007 the proportion had risen to 45.5%. At the same time, the 65- to 80-year-old group dropped from 38% to 25%. While the proportion of infections due to drug-resistant organisms rose in all age groups, the greatest rise was among working-age adults, Dr. Foster noted.
Not surprisingly, then, was the concurrent payer shift: Medicare's proportion of the cost dropped from 73% in 2000 to 58% in 2007, while Medicaid's rose from 6% to 15%. The proportion paid by “other,” including private insurance, rose from 20.5% to 28%, she said.
There were also declines in inpatient mortality due to drug-resistant infections (from 11% to 5%) and in discharge of patients to nursing homes (32% to 28%), with a concomitant increase in patients returning home from the hospital (33% to 48%).
The second study, conducted by Dr. Rebecca Roberts and her associates for the Chicago Antimicrobial Resistance Project, analyzed discharge data at Cook County Hospital for a random sample of 1,391 high-risk (more than five ICD-9 codes, excluding trauma, burn, or obstetric care) adult patients, of whom 13.5% (188) had an antibiotic-resistant infection (ARI). Societal costs for the study year 2000 were estimated at $10.7-$15 million, or $13.35 million in 2008 dollars (Clin. Infect. Dis. 2009;49:1175-84).
In that study, LOS was three times longer for the patients with ARIs (24 vs. 8 days) and mortality 6 times higher (18% vs. 3%). Total inpatient costs were $58,029, compared with $13,210 for non-ARI patients. Even the daily cost was $517 greater for the ARI group, she noted.
The most common type of ARI was MRSA (43%), followed by vancomycin-resistant enterococci (VRE, 31%), Escherichia coli/Klebsiella species (16%), and multiple infections (6%). By cost, however, VRE accounted for the greatest proportion (36%), followed by MRSA (34%), and multiple infections (16%).
After publication of the study, Dr. Foster collaborated with Dr. Roberts in extrapolating the Chicago data to the entire United States: In 2000, there were 900,000 admissions with the same criteria the study used. Applying the costs found in that study gives $16.6-$26 billion in additional health care costs (the range reflects different inflation adjustments). Updating the figure to 2009 costs using the Consumer Price Index gives an estimated $21-$34 billion, while using medical inflation rates boosts the figures to as high as $24-$38 billion.
The third study, also unpublished work by Dr. Foster and her associates, was an Internet-based survey of more than 300 respondents recruited from MRSA chat rooms, listservs, and Google Adwords. Acknowledging the limitations of such surveys—particularly the bias toward younger, healthier Internet users with strong opinions—she described “some heart-rending responses,” including one from parents who felt they had to send their children away to prevent transmission.
Respondents reported a mean out-of-pocket expenditure of $2,251, including copays for office visits, prescription drugs, and hospital stays. Nearly 70% reported having private insurance (HMO or PPO), and 14% said they were uninsured, which approximately reflects the national average, Dr. Foster said.
“Individuals and households affected by drug resistance bear a large uncompensated burden in terms of out-of-pocket expenses and lost wages,” she concluded.
A related video is at www.youtube.com/InternalMedicineNews
High-Dose Flu Vaccine May Be Better for Older Adults
Major Finding: Fluzone High-Dose influenza vaccine was more immunogenic and reactogenic than the standard dose in adults aged 65 years and older.
Data Source: Phase III, multicenter, randomized, double-blind study of 3,876 participants.
Disclosures: The study was funded by Sanofi-Pasteur.
ATLANTA — Fluzone High-Dose vaccine was significantly more immunogenic than standard-dose influenza vaccine in a study of 3,876 individuals aged 65 years or older.
Sanofi-Pasteur's Fluzone High-Dose was licensed last December for use in that age group. In the phase III, multicenter, double-blind study, the participants were randomized in a 2:1 ratio to receive either high-dose (HD) vaccine containing 60 mcg hemagglutinin per strain or standard dose (SD) with 15 mcg hemagglutinin per strain. Blood specimens were obtained before vaccination and on day 28 for evaluation of influenza antibodies. Safety data were collected by diary card at 1-week and 4-week visits, and by telephone for up to 6 months after vaccination, Dr. David Greenberg said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.
Reported injection site reactions within 7 days of vaccination were more common with HD. Pain was reported by 36% of the 2,573 participants who were assessed after receiving the HD vaccine and in 24% of the 1,260 in the SD group. Grade III pain was uncommon in both groups (0.3% with HD and 0.2% with SD). Erythema occurred in 15% with HD and 11% with SD, and swelling in 9% and 6%, respectively. Grade III erythema and swelling occurred in less than 2% of both groups. Most injection site reactions were mild to moderate and resolved within 3 days, said Dr. Greenberg, Sanofi-Pasteur's senior director of scientific and medical affairs.
Rates of systemic reactions were similar between the HD and SD groups, including myalgia (21% HD, 18% SD), malaise (18%, 14%), headache (17%, 14%), and fever (0%, 0.1%). Adverse events in the 30 minutes following vaccination were comparable (about 0.3% in both groups), as were rates of unsolicited adverse events within 28 days post vaccination (22% of both groups) (J. Infect. Dis. 2009;200:172-80).
Only two serious adverse events were reported by investigators as being vaccine-related: an exacerbation of Crohn's disease 2 days after receipt of HD vaccine, and a new diagnosis of myasthenia gravis 1 month after SD vaccination.
To satisfy requirements of the Food and Drug Administration, Fluzone was required to demonstrate superiority to SD vaccine for at least two of the three vaccine influenza strains, without inferiority for any strain. Fluzone achieved superiority—as determined by significantly greater geometric mean antibody titers—for the H1N1 and H3N2 strains and noninferiority for the B strain. The HD/SD geometric mean antibody titer ratios were 1.7 for H1N1, 1.8 for H3N2, and 1.3 for B, Dr. Greenberg reported.
The differences in immunogenicity were maintained for persons younger than 75 years vs. those 75 and older, for those with or without a history of cardiovascular or respiratory disease, and for both males and females, he added.
Sanofi-Pasteur began a 3-year randomized, blinded postlicensure efficacy trial of Fluzone High-Dose in September 2009. The vaccine will be available for the 2010-2011 flu immunization season.
Major Finding: Fluzone High-Dose influenza vaccine was more immunogenic and reactogenic than the standard dose in adults aged 65 years and older.
Data Source: Phase III, multicenter, randomized, double-blind study of 3,876 participants.
Disclosures: The study was funded by Sanofi-Pasteur.
ATLANTA — Fluzone High-Dose vaccine was significantly more immunogenic than standard-dose influenza vaccine in a study of 3,876 individuals aged 65 years or older.
Sanofi-Pasteur's Fluzone High-Dose was licensed last December for use in that age group. In the phase III, multicenter, double-blind study, the participants were randomized in a 2:1 ratio to receive either high-dose (HD) vaccine containing 60 mcg hemagglutinin per strain or standard dose (SD) with 15 mcg hemagglutinin per strain. Blood specimens were obtained before vaccination and on day 28 for evaluation of influenza antibodies. Safety data were collected by diary card at 1-week and 4-week visits, and by telephone for up to 6 months after vaccination, Dr. David Greenberg said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.
Reported injection site reactions within 7 days of vaccination were more common with HD. Pain was reported by 36% of the 2,573 participants who were assessed after receiving the HD vaccine and in 24% of the 1,260 in the SD group. Grade III pain was uncommon in both groups (0.3% with HD and 0.2% with SD). Erythema occurred in 15% with HD and 11% with SD, and swelling in 9% and 6%, respectively. Grade III erythema and swelling occurred in less than 2% of both groups. Most injection site reactions were mild to moderate and resolved within 3 days, said Dr. Greenberg, Sanofi-Pasteur's senior director of scientific and medical affairs.
Rates of systemic reactions were similar between the HD and SD groups, including myalgia (21% HD, 18% SD), malaise (18%, 14%), headache (17%, 14%), and fever (0%, 0.1%). Adverse events in the 30 minutes following vaccination were comparable (about 0.3% in both groups), as were rates of unsolicited adverse events within 28 days post vaccination (22% of both groups) (J. Infect. Dis. 2009;200:172-80).
Only two serious adverse events were reported by investigators as being vaccine-related: an exacerbation of Crohn's disease 2 days after receipt of HD vaccine, and a new diagnosis of myasthenia gravis 1 month after SD vaccination.
To satisfy requirements of the Food and Drug Administration, Fluzone was required to demonstrate superiority to SD vaccine for at least two of the three vaccine influenza strains, without inferiority for any strain. Fluzone achieved superiority—as determined by significantly greater geometric mean antibody titers—for the H1N1 and H3N2 strains and noninferiority for the B strain. The HD/SD geometric mean antibody titer ratios were 1.7 for H1N1, 1.8 for H3N2, and 1.3 for B, Dr. Greenberg reported.
The differences in immunogenicity were maintained for persons younger than 75 years vs. those 75 and older, for those with or without a history of cardiovascular or respiratory disease, and for both males and females, he added.
Sanofi-Pasteur began a 3-year randomized, blinded postlicensure efficacy trial of Fluzone High-Dose in September 2009. The vaccine will be available for the 2010-2011 flu immunization season.
Major Finding: Fluzone High-Dose influenza vaccine was more immunogenic and reactogenic than the standard dose in adults aged 65 years and older.
Data Source: Phase III, multicenter, randomized, double-blind study of 3,876 participants.
Disclosures: The study was funded by Sanofi-Pasteur.
ATLANTA — Fluzone High-Dose vaccine was significantly more immunogenic than standard-dose influenza vaccine in a study of 3,876 individuals aged 65 years or older.
