new england                        The              journal of medicine              established in 1812                  ...
The   n e w e ng l a n d j o u r na l      of   m e dic i n e               A                       ntibiotic-resistant pn...
pneumococcal vaccine and drug-resistant infectionnumbers of cases for 2004 were calculated on                             ...
The   n e w e ng l a n d j o u r na l      of   m e dic i n e               a decline of 51 percent [95 percent confidence...
7 efecto de introducción de vacuna conjugada neumocócica sobre el sp resistente
7 efecto de introducción de vacuna conjugada neumocócica sobre el sp resistente
7 efecto de introducción de vacuna conjugada neumocócica sobre el sp resistente
7 efecto de introducción de vacuna conjugada neumocócica sobre el sp resistente
7 efecto de introducción de vacuna conjugada neumocócica sobre el sp resistente
7 efecto de introducción de vacuna conjugada neumocócica sobre el sp resistente
Upcoming SlideShare
Loading in …5
×

7 efecto de introducción de vacuna conjugada neumocócica sobre el sp resistente

543 views

Published on

Published in: Health & Medicine, Education
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
543
On SlideShare
0
From Embeds
0
Number of Embeds
1
Actions
Shares
0
Downloads
7
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

7 efecto de introducción de vacuna conjugada neumocócica sobre el sp resistente

  1. 1. new england The journal of medicine established in 1812 april 6, 2006 vol. 354 no. 14 Effect of Introduction of the Pneumococcal Conjugate Vaccine on Drug-Resistant Streptococcus pneumoniae Moe H. Kyaw, Ph.D., M.P.H., Ruth Lynfield, M.D., William Schaffner, M.D., Allen S. Craig, M.D., James Hadler, M.D., M.P.H., Arthur Reingold, M.D., Ann R. Thomas, M.D., M.P.H., Lee H. Harrison, M.D., Nancy M. Bennett, M.D., Monica M. Farley, M.D., Richard R. Facklam, Ph.D., James H. Jorgensen, Ph.D., John Besser, M.S., Elizabeth R. Zell, M.Stat., Anne Schuchat, M.D., and Cynthia G. Whitney, M.D., M.P.H., for Active Bacterial Core Surveillance of the Emerging Infections Program Network A bs t r ac tBackgroundFive of seven serotypes in the pneumococcal conjugate vaccine, introduced for in- From the Respiratory Diseases Branch,fants in the United States in 2000, are responsible for most penicillin-resistant infec- Division of Bacterial and Mycotic Diseas- es, National Center for Infectious Diseases,tions. We examined the effect of this vaccine on invasive disease caused by resistant Centers for Disease Control and Preven-strains. tion, Atlanta (M.H.K., R.R.F., E.R.Z., A.S., C.G.W.); the Minnesota Department ofMethods Health, Minneapolis (R.L., J.B.); Vander-We used laboratory-based data from Active Bacterial Core surveillance to measure bilt University School of Medicine (W.S.) and the Tennessee Department of Healthdisease caused by antibiotic-nonsusceptible pneumococci from 1996 through 2004. (A.S.C.) — both in Nashville; the Connecti-Cases of invasive disease, defined as disease caused by pneumococci isolated from cut Department of Public Health, Hart-a normally sterile site, were identified in eight surveillance areas. Isolates underwent ford (J.H.); the School of Public Health, University of California, Berkeley (A.R.);serotyping and susceptibility testing. the Emerging Infections Programs, Ore- gon Department of Human Services,Results Health Division, Portland (A.R.T.); JohnsRates of invasive disease caused by penicillin-nonsusceptible strains and strains not Hopkins University Bloomberg School of Public Health, Baltimore (L.H.H.); thesusceptible to multiple antibiotics peaked in 1999 and decreased by 2004, from 6.3 Monroe County Department of Healthto 2.7 cases per 100,000 (a decline of 57 percent; 95 percent confidence interval, 55 and the University of Rochester — bothto 58 percent) and from 4.1 to 1.7 cases per 100,000 (a decline of 59 percent; 95 percent in