Mechanisms by Which Antibiotics Promote Dissemination of Resistant Pneumococci in Human Populations

Abstract

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 <or=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 (OR(res)) and of susceptible pneumococci (OR(sus)) were estimated. Dynamic transmission models were developed to facilitate a mechanistic interpretation of OR(res) and OR(sus) 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 OR(res). Rather, recent use of penicillins was associated with decreased carriage of susceptible pneumococci (OR(sus) = 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.

Impact of a 16-Community Trial to Promote Judicious Antibiotic Use in Massachusetts

“…10,11 Attention to antibiotic overuse and resistance has increased from physicians, public health authorities, and the lay press. The greatest cause for optimism is the marked decrease in antibioticuse rates for children and adults in the United States, even in the absence of concerted community-level intervention of the type that we report here 12,21 ; however, we conclude that community-level approaches can be successful in further reducing antibiotic use for children, especially when targeted toward specific populations (eg, Medicaid-insured children) and specific medication classes.…”

“…1,2 The rapid increase in resistance among common bacterial pathogens, such as Streptococcus pneumoniae, [3][4][5][6] is widely believed to be fueled by high rates of antibiotic use, much of which is unnecessary. [7][8][9][10][11] Because of the communicability of bacterial pathogens, the consequences of resis-tance have an impact on communities in addition to individual carriers. Young children have had the highest antibiotic-use rates of any age group 12 and may be at particular risk for acquiring and spreading resistant organisms, especially in group settings such as child care.…”

Macrolide and Azithromycin Use Are Linked to Increased Macrolide Resistance in Streptococcus pneumoniae

“…While the use of oral penicillins primarily diminished susceptible pneumococci in the nasopharynx, thus giving a competitive advantage to resistant strains at the population level, the use of oral cephalosporins appeared to directly increase acquisition of resistant S. pneumoniae isolates (22). Although both types of effects contribute to the dissemination of resistant pneumococcal strains, the latter effect is more powerful (22). Such an effect caused by outpatient use of cephalosporins may have accounted for the increased penicillin nonsusceptibility rates in the community-acquired S. pneumoniae strains in our study.…”

“…To combine individual data with population-level data in the investigation of the relation of antimicrobial resistance and consumption in the future will be a challenge (7,22). The development of resistance on an individual level is dependent on many factors, such as the antimicrobial resistance mechanism and the immunity status of the host.…”

Origin and Proliferation of Multiple-Drug Resistance in Bacterial Pathogens

“…In S. pneumoniae infections, antibiotics other than penicillin, such as azithromycin (72), erythromycin, trimethoprim-sulfamethoxazole (73,74), and cephalosporins (75), may select more efficiently for penicillin-resistant strains than penicillin itself. While the MICs associated with resistance to azithromycin are farther above clinically achievable concentrations, penicillin dosing can be increased to combat less-susceptible strains and still have limited effects on toxicity experienced by the patient.…”