Sanofi-Pasteur's Fluzone High-Dose was licensed last December for use in that age group. In the phase III, multicenter, double-blind study, the participants were randomized in a 2:1 ratio to receive either high-dose (HD) vaccine containing 60 mcg hemagglutinin per strain or standard dose (SD) with 15 mcg hemagglutinin per strain. Blood specimens were obtained before vaccination and on day 28 for evaluation of influenza antibodies. Safety data were collected by diary card at 1-week and 4-week visits, and by telephone for up to 6 months after vaccination, Dr. David Greenberg said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.
Reported injection site reactions within 7 days of vaccination were more common with HD. Pain was reported by 36% of the 2,573 participants who were assessed after receiving the HD vaccine and in 24% of the 1,260 in the SD group. Grade III pain was uncommon in both groups (0.3% with HD and 0.2% with SD). Erythema occurred in 15% with HD and 11% with SD, and swelling in 9% and 6%, respectively. Grade III erythema and swelling occurred in less than 2% of both groups. Most injection site reactions were mild to moderate and resolved within 3 days, said Dr. Greenberg, Sanofi-Pasteur's senior director of scientific and medical affairs.
Rates of systemic reactions were similar between the HD and SD groups, including myalgia (21% HD, 18% SD), malaise (18%, 14%), headache (17%, 14%), and fever (0%, 0.1%). Adverse events in the 30 minutes following vaccination were comparable (about 0.3% in both groups), as were rates of unsolicited adverse events within 28 days post vaccination (22% of both groups) (J. Infect. Dis. 2009;200:172-80).
Only two serious adverse events were reported by investigators as being vaccine-related: an exacerbation of Crohn's disease 2 days after receipt of HD vaccine, and a new diagnosis of myasthenia gravis 1 month after SD vaccination.
To satisfy requirements of the Food and Drug Administration, Fluzone was required to demonstrate superiority to SD vaccine for at least two of the three vaccine influenza strains, without inferiority for any strain. Fluzone achieved superiority—as determined by significantly greater geometric mean antibody titers—for the H1N1 and H3N2 strains and noninferiority for the B strain. The HD/SD geometric mean antibody titer ratios were 1.7 for H1N1, 1.8 for H3N2, and 1.3 for B, Dr. Greenberg reported.
The differences in immunogenicity were maintained for persons younger than 75 years vs. those 75 and older, for those with or without a history of cardiovascular or respiratory disease, and for both males and females, he added.
Sanofi-Pasteur began a 3-year randomized, blinded postlicensure efficacy trial of Fluzone High-Dose in September 2009. The vaccine will be available for the 2010-2011 flu immunization season.
Flu Vaccination for All Adults Endorsed for 2010-2011 Season
ATLANTA — The recommended target groups for annual influenza immunization have finally been broadened to include virtually the entire U.S. population.
Starting with the 2010-2011 season, universal immunization against influenza for everyone aged 6 months and older has the backing of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.
The committee voted unanimously (with one member abstaining) to recommend annual influenza immunization for people aged 19-49 years who had not already been targeted in previous recommendations. The new group comprises 15% of the U.S. population aged 6 months and older. About 50% of 19- to 49-year-olds already had indications for immunization, including individuals with chronic medical conditions, pregnant women, health care workers, and household contacts of high-risk individuals.
Despite previous recommendations aimed at expanded immunization of adults, “coverage among 19- to 49-year-olds has been low regardless of indication for vaccination,” said Dr. Anthony Fiore of the CDC's National Center for Immunization and Respiratory Diseases.
Atlanta internist Sandra Fryhofer, American College of Physicians liasion to the ACIP, enthusiastically endorsed the move. “This is really exciting. It's about time, and it makes giving flu vaccines in the office much simpler. You won't have to wade through risk factors. The only decision will be whether you give a shot—the inactivated vaccine—or the live vaccine,” she said in an interview.
Dr. Doug Campos-Outcalt, liaison to the ACIP from the American Academy of Family Physicians, expressed similar support. “We polled our members, and a very large majority is in favor of just a uniform [recommendation] because it will be so much easier to remember. The implementation with that 15% is not going to be a huge challenge,” particularly with vaccination available at pharmacies and other alternative sites.
He added that the move should not overshadow the need to target health care workers specifically for influenza immunization. “All professional organizations need to work on that,” said Dr. Campos-Outcalt, of the department of family and community medicine at the University of Arizona, Phoenix.
The ACIP vote was made amidst a confluence of factors, most notably the 2009 influenza A(H1N1) pandemic. About 90% of hospitalizations and deaths caused by the pandemic strain occurred among individuals younger than 65 years, many of them adults aged 19-49 years. It's likely that 2009 H1N1–like viruses will continue circulating in 2010-2011, and it's unknown what proportion of healthy adults now have immunity, Dr. Fiore said.
Adults aged 19-24 years had been among the targeted priority groups for the 2009 H1N1 monovalent vaccine. Obesity, which affects 28% of U.S. adults, was identified as a new independent risk factor for severe illness with the 2009 H1N1 strain, he noted.
The composition of the northern hemisphere's 2010-2011 seasonal influenza vaccine, which was announced at a recent Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee meeting, will contain the same H1N1 virus used in the 2009 H1N1 monovalent vaccine.
Two newly licensed influenza vaccines and expanded age indications for two others should help ensure an adequate supply. These include Agriflu (Novartis) for adults 18 years and older and Fluzone High-Dose (Sanofi-Pasteur) for those aged 65 years and older. (See related story at right.) CSL's Afluria indication has been expanded to include people aged 6 months and older, and GlaxoSmithKline's Fluarix is now licensed for those aged 36 months and older, Dr. Fiore said.
“It's just exciting to have new things happening in flu,” Dr. Fryhofer said. “This is a deadly disease that kills 36,000 people a year. It's great that now we have a uniform indication to get people protected, and that we have more things to protect them with and more companies making them, so hopefully we won't have more shortages and delays like we've had in the past.”
Disclosures: Dr. Fiore and Dr. Fryhofer had no financial disclosures. Dr. Campos-Outcalt has given vaccine talks for the France Foundation, an independent medical education company that receives grants from various sources.
Healthy adults aged 19-49 years should receive the influenza vaccination annually, according to new recommendations.
Source ©Joe Raedle/Getty Images www.DavidLubarsky.com
This Month's Talk Back Question
How will your practice respond to the endorsement of universal influenza immunization?
ATLANTA — The recommended target groups for annual influenza immunization have finally been broadened to include virtually the entire U.S. population.
Starting with the 2010-2011 season, universal immunization against influenza for everyone aged 6 months and older has the backing of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.
The committee voted unanimously (with one member abstaining) to recommend annual influenza immunization for people aged 19-49 years who had not already been targeted in previous recommendations. The new group comprises 15% of the U.S. population aged 6 months and older. About 50% of 19- to 49-year-olds already had indications for immunization, including individuals with chronic medical conditions, pregnant women, health care workers, and household contacts of high-risk individuals.
Despite previous recommendations aimed at expanded immunization of adults, “coverage among 19- to 49-year-olds has been low regardless of indication for vaccination,” said Dr. Anthony Fiore of the CDC's National Center for Immunization and Respiratory Diseases.
Atlanta internist Sandra Fryhofer, American College of Physicians liasion to the ACIP, enthusiastically endorsed the move. “This is really exciting. It's about time, and it makes giving flu vaccines in the office much simpler. You won't have to wade through risk factors. The only decision will be whether you give a shot—the inactivated vaccine—or the live vaccine,” she said in an interview.
Dr. Doug Campos-Outcalt, liaison to the ACIP from the American Academy of Family Physicians, expressed similar support. “We polled our members, and a very large majority is in favor of just a uniform [recommendation] because it will be so much easier to remember. The implementation with that 15% is not going to be a huge challenge,” particularly with vaccination available at pharmacies and other alternative sites.
He added that the move should not overshadow the need to target health care workers specifically for influenza immunization. “All professional organizations need to work on that,” said Dr. Campos-Outcalt, of the department of family and community medicine at the University of Arizona, Phoenix.
The ACIP vote was made amidst a confluence of factors, most notably the 2009 influenza A(H1N1) pandemic. About 90% of hospitalizations and deaths caused by the pandemic strain occurred among individuals younger than 65 years, many of them adults aged 19-49 years. It's likely that 2009 H1N1–like viruses will continue circulating in 2010-2011, and it's unknown what proportion of healthy adults now have immunity, Dr. Fiore said.
Adults aged 19-24 years had been among the targeted priority groups for the 2009 H1N1 monovalent vaccine. Obesity, which affects 28% of U.S. adults, was identified as a new independent risk factor for severe illness with the 2009 H1N1 strain, he noted.
The composition of the northern hemisphere's 2010-2011 seasonal influenza vaccine, which was announced at a recent Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee meeting, will contain the same H1N1 virus used in the 2009 H1N1 monovalent vaccine.
Two newly licensed influenza vaccines and expanded age indications for two others should help ensure an adequate supply. These include Agriflu (Novartis) for adults 18 years and older and Fluzone High-Dose (Sanofi-Pasteur) for those aged 65 years and older. (See related story at right.) CSL's Afluria indication has been expanded to include people aged 6 months and older, and GlaxoSmithKline's Fluarix is now licensed for those aged 36 months and older, Dr. Fiore said.
“It's just exciting to have new things happening in flu,” Dr. Fryhofer said. “This is a deadly disease that kills 36,000 people a year. It's great that now we have a uniform indication to get people protected, and that we have more things to protect them with and more companies making them, so hopefully we won't have more shortages and delays like we've had in the past.”
Disclosures: Dr. Fiore and Dr. Fryhofer had no financial disclosures. Dr. Campos-Outcalt has given vaccine talks for the France Foundation, an independent medical education company that receives grants from various sources.
Healthy adults aged 19-49 years should receive the influenza vaccination annually, according to new recommendations.