Rochester, N.Y. (N.M.B.); Emory Uni- versity School of Medicine and the Veter-confidence interval, 58 to 60 percent), respectively. Among children under two years ans Affairs Medical Center — both in At-of age, disease caused by penicillin-nonsusceptible strains decreased from 70.3 to lanta (M.M.F.); and the University of Texas13.1 cases per 100,000 (a decline of 81 percent; 95 percent confidence interval, 80 to Health Science Center, San Antonio (J.H.J.). Address reprint requests to Dr. Whitney82 percent). Among persons 65 years of age or older, disease caused by penicillin- at CDC Mailstop C-23, 1600 Clifton Rd. NE,nonsusceptible strains decreased from 16.4 to 8.4 cases per 100,000 (a decline of Atlanta, GA 30333, or at cwhitney@cdc.gov.49 percent). Rates of resistant disease caused by vaccine serotypes fell 87 percent. N Engl J Med 2006;354:1455-63.An increase was seen in disease caused by serotype 19A, a serotype not included in the Copyright © 2006 Massachusetts Medical Society.vaccine (from 2.0 to 8.3 per 100,000 among children under two years of age).ConclusionsThe rate of antibiotic-resistant invasive pneumococcal infections decreased in youngchildren and older persons after the introduction of the conjugate vaccine. Therewas an increase in infections caused by serotypes not included in the vaccine. n engl j med 354;14 www.nejm.org april 6, 2006 1455 Downloaded from www.nejm.org on July 31, 2008 . Copyright © 2006 Massachusetts Medical Society. All rights reserved.
  2. 2. The n e w e ng l a n d j o u r na l of m e dic i n e A ntibiotic-resistant pneumococci eight surveillance areas: the Atlanta metropoli- complicate treatment decisions, cause treat- tan area (eight counties); Portland, Oregon (three ment failures, and increase the costs of counties); San Francisco County, California; Min- medical care. Worldwide, most antibiotic-resis- neapolis and St. Paul (seven counties); the Balti- tant infections are caused by five of the seven sero- more metropolitan area (six counties); the state types in the 7-valent pneumococcal conjugate of Connecticut; and parts of Tennessee (four coun- vaccine (6B, 9V, 14, 19F, and 23F).1 In 1998, 24 per- ties). Seven counties comprising the Rochester, cent of invasive pneumococcal isolates in the Unit- New York, metropolitan area were added in 1998. ed States were nonsusceptible to penicillin, and The surveillance methods for detecting cases of these five serotypes comprised 78 percent of such invasive pneumococcal disease did not change strains.2 Modeling predicted that in the absence during the study period. The population under of a pneumococcal conjugate vaccine, the propor- surveillance for this analysis ranged from 14.3 mil- tion of pneumococcal strains that were nonsus- lion to 16.9 million, including nearly 500,000 chil- ceptible to both penicillin and erythromycin could dren under two years of age. reach 41 percent by 2004.3 Because of the asso- Active Bacterial Core surveillance methods de- ciation between serotype and resistance, the con- fined a case of invasive disease as an illness in jugate vaccine would be expected to reduce the which pneumococcus was isolated from a nor- incidence of disease caused by resistant strains, mally sterile site, such as blood, cerebrospinal even though the vaccine is designed to induce fluid, or pleural fluid. Isolates underwent suscep- antibodies against certain capsular types. tibility testing by broth microdilution at the CDC, A pneumococcal conjugate vaccine was licensed the Minnesota Department of Health, or the Uni- for use in young children in the United States in versity of Texas Health Science Center at San 2000. The vaccine is recommended for all chil- Antonio. Antibiotic susceptibility was defined ac- dren under two years of age and for children two cording to break points for minimal inhibitory to four years of age who have certain chronic ill- concentrations as determined in 2004 