In vitro antibacterial activities of telithromycin, a new ketolide, against bacteria causing infections in obstetric and gynaecological patients.

Abstract

Sir, Telithromycin is a new, semi-synthetic 14-membered ring agent belonging to a new chemical family, the ketolides, characterized by a 3-keto group instead of L-cladinose, and a C11–C12 carbamate link by an alkyl chain to a pyridinum and imidazolium ring side chain. The antibacterial spectrum of telithromycin includes Gram-positive cocci and bacilli, Gram-negative cocci and some Gram-negative bacilli, some enteric pathogens and anaerobic bacteria. Telithromycin is generally inactive against species of the Enterobacteriaceae, Pseudomonas aeruginosa and other non-fermentative Gram-negative bacilli. To date, however, there have been no studies of in vitro telithromycin activity on causative organisms in obstetric and gynaecological infections. The aim of the present study was to assess the in vitro activity of telithromycin, for the use in obstetric and gynaecological bacterial infections. Telithromycin and roxithromycin were provided by Aventis Pharma, Romainville, France; erythromycin and cefaclor by Shionogi Co., Ltd., Osaka, Japan; clarithromycin by Dinabot Co., Ltd., Tokyo, Japan; azithromycin by Pfizer Inc., New York, USA; levofloxacin by Daiichi Pharmaceutical Co., Tokyo, Japan; ampicillin by Sigma Chemical Co., St Louis, MO, USA; and clindamycin by Pharmacia & Upjohn Co., Kalamazoo, MI, USA. A total of 139 recent clinical isolates (68 isolates of aerobes and 71 isolates of anaerobes) were collected from patients in the Department of Obstetrics and Gynaecology, Gifu University School of Medicine, during the period between January 1998 and December 1998. The organisms were identified using the API STREP identification system (bioMerieux SA, Marcy l’Etoile, France), the Enterotube II identification system (Becton Dickinson and Co., Cockeysville, MD, USA) and the Oxi/Ferm Tube II system (Becton Dickinson) for aerobic bacteria, and with the RAP ID ANA system II (Innovative Diagnosis System, Norcross, GA, USA) for anaerobic bacteria. Organisms tested were as follows; 33 isolates of Streptococcus agalactiae, 35 isolates of Enterococcus faecalis, 21 isolates of Peptostreptococcus magnus, 22 isolates of Bacteroides fragilis and 28 isolates of Prevotella bivia. MICs were determined by an agar dilution method. Aerobic and anaerobic organisms grown on agar plates; [Mueller–Hinton agar (Difco Laboratories, Detroit, MI, USA) for E. faecalis; Mueller–Hinton agar (Difco) supplemented with 5% sheep serum (Irvine Scientific, Santa Ana, CA, USA) for S. agalactiae; Modified GAM (Gifu Anaerobic Medium) agar (Nissui Pharmaceutical Co., Tokyo, Japan) for P. magnus and B. fragilis and Brucella HK agar (Kyokuto Pharmaceutical Co., Tokyo, Japan) supplemented with 5% laked sheep blood for P. bivia] were suspended in Mueller–Hinton broth (Difco) and GAM (Gifu Anaerobic Medium) broth (Nissui), respectively, to obtain concentrations of approximately 5 10 cfu/L. After a 200-fold dilution of the suspension, the bacteria were inoculated on to agar plates containing each antimicrobial agent (0.00156–100 mg/L) with a multipoint inoculator (Microplanter, Sakuma Seisakusho, Tokyo, Japan) giving an inoculum density of approximately 2.5 10 cfu/spot. All aerobic cultures were incubated at 37 C for 24 h and all anaerobic cultures at 37 C for 48 h in the Anaero Pack (Mitsubishi Gas Chemical Co.,Tokyo, Japan). MICs were defined as the lowest concentration of antimicrobial agent that prevented the visible growth of organisms. The Table shows the MICs of antimicrobial agents for the strains tested. Telithromycin inhibited 90% of the clinical isolates of S. agalactiae, E. faecalis, P. magnus, B. fragilis and P. bivia at a concentration of 3.13 mg/L. It should be appreciated that the use of CO2 in anaerobic jars may elevate macrolide/ketolide MICs by two to three doubling dilutions. Obstetric and gynaecological bacterial infections are often complicated by, or associated with, sexually transmitted diseases, especially chlamydia and Neisseria gonorrhoeae infection. The antichlamydial activity of telithromycin was generally greater than that of commonly used antichlamydial antimicrobials. Also, teliCorrespondence Journal of Antimicrobial Chemotherapy (2000) 46, 323–342