title: In vitro activity of colistin in antimicrobial combination against carbapenem-resistant Acinetobacter baumannii isolated from patients with ventilator-associated pneumonia in Vietnam.
abstract: Acinetobacter baumannii has become one of the major infection threats in intensive care units (ICUs) globally. Since 2008, A. baumannii has been the leading cause of ventilator-associated pneumonia (VAP) in our ICU at an infectious disease hospital in southern Vietnam. The emergence of this pathogen in our setting is consistent with the persistence of a specific clone exhibiting resistance to carbapenems. Antimicrobial combinations may be a strategy to treat infections caused by these carbapenem-resistant A. baumannii. Therefore, we assessed potential antimicrobial combinations against local carbapenem-resistant A. baumannii by measuring in vitro interactions of colistin with four antimicrobials that are locally certified for treating VAP. We first performed antimicrobial susceptibility testing and multilocus variable number tandem repeat analysis (MLVA) genotyping on 74 A. baumannii isolated from quantitative tracheal aspirates from patients with VAP over an 18-month period. These 74 isolates could be subdivided into 21 main clusters by MLVA and >80 % were resistant to carbapenems. We selected 56 representative isolates for in vitro combination synergy testing. Synergy was observed in four (7 %), seven (13 %), 20 (36 %) and 38 (68 %) isolates with combinations of colistin with ceftazidime, ceftriaxone, imipenem and meropenem, respectively. Notably, more carbapenem-resistant A. baumannii isolates (36/43; 84 %) exhibited synergistic activity with a combination of colistin and meropenem than carbapenem-susceptible A. baumannii isolates (2/13; 15 %) (P = 0.023; Fisher's exact test). Our findings suggest that combinations of colistin and meropenem should be considered when treating carbapenem-resistant A. baumannii infections in Vietnam, and we advocate clinical trials investigating combination therapy for VAP.
authors: Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Division of Infectious Diseases, Department of Medicine, University of California San Francisco, CA, USA.
authors: Vien
authors: V
authors: Le Minh
authors: Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia.
authors: Nguyen
authors: N
authors: Thi Khanh Nhu
authors: Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors: Voong
authors: V
authors: Vinh Phat
authors: Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, UK.
authors: Corinne
authors: C
authors: Thompson
authors: Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors: Nguyen Phu
authors: NP
authors: Huong Lan
authors: Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors: Tran Vu
authors: TV
authors: Thieu Nga
authors: Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors: Pham Thi
authors: PT
authors: Thanh Tam
authors: Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors: Ha Thanh
authors: HT
authors: Tuyen
authors: Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors: Tran Do
authors: TD
authors: Hoang Nhu
authors: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors: Nguyen
authors: N
authors: Van Hao
authors: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors: Huynh
authors: H
authors: Thi Loan
authors: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors: Lam
authors: L
authors: Minh Yen
authors: Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, UK.|Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
authors: Christopher M
authors: CM
authors: Parry
authors: Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.|Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam.
authors: Ho Dang
authors: HD
authors: Trung Nghia
authors: Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, UK.
authors: James I
authors: JI
authors: Campbell
authors: Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, UK.
authors: Tran Tinh
authors: TT
authors: Hien
authors: Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, UK.
authors: Louise
authors: L
authors: Thwaites
authors: Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, UK.
authors: Guy
authors: G
authors: Thwaites
authors: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors: Nguyen
authors: N
authors: Van Vinh Chau
authors: Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, UK.|London School of Hygiene and Tropical Medicine, London, UK.|Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors: Stephen
authors: S
authors: Baker
mesh_terms: D040981:Acinetobacter baumannii / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015780:Carbapenems / Q000494:pharmacology*; D016000:Cluster Analysis; D003091:Colistin / Q000494:pharmacology*; D004357:Drug Synergism; D005838:Genotype; D006761:Hospitals; D006801:Humans; D008826:Microbial Sensitivity Tests; D058885:Multilocus Sequence Typing; D053717:Pneumonia, Ventilator-Associated / Q000453:epidemiology / Q000382:microbiology*; D014744:Vietnam / Q000453:epidemiology; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D003091:Colistin