by the nesses or other high-risk conditions.4 Data from Clinical and Laboratory Standards Institute (for- 20015 and from a single site in 20026 indicated merly the National Committee for Clinical Labo- that there had been a large decrease in invasive ratory Standards).7 Isolates with intermediate or disease, including infections caused by resistant high-level resistance were defined as nonsuscep- strains. Whether vaccine use would induce the tible. Isolates were considered nonsusceptible to emergence of serotypes that were typically not multiple antibiotics if they were nonsusceptible resistant as clinically significant causes of resis- to at least three of the following: penicillin, eryth- tant infections was unknown. In addition, the romycin, trimethoprim–sulfamethoxazole, tetra- possibility that use of a vaccine that targets only cycline, chloramphenicol, clindamycin, rifampin, 7 of 90 pneumococcal serotypes would lead to an and levofloxacin. increase in disease by nonvaccine types (so-called Serotyping was performed at the CDC or the replacement disease) was a concern. We used Minnesota Department of Health by the Quellung population-based data from Active Bacterial Core reaction. The 7-valent conjugate vaccine serotypes surveillance, part of the Emerging Infections Pro- included types 4, 6B, 9V, 14, 18C, 19F, and 23F. gram of the Centers for Disease Control and Pre- Other serotypes in these serogroups, including vention (CDC), to evaluate further the effect of 6A, 9A, 9L, 9 N, 18A, 18B, 18F, 19A, 19B, 19C, the conjugate pneumococcal vaccine on invasive 23A, and 23B, were regarded as vaccine-related. disease caused by antibiotic-resistant strains in All others were nonvaccine types. the United States. Rates of invasive pneumococcal disease, ex- pressed as the number of cases per 100,000 popu- Me thods lation, were calculated for the surveillance areas with the use of estimates from the U.S. Census Active Bacterial Core surveillance is an active, Bureau for each respective year, followed by ad- population-based system that has been described justment for race and age according to the U.S. previously (www.cdc.gov/abcs).2 We included cases population. Projected numbers of cases in the of invasive pneumococcal disease identified from United States were determined by multiplying the January 1, 1996, through December 31, 2004, in adjusted rate by the U.S. population. Estimated1456 n engl j med 354;14 www.nejm.org april 6, 2006 Downloaded from www.nejm.org on July 31, 2008 . Copyright © 2006 Massachusetts Medical Society. All rights reserved.
  3. 3. pneumococcal vaccine and drug-resistant infectionnumbers of cases for 2004 were calculated on +208 (+164 to +259)the basis of the 2003 population. Because isolates % Change (95% CI) −100 (−93 to −100) −100 (−93 to −100) +72 (+53 to +93) −73 (−67 to −77) −73 (−69 to −76) −82 (−80 to −84) −85 (−76 to −87) −49 (−46 to −51) −79 (−78 to −81) −83 (−79 to −85) −27 (−18 to −36) +15 (+6 to +24)were not available for all cases, rates of antibiotic-nonsusceptible disease were computed by multi- Persons ≥65 Yr of Ageplying the percentage of cases that were nonsus-ceptible by the total rate of disease calculated withall cases. Likewise, we calculated serotype-spe-cific rates according to the assumption that thedistribution of serotypes among cases without 2004 8.4 2.6 0.4 0.8 0.8 0.1 0.4 4.0 1.2 2.2 1.9 cases/100,000serotype data was the same as that among cases 0 0with serotype data. Changes in the rates of anti-biotic-nonsusceptible disease were calculated for 1999 16.4 12.3 1.5 2.8 4.7 0.7 2.4 3.5 1.7 1.3 0.6 0.1 0.1the comparison between 1999 — the year before Table 1. Incidence of Invasive Pneumococcal Disease Caused by Penicillin-Nonsusceptible Strains in 1999 and 2004, According to Serotype.