Genetics of oxacillin resistance in clinical isolates of Streptococcus pneumoniae that are oxacillin resistant and penicillin susceptible

Abstract

It has recently been reported that penicillin-sensitive pneumococci may exhibit reduced susceptibility to oxacillin, resulting in their misclassification as being penicillin resistant by oxacillin disk testing. Intermediate oxacillin resistance (MIC, 1.0 microgram/ml) in three of these apparently unrelated penicillin-susceptible clinical isolates of Streptococcus pneumoniae isolated in the United Kingdom and in four Spanish isolates was shown to be solely due to the acquisition of a gene encoding an altered penicillin-binding protein (PBP), PBP2X. PBP2X genes cloned from typical penicillin-resistant isolates of S. pneumoniae that possessed high-level oxacillin resistance were shown to be able to transform susceptible isolates of S. pneumoniae to intermediate oxacillin resistance. In all instances, the intermediately oxacillin-resistant PBP2X transformants retained susceptibility to penicillin (MIC, 0.06 microgram/ml). Under appropriate selective pressure, the acquisition of a low-affinity PBP2X by penicillin-susceptible pneumococci could result in an increasing number of false positives for penicillin resistance among isolates of S. pneumoniae screened with oxacillin. Additionally, these intermediately oxacillin-resistant isolates showed reduced susceptibility to cefotaxime, an agent likely to be prescribed in place of penicillin for the treatment of serious infections due to these apparently penicillin-resistant organisms.