RESUMO
OBJECTIVES: External validity, or generalisability, is the measure of how well results from a study pertain to individuals in the target population. We assessed generalisability, with respect to socioeconomic status, of estimates from a matched case-control study of 13-valent pneumococcal conjugate vaccine effectiveness for the prevention of invasive pneumococcal disease in children in the USA. DESIGN: Matched case-control study. SETTING: Thirteen active surveillance sites for invasive pneumococcal disease in the USA. PARTICIPANTS: Cases were identified from active surveillance and controls were age and zip code matched. OUTCOME MEASURES: Socioeconomic status was assessed at the individual level via parent interview (for enrolled individuals only) and birth certificate data (for both enrolled and unenrolled individuals) and at the neighbourhood level by geocoding to the census tract (for both enrolled and unenrolled individuals). Prediction models were used to determine if socioeconomic status was associated with enrolment. RESULTS: We enrolled 54.6% of 1211 eligible cases and found a trend toward enrolled cases being more affluent than unenrolled cases. Enrolled cases were slightly more likely to have private insurance at birth (p=0.08) and have mothers with at least some college education (p<0.01). Enrolled cases also tended to come from more affluent census tracts. Despite these differences, our best predictive model for enrolment yielded a concordance statistic of only 0.703, indicating mediocre predictive value. Variables retained in the final model were assessed for effect measure modification, and none were found to be significant modifiers of vaccine effectiveness. CONCLUSIONS: We conclude that although enrolled cases are somewhat more affluent than unenrolled cases, our estimates are externally valid with respect to socioeconomic status. Our analysis provides evidence that this study design can yield valid estimates and the assessing generalisability of observational data is feasible, even when unenrolled individuals cannot be contacted.
Assuntos
Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Classe Social , Cobertura Vacinal , Vacinas Conjugadas , Estudos de Casos e Controles , Pré-Escolar , Escolaridade , Humanos , Esquemas de Imunização , Lactente , Seguro Saúde , Avaliação de Resultados em Cuidados de Saúde , Pais , Infecções Pneumocócicas/microbiologia , Reprodutibilidade dos Testes , Características de Residência , Streptococcus pneumoniae , Estados UnidosRESUMO
A quadriplex real-time polymerase chain reaction assay was developed for detecting pneumococci, penicillin susceptibility, and macrolide/lincosamide resistance. The assay was sensitive for all 4 targets (<10 copies) and correlated with antimicrobial susceptibilities in 172/180 isolates and 28/29 culture-positive clinical specimens. For 29 lytA-positive culture-negative specimens, the assay allowed interpretation of antimicrobial susceptibility.
Assuntos
Farmacorresistência Bacteriana , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase Multiplex/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Streptococcus pneumoniae/genética , Antibacterianos/farmacologia , Humanos , Lincosamidas/farmacologia , Macrolídeos/farmacologia , Testes de Sensibilidade Microbiana/métodos , Penicilinas/farmacologia , Sensibilidade e Especificidade , Streptococcus pneumoniae/efeitos dos fármacosRESUMO
The fitness cost of the genes responsible for resistance to fluoroquinolones in clinical isolates of Streptococcus pneumoniae were estimated in vitro in a common genetic background. Naturally occurring parC, parE, and gyrA loci containing mutations in the quinolone-resistance-determining regions were introduced by transformation into S. pneumoniae strain R6 individually and in combinations. The fitness of these transformants was estimated by pairwise competition experiments with a common R6 strain. On average, single par and gyr mutants responsible for low-level MIC resistance (first-step resistance) impose a fitness burden of approximately 8%. Some of these mutants engender no measurable cost, while one, a parE mutant, reduces the fitness of these bacteria by more than 40%. Most interestingly, the addition of the second par or gyr mutations required for clinically significant, high-MIC fluoroquinolone resistance does not increase the fitness burden imposed by these single genes and can even reduce it. We discuss the implications of these results for the epidemiology of fluoroquinolone resistance and the evolution of acquired resistance in treated patients.