High rates of multiple antibiotic resistance in Streptococcus pneumoniae from healthy children living in isolated rural communities: Association with cephalosporin use and intrafamilial transmission

Objective. Streptococcus pneumoniae is one of the most clinically significant pathogens with emerging antibiotic resistance. We performed a surveillance study in isolated rural populations of healthy children to estimate the prevalence of pneumococcal resistance and to contrast factors that predict pneumococcal carriage with those that specifically predict resistant pneumococcal carriage. Methods. The study was conducted in 1998 in 2 rural communities in Utah. Families were recruited directly for participation through community canvassing. Surveillance nasopharyngeal cultures were obtained from children who were younger than 8 years. Antibiotic usage and information on other potential risk factors were obtained from questionnaires and local pharmacy records. Resistance was determined by testing isolates for susceptibility to penicillin, cefaclor, trimethoprim-sulfamethoxazole, erythromycin, ceftriaxone, and trovafloxacin. Selected resistant isolates were characterized further by serotyping, pulsed field gel electrophoresis, and Southern blot with DNA probes specific for the pneumococcal lytA gene and for antibiotic resistance genes. Results. In April 1998, surveillance nasopharyngeal cultures were obtained from 368 children aged ≤8 years in community A and 369 children in community B. The number of antibiotic courses per child within 1 year before culture was higher in community B than A (mean: 2.2 vs 1.7). Conversely, oral cephalosporins were more frequently used in community A than B (community A: 22% received cephalosporins within 4 months; community B: 12%). Colonization with S pneumoniae was detected in 24% of children in community A and 14% in community B; 36% of isolates from community A and 28% of isolates from community B were resistant or intermediately susceptible to at least 1 antibiotic tested. Reduced susceptibility was most common to trimethoprim-sulfamethoxazole and cefaclor (28% and 26%, respectively). Pneumococcal carriage (susceptible or resistant) was independently associated with age <5 years (odds ratio [OR]: 2.2), child care exposure (OR: 2.4), presence of a sibling with a positive culture (OR: 3.3), and residence in community A (OR: 1.7). Among carriers, age <2 years (OR: 2.6), use of cephalosporins within the preceding 4 months (OR: 2.7), and having a sibling colonized with resistant S pneumoniae (OR: 5.5) were independent predictors of reduced susceptibility or resistance. Each pair of resistant isolates from siblings was indistinguishable by pulsed field gel electrophoresis and other molecular typing techniques. Several pneumococcal isolates from these isolated rural areas had the molecular characteristics of international clones of multiple-drug-resistant pneumococci that have been associated with worldwide spread. Conclusions. Young age and intrafamilial transmission were important risk factors for carriage of both susceptible and resistant S pneumoniae. In contrast, previous cephalosporin use was linked specifically to resistant pneumococcal carriage, which suggests that modifications in antibiotic usage patterns may have salutary effects on antimicrobial resistance. These results extend previous observations in large cities regarding the penetration of multiple-drug-resistant clones of pneumococci into community populations.