Antimicrobial Susceptibility Studies High mortality rates among solid organ transplant recipients infected with extensively drug-resistant Acinetobacter baumannii: using in vitro antibiotic combination testing to identify the combination of a carbapenem and colistin as an effective treatment regimen ☆,☆☆,★ Ryan K. Shields a,1 , Eun J. Kwak a,1 , Brian A. Potoski a , Yohei Doi a , Jennifer M. Adams-Haduch a , Fernanda P. Silviera a , Yoshiya Toyoda a , Joseph M. Pilewski a , Maria Crespo a , A. William Pasculle a , Cornelius J. Clancy a,b, ⁎ , M. Hong Nguyen a a University of Pittsburgh, Pittsburgh, Pennsylvania, USA b V.A. Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA Received 18 June 2010; accepted 27 December 2010 Abstract Extensively drug-resistant (XDR) Acinetobacter baumannii infections caused 91% (10/11) mortality in transplant recipients. Isolates were colistin-susceptible initially, but susceptibility decreased during therapy in 40% (4/10). We tested antibiotic combinations against XDR Acinetobacter in vitro and demonstrated positive interactions for carbapenem–colistin. Subsequently, 80% (4/5) of transplant patients were treated successfully with carbepenem–colistin regimens. Published by Elsevier Inc. Keywords: Acinetobacter; Synergy; Colistin; Doripenem; Transplant 1. Introduction Acinetobacter baumannii has emerged as a major cause of nosocomial infections. Indeed, A. baumannii has been identified by the Infectious Diseases Society of America as 1 of the 6 particularly problematic pathogens (ESKAPE) (Boucher et al., 2009). The organism is notable for its wide range of resistance mechanisms (Mak et al., 2009). Multidrug-resistant (MDR) A. baumannii is generally defined by resistance to more than 2 of the following broad-spectrum antimicrobial classes: antipseudomonal cephalosporins, antipseudomonal carbapenems, ampicillin– sulbactam, fluoroquinolones, and aminoglycosides (Adams- Haduch et al., 2008). Increased use of broad-spectrum antibiotics has induced the development of extensively drug- resistant (XDR) isolates, defined by resistance to all agents with the exception of tigecycline and polymyxins (colistin) (Souli et al., 2008). The treatment of XDR A. baumannii infections is challenging because of the lack of treatment options and management experience. Previously, the case of a lung transplant recipient who developed pneumonia due to XDR A. baumannii was reported from our institution (Doi, Husain, Potoski et al., 2009). The patient was treated with colistin plus tigecycline, but failed to clear the infection and died. We continued to encounter serious XDR A. baumannii infections among our solid organ transplant (SOT) recipients. In general, our therapeutic strategies consisted of various combinations of antimicrobials that have included colistin Available online at www.sciencedirect.com Diagnostic Microbiology and Infectious Disease 70 (2011) 246 – 252 www.elsevier.com/locate/diagmicrobio ☆ This work was completed at the University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15213, USA. ☆☆ Financial Support. The study was funded by the University of Pittsburgh School of Pharmacy and by seed support from the University of Pittsburgh, Department of Medicine to the Transplant Infectious Diseases Program (MHN and CJC). ★ Potential Conflicts of Interest. RKS, YD, EJK, BAP, JMA, FS, YT, JMP, MC, CJC and MHN: no conflict. ⁎ Corresponding author. Tel.: +1-412-383-5193; fax: +1-412-648-6399. E-mail address: cjc76@pitt.edu (C.J. Clancy). 1 These authors contributed equally to this study. 0732-8893/$ – see front matter. Published by Elsevier Inc. doi:10.1016/j.diagmicrobio.2010.12.023