In Vitro Susceptibility of Coxiella burnetii to Trovafloxacin in Comparison with Susceptibilities to Pefloxacin, Ciprofloxacin, Ofloxacin, Doxycycline, and Clarithromycin

摘要: Coxiella burnetii is the etiologic agent of Q fever. Two major forms disease are known: acute and chronic (1). The form usually a self-limiting febrile illness, during which pneumonia or hepatitis may occur. However, severe in endocarditis predominates (8). Whereas C. infections respond to antibiotic therapy, hard cure (3, 12). The efficacies quinolones against these types infection have yet be established. In this paper we studied activity new quinolone, trovafloxacin, burnetii, using Vero cell tissue cultures. We also compared its bacteriostatic effect with those five other compounds on eight Greek isolates derived from human samples. Stock solutions trovafloxacin (20 mg/ml; kindly provided by Pfizer Inc., New York, N.Y.), pefloxacin (400 mg/5 ml; Rhone Poulenc S.A., Paris, France), ciprofloxacin (100 mg/50 Bayer AG, Leverkuzen, Germany), ofloxacin (220 mg/100 Hoechst Frankfurt am Main, Germany) were prepared. For doxycycline (Pfizer Inc.) clarithromycin (Abbott Laboratories, Chicago, Ill.), stock at 6 mg/ml prepared methanol. All strains grown cells as previously described (10). bactericidal effects tested shell vial assay. purpose an acute-infection model Nine-Mile strain chronic-infection Q212 employed (1, 10). addition, concentration inoculum that was determined infect 30 50% used vials for challenge Bacterial growth evaluated after days incubation indirect immunofluorescence, results scored follows: R resistance, comparable control; I intermediate susceptibility, less than 10% infected cells; S absence (10). The assessed quantitative method Maurin Raoult (6). Trovafloxacin added culture medium 4 μg/ml. Viable organisms identified culture, corresponded significant reduction bacterial titer (at least 2 3 dilutions) exposure, primary dose (5, 6). Trovafloxacin showed toward burnetii. Complete inhibition obtained 1 μg per ml tests isolate seven isolates. Inhibition μg/ml last (Table ​(Table1).1). These concentrations below achieved serum recommended single oral 200 mg (2.2 μg/ml). TABLE 1 Susceptibilities vial technique Vero persistently 5 months before being tested. Only two experiments trovafloxacin. No demonstrated when examined. All MICs recorded each peak serum. all antibiotics summarized Table ​Table2.2. 2 Antibiotic susceptibilities burnetii isolates At tested, ofloxacin, improved activities vitro well reference strains. same susceptible clarithromycin. Ciprofloxacin presented higher strains. Two problems associated evaluation treatment First, it self-limited mostly retrospectively diagnosed form, success therapy requires prolonged follow-up due late relapses (3–5, 7–9). Second, experimental problematic because strictly intracellular pathogen no successful animal fever has been so far (9). cases fever, sufficient enabling recovery, whereas regimen not curative (9). Tetracycline mainstay (8, 9). recovery viable valve years reported use cotrimoxazole alone failed Combinations rifampin either treating endocarditis, apparent Clinical data macrolides lacking (4). More recently, combination lysosomotropic chloroquine displayed vitro, but definitive clinical (4). Quinolones exhibit rickettsiae produced encouraging patients (2, 3). our study, (MIC, μg/ml) better pefloxacin, clarithromycin, ciprofloxacin. trovafloxacin. A comparison between MIC cannot evidence trovafloxacin’s efficacy, since pathogen. It is, however, interesting (Q212 CP1) needed their order achieve levels. This true type favorable ​(Table2).2). determination μg/ml, strain. In conclusion, indicate possesses promising bacteria species. Careful studies now required evaluate infection.