Source ©Joe Raedle/Getty Images www.DavidLubarsky.com
This Month's Talk Back Question
How will your practice respond to the endorsement of universal influenza immunization?
ATLANTA — The recommended target groups for annual influenza immunization have finally been broadened to include virtually the entire U.S. population.
Starting with the 2010-2011 season, universal immunization against influenza for everyone aged 6 months and older has the backing of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.
The committee voted unanimously (with one member abstaining) to recommend annual influenza immunization for people aged 19-49 years who had not already been targeted in previous recommendations. The new group comprises 15% of the U.S. population aged 6 months and older. About 50% of 19- to 49-year-olds already had indications for immunization, including individuals with chronic medical conditions, pregnant women, health care workers, and household contacts of high-risk individuals.
Despite previous recommendations aimed at expanded immunization of adults, “coverage among 19- to 49-year-olds has been low regardless of indication for vaccination,” said Dr. Anthony Fiore of the CDC's National Center for Immunization and Respiratory Diseases.
Atlanta internist Sandra Fryhofer, American College of Physicians liasion to the ACIP, enthusiastically endorsed the move. “This is really exciting. It's about time, and it makes giving flu vaccines in the office much simpler. You won't have to wade through risk factors. The only decision will be whether you give a shot—the inactivated vaccine—or the live vaccine,” she said in an interview.
Dr. Doug Campos-Outcalt, liaison to the ACIP from the American Academy of Family Physicians, expressed similar support. “We polled our members, and a very large majority is in favor of just a uniform [recommendation] because it will be so much easier to remember. The implementation with that 15% is not going to be a huge challenge,” particularly with vaccination available at pharmacies and other alternative sites.
He added that the move should not overshadow the need to target health care workers specifically for influenza immunization. “All professional organizations need to work on that,” said Dr. Campos-Outcalt, of the department of family and community medicine at the University of Arizona, Phoenix.
The ACIP vote was made amidst a confluence of factors, most notably the 2009 influenza A(H1N1) pandemic. About 90% of hospitalizations and deaths caused by the pandemic strain occurred among individuals younger than 65 years, many of them adults aged 19-49 years. It's likely that 2009 H1N1–like viruses will continue circulating in 2010-2011, and it's unknown what proportion of healthy adults now have immunity, Dr. Fiore said.
Adults aged 19-24 years had been among the targeted priority groups for the 2009 H1N1 monovalent vaccine. Obesity, which affects 28% of U.S. adults, was identified as a new independent risk factor for severe illness with the 2009 H1N1 strain, he noted.
The composition of the northern hemisphere's 2010-2011 seasonal influenza vaccine, which was announced at a recent Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee meeting, will contain the same H1N1 virus used in the 2009 H1N1 monovalent vaccine.
Two newly licensed influenza vaccines and expanded age indications for two others should help ensure an adequate supply. These include Agriflu (Novartis) for adults 18 years and older and Fluzone High-Dose (Sanofi-Pasteur) for those aged 65 years and older. (See related story at right.) CSL's Afluria indication has been expanded to include people aged 6 months and older, and GlaxoSmithKline's Fluarix is now licensed for those aged 36 months and older, Dr. Fiore said.
“It's just exciting to have new things happening in flu,” Dr. Fryhofer said. “This is a deadly disease that kills 36,000 people a year. It's great that now we have a uniform indication to get people protected, and that we have more things to protect them with and more companies making them, so hopefully we won't have more shortages and delays like we've had in the past.”
Disclosures: Dr. Fiore and Dr. Fryhofer had no financial disclosures. Dr. Campos-Outcalt has given vaccine talks for the France Foundation, an independent medical education company that receives grants from various sources.
Healthy adults aged 19-49 years should receive the influenza vaccination annually, according to new recommendations.
Source ©Joe Raedle/Getty Images www.DavidLubarsky.com
This Month's Talk Back Question
How will your practice respond to the endorsement of universal influenza immunization?
Invasive CA-MRSA Infections Increasing in Children
Bethesda, Md. — Invasive infections in children caused by community-acquired methicillin-resistant Staphylococcus aureus are on the rise.
Rates of severe infection have been rising as MRSA has become more common in the community. Recommendations from the American Academy of Pediatrics state that in areas where MRSA accounts for 10% or more of CA-MRSA isolates, initial empiric therapy of severe infections that could be due to S. aureus should include vancomycin. Naficillin should also be included because it’s superior to vancomycin for treating methicillin-sensitive S. aureus (MSSA).
Use of clindamycin should be based on local susceptibility. “You need to know the clindamycin susceptibility of CA-MRSA isolates in your area,” said Dr. Kaplan, head of the pediatric infectious disease section at Baylor College of Medicine and chief of the infectious disease service at Texas Children’s Hospital, both in Houston.
At Le Bonheur Children’s Medical Center in Memphis, the rate of acute osteoarticular infections increased from 2.6 to 6.0 per 1,000 admissions between 2000 and 2004. While the proportion of those infections caused by MSSA remained constant at 10%-13%, those caused by MRSA rose from 4% to 40%. Moreover, 71% of the patients with MRSA had subperiosteal abscesses, compared with 38% of those with MSSA, and surgical procedures were required in 91% with MRSA versus 62% with MSSA (J. Pediatr. Orthop. 2006;26:701-2). Similar findings have been reported elsewhere, Dr. Kaplan noted.
Recent studies have shown that osteomyelitis caused by PVL-positive S. aureus strains was associated with more severe local disease and a greater systemic inflammatory response, compared with osteomyelitis caused by S. aureus not containing that gene (Pediatrics 2006;117:433-40), and that PVL-positive isolates were associated with an increased likelihood of complications in children with osteomyelitis (Pediatr. Infect. Dis. J. 2005;24:284-5).
MRI appears to be the optimal method for detection of osteomyelitis resulting from community-acquired S. aureus.
In a retrospective study by Dr. Kaplan and his associates of 199 such children seen between August 2001 and December 2006, MRI had a sensitivity of 98% for diagnosing the infection, compared with a 53% sensitivity with bone scintigraphy. Of 36 patients who had both imaging studies done, results were discordant in 17 cases. In all of those, the MRI diagnosis proved to be the correct one (Pediatr. Radiol. 2008;38:841-7).
The study also showed that MRI – but not bone scan – allowed for visualization of extraosseous complications, including subperiosteal abscesses in 77 patients, pyomyositis in 43, septic arthritis in 31, and deep vein thrombosis in 12. “Clearly, MRI was superior to bone scan in detecting bone infection. In our institution, MRI is the first thing we use. It can help pick up other areas of concern,” Dr. Kaplan noted.
Some of these extraosseous complications also appear to be on the rise. At least two recent reports have documented cases of venous thrombophlebitis among children with invasive S. aureus infections. At Children’s Medical Center in Dallas, 10 of 35 children with confirmed osteomyelitis developed deep vein thrombosis during the acute infection, with evidence of dissemination in six (J. Pediatr. 2006;149:537-41).
And at Texas Children’s, Dr. Kaplan and his associates reported on 9 children seen between 1999 and 2004 who had venous thrombosis adjacent to the site of staphylococcal osteomyelitis. Seven patients had community-acquired infections caused by MRSA belonging to the same USA300 clonal group, and all 7 carried PVL genes. The USA300 clone may “have a unique propensity to cause [venous thrombosis] in association with osteomyelitis,” they concluded (Pediatrics 2006;117:1673-9).
Since then, they’ve seen about 40-50 children with osteomyelitis who developed thrombosis, despite not having genetic prothrombotic conditions. “We don’t understand what’s going on. There’s clearly something different about these community isolates, especially the USA300 strain,” Dr. Kaplan commented.
The USA300 MRSA genotype has also been implicated in septic arthritis. Among 44 isolates taken from 45 patients at Texas Children’s with septic arthritis caused by S. aureus, 16 were MRSA; of these, 13 were USA300 and 14 were PVL-positive. Infections caused by USA300 were more likely to be associated with a longer duration of fever, bacteremia, and a C-reactive protein level of 10 mg/dL or greater (Pediatr. Infect. Dis. J. 2009;28:1076-80).
Rates of pyomyositis and myositis also have been on the rise at Texas Children’s, and can be correlated to the emergence of CA-MRSA. Among 45 previously healthy children with bacterial pyomyositis or myositis, the cause was S. aureus in 58%. Of 24 community-acquired S. aureus isolates that were available, 15 were MRSA and 9 were MSSA. A total of 16 (including all the MRSA) isolates were found to be USA300, and 17 carried the PVL genes. The presence of MRSA, USA300, and/or the PVL genes was associated with a greater requirement for drainage procedures (Clin. Infect. Dis. 2006;43:953-60).
“Infection of muscles is something we just never saw in the past,” Dr. Kaplan commented.
Pulmonary manifestations are another increasingly common complication of CA-MRSA. An investigation of 70 children with invasive staphylococcal infections at Texas Children’s between 2001 and 2004 showed that 47 had MRSA. Compared with 10 who had MSSA, those with MRSA were more likely to have pneumonia, empyema, lung abscess, and atelectasis. The presence of PVL was associated with abnormal chest image findings in patients with secondary pneumonia (Clin. Infect. Dis. 2005;41:583-90).
Influenza complicated by staph infections is also becoming more common, with most of these cases attributable to MRSA. A study by the U. S. Centers for Disease Control and Prevention comparing pediatric deaths during three influenza seasons revealed that bacterial coinfection increased substantially, from 6% in 2004-2005 to 15% in 2005-2006 to 34% in 2006-2007. Isolation of S. aureus from a sterile site rose from just one case in 2004-2005 to 22 in 2006-2007, of which two-thirds were MRSA. Children with staph coinfection were significantly older and more likely to have pneumonia and acute respiratory distress syndrome than those not coinfected (Pediatrics 2008;122:805-11).
