Background: In recent years, multidrug-resistant Acinetobacter baumannii has been reported as an important nosocomial pathogen, and treatment options are limited. The aim of this study was to investigate the additional effect of sulbactam on monotherapy with colistin, tigecycline and imipenem in experimental sepsis with carbapenem-resistant A. baumannii in mice. Methods: Sepsis was developed in 8- to 10-week-old BALB/c mice by an intraperitoneal injection of A. baumannii. Antibiotic was given intraperitoneally 2 h after bacterial inoculation. Each experimental group had 15 mice and was divided into 3 subgroups. Mice were sacrificed at 24, 48 or 72 h. Lung, liver, heart and spleen samples were cultured, and homogenates of lung and liver were used to detect the number of colony-forming units per gram. Bacterial clearance was compared in lung and liver at different time points. Results: Imipenem did not decrease the bacterial load, but the other antibiotics showed significant bactericidal activity compared with the control group, and the combination of imipenem with sulbactam decreased the bacterial load in lung and liver. However, the addition of sulbactam to colistin and tigecycline had no significant effect on bacterial counts. Only the addition of sulbactam to imipenem showed better bactericidal activity compared to imipenem alone. Conclusions: These results suggested that combining sulbactam with tigeycline or colistin does not increase the efficiency of these antibiotics.

1.
Montero A, Ariza J, Corbella X, Doménech A, Cabellos C, Ayats J, Tubau F, Ardanuy C, Gudiol F: Efficacy of colistin versus β-lactams, aminoglycosides, and rifampin as monotherapy in a mouse model of pneumonia caused by multiresistant Acinetobacter baumannii. Antimicrob Agents Chemother 2002;46:1946-1952.
2.
Pachón-Ibáñez ME, Docobo-Pérez F, López-Rojas R, Domínguez-Herrera J, Jiménez-Mejias ME, García-Curiel A, Pichardo C, Jiménez L, Pachón J: Efficacy of rifampin and its combinations with imipenem, sulbactam, and colistin in experimental models of infection caused by imipenem-resistant Acinetobacter baumannii. Antimicrob Agents Chemother 2010;54:1165-1172.
3.
Song JY, Cheong HJ, Lee J, Sung AK, Kim WJ: Efficacy of monotherapy and combined antibiotic therapy for carbapenem-resistant Acinetobacter baumannii pneumonia in an immunosuppressed mouse model. Int J Antimicrob Agents 2009;33:33-39.
4.
Corbella X, Ariza J, Ardanuy C, Vuelta M, Tubau F, Sora M, Pujol M, Gudiol F: Efficacy of sulbactam alone and in combination with ampicillin in nosocomial infections caused by multiresistant Acinetobacter baumannii. J Antimicrob Chemother 1998;42:793-802.
5.
Oliveira MS, Prado GVB, Costa SF, Grinbaum RS, Levin AS: Ampicillin/sulbactam compared with polymyxins for the treatment of infections caused by carbapenem-resistant Acinetobacter spp. J Antimicrob Chemother 2008;61:1369-1375.
6.
Kempf M, Djouhri-Bouktab L, Brunel J, Raoult D, Rolain J: Synergistic activity of sulbactam combined with colistin-resistant Acinetobacter baumannii. Int J Antimicrob Agents 2012;39:180-181.
7.
Cisneros JM, Rodriquez-Bano J: Nosocomial bacteremia due to Acinetobacter baumannii: epidemiology, clinical features and treatment. Clin Microbiol Infect 2002;8:687-693.
8.
Rodríguez-Hernández MJ, Cuberos L, Pichardo C, Caballero FJ, Moreno I, Jiménez-Mejías ME, García-Curiel A, Pachón J: Sulbactam efficacy in experimental models caused by susceptible and intermediate Acinetobacter baumannii strains. J Antimicrob Chemother 2001;47:479-482.
9.
Petrosillo N, Ioannidou E, Falagas ME: Colistin monotherapy vs. combination therapy: evidence from microbiological, animal and clinical studies. Clin Microbiol Infect 2008;14:816-827.
10.
Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard M07-A9, ed 9. Wayne, National Committee for Clinical Laboratory Standards, 2012.
11.
The European Committee on Antimicrobial Susceptibility Testing: Breakpoint tables for interpretation of MICs and zone diameters, version 3.1, 2013. http://www.eucast.org.
12.
Cisneros JM, Reyes MJ, Pachón J, Becerril B, Caballero FJ, García-Garmendía JL, Ortiz C, Cobacho AR: Bacteremia due to Acinetobacter baumannii: epidemiology, clinical findings, and prognostic features. Clin Infect Dis 1996;22:1026-1032.
13.
Song JY, Kee SY, Hwang IS, Seo YB, Jeong HW, Kim WJ, Cheong HJ: In vitro activities of carbapenem/sulbactam combination, colistin, cilistin/rifampicin combination and tigecycline against carbapenem-resistant Acinetobacter baumannii. J Antimicrob Chemother 2007;60:317-322.
14.
Llaca-Díaz JM, Mendoza-Olazarán S, Camacho-Ortiz A, Flores S, Garza-González E: One-year surveillance of ESKAPE pathogens in an intensive care unit of Monterrey, Mexico. Chemotherapy 2012;58:475-481.
15.
Luo L, Jiang X, Wu Q, Wei L, Li J, Ying C: Efflux pump overexpression in conjunction with alternation of outer membrane protein may induce Acinetobacter baumannii resistant to imipenem. Chemotherapