S. pneumoniae is the most important causative agent of pneumonia, sinusitis and otitis media in pediatric, geriatric, and immunocompromised populations. Morbidity and mortality figures are estimate at 3,000 cases of meningitis, 50,000 cases of bacteremia, 500,000 cases of pneumonia and more than seven million cases of otitis media in the United States, annually. In the mid-sixties, penicillin resistant streptococci to began to emerge worldwide. In a collaborative study with Children's National Medical Center in Washington, DC, we reported that the incidence of penicillin resistance in this area was significantly greater than nationwide. In a companion study, we unexpectedly found that all penicillin-sensitive and resistant pneumococci isolated during our study were resistant to trimethoprim/sulfamethoxazole (TMP/SMZ), a drug combination that is commonly used to treat infection in ambulatory patients. Our current research has focused on determining the molecular mechanism for TMP resistance in streptococci isolated from several clinical cases from this earlier study. We have succeed in cloning and sequencing the genetic determinant responsible for TMP resistance in five independent clinical isolates. Utilizing PCR amplification based on our cloned determinant, we have conducted a comparative study of both TMP- sensitive and resistant strains of S. pneumoniae . From this data we have determined the nature of TMP-resistance at the molecular level. In a similar clinical study, we have also determined the molecular bases for resistance of S. pneumoniae to optochin, an antibiotic used in clinical diagnosis of streptococci infections.