Severe staphylococcal infections also are emerging along with CA-MRSA. In a descriptive report of 14 previously healthy adolescents with severe community-acquired S. aureus infections admitted to intensive care at Texas Children’s with coagulopathy and sepsis, 12 were found to have MRSA and 2 had MSSA. Thirteen also had pulmonary involvement and/or bone and joint infection, four developed vascular complications, and three died. All isolates were identical or closely related to the USA300 clone (Pediatrics 2005;115:642-8).
The typical patient is an adolescent, usually with some trauma to an extremity, who may have underlying osteomyelitis and may develop pulmonary manifestations, and then becomes very ill. “We’ve now had seven deaths due to S. aureus sepsis in otherwise completely healthy children,” Dr. Kaplan said.
Dr. Kaplan (pictured above) has received research grants from Pfizer and Cubist Pharmaceuticals.
Bethesda, Md. — Invasive infections in children caused by community-acquired methicillin-resistant Staphylococcus aureus are on the rise.
Rates of severe infection have been rising as MRSA has become more common in the community. Recommendations from the American Academy of Pediatrics state that in areas where MRSA accounts for 10% or more of CA-MRSA isolates, initial empiric therapy of severe infections that could be due to S. aureus should include vancomycin. Naficillin should also be included because it’s superior to vancomycin for treating methicillin-sensitive S. aureus (MSSA).
Use of clindamycin should be based on local susceptibility. “You need to know the clindamycin susceptibility of CA-MRSA isolates in your area,” said Dr. Kaplan, head of the pediatric infectious disease section at Baylor College of Medicine and chief of the infectious disease service at Texas Children’s Hospital, both in Houston.
At Le Bonheur Children’s Medical Center in Memphis, the rate of acute osteoarticular infections increased from 2.6 to 6.0 per 1,000 admissions between 2000 and 2004. While the proportion of those infections caused by MSSA remained constant at 10%-13%, those caused by MRSA rose from 4% to 40%. Moreover, 71% of the patients with MRSA had subperiosteal abscesses, compared with 38% of those with MSSA, and surgical procedures were required in 91% with MRSA versus 62% with MSSA (J. Pediatr. Orthop. 2006;26:701-2). Similar findings have been reported elsewhere, Dr. Kaplan noted.
Recent studies have shown that osteomyelitis caused by PVL-positive S. aureus strains was associated with more severe local disease and a greater systemic inflammatory response, compared with osteomyelitis caused by S. aureus not containing that gene (Pediatrics 2006;117:433-40), and that PVL-positive isolates were associated with an increased likelihood of complications in children with osteomyelitis (Pediatr. Infect. Dis. J. 2005;24:284-5).
MRI appears to be the optimal method for detection of osteomyelitis resulting from community-acquired S. aureus.
In a retrospective study by Dr. Kaplan and his associates of 199 such children seen between August 2001 and December 2006, MRI had a sensitivity of 98% for diagnosing the infection, compared with a 53% sensitivity with bone scintigraphy. Of 36 patients who had both imaging studies done, results were discordant in 17 cases. In all of those, the MRI diagnosis proved to be the correct one (Pediatr. Radiol. 2008;38:841-7).
The study also showed that MRI – but not bone scan – allowed for visualization of extraosseous complications, including subperiosteal abscesses in 77 patients, pyomyositis in 43, septic arthritis in 31, and deep vein thrombosis in 12. “Clearly, MRI was superior to bone scan in detecting bone infection. In our institution, MRI is the first thing we use. It can help pick up other areas of concern,” Dr. Kaplan noted.
Some of these extraosseous complications also appear to be on the rise. At least two recent reports have documented cases of venous thrombophlebitis among children with invasive S. aureus infections. At Children’s Medical Center in Dallas, 10 of 35 children with confirmed osteomyelitis developed deep vein thrombosis during the acute infection, with evidence of dissemination in six (J. Pediatr. 2006;149:537-41).
And at Texas Children’s, Dr. Kaplan and his associates reported on 9 children seen between 1999 and 2004 who had venous thrombosis adjacent to the site of staphylococcal osteomyelitis. Seven patients had community-acquired infections caused by MRSA belonging to the same USA300 clonal group, and all 7 carried PVL genes. The USA300 clone may “have a unique propensity to cause [venous thrombosis] in association with osteomyelitis,” they concluded (Pediatrics 2006;117:1673-9).
Since then, they’ve seen about 40-50 children with osteomyelitis who developed thrombosis, despite not having genetic prothrombotic conditions. “We don’t understand what’s going on. There’s clearly something different about these community isolates, especially the USA300 strain,” Dr. Kaplan commented.
The USA300 MRSA genotype has also been implicated in septic arthritis. Among 44 isolates taken from 45 patients at Texas Children’s with septic arthritis caused by S. aureus, 16 were MRSA; of these, 13 were USA300 and 14 were PVL-positive. Infections caused by USA300 were more likely to be associated with a longer duration of fever, bacteremia, and a C-reactive protein level of 10 mg/dL or greater (Pediatr. Infect. Dis. J. 2009;28:1076-80).
Rates of pyomyositis and myositis also have been on the rise at Texas Children’s, and can be correlated to the emergence of CA-MRSA. Among 45 previously healthy children with bacterial pyomyositis or myositis, the cause was S. aureus in 58%. Of 24 community-acquired S. aureus isolates that were available, 15 were MRSA and 9 were MSSA. A total of 16 (including all the MRSA) isolates were found to be USA300, and 17 carried the PVL genes. The presence of MRSA, USA300, and/or the PVL genes was associated with a greater requirement for drainage procedures (Clin. Infect. Dis. 2006;43:953-60).
“Infection of muscles is something we just never saw in the past,” Dr. Kaplan commented.
Pulmonary manifestations are another increasingly common complication of CA-MRSA. An investigation of 70 children with invasive staphylococcal infections at Texas Children’s between 2001 and 2004 showed that 47 had MRSA. Compared with 10 who had MSSA, those with MRSA were more likely to have pneumonia, empyema, lung abscess, and atelectasis. The presence of PVL was associated with abnormal chest image findings in patients with secondary pneumonia (Clin. Infect. Dis. 2005;41:583-90).
Influenza complicated by staph infections is also becoming more common, with most of these cases attributable to MRSA. A study by the U. S. Centers for Disease Control and Prevention comparing pediatric deaths during three influenza seasons revealed that bacterial coinfection increased substantially, from 6% in 2004-2005 to 15% in 2005-2006 to 34% in 2006-2007. Isolation of S. aureus from a sterile site rose from just one case in 2004-2005 to 22 in 2006-2007, of which two-thirds were MRSA. Children with staph coinfection were significantly older and more likely to have pneumonia and acute respiratory distress syndrome than those not coinfected (Pediatrics 2008;122:805-11).
Severe staphylococcal infections also are emerging along with CA-MRSA. In a descriptive report of 14 previously healthy adolescents with severe community-acquired S. aureus infections admitted to intensive care at Texas Children’s with coagulopathy and sepsis, 12 were found to have MRSA and 2 had MSSA. Thirteen also had pulmonary involvement and/or bone and joint infection, four developed vascular complications, and three died. All isolates were identical or closely related to the USA300 clone (Pediatrics 2005;115:642-8).
The typical patient is an adolescent, usually with some trauma to an extremity, who may have underlying osteomyelitis and may develop pulmonary manifestations, and then becomes very ill. “We’ve now had seven deaths due to S. aureus sepsis in otherwise completely healthy children,” Dr. Kaplan said.
Dr. Kaplan (pictured above) has received research grants from Pfizer and Cubist Pharmaceuticals.
Bethesda, Md. — Invasive infections in children caused by community-acquired methicillin-resistant Staphylococcus aureus are on the rise.
Rates of severe infection have been rising as MRSA has become more common in the community. Recommendations from the American Academy of Pediatrics state that in areas where MRSA accounts for 10% or more of CA-MRSA isolates, initial empiric therapy of severe infections that could be due to S. aureus should include vancomycin. Naficillin should also be included because it’s superior to vancomycin for treating methicillin-sensitive S. aureus (MSSA).
Use of clindamycin should be based on local susceptibility. “You need to know the clindamycin susceptibility of CA-MRSA isolates in your area,” said Dr. Kaplan, head of the pediatric infectious disease section at Baylor College of Medicine and chief of the infectious disease service at Texas Children’s Hospital, both in Houston.
At Le Bonheur Children’s Medical Center in Memphis, the rate of acute osteoarticular infections increased from 2.6 to 6.0 per 1,000 admissions between 2000 and 2004. While the proportion of those infections caused by MSSA remained constant at 10%-13%, those caused by MRSA rose from 4% to 40%. Moreover, 71% of the patients with MRSA had subperiosteal abscesses, compared with 38% of those with MSSA, and surgical procedures were required in 91% with MRSA versus 62% with MSSA (J. Pediatr. Orthop. 2006;26:701-2). Similar findings have been reported elsewhere, Dr. Kaplan noted.
Recent studies have shown that osteomyelitis caused by PVL-positive S. aureus strains was associated with more severe local disease and a greater systemic inflammatory response, compared with osteomyelitis caused by S. aureus not containing that gene (Pediatrics 2006;117:433-40), and that PVL-positive isolates were associated with an increased likelihood of complications in children with osteomyelitis (Pediatr. Infect. Dis. J. 2005;24:284-5).
MRI appears to be the optimal method for detection of osteomyelitis resulting from community-acquired S. aureus.
