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The clinical and molecular epidemiology of penicillin-resistant Streptococcus pneumoniae and the diagnostic accuracy of a six-primer PCR assay in identifying penicillin resistance were analyzed by using clinical isolates recovered over a 10-year period in middle Tennessee. The prevalence of non-penicillin-susceptible S. pneumoniae isolates (MIC, > or =0.1 microg/ml) increased from 10% in 1990 to 70% in 1999 (P < 0.001). Among S. pneumoniae isolates for which the penicillin MIC was > or =2 microg/ml (highly penicillin-resistant S. pneumoniae [PRSP]), 23 and 5% were resistant to at least three and at least five other antimicrobial classes, respectively. Pulsed-field gel electrophoresis identified 13 unique strain types, with type B accounting for 33% of PRSP isolates. The sensitivity, specificity, and negative and positive predictive values of the PCR assay in detecting PRSP were 99, 100, 99, and 100%, respectively. Penicillin resistance is rapidly increasing among S. pneumoniae isolates in Tennessee. The simultaneous detection of S. pneumoniae and high-level penicillin resistance can be accurately performed with the six-primer PCR assay.
PURPOSE - To evaluate the consequences of prolonged prophylactic penicillin use on the rates of nasopharyngeal colonization with Streptococcus pneumoniae and the prevalence of resistant pneumococcal strains in children with sickle cell anemia.
METHODS - Nasopharyngeal specimens were obtained from children with sickle cell anemia (Hb SS or Hb S beta degrees thalassemia) at 10 teaching hospitals throughout the United States. These patients were participating in a prospective, randomized, placebo-controlled trial in which they were prescribed prophylactic penicillin before their fifth birthday and were randomized to prophylactic penicillin or placebo after their fifth birthday (PROPS II). The specimens were cultured for S. pneumoniae, and isolates were analyzed for antimicrobial susceptibility to nine commonly prescribed antimicrobial agents.
RESULTS - Of the 226 patients observed, an average of 8.4 specimens were collected per patient. From 1,896 individual culture specimens, 5.5% of the specimens were positive for S. pneumoniae; 27% of patients had at least one positive culture. Nine percent of the study patients had at least one isolate of penicillin intermediate or resistant pneumococci. There was no significant difference in the percent of positive cultures for S. pneumoniae in those patients given penicillin prophylaxis after 5 years of age (4.1%) compared with those patients given placebo after 5 years of age (6.4%). Likewise, there was no significant difference (p = 0.298) in the percent of patients with at least one positive culture for S. pneumoniae in the group given prophylactic penicillin after 5 years of age (21.8%) compared with the group given placebo after 5 years of age (28.3%). There was no difference between the penicillin and placebo groups in the proportion of patients with penicillin intermediate or resistant pneumococci, but there was a trend toward increased carriage of multiply drug-resistant pneumococci in children > 5 years of age receiving prophylactic penicillin compared to children > 5 years of age receiving placebo. The increased colonization rate with multiply drug-resistant organisms of children > 5 years of age receiving penicillin prophylaxis is not statistically significant.
CONCLUSIONS - The potential for continued penicillin prophylaxis to contribute to the development of multiply resistant pneumococci should be considered before continuing penicillin prophylaxis in children with sickle cell anemia who are older than 5 years of age. Added to the published data from PROPS II, which demonstrated no apparent advantage to continue prophylaxis, the data support the conclusion that, for children with no history of invasive pneumococcal disease, consideration should be given to discontinue prophylactic penicillin after their fifth birthday.
Previous reports documenting the essentially identical spectra of activity of ceftizoxime, cefotaxime, and ceftriaxone prompted our hospital formulary committee to replace the latter two drugs with ceftizoxime on the basis of cost differences. However, we subsequently observed that every one of 60 isolates of Streptococcus pneumoniae tested was less susceptible to ceftizoxime than to either cefotaxime or ceftriaxone. The difference between minimal inhibitory concentrations (MICs) was greatest for strains moderately or fully resistant to penicillin, which at our institution represent approximately 32% of all isolates of S. pneumoniae. Ten isolates with cefotaxime and ceftriaxone MICs of 2.0-6.0 micrograms/mL had ceftizoxime MICs of > or = 256 micrograms/mL. Time-kill kinetic studies assessing bactericidal activity confirmed the diminished activity of ceftizoxime against penicillin-resistant isolates of S. pneumoniae. Ceftizoxime should not be used to treat proven or suspected pneumococcal infection in areas where resistance to penicillin is prevalent.