Institute of Medical Microbiology, Westfälische Wilhelms-Universität Münster, Domagkstraße 10, 48149 Münster, Germany
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Abstract |
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Introduction |
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Moxifloxacin, a newly developed 8-methoxyfluoroquinolone, and trovafloxacin, a new fluoronaphthyridone derivative, were reported to be effective against Gram- positive bacteria. 1,2 Similarly, quinupristin/dalfopristin (in a ratio of 30:70), the first semisynthetic injectable pristinamycin, and linezolid, a novel oxazolidinone, have potent activity against a variety of Gram-positive bacteria. 3,4
The aims of this study were (i) to evaluate the in-vitro activity of moxifloxacin, trovafloxacin, quinupristin/dalfopristin, and linezolid against a large number of different and well-characterized staphylococcal strains, particularly against clonally different methicillin-resistant strains isolated from several geographic locations in Germany, and (ii) to compare the in-vitro antistaphylococcal activities of the newly developed antimicrobial agents with compounds such as ciprofloxacin, vancomycin and teicoplanin.
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Materials and methods |
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The 104 S. aureus strains included 17 penicillin-susceptible (PSSA), 27 methicillin-susceptible (MSSA) and 60 methicillin-resistant (MRSA) strains. The 141 coagulase-negative staphylococci (CoNS) comprised 20 methicillin-susceptible Staphylococcus epidermidis (MSSE), 29 methicillin-resistant S. epidermidis (MRSE), 16 methicillin-susceptible Staphylococcus haemolyticus (MSSH), 43 methicillin-resistant S. haemolyticus (MRSH) and 33 other coagulase-negative staphylococci belonging tothe following species: nine Staphylococcus hominis, eightStaphylococcus lugdunensis, four Staphylococcus warneri, four Staphylococcus capitis, two Staphylococcus schleiferi, two Staphylococcus simulans, two Staphylococcus caprae, one Staphylococcus saprophyticus and one Staphylococcus sciuri. The staphylococci were identified from a variety of conventional phenotypic characteristics and by using the API-Staph system (ATB32 Staph, BioMérieux, Marcy- l'Etoile, France). Erythromycin-resistant and clindamycin-resistant strains were included. The MICs were determined on Mueller-Hinton agar (Difco, Augsburg, Germany), using an agar dilution technique with an inoculum of 10 5 cfu. Isolates were confirmed to be methicillin resistant by supplementing the agar with 2% NaCl (read after incubation for 48 h at 30°C), as well as by detection of the mecA gene in strains with non-definable resistance phenotypes. The following antimicrobial agents were used and obtained from their respective manufacturers: moxifloxacin and ciprofloxacin (both supplied by Bayer AG, Leverkusen, Germany), trovafloxacin (Pfizer Central Research, Groton, CT, USA), linezolid (Pharmacia & Upjohn Co., Kalamazoo, MI, USA), quinupristin/dalfopristin (Rhône-Poulenc Rorer R-D, Vitry-sur-Seine, France), vancomycin (Eli Lilly & Co., Indianapolis, IN, USA), teicoplanin (Hoechst Marion Roussel Deutschland GmbH, Frankfurt, Germany).The quinolones were tested in concentrations in the range 0.031- 128 mg/L; quinupristin/dalfopristin, linezolid and the glycopeptides were tested in concentrations in the range 0.031- 8 mg/L. The results were read after 18 h incubation at 36°C. The following reference strains were included as controls: S. aureus ATCC 25923; ATCC 29213; ATCC 43300; Escherichia coli ATCC 35218; Pseudomonas aeruginosaATCC 27853. Additionally, sterility and growth controls were always performed.
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Results |
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Discussion |
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The antimicrobial susceptibilities of our staphylococci were generally in agreement with those reported by other investigators, indicating that the newly developed agents tested appear promising for treatment of multi-resistant Gram-positive organisms. 1 ,2 ,3 ,4However, in contrast to previous studies, we observed a larger number of strains with elevated MICs, particularly of the quinolones, resulting in MIC 90 values up to 16-fold higher than reported by other investigators. 2,3,7,8,9 This finding might be explained by the fact that in most of the aforementioned studies, only a limited number of different staphylococcal species, especially of methicillin-resistant strains, were studied and multiple isolates of the same strain were not excluded by phenotypic or genomic typing, 1 ,2 ,3 ,4 ,8 which is particularly important for MRSA, which often cause at least regional outbreaks with the same strain. 10
In summary, our data indicate that the newly developed agents tested exhibit sufficient antistaphylococcal activity against both methicillin-susceptible and methicillin-resistant strains, stimulating further evaluation of these agents for therapy of infections caused by multi-resistant staphylococci. However, single strains of S. aureus, S. epidermidis and S. haemolyticus with elevated MICs of moxifloxacin or trovafloxacin may be found.
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Acknowledgments |
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Notes |
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References |
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8 . Mulazimoglu, L., Drenning, S. D. & Yu, V. L. (1996). In vitro activities of two novel oxazolidinones (U-100592 and U-100766), a new fluoroquinolone (trovafloxacin) and dalfopristin- quinupristin against Staphylococcus aureus and Staphylococcus epidermidis.Antimicrobial Agents and Chemotherapy 40, 242830.[Abstract]
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Received 30 June 1998; returned 15 September 1998; revised 26 October 1998; accepted 20 November 1998