In a retrospective study by Dr. Kaplan and his associates of 199 such children seen between August 2001 and December 2006, MRI had a sensitivity of 98% for diagnosing the infection, compared with a 53% sensitivity with bone scintigraphy. Of 36 patients who had both imaging studies done, results were discordant in 17 cases. In all of those, the MRI diagnosis proved to be the correct one (Pediatr. Radiol. 2008;38:841-7).
The study also showed that MRI – but not bone scan – allowed for visualization of extraosseous complications, including subperiosteal abscesses in 77 patients, pyomyositis in 43, septic arthritis in 31, and deep vein thrombosis in 12. “Clearly, MRI was superior to bone scan in detecting bone infection. In our institution, MRI is the first thing we use. It can help pick up other areas of concern,” Dr. Kaplan noted.
Some of these extraosseous complications also appear to be on the rise. At least two recent reports have documented cases of venous thrombophlebitis among children with invasive S. aureus infections. At Children’s Medical Center in Dallas, 10 of 35 children with confirmed osteomyelitis developed deep vein thrombosis during the acute infection, with evidence of dissemination in six (J. Pediatr. 2006;149:537-41).
And at Texas Children’s, Dr. Kaplan and his associates reported on 9 children seen between 1999 and 2004 who had venous thrombosis adjacent to the site of staphylococcal osteomyelitis. Seven patients had community-acquired infections caused by MRSA belonging to the same USA300 clonal group, and all 7 carried PVL genes. The USA300 clone may “have a unique propensity to cause [venous thrombosis] in association with osteomyelitis,” they concluded (Pediatrics 2006;117:1673-9).
Since then, they’ve seen about 40-50 children with osteomyelitis who developed thrombosis, despite not having genetic prothrombotic conditions. “We don’t understand what’s going on. There’s clearly something different about these community isolates, especially the USA300 strain,” Dr. Kaplan commented.
The USA300 MRSA genotype has also been implicated in septic arthritis. Among 44 isolates taken from 45 patients at Texas Children’s with septic arthritis caused by S. aureus, 16 were MRSA; of these, 13 were USA300 and 14 were PVL-positive. Infections caused by USA300 were more likely to be associated with a longer duration of fever, bacteremia, and a C-reactive protein level of 10 mg/dL or greater (Pediatr. Infect. Dis. J. 2009;28:1076-80).
Rates of pyomyositis and myositis also have been on the rise at Texas Children’s, and can be correlated to the emergence of CA-MRSA. Among 45 previously healthy children with bacterial pyomyositis or myositis, the cause was S. aureus in 58%. Of 24 community-acquired S. aureus isolates that were available, 15 were MRSA and 9 were MSSA. A total of 16 (including all the MRSA) isolates were found to be USA300, and 17 carried the PVL genes. The presence of MRSA, USA300, and/or the PVL genes was associated with a greater requirement for drainage procedures (Clin. Infect. Dis. 2006;43:953-60).
“Infection of muscles is something we just never saw in the past,” Dr. Kaplan commented.
Pulmonary manifestations are another increasingly common complication of CA-MRSA. An investigation of 70 children with invasive staphylococcal infections at Texas Children’s between 2001 and 2004 showed that 47 had MRSA. Compared with 10 who had MSSA, those with MRSA were more likely to have pneumonia, empyema, lung abscess, and atelectasis. The presence of PVL was associated with abnormal chest image findings in patients with secondary pneumonia (Clin. Infect. Dis. 2005;41:583-90).
Influenza complicated by staph infections is also becoming more common, with most of these cases attributable to MRSA. A study by the U. S. Centers for Disease Control and Prevention comparing pediatric deaths during three influenza seasons revealed that bacterial coinfection increased substantially, from 6% in 2004-2005 to 15% in 2005-2006 to 34% in 2006-2007. Isolation of S. aureus from a sterile site rose from just one case in 2004-2005 to 22 in 2006-2007, of which two-thirds were MRSA. Children with staph coinfection were significantly older and more likely to have pneumonia and acute respiratory distress syndrome than those not coinfected (Pediatrics 2008;122:805-11).
Severe staphylococcal infections also are emerging along with CA-MRSA. In a descriptive report of 14 previously healthy adolescents with severe community-acquired S. aureus infections admitted to intensive care at Texas Children’s with coagulopathy and sepsis, 12 were found to have MRSA and 2 had MSSA. Thirteen also had pulmonary involvement and/or bone and joint infection, four developed vascular complications, and three died. All isolates were identical or closely related to the USA300 clone (Pediatrics 2005;115:642-8).
The typical patient is an adolescent, usually with some trauma to an extremity, who may have underlying osteomyelitis and may develop pulmonary manifestations, and then becomes very ill. “We’ve now had seven deaths due to S. aureus sepsis in otherwise completely healthy children,” Dr. Kaplan said.
Dr. Kaplan (pictured above) has received research grants from Pfizer and Cubist Pharmaceuticals.
Closed-Loop System Improves Glucose Control
Major Finding: Compared to continuous insulin infusion, a closed-loop insulin delivery system increased the time plasma glucose was in the target range (60% vs. 40%) and significantly reduced the time in the hypoglycemic range (2.1% vs. 4.1%).
Data Source: A three-part randomized crossover study of 17 children and adolescents with type 1 diabetes.
Disclosures: Funding by the Juvenile Diabetes Research Foundation and three European research foundations. Dr. Hovorka has received lecture fees from Minimed Medtronic, Abbott Diabetes Care, Lifescan, Novo-Nordisk, and B. Braun. He reported two patent applications. Dr. Renard stated he had no conflicts of interest.
A closed-loop system linking continuous glucose measurements to insulin delivery reduced the risk of nocturnal hypoglycemia compared with standard continuous subcutaneous insulin infusion in a three-part randomized crossover study involving 17 children and adolescents with type 1 diabetes.
Previous studies have assessed the feasibility of closed-loop systems using various types of control algorithms, but this is the first to compare closed-loop delivery with traditional continuous subcutaneous insulin infusion (CSII) and the first to assess the effect of evening meals and exercise, said Dr. Roman Hovorka of the University of Cambridge, England, and his associates (Lancet 2010 Feb. 5 [doi:10.1016/S0140-6736(09)61998-X).
“Closed-loop systems could transform management of type 1 diabetes, but their introduction is likely to be gradual, starting from straightforward applications such as shutting off the pump at low glucose concentrations or overnight closed-loop delivery, proceeding to more complex applications providing 24-[hour] control,” the investigators said.
The study subjects were aged 5–18 years and had type 1 diabetes for a mean duration of 6.4 years. Thirteen of the children were assigned to be treated with overnight (8:00 p.m. to 8:00 a.m.) closed-loop delivery (using Medtronic's Guardian Real-Time) or standard CSII on two separate occasions. Seven of those 13 were evaluated overnight with the closed-loop device (Abbott's Freestyle Navigator) on two further occasions, this time after having consumed either rapidly or slowly-absorbed large meals matched for total carbohydrates (129 grams), but differing in glycemic load.
In a third overnight evaluation, 10 adolescents aged 12–18 (including 4 from the first evaluation) rode a treadmill from 6:00 to 6:45 p.m. after having eaten a light meal at 4:00 p.m., again comparing closed loop (Navigator) with CSII. (All patients used Smiths Medical's Deltec Cosmo insulin pumps for the study.)
During closed-loop nights, glucose measurements were fed every 15 minutes into a control algorithm calculating rate of insulin infusion, and a nurse adjusted the insulin pump. Standard pump settings were used on control nights.
Primary outcomes—time for which plasma glucose concentration was in the target range of 3.91–8.00 mmol/L (70.4–144 mg/dL) or a hypoglycemic level of 3.90 mmol/L (70.2 mg/dL) or lower—did not differ significantly between closed loop and CSII for the first evaluation. Time spent in target range was 52% with closed loop versus 39% for CSII, and time spent with hypoglycemia, 1.0% vs. 2.0%. For the exercise evaluation, the proportions for closed loop vs. CSII were 78% vs. 43% of time in target range and 10.0% vs. 6.1% of time with hypoglycemia, respectively.
For the meal comparison, there was no significant difference in overnight control between the two meals: Time spent in target range after midnight was 86% for the rapidly-absorbed meal and 83% for the slowly absorbed meal. From the start of the closed-loop delivery, those proportions were 53% and 55%, respectively, Dr. Hovorka and his associates reported.
In a secondary analysis pooling the data from the first and third evaluations, closed-loop delivery significantly increased the time for which plasma glucose was in the target range (60% vs. 40%) and significantly reduced the time in hypoglycemic range (2.1% vs. 4.1%). The difference was even more significant after midnight, when closed-loop became fully effective (79% vs. 35% in target range, 3.0% vs. 6.1% hypoglycemic), they said.
In an accompanying editorial, Dr. Eric Renard of Universitaire de Montpellier, France, commented that although overall mean blood glucose levels were not significantly different with closed-loop delivery, the fact that the closed loop stabilized blood glucose levels overnight while keeping hypoglycemia to a minimum is “an important step forward for young patients and their parents.”
Major Finding: Compared to continuous insulin infusion, a closed-loop insulin delivery system increased the time plasma glucose was in the target range (60% vs. 40%) and significantly reduced the time in the hypoglycemic range (2.1% vs. 4.1%).
Data Source: A three-part randomized crossover study of 17 children and adolescents with type 1 diabetes.
Disclosures: Funding by the Juvenile Diabetes Research Foundation and three European research foundations. Dr. Hovorka has received lecture fees from Minimed Medtronic, Abbott Diabetes Care, Lifescan, Novo-Nordisk, and B. Braun. He reported two patent applications. Dr. Renard stated he had no conflicts of interest.
A closed-loop system linking continuous glucose measurements to insulin delivery reduced the risk of nocturnal hypoglycemia compared with standard continuous subcutaneous insulin infusion in a three-part randomized crossover study involving 17 children and adolescents with type 1 diabetes.
