RESUMO
The rate of macrolide resistance among Streptococcus pneumoniae is increasing, but some investigators have questioned its clinical relevance. We conducted a matched case-control study of patients with bacteremic pneumococcal infection at 4 hospitals to determine whether development of breakthrough bacteremia during macrolide treatment was related to macrolide susceptibility of the pneumococcal isolate. Case patients (n=86) were patients who had pneumococcal bacteremia and an isolate that was either resistant or intermediately resistant to erythromycin. Controls (n=141) were patients matched for age, sex, location, and year that bacteremia developed who had an erythromycin-susceptible pneumococcus isolated. Excluding patients with meningitis, 18 (24%) of 76 case patients and none of 136 matched controls were taking a macrolide when blood was obtained for culture (P=.00000012). Moreover, 5 (24%) of 21 case patients with the low-level-resistant M phenotype and none of 40 controls were taking a macrolide (P=.00157). These data show that development of breakthrough bacteremia during macrolide or azalide therapy is more likely to occur among patients infected with an erythromycin-resistant pneumococcus, and they also indicate that in vitro macrolide resistance resulting from both the efflux and methylase mechanisms is clinically relevant.
Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Streptococcus pneumoniae , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/microbiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Resistência a Medicamentos/fisiologia , Eritromicina/farmacologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Falha de TratamentoRESUMO
beta-Lactamase-mediated resistance to beta-lactam antibiotics is a feature of great clinical significance. beta-Lactamases are a diverse group of bacterial enzymes that vary in their abilities to hydrolyze beta-lactam antibiotics. beta-Lactamases possess an active site containing either a serine moiety or a zinc atom; serine beta-lactamases are currently of greater clinical prevalence. This review considers the molecular classification of beta-lactamases, the structure of the serine beta-lactamase active site and the mechanisms by which beta-lactamase production may become derepressed. The spread of beta-lactamases in the clinical setting and some important structural mutations that have extended the hydrolysis profiles of serine beta-lactamases are also discussed.