In Vitro Activities of Quinupristin-Dalfopristin and Cefepime, Alone and in Combination with Various Antimicrobials, against Multidrug-Resistant Staphylococci and Enterococci in an In Vitro Pharmacodynamic Model

Abstract

Use of combinations of antimicrobials that together achieve synergistic activities against targeted microorganisms is one potential strategy for overcoming bacterial resistance. As the incidence of infections caused by multidrug-resistant staphylococci and enterococci increases, the importance of devising additional synergistic drug combinations for these bacteria is magnified. We evaluated a number of antimicrobial combinations, with a focus on quinupristin-dalfopristin (Q-D), cefepime, and linezolid, using a previously described in vitro pharmacodynamic model.

Novel pharmaceutical molecules against emerging resistant gram-positive cocci

“…89,[92][93][94][95][98][99][100][101][102][103][104][105][106][107] For instance, a synergistic interaction was found for quinupristin/dalfopristin and vancomycin in two independent studies. 92,93 On the other hand, antagonistic interactions were demonstrated for the combination of linezolid plus vancomycin, 94 and linezolid plus gentamicin.…”

<i>In vitro</i> Synergy and Time-kill Assessment of Interaction between Kanamycin and Metronidazole against Resistant Bacteria

“…The use of antimicrobial combinations to achieve synergistic activities against targeted microorganisms is a potential strategy for overcoming bacterial resistance [5]. Theoretically, it is aimed at broadening antimicrobial empirical coverage, improving efficacy against isolates with a minimum inhibitory concentration (MIC) at or approaching the breakpoint for susceptibility as well as preventing the further emergence of resistant organisms [6].…”

Pharmacodynamics of Cefepime Alone and in Combination with Various Antimicrobials against Methicillin-Resistant Staphylococcus aureus in an In Vitro Pharmacodynamic Infection Model

“…Previous investigations have evaluated the usefulness of various combinations of antibiotics against MRSA, including combinations of quinupristin-dalfopristin and cefepime, linezolid, doxycycline, and vancomycin (3). Several studies have demonstrated additive or synergistic activity when cefepime was combined with various antibiotics, such as vancomycin plus ␤-lactams, ampicillin-sulbactam Ϯ arbekacin, and trimethoprim-sulfamethoxazole (3,9,26,32,47).…”

“…Several studies have demonstrated additive or synergistic activity when cefepime was combined with various antibiotics, such as vancomycin plus ␤-lactams, ampicillin-sulbactam Ϯ arbekacin, and trimethoprim-sulfamethoxazole (3,9,26,32,47). Cefepime is commonly used in combination with an aminoglycosides for empirical therapy in the ICU for gram-negative organisms or for definitive treatment of P. aeruginosa infections in critical care settings (22).…”

“…In vitro pharmacodynamic model. The in vitro pharmacodynamic model consists of a 250-ml one-compartment glass chamber with multiple ports for the removal of SMHB, delivery of antibiotics, and collection of bacterial and antimicrobial samples was utilized (3). All experiments were conducted over 48 h and were performed in duplicate to ensure reproducibility.…”