Previous studies have assessed the feasibility of closed-loop systems using various types of control algorithms, but this is the first to compare closed-loop delivery with traditional continuous subcutaneous insulin infusion (CSII) and the first to assess the effect of evening meals and exercise, said Dr. Roman Hovorka of the University of Cambridge, England, and his associates (Lancet 2010 Feb. 5 [doi:10.1016/S0140-6736(09)61998-X).
“Closed-loop systems could transform management of type 1 diabetes, but their introduction is likely to be gradual, starting from straightforward applications such as shutting off the pump at low glucose concentrations or overnight closed-loop delivery, proceeding to more complex applications providing 24-[hour] control,” the investigators said.
The study subjects were aged 5–18 years and had type 1 diabetes for a mean duration of 6.4 years. Thirteen of the children were assigned to be treated with overnight (8:00 p.m. to 8:00 a.m.) closed-loop delivery (using Medtronic's Guardian Real-Time) or standard CSII on two separate occasions. Seven of those 13 were evaluated overnight with the closed-loop device (Abbott's Freestyle Navigator) on two further occasions, this time after having consumed either rapidly or slowly-absorbed large meals matched for total carbohydrates (129 grams), but differing in glycemic load.
In a third overnight evaluation, 10 adolescents aged 12–18 (including 4 from the first evaluation) rode a treadmill from 6:00 to 6:45 p.m. after having eaten a light meal at 4:00 p.m., again comparing closed loop (Navigator) with CSII. (All patients used Smiths Medical's Deltec Cosmo insulin pumps for the study.)
During closed-loop nights, glucose measurements were fed every 15 minutes into a control algorithm calculating rate of insulin infusion, and a nurse adjusted the insulin pump. Standard pump settings were used on control nights.
Primary outcomes—time for which plasma glucose concentration was in the target range of 3.91–8.00 mmol/L (70.4–144 mg/dL) or a hypoglycemic level of 3.90 mmol/L (70.2 mg/dL) or lower—did not differ significantly between closed loop and CSII for the first evaluation. Time spent in target range was 52% with closed loop versus 39% for CSII, and time spent with hypoglycemia, 1.0% vs. 2.0%. For the exercise evaluation, the proportions for closed loop vs. CSII were 78% vs. 43% of time in target range and 10.0% vs. 6.1% of time with hypoglycemia, respectively.
For the meal comparison, there was no significant difference in overnight control between the two meals: Time spent in target range after midnight was 86% for the rapidly-absorbed meal and 83% for the slowly absorbed meal. From the start of the closed-loop delivery, those proportions were 53% and 55%, respectively, Dr. Hovorka and his associates reported.
In a secondary analysis pooling the data from the first and third evaluations, closed-loop delivery significantly increased the time for which plasma glucose was in the target range (60% vs. 40%) and significantly reduced the time in hypoglycemic range (2.1% vs. 4.1%). The difference was even more significant after midnight, when closed-loop became fully effective (79% vs. 35% in target range, 3.0% vs. 6.1% hypoglycemic), they said.
In an accompanying editorial, Dr. Eric Renard of Universitaire de Montpellier, France, commented that although overall mean blood glucose levels were not significantly different with closed-loop delivery, the fact that the closed loop stabilized blood glucose levels overnight while keeping hypoglycemia to a minimum is “an important step forward for young patients and their parents.”
Major Finding: Compared to continuous insulin infusion, a closed-loop insulin delivery system increased the time plasma glucose was in the target range (60% vs. 40%) and significantly reduced the time in the hypoglycemic range (2.1% vs. 4.1%).
Data Source: A three-part randomized crossover study of 17 children and adolescents with type 1 diabetes.
Disclosures: Funding by the Juvenile Diabetes Research Foundation and three European research foundations. Dr. Hovorka has received lecture fees from Minimed Medtronic, Abbott Diabetes Care, Lifescan, Novo-Nordisk, and B. Braun. He reported two patent applications. Dr. Renard stated he had no conflicts of interest.
A closed-loop system linking continuous glucose measurements to insulin delivery reduced the risk of nocturnal hypoglycemia compared with standard continuous subcutaneous insulin infusion in a three-part randomized crossover study involving 17 children and adolescents with type 1 diabetes.
Previous studies have assessed the feasibility of closed-loop systems using various types of control algorithms, but this is the first to compare closed-loop delivery with traditional continuous subcutaneous insulin infusion (CSII) and the first to assess the effect of evening meals and exercise, said Dr. Roman Hovorka of the University of Cambridge, England, and his associates (Lancet 2010 Feb. 5 [doi:10.1016/S0140-6736(09)61998-X).
“Closed-loop systems could transform management of type 1 diabetes, but their introduction is likely to be gradual, starting from straightforward applications such as shutting off the pump at low glucose concentrations or overnight closed-loop delivery, proceeding to more complex applications providing 24-[hour] control,” the investigators said.
The study subjects were aged 5–18 years and had type 1 diabetes for a mean duration of 6.4 years. Thirteen of the children were assigned to be treated with overnight (8:00 p.m. to 8:00 a.m.) closed-loop delivery (using Medtronic's Guardian Real-Time) or standard CSII on two separate occasions. Seven of those 13 were evaluated overnight with the closed-loop device (Abbott's Freestyle Navigator) on two further occasions, this time after having consumed either rapidly or slowly-absorbed large meals matched for total carbohydrates (129 grams), but differing in glycemic load.
In a third overnight evaluation, 10 adolescents aged 12–18 (including 4 from the first evaluation) rode a treadmill from 6:00 to 6:45 p.m. after having eaten a light meal at 4:00 p.m., again comparing closed loop (Navigator) with CSII. (All patients used Smiths Medical's Deltec Cosmo insulin pumps for the study.)
During closed-loop nights, glucose measurements were fed every 15 minutes into a control algorithm calculating rate of insulin infusion, and a nurse adjusted the insulin pump. Standard pump settings were used on control nights.
Primary outcomes—time for which plasma glucose concentration was in the target range of 3.91–8.00 mmol/L (70.4–144 mg/dL) or a hypoglycemic level of 3.90 mmol/L (70.2 mg/dL) or lower—did not differ significantly between closed loop and CSII for the first evaluation. Time spent in target range was 52% with closed loop versus 39% for CSII, and time spent with hypoglycemia, 1.0% vs. 2.0%. For the exercise evaluation, the proportions for closed loop vs. CSII were 78% vs. 43% of time in target range and 10.0% vs. 6.1% of time with hypoglycemia, respectively.
For the meal comparison, there was no significant difference in overnight control between the two meals: Time spent in target range after midnight was 86% for the rapidly-absorbed meal and 83% for the slowly absorbed meal. From the start of the closed-loop delivery, those proportions were 53% and 55%, respectively, Dr. Hovorka and his associates reported.
In a secondary analysis pooling the data from the first and third evaluations, closed-loop delivery significantly increased the time for which plasma glucose was in the target range (60% vs. 40%) and significantly reduced the time in hypoglycemic range (2.1% vs. 4.1%). The difference was even more significant after midnight, when closed-loop became fully effective (79% vs. 35% in target range, 3.0% vs. 6.1% hypoglycemic), they said.
In an accompanying editorial, Dr. Eric Renard of Universitaire de Montpellier, France, commented that although overall mean blood glucose levels were not significantly different with closed-loop delivery, the fact that the closed loop stabilized blood glucose levels overnight while keeping hypoglycemia to a minimum is “an important step forward for young patients and their parents.”
HPV 16/18 Vaccine Shows Efficacy Beyond 6 Years
The human papillomavirus 16/18 vaccine showed efficacy, sustained immunogenicity, and continued safety for up to 6.4 years in a combination of initial and follow-up placebo-controlled studies involving more than 1,000 women aged 15–26 years.
The three-country, 27-site study of the human papillomavirus (HPV) vaccine Cervarix—which is now licensed in the United States, Europe, and elsewhere around the world—was funded by GlaxoSmithKline (GSK) Biologricals. It contains the HPV types 16 and 18 adjuvanted with ASO4, comprising aluminum salt and an immunostimulatory molecule that has been shown to produce higher antibody titers that are sustained over a longer period of time, compared with the same antigens adjuvanted with aluminum salts alone, according to the GSK Vaccine HPV-007 Study Group, led by Dr. Barbara Romanowski (Lancet 2009 Dec. 3 [doi:10.1016/S0140-6736(09)61567-1]).
Of 1,113 women included in the initial study, a total of 700 completed the follow-up study. The total vaccinated cohort included 560 women in the vaccine group and 553 in the placebo group, while the according-to-protocol (ATP) efficacy cohort included 465 in the vaccine group and 454 in the placebo group. At baseline, all had normal cervical cytology and were negative for both HPV-16 and -18.
The mean follow-up period from the start of the initial study was 5.9 years, with a maximum duration of 6.4 years. The study population was racially diverse and had a mean age of 20 years (range, 15–26 years) at entry to the initial study and 23 years at the beginning of follow-up.
At 6.4 years, vaccine efficacy against incident HPV-16 or HPV-18 infection in the ATP analysis was 95.3%, and long-term efficacy against persistent infection was 100% at both 6 and 12 months. said Dr. Romanowski of the University of Alberta, Edmonton, and her study group associates.
Almost all vaccine recipients (99%) remained seropositive for anti–HPV-16 and anti–HPV-18 total IgG antibodies.
In an accompanying editorial, Dr. Gary M. Cliffordsaid that the immunogenicity data showing no evidence of further decline from 3 to 6 years are “perhaps the most interesting” because they suggest that mean antibody concentrations should remain well above those associated with natural infection long into the future.
