Treatment of Endocarditis Due to Vancomycin‐ResistantEnterococcus faeciumwith Quinupristin/Dalfopristin, Doxycycline, and Rifampin: A Synergistic Drug Combination

Abstract

identification revealed a lack of gelatin, esculin, and tyrosine hyVeterinary Medicine, University of Ghent, Ghent, and the Laboratorium drolysis, a lack of urease activity, and the presence of nitratevoor Dierenziektebestrijding, Torhout, Belgium; and the Laboratory for reductase activity. Glucose and maltose were acidified, whereas Bacteriology, Faculty of Medicine, Strasbourg, France sucrose, mannitol, lactose, and glycogen were not. Propionic acid was produced by anaerobic fermentation of glucose, as reported References previously [6].In retrospect, the acute symptoms of our patient can be attributed Combinationand time-kill studies for synergy, were done to help predict the clinical response to therapy. The incidence of infections due to vancomycin-resistant Entero-A 76-year-old man with ischemic heart disease and aortic stenococcus faecium (VREF) has continued to increase during the past sis, underwent gastrectomy for gastric adenocarcinoma. His post-10 years. These organisms are typically multidrug resistant, and operative course was complicated by pneumonia, respiratory failoptimal antimicrobial therapy for serious VREF infections is unure, and central venous catheter-associated bacteremia due to known. None of the agents tested demonstrated bactericidal activity when used alone. However, the combinations of quinupristin/dalfopristin with doxycycline, quinupristin/dalfopristin with rifampin, and doxycycline with rifampin, were each synergistic against the patient's VREF isolate (figure 1). Although VREF bacteremia is now a well-recognized clinical entity, there is still only limited experience in treating endocarditis due to this organism (only two previously reported cases) [4,5]. Successful treatment of bacterial endocarditis generally requires the use of an agent or combination of agents with bactericidal activity against the infecting organism. This is often difficult to achieve in the management of infections due to vancomycin- Figure 1. Time-kill studies displaying the interaction of quinuprisresistant enterococci, especially VREF, as these organisms are tin/dalfopristin, doxycycline, and rifampin. -ࡗ -Å growth contypically multidrug resistant [6]. Although teicoplanin has been trol; -l -Å quinupristin/dalfopristin (0.25 mg/mL); -᭡ -Å used to treat selected infections caused by vancomycin-resistant doxycycline (0.06 mg/mL); --Å rifampin (1.0 mg/mL); enterococci with the vanB resistance phenotype, emergence of rrr᭝rrr Å quinupristin/dalfopristin (0.25 mg/mL) and doxycycline resistance during therapy has occurred [6], and Vijayvargiya and (0.06 mg/mL); -rr-ᮀ-rr -Å quinupristin/dalfopristin (0.25 mg/mL) Veis [4] described a patient with VREF endocarditis who failed and rifampin (1.0 mg/mL); ---᭺---Å doxycycline (0.06 mg/mL) and to respond to treatment with teicoplanin and gentamicin. Moreover, rifampin (1.0 mg/mL).most North American strains of VREF possess the vanA phenotype that is resistant to teicoplanin [6]. The investigational drug quinupristin/dalfopristin has in vitro activity against many...

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

“…We failed to detect MIC elevations even in those models where significant bacterial regrowth occurred. Interactions of Q-D and other antimicrobials have also been studied in animal models of infection (20,33,34).…”

A Re-Emerging Class of Antimicrobial Agents: Streptogramins (Quinupristin/Dalfopristin) in the Management of Multiresistant Gram- Positive Nosocomial Cocci in Hospital Setting

“…Among disease localizations described in the first literature repors, we underline a wide spectrum of difficult-totreat and life-threatening endocarditis,such as enterococcal endocarditis on a prosthetic valve [22], multiresistant S. epidermidis endocarditis [23], those due to multiresistant S. aureus occurring artificial valve and no chance of surgery [24], as well as Enterococcus faecium heart localization, where a combination with doxicyclin, rifampicin, and highdose ampicillin was successfully experimented, and a demonstration of sinergystic activity given [25,26].…”

Increasing antimicrobial resistance: Therapeutic implications for enterococcal infections

“…Quinupristin-dalfopristin has been used successfully against a variety of infections due to VRE faecium [35•]. Endocarditis caused by VRE has been treated with quinupristin-dalfopristin alone [36] and in combination [37], with apparent success in some patients. Of patients with VRE faecium bacteremia of unknown source, 90% had clearance of their bacteremia within the first 48 to 72 hours of quinupristin-dalfopristin therapy.…”