TY - JOUR
T1 - Mechanisms by which antibiotics promote dissemination of resistant pneumococci in human populations
AU - Samore, Matthew H.
AU - Lipsitch, Marc
AU - Alder, Stephen C.
AU - Haddadin, Bassam
AU - Stoddard, Greg
AU - Williamson, Jacquelyn
AU - Sebastian, Katherine
AU - Carroll, Karen
AU - Ergonul, Onder
AU - Carmeli, Yehuda
AU - Sande, Merle A.
N1 - Funding Information:
Dr. Carmeli, his laboratory, and studies that he has conducted during the past 4 years received grants, honoraria, travel support, and other forms of financial support from the following companies: Bayer Corp., West Haven, Connecticut; Biomedicum Ltd., Jerusalem, Israel; Bristol-Myers Squibb, Wallingford, Connecticut; Merck & Co., Inc., Whitehouse Station, New Jersey; Neopharm Ltd., Petach Tikva, Israel; Pfizer Pharmaceuticals, New York, New York; Teva Ltd., Cumbria, United Kingdom; Vicuron Pharmaceuticals, King of Prussia, Pennsylvania; Wyeth, Madison, New Jersey; and XTL Pharmaceuticals Ltd., Rehovot, Israel.
Funding Information:
Funding was provided by Centers for Disease Control and Prevention grant RS1 CCR820631 and the Thrasher Research Fund. M. L.’s work was supported by the Ellison Medical Foundation and National Institutes of Health grant 5R01AI048935.
PY - 2006/1
Y1 - 2006/1
N2 - Mechanisms by which antimicrobials contribute to dissemination of pneumococcal resistance are incompletely characterized. A serial cross-sectional study of nasopharyngeal pneumococcal carriage in healthy, home-living children ≤6 years of age was conducted in four rural communities - two in Utah (1998-2003) and two in Idaho (2002-2003). Prevalence odds ratios for carriage of resistant pneumococci (ORres) and of susceptible pneumococci (ORsus) were estimated. Dynamic transmission models were developed to facilitate a mechanistic interpretation of ORres and ORsus and to compare the population impact of distinct antimicrobial classes. A total of 5,667 cultures were obtained; 25% of the cultures were positive, and 29% of isolates exhibited reduced susceptibility to penicillin. The adjusted OR res for recent individual and sibling cephalosporin use was 2.2 (95% confidence interval: 1.4, 3.4) and 1.8 (95% confidence interval: 1.0, 3.3), respectively. Neither individual nor sibling penicillin use was associated with increased ORres. Rather, recent use of penicillins was associated with decreased carriage of susceptible pneumococci (ORsus = 0.2, 95% confidence interval: 0.1, 0.3). In simulations, both types of effects promoted dissemination of resistant pneumococci at the population level. Findings show that oral cephalosporins enhance the risk of acquiring resistant pneumococci. Penicillins accelerate clearance of susceptible strains. The effect of penicillins in increasing resistance is shared equally by treated and untreated members of the population.
AB - Mechanisms by which antimicrobials contribute to dissemination of pneumococcal resistance are incompletely characterized. A serial cross-sectional study of nasopharyngeal pneumococcal carriage in healthy, home-living children ≤6 years of age was conducted in four rural communities - two in Utah (1998-2003) and two in Idaho (2002-2003). Prevalence odds ratios for carriage of resistant pneumococci (ORres) and of susceptible pneumococci (ORsus) were estimated. Dynamic transmission models were developed to facilitate a mechanistic interpretation of ORres and ORsus and to compare the population impact of distinct antimicrobial classes. A total of 5,667 cultures were obtained; 25% of the cultures were positive, and 29% of isolates exhibited reduced susceptibility to penicillin. The adjusted OR res for recent individual and sibling cephalosporin use was 2.2 (95% confidence interval: 1.4, 3.4) and 1.8 (95% confidence interval: 1.0, 3.3), respectively. Neither individual nor sibling penicillin use was associated with increased ORres. Rather, recent use of penicillins was associated with decreased carriage of susceptible pneumococci (ORsus = 0.2, 95% confidence interval: 0.1, 0.3). In simulations, both types of effects promoted dissemination of resistant pneumococci at the population level. Findings show that oral cephalosporins enhance the risk of acquiring resistant pneumococci. Penicillins accelerate clearance of susceptible strains. The effect of penicillins in increasing resistance is shared equally by treated and untreated members of the population.
KW - Cephalosporins
KW - Drug resistance, microbial
KW - Nasopharyngeal diseases
KW - Penicillins
KW - Streptococcus pneumoniae
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U2 - 10.1093/aje/kwj021
DO - 10.1093/aje/kwj021
M3 - Article
C2 - 16319292
AN - SCOPUS:30344460680
VL - 163
SP - 160
EP - 170
JO - American Journal of Epidemiology
JF - American Journal of Epidemiology
SN - 0002-9262
IS - 2
ER -