The target age of vaccination is a balance between “being early enough to catch girls before sexual debut, but late enough to provide an as yet unknown duration of immunity that protects during as many subsequent years of sexual activity as possible,” wrote Dr. Clifford of the International Agency for Research on Cancer, Lyon, France (Lancet 2009 Dec. 3 [doi:10.1016/S0140-6736(09)61789-X]).
Disclosures: Dr. Clifford said that he had no conflicts of interest.
The human papillomavirus 16/18 vaccine showed efficacy, sustained immunogenicity, and continued safety for up to 6.4 years in a combination of initial and follow-up placebo-controlled studies involving more than 1,000 women aged 15–26 years.
The three-country, 27-site study of the human papillomavirus (HPV) vaccine Cervarix—which is now licensed in the United States, Europe, and elsewhere around the world—was funded by GlaxoSmithKline (GSK) Biologricals. It contains the HPV types 16 and 18 adjuvanted with ASO4, comprising aluminum salt and an immunostimulatory molecule that has been shown to produce higher antibody titers that are sustained over a longer period of time, compared with the same antigens adjuvanted with aluminum salts alone, according to the GSK Vaccine HPV-007 Study Group, led by Dr. Barbara Romanowski (Lancet 2009 Dec. 3 [doi:10.1016/S0140-6736(09)61567-1]).
Of 1,113 women included in the initial study, a total of 700 completed the follow-up study. The total vaccinated cohort included 560 women in the vaccine group and 553 in the placebo group, while the according-to-protocol (ATP) efficacy cohort included 465 in the vaccine group and 454 in the placebo group. At baseline, all had normal cervical cytology and were negative for both HPV-16 and -18.
The mean follow-up period from the start of the initial study was 5.9 years, with a maximum duration of 6.4 years. The study population was racially diverse and had a mean age of 20 years (range, 15–26 years) at entry to the initial study and 23 years at the beginning of follow-up.
At 6.4 years, vaccine efficacy against incident HPV-16 or HPV-18 infection in the ATP analysis was 95.3%, and long-term efficacy against persistent infection was 100% at both 6 and 12 months. said Dr. Romanowski of the University of Alberta, Edmonton, and her study group associates.
Almost all vaccine recipients (99%) remained seropositive for anti–HPV-16 and anti–HPV-18 total IgG antibodies.
In an accompanying editorial, Dr. Gary M. Cliffordsaid that the immunogenicity data showing no evidence of further decline from 3 to 6 years are “perhaps the most interesting” because they suggest that mean antibody concentrations should remain well above those associated with natural infection long into the future.
The target age of vaccination is a balance between “being early enough to catch girls before sexual debut, but late enough to provide an as yet unknown duration of immunity that protects during as many subsequent years of sexual activity as possible,” wrote Dr. Clifford of the International Agency for Research on Cancer, Lyon, France (Lancet 2009 Dec. 3 [doi:10.1016/S0140-6736(09)61789-X]).
Disclosures: Dr. Clifford said that he had no conflicts of interest.
The human papillomavirus 16/18 vaccine showed efficacy, sustained immunogenicity, and continued safety for up to 6.4 years in a combination of initial and follow-up placebo-controlled studies involving more than 1,000 women aged 15–26 years.
The three-country, 27-site study of the human papillomavirus (HPV) vaccine Cervarix—which is now licensed in the United States, Europe, and elsewhere around the world—was funded by GlaxoSmithKline (GSK) Biologricals. It contains the HPV types 16 and 18 adjuvanted with ASO4, comprising aluminum salt and an immunostimulatory molecule that has been shown to produce higher antibody titers that are sustained over a longer period of time, compared with the same antigens adjuvanted with aluminum salts alone, according to the GSK Vaccine HPV-007 Study Group, led by Dr. Barbara Romanowski (Lancet 2009 Dec. 3 [doi:10.1016/S0140-6736(09)61567-1]).
Of 1,113 women included in the initial study, a total of 700 completed the follow-up study. The total vaccinated cohort included 560 women in the vaccine group and 553 in the placebo group, while the according-to-protocol (ATP) efficacy cohort included 465 in the vaccine group and 454 in the placebo group. At baseline, all had normal cervical cytology and were negative for both HPV-16 and -18.
The mean follow-up period from the start of the initial study was 5.9 years, with a maximum duration of 6.4 years. The study population was racially diverse and had a mean age of 20 years (range, 15–26 years) at entry to the initial study and 23 years at the beginning of follow-up.
At 6.4 years, vaccine efficacy against incident HPV-16 or HPV-18 infection in the ATP analysis was 95.3%, and long-term efficacy against persistent infection was 100% at both 6 and 12 months. said Dr. Romanowski of the University of Alberta, Edmonton, and her study group associates.
Almost all vaccine recipients (99%) remained seropositive for anti–HPV-16 and anti–HPV-18 total IgG antibodies.
In an accompanying editorial, Dr. Gary M. Cliffordsaid that the immunogenicity data showing no evidence of further decline from 3 to 6 years are “perhaps the most interesting” because they suggest that mean antibody concentrations should remain well above those associated with natural infection long into the future.
The target age of vaccination is a balance between “being early enough to catch girls before sexual debut, but late enough to provide an as yet unknown duration of immunity that protects during as many subsequent years of sexual activity as possible,” wrote Dr. Clifford of the International Agency for Research on Cancer, Lyon, France (Lancet 2009 Dec. 3 [doi:10.1016/S0140-6736(09)61789-X]).
Disclosures: Dr. Clifford said that he had no conflicts of interest.
Adalimumab, Etanercept Best Infliximab
Treatment response and disease remission rates were lowest with infliximab and highest with adalimumab in a large Danish cohort analysis of patients who were treated for rheumatoid arthritis with tumor necrosis factor–alpha inhibitors, judging from recent findings.
Data from the DANBIO (Dansk Reumatologisk Database) registry also revealed that TNF-alpha adherence was lowest with infliximab and highest with etanercept, and that older age, low functional status, and concomitant prednisolone treatment were negative predictors of clinical response and remission, according to Dr. Merete Lund Hetland of Copenhagen University and her associates.
The DANBIO registry has monitored and reported details of TNF-alpha inhibitor therapy for RA patients since October 2000.
Sponsored by Danish hospital owners and the pharmaceutical companies that offer biologic treatments for rheumatologic disease (Abbott, Wyeth, Schering-Plough, Bristol-Myers Squibb, Roche, and UCB-Nordic), DANBIO is approved by the Danish National Board of Health as a national quality registry, Dr. Hetland and her associates wrote (Arthritis Rheum. 2010;62:22-32).
This study is believed to be the first direct comparison between adalimumab, etanercept, and infliximab and the ability of the three agents to elicit treatment goals including remission, they noted.
All patients included in the study had RA and had been treated with one or more conventional disease-modifying antirheumatic drugs (DMARDs), but those treatments had failed, and one of the three biologic agents was initiated. Concomitant methotrexate or other DMARD and prednisolone were administered based on the decision of the treating rheumatologist.
The initial study population comprised 2,326 patients, of whom 449 withdrew prior to the first 6 months of the study. Of those 449, 52% withdrew because of lack of efficacy and 38% from adverse events.
Among the 1,877 patients who had not withdrawn, an ACR 70 (American College of Rheumatology 70) response was achieved after 6 months in 19% of them (Arthritis Rheum. 1995;38:727-35), a good response by the EULAR (European League Against Rheumatism) criteria in 41% of them (Arthritis Rheum. 1996;39:34-40), remission by DAS28 (Disease Activity Score in 28 joints) in 25% of them, and CDAI (Clinical Disease Activity Index) remission in 13%.
Older age, low functional status as reflected in a high score on the Health Assessment Questionnaire, and concomitant prednisolone treatment were negative predictors of an ACR 70 response, whereas concomitant methotrexate, male sex, number of previous DMARD treatments, and disease duration were not predictors.
The patterns were similar for all outcome measures at 6 and 12 months, according to Dr. Hetland and her associates.
Overall, the crude treatment response rates after 6 and 12 months were highest for adalimumab (544 patients), intermediate for etanercept (425), and poorest for infliximab (908).
After correction for withdrawals from the study, ACR 70 was achieved at 6 months by 19% of those receiving adalimumab, by 17% of those using etanercept, and by 11% of those on infliximab. A good EULAR response was reported at 6 months in 41%, 34%, and 27%, respectively.
Similarly, DAS28 remission at 6 months occurred in 26% with adalimumab, 21% with etanercept, and 17% with infliximab; CDAI remission occurred in 15%, 10%, and 8%, respectively.
Combination therapy with methotrexate and prednisolone was used more often by those taking infliximab than by those using the other two TNF-alpha inhibitors.
After adjustment for that, as well as previous DMARD use, sex, age, disease duration, seropositivity, and baseline functional status, the odds ratios for achieving an ACR 70 response after 6 months of treatment were 2.05 for adalimumab and 1.78 for etanercept, compared with infliximab.
Adalimumab and etanercept were not significantly different, the investigators reported.
The odds ratios for adalimumab vs. infliximab were statistically significant for all outcome measures, ranging from 1.78 to 2.76. For etanercept vs. infliximab, odds ratios ranged from 1.16 to 1.99, which were statistically significant for ACR 70 and EULAR response measures, but not for the two remission outcomes.
Adalimumab produced a significantly higher EULAR good response (OR, 1.49) and CDAI remission (OR, 1.58) than did etanercept.
Drug adherence was highest for etanercept and lowest for infliximab. At 48 months, unadjusted adherence rates were 52% for adalimumab, 56% for etanercept, and 41% for infliximab, Dr. Hetland and her associates said.
Disclosures: This study was supported by unrestricted grants to DANBIO from its participating companies, which had no role in the study design, nor the collection, analysis, or interpretation of the data or the decision to submit the manuscript for publication.