*the vaccine was introduced — and 2004. Two-sidedP values of less than 0.05 were considered to in- −98 (−97.6 to −98.4) −99 (−98.7 to −99.5) +313 (+247 to +393) % Change (95% CI)dicate statistical significance and were not ad- +150 (+84 to +238) −100 (−99 to −100) +25 (+13 to +39) −81 (−80 to −82) −97 (−96 to −98) −94 (−92 to −96) −65 (−56 to −72) −97 (−96 to −98)justed for multiple testing. Undefined Undefined SAS (version 9.1, SAS Institute) and StatXact * CI denotes confidence interval. Values for the serotype subgroups may not sum to the total number because of rounding.programs were used for data analysis. We used Children <2 Yr of Agemultivariable logistic-regression modeling to as-sess factors associated with invasive disease causedby penicillin-nonsusceptible pneumococci in 2004.We assessed collinearity and interactions among 2004 1.2 0.2 0.3 0.2 0.5 10.2 1.4 8.3 1.9 13.1 cases/100,000variables in the final model. 0 0 0 R e sult s 1999 70.3 61.5 8.6 6.1 30.5 8.4 7.9 8.2 4.1 2.0 0.8 0 0All AgesWe identified 28,336 cases from 1996 through2004; isolates were available for 24,825 (87.6 per- % Change (95% CI) +238 (+214 to +263) +195 (+165 to +230) −100 (−96 to −100) +54 (+47 to +61)cent). For 96.4 percent of the cases, isolates were −57 (−55 to −58) −87 (−86 to −88) −78 (−75 to −80) −78 (−76 to −79) −92 (−92 to −79) −73 (−54 to −84) −73 (−69 to −76) −91 (−89 to −92) −22 (−15 to −28)available from blood; for 3.8 percent, from cere-brospinal fluid; for 1.5 percent, from pleural fluid; Persons of Any Ageand for 1.0 percent, from other sources (for somecases, isolates were available from more than onesource). All isolates were serotyped and testedfor antibiotic susceptibility. 2004 0.07 0.08 Overall rates of invasive pneumococcal dis- 2.7 0.7 0.1 0.2 0.2 1.6 0.3 1.2 0.5 cases/100,000 0 0ease ranged from 23.7 to 25.1 cases per 100,000persons between 1996 and 1999; the number ofcases per 100,000 persons decreased to 20.9 in 1999 0.03 0.02 6.3 5.0 0.6 1.1 2.0 0.5 0.8 1.0 0.4 0.3 0.22000, 16.9 in 2001, 14.0 in 2002, 14.0 in 2003, and12.6 in 2004. The incidence of penicillin-nonsus-ceptible disease increased from 5.4 cases per All vaccine-related serotypes100,000 in 1996 to a peak of 6.3 per 100,000 in All nonvaccine serotypes1999 (P<0.04). Comparing 1999 and 2004 data, All vaccine serotypeswe found that the overall rate of penicillin-non-susceptible disease decreased from 6.3 to 2.7 per All serotypes100,000 (a decline of 57 percent; 95 percent con- Serotypefidence interval, 55 to 58 percent) (Table 1). Simi- 18C 19A 19F 23F 6A 6B 9V 14 4lar decreases were found for erythromycin-non-susceptible disease (from 4.7 to 2.3 per 100,000, n engl j med 354;14 www.nejm.org april 6, 2006 1457 Downloaded from www.nejm.org on July 31, 2008 . Copyright © 2006 Massachusetts Medical Society. All rights reserved.
  4. 4. The n e w e ng l a n d j o u r na l of m e dic i n e a decline of 51 percent [95 percent confidence were no significant changes in the proportion of interval, 50 to 53 percent]) and for disease caused isolates that were nonsusceptible to cefotaxime, by strains with reduced susceptibility to mul- tetracycline, or levofloxacin. The proportion of tiple antibiotics (from 4.1 to 1.7 per 100,000, a isolates that were nonsusceptible to any tested decline of 59 percent [95 percent confidence inter- antibiotic was 37.7 percent in 1999 and 33.6 per- val, 58 to 60 percent]). Rates of penicillin-non- cent in 2004 (P = 0.002). Most individual serotypes susceptible disease due to vaccine serotypes fell were not less resistant in 2004 than in 1999 (Ta- from 5.0 to 0.7 per 100,000 (a decline of 87 per- ble 2). Among the vaccine serotypes, only sero- cent; 95 percent confidence interval, 86 to 88 type 23F was significantly less often resistant in percent) (Table 1). Rates of disease caused by 2004 than in 1999; vaccine-related serotype 19A vaccine-related strains increased by 54 percent was resistant more often. (from 1.0 to 1.6 per 100,000); this change re- flected a decrease (by 22 percent) in the rate of Rates of Disease According to