In vitro antimicrobial activities of a novel everninomicin for multiple drug-resistant Streptococcus pneumoniae isolates in Japan

Sir, In recent years, there has been an increase in penicillinresistant Streptococcus pneumoniae (PRSP) harbouring the erm or mef gene. In Japan, the frequency of PRSP was c. 40% during 1994–1995. This trend has made the selection of optimal drug therapy for infections caused by PRSP very difficult. Everninomicin is an investigational oligosaccharide antibiotic; its antimicrobial activity was first recognized over 30 years ago. The present study was designed to assay the in vitro antibacterial activities of everninomicin against penicillin-susceptible and -resistant S. pneumoniae harbouring the erm or mef gene in order to clarify the usefulness of a novel everninomicin, SCH27899, in patients infected with S. pneumoniae, including multiple drug-resistant organisms. The following antimicrobial agents were used: SCH27899 and gentamicin (Schering-Plough K.K., Osaka, Japan), vancomycin (Shionogi & Co., Osaka, Japan), teicoplanin (Aventis Pharma, Tokyo, Japan), arbekacin and ampicillin (Meiji Seika Kaisha, Tokyo), minocycline (Wyeth Lederle Japan, Tokyo, Japan) and imipenem (Banyu Pharmaceutical Co., Tokyo, Japan). Clinical isolates of S. pneumoniae were collected at Toho University Hospital during 1994–1996 and stored at –80°C in 10% skimmed milk until use. DNA was obtained according to the instructions provided by the manufacturer of SepaGene (Sanko junyaku Co., Tokyo, Japan). Genes encoding macrolide resistance were detected by a PCR method as described by Sutcliffe and colleagues. Strain 3585 (ermB) and strain 02J1175 [mef(E)], kindly provided by Dr Joyce de Aavedo, University of Toronto, were used as positive controls. MICs were determined by broth microdilution methods. The medium used was cation-adjusted Mueller– Hinton broth (Difco Laboratories, Detroit, MI, USA) supplemented with 5% lysed horse blood; the inoculum was 10 cfu/L. The MICs were determined following incubation at 35°C for 18 h. The Table shows the comparison of the in vitro activities of SCH27899 and other drugs against clinical isolates of S. pneumoniae. SCH27899 exhibited potent activity against penicillin-susceptible S. pneumoniae, with an MIC90 of 0.063 mg/L. Against this species, SCH27899 had almost the same activity as teicoplanin, imipenem and ampicillin, and was at least eight times more active than the other drugs tested. Against penicillin-resistant S. pneumoniae, the activity of SCH27899 (MIC90 0.063 mg/L) was the same as that of teicoplanin. The activity of SCH27899 was almost the same as that against penicillin-susceptible S. pneumoniae, but the activities of imipenem and ampicillin against penicillin-resistant isolates were lower than those against penicillin-susceptible isolates. The MIC90s of everninomicin for S. pneumoniae isolates harbouring the erm or mef gene were both 0.063 mg/L, which was comparable to those of teicoplanin and represents a potency at least four times greater than those of the other antimicrobial agents tested. The incidence of PRSP (MIC of penicillin G 0.125 mg/L) in Japan during 1993–1995 was c. 40%. Nakashio et al. reported that everninomicin had high potency against streptococci including S. pneumoniae, almost all of which were penicillin susceptible. Urban et al. reported that everninomicin exhibited superior activity in vitro against S. pneumoniae isolated in the USA and demonstrated that this drug had high potency against a diverse group of Gram-positive bacteria including methicillin resistant staphylococci and vancomycin-resistant enterococci. More recently, Marshall et al. reported that everninomicin was highly potent against both penicillin-susceptible and penicillin-resistant S. pneumoniae, and its activity against penicillin-susceptible organisms was almost the same as that against penicillin-resistant organisms. Our results are in agreement with the above findings. In a murine pulmonary infection model of PRSP, the efficacy of SCH27899 was superior to that of vancomycin, imipenem–cilastatin and ampicillin (unpublished data). There is, however, no report concerning the antibacterial activity of everninomicin against macrolide-resistant S. pneumoniae. The present study demonstrated that SCH27899 is highly potent against penicillin-resistant, macrolide-resistant and penicillin/macrolide-resistant organisms. Our results indicate that SCH27899 may prove useful in the treatment of infec-