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• W2123234505 abstract "ABSTRACT Quinupristin-dalfopristin (Q-D) is an injectable streptogramin active against most gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). In experimental endocarditis, however, Q-D was less efficacious against MRSA isolates constitutively resistant to macrolide-lincosamide-streptogram B (C-MLS B ) than against MLS B -susceptible isolates. To circumvent this problem, we used the checkerboard method to screen drug combinations that would increase the efficacy of Q-D against such bacteria. β-Lactams consistently exhibited additive or synergistic activity with Q-D. Glycopeptides, quinolones, and aminoglycosides were indifferent. No drugs were antagonistic. The positive Q-D–β-lactam interaction was independent of MLS B or β-lactam resistance. Moreover, addition of Q-D at one-fourth the MIC to flucloxacillin-containing plates decreased the flucloxacillin MIC for MRSA from 500 to 1,000 mg/liter to 30 to 60 mg/liter. Yet, Q-D–β-lactam combinations were not synergistic in bactericidal tests. Rats with aortic vegetations were infected with two C-MLS B -resistant MRSA isolates (isolates AW7 and P8) and were treated for 3 or 5 days with drug dosages simulating the following treatments in humans: (i) Q-D at 7 mg/kg two times a day (b.i.d.) (a relatively low dosage purposely used to help detect positive drug interactions), (ii) cefamandole at constant levels in serum of 30 mg/liter, (iii) cefepime at 2 g b.i.d., (iv) Q-D combined with either cefamandole or cefepime. Any of the drugs used alone resulted in treatment failure. In contrast, Q-D plus either cefamandole or cefepime significantly decreased valve infection compared to the levels of infection for both untreated controls and those that received monotherapy ( P < 0.05). Importantly, Q-D prevented the growth of highly β-lactam-resistant MRSA in vivo. The mechanism of this beneficial drug interaction is unknown. However, Q-D–β-lactam combinations might be useful for the treatment of complicated infections caused by multiple organisms, including MRSA." @default.
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• W2123234505 date "2000-07-01" @default.
• W2123234505 modified "2023-10-18" @default.
• W2123234505 title "Quinupristin-Dalfopristin Combined with β-Lactams for Treatment of Experimental Endocarditis Due to <i>Staphylococcus aureus</i> Constitutively Resistant to Macrolide-Lincosamide-Streptogramin B Antibiotics" @default.
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• W2123234505 doi "https://doi.org/10.1128/aac.44.7.1789-1795.2000" @default.
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