Age disease due to serotype 6A and a large increase Children under Five Years of Age (by 238 percent) in the rate of disease due to sero- The rates of penicillin-nonsusceptible invasive dis- type 19A. The rate of penicillin-nonsusceptible ease among children under five years of age disease due to nonvaccine serotypes increased ranged from 25.9 to 33.8 per 100,000 between from 0.2 per 100,000 in 1999 to 0.5 per 100,000 1996 and 1999, before the introduction of the con- in 2004. jugate vaccine, and fell to 7.5 per 100,000 in 2004. The decrease in the rate of penicillin-nonsus- Rates of resistant infections were highest among ceptible disease was largest in Georgia (a decrease children under two years of age, the target age of 68 percent, from 11.1 per 100,000 in 1999 to for use of the conjugate vaccine. In this age group, 3.6 per 100,000 in 2004) and smallest in New the rate of invasive disease caused by penicillin- York (a decrease of 11 percent, from 3.3 to 2.9 per nonsusceptible pneumococci decreased by 81 per- 100,000). The rate of penicillin-nonsusceptible cent (95 percent confidence interval, 80 to 82 per- disease decreased by 65 percent (from 11.7 to 4.1 cent), from a peak of 70.3 per 100,000 in 1999 to per 100,000) in Tennessee, by 60 percent (from 13.1 per 100,000 in 2004 (Fig. 1). The rate of in- 5.5 to 2.2 per 100,000) in Minnesota, by 57 per- vasive disease due to erythromycin-nonsuscep- cent (from 3.7 to 1.6 per 100,000) in Oregon, by tible strains decreased by 80 percent (95 percent 53 percent (from 3.8 to 1.8 per 100,000) in Califor- confidence interval, 78 to 81 percent), from 58.6 nia, by 53 percent (from 5.8 to 2.7 per 100,000) in to 12.0 per 100,000, and the rate of disease due to Maryland, and by 42 percent (from 4.9 to 2.9 per strains with reduced susceptibility to both peni- 100,000) in Connecticut. The change in rate was cillin and erythromycin decreased by 83 percent significant at all sites except New York. (95 percent confidence interval, 82 to 85 percent), The proportion of isolates that were penicil- from 51.5 to 8.6 per 100,000. Among children two lin-nonsusceptible increased from 21.6 percent to four years of age, the rate of penicillin-nonsus- in 1996 to 25.8 percent in 1999 and 25.9 percent ceptible disease decreased by 60 percent (95 per- in 2000 and fell to 21.6 percent in 2004 (P<0.001 cent confidence interval, 56 to 65 percent), from for the comparison between 1999 and 2004). The 9.4 to 3.7 per 100,000 (Fig. 2). The rate of disease proportion of erythromycin-nonsusceptible iso- caused by strains nonsusceptible to multiple an- lates ranged from 10.7 percent in 1996 to 19.4 tibiotics decreased by 84 percent (95 percent con- percent in 1999 and 20.6 percent in 2000; the fidence interval, 82 to 85 percent), from 53.8 to proportion of isolates that were erythromycin- 8.8 per 100,000, among children under two years nonsusceptible did not change significantly af- of age, and by 64 percent (95 percent confidence ter the introduction of the vaccine and was 18.1 interval, 58 to 68 percent), from 6.2 to 2.3 per percent in 2004 (P = 0.23 for the comparison with 100,000, among children two to four years of age. 1999 rates). When data from 1999 and 2004 were Among children under two years of age, almost compared with respect to other drugs, significant all infections caused by penicillin-nonsuscepti- decreases were seen in the proportion of isolates ble strains were due to vaccine and vaccine-related that were nonsusceptible to trimethoprim–sulfa- serotypes, both before and after introduction of methoxazole, cefuroxime, meropenem, or clinda- the vaccine (Table 1). In this age group, a large mycin or to three or more drug classes, but there reduction in disease caused by vaccine serotypes1458 n engl j med 354;14 www.nejm.org april 6, 2006 Downloaded from www.nejm.org on July 31, 2008 . Copyright © 2006 Massachusetts Medical Society. All rights reserved.

×