Dr. Hetland's work on this study was supported by a grant from the Danish Rheumatism Association and a private foundation.
She has received consulting fees, speaking fees, and/or research grants of less than $10,000 each from all of the companies (except Bristol-Myers Squibb) that were involved in DANBIO, and grants of more than $10,000 each from all the participating companies on behalf of DANBIO.
Several of the 14 other coauthors have similar disclosures.
Treatment response and disease remission rates were lowest with infliximab and highest with adalimumab in a large Danish cohort analysis of patients who were treated for rheumatoid arthritis with tumor necrosis factor–alpha inhibitors, judging from recent findings.
Data from the DANBIO (Dansk Reumatologisk Database) registry also revealed that TNF-alpha adherence was lowest with infliximab and highest with etanercept, and that older age, low functional status, and concomitant prednisolone treatment were negative predictors of clinical response and remission, according to Dr. Merete Lund Hetland of Copenhagen University and her associates.
The DANBIO registry has monitored and reported details of TNF-alpha inhibitor therapy for RA patients since October 2000.
Sponsored by Danish hospital owners and the pharmaceutical companies that offer biologic treatments for rheumatologic disease (Abbott, Wyeth, Schering-Plough, Bristol-Myers Squibb, Roche, and UCB-Nordic), DANBIO is approved by the Danish National Board of Health as a national quality registry, Dr. Hetland and her associates wrote (Arthritis Rheum. 2010;62:22-32).
This study is believed to be the first direct comparison between adalimumab, etanercept, and infliximab and the ability of the three agents to elicit treatment goals including remission, they noted.
All patients included in the study had RA and had been treated with one or more conventional disease-modifying antirheumatic drugs (DMARDs), but those treatments had failed, and one of the three biologic agents was initiated. Concomitant methotrexate or other DMARD and prednisolone were administered based on the decision of the treating rheumatologist.
The initial study population comprised 2,326 patients, of whom 449 withdrew prior to the first 6 months of the study. Of those 449, 52% withdrew because of lack of efficacy and 38% from adverse events.
Among the 1,877 patients who had not withdrawn, an ACR 70 (American College of Rheumatology 70) response was achieved after 6 months in 19% of them (Arthritis Rheum. 1995;38:727-35), a good response by the EULAR (European League Against Rheumatism) criteria in 41% of them (Arthritis Rheum. 1996;39:34-40), remission by DAS28 (Disease Activity Score in 28 joints) in 25% of them, and CDAI (Clinical Disease Activity Index) remission in 13%.
Older age, low functional status as reflected in a high score on the Health Assessment Questionnaire, and concomitant prednisolone treatment were negative predictors of an ACR 70 response, whereas concomitant methotrexate, male sex, number of previous DMARD treatments, and disease duration were not predictors.
The patterns were similar for all outcome measures at 6 and 12 months, according to Dr. Hetland and her associates.
Overall, the crude treatment response rates after 6 and 12 months were highest for adalimumab (544 patients), intermediate for etanercept (425), and poorest for infliximab (908).
After correction for withdrawals from the study, ACR 70 was achieved at 6 months by 19% of those receiving adalimumab, by 17% of those using etanercept, and by 11% of those on infliximab. A good EULAR response was reported at 6 months in 41%, 34%, and 27%, respectively.
Similarly, DAS28 remission at 6 months occurred in 26% with adalimumab, 21% with etanercept, and 17% with infliximab; CDAI remission occurred in 15%, 10%, and 8%, respectively.
Combination therapy with methotrexate and prednisolone was used more often by those taking infliximab than by those using the other two TNF-alpha inhibitors.
After adjustment for that, as well as previous DMARD use, sex, age, disease duration, seropositivity, and baseline functional status, the odds ratios for achieving an ACR 70 response after 6 months of treatment were 2.05 for adalimumab and 1.78 for etanercept, compared with infliximab.
Adalimumab and etanercept were not significantly different, the investigators reported.
The odds ratios for adalimumab vs. infliximab were statistically significant for all outcome measures, ranging from 1.78 to 2.76. For etanercept vs. infliximab, odds ratios ranged from 1.16 to 1.99, which were statistically significant for ACR 70 and EULAR response measures, but not for the two remission outcomes.
Adalimumab produced a significantly higher EULAR good response (OR, 1.49) and CDAI remission (OR, 1.58) than did etanercept.
Drug adherence was highest for etanercept and lowest for infliximab. At 48 months, unadjusted adherence rates were 52% for adalimumab, 56% for etanercept, and 41% for infliximab, Dr. Hetland and her associates said.
Disclosures: This study was supported by unrestricted grants to DANBIO from its participating companies, which had no role in the study design, nor the collection, analysis, or interpretation of the data or the decision to submit the manuscript for publication.
Dr. Hetland's work on this study was supported by a grant from the Danish Rheumatism Association and a private foundation.
She has received consulting fees, speaking fees, and/or research grants of less than $10,000 each from all of the companies (except Bristol-Myers Squibb) that were involved in DANBIO, and grants of more than $10,000 each from all the participating companies on behalf of DANBIO.
Several of the 14 other coauthors have similar disclosures.
Treatment response and disease remission rates were lowest with infliximab and highest with adalimumab in a large Danish cohort analysis of patients who were treated for rheumatoid arthritis with tumor necrosis factor–alpha inhibitors, judging from recent findings.
Data from the DANBIO (Dansk Reumatologisk Database) registry also revealed that TNF-alpha adherence was lowest with infliximab and highest with etanercept, and that older age, low functional status, and concomitant prednisolone treatment were negative predictors of clinical response and remission, according to Dr. Merete Lund Hetland of Copenhagen University and her associates.
The DANBIO registry has monitored and reported details of TNF-alpha inhibitor therapy for RA patients since October 2000.
Sponsored by Danish hospital owners and the pharmaceutical companies that offer biologic treatments for rheumatologic disease (Abbott, Wyeth, Schering-Plough, Bristol-Myers Squibb, Roche, and UCB-Nordic), DANBIO is approved by the Danish National Board of Health as a national quality registry, Dr. Hetland and her associates wrote (Arthritis Rheum. 2010;62:22-32).
This study is believed to be the first direct comparison between adalimumab, etanercept, and infliximab and the ability of the three agents to elicit treatment goals including remission, they noted.
All patients included in the study had RA and had been treated with one or more conventional disease-modifying antirheumatic drugs (DMARDs), but those treatments had failed, and one of the three biologic agents was initiated. Concomitant methotrexate or other DMARD and prednisolone were administered based on the decision of the treating rheumatologist.
The initial study population comprised 2,326 patients, of whom 449 withdrew prior to the first 6 months of the study. Of those 449, 52% withdrew because of lack of efficacy and 38% from adverse events.
Among the 1,877 patients who had not withdrawn, an ACR 70 (American College of Rheumatology 70) response was achieved after 6 months in 19% of them (Arthritis Rheum. 1995;38:727-35), a good response by the EULAR (European League Against Rheumatism) criteria in 41% of them (Arthritis Rheum. 1996;39:34-40), remission by DAS28 (Disease Activity Score in 28 joints) in 25% of them, and CDAI (Clinical Disease Activity Index) remission in 13%.
Older age, low functional status as reflected in a high score on the Health Assessment Questionnaire, and concomitant prednisolone treatment were negative predictors of an ACR 70 response, whereas concomitant methotrexate, male sex, number of previous DMARD treatments, and disease duration were not predictors.
The patterns were similar for all outcome measures at 6 and 12 months, according to Dr. Hetland and her associates.
Overall, the crude treatment response rates after 6 and 12 months were highest for adalimumab (544 patients), intermediate for etanercept (425), and poorest for infliximab (908).
After correction for withdrawals from the study, ACR 70 was achieved at 6 months by 19% of those receiving adalimumab, by 17% of those using etanercept, and by 11% of those on infliximab. A good EULAR response was reported at 6 months in 41%, 34%, and 27%, respectively.
Similarly, DAS28 remission at 6 months occurred in 26% with adalimumab, 21% with etanercept, and 17% with infliximab; CDAI remission occurred in 15%, 10%, and 8%, respectively.
Combination therapy with methotrexate and prednisolone was used more often by those taking infliximab than by those using the other two TNF-alpha inhibitors.
After adjustment for that, as well as previous DMARD use, sex, age, disease duration, seropositivity, and baseline functional status, the odds ratios for achieving an ACR 70 response after 6 months of treatment were 2.05 for adalimumab and 1.78 for etanercept, compared with infliximab.
Adalimumab and etanercept were not significantly different, the investigators reported.
The odds ratios for adalimumab vs. infliximab were statistically significant for all outcome measures, ranging from 1.78 to 2.76. For etanercept vs. infliximab, odds ratios ranged from 1.16 to 1.99, which were statistically significant for ACR 70 and EULAR response measures, but not for the two remission outcomes.
Adalimumab produced a significantly higher EULAR good response (OR, 1.49) and CDAI remission (OR, 1.58) than did etanercept.
Drug adherence was highest for etanercept and lowest for infliximab. At 48 months, unadjusted adherence rates were 52% for adalimumab, 56% for etanercept, and 41% for infliximab, Dr. Hetland and her associates said.
Disclosures: This study was supported by unrestricted grants to DANBIO from its participating companies, which had no role in the study design, nor the collection, analysis, or interpretation of the data or the decision to submit the manuscript for publication.
Dr. Hetland's work on this study was supported by a grant from the Danish Rheumatism Association and a private foundation.
She has received consulting fees, speaking fees, and/or research grants of less than $10,000 each from all of the companies (except Bristol-Myers Squibb) that were involved in DANBIO, and grants of more than $10,000 each from all the participating companies on behalf of DANBIO.
Several of the 14 other coauthors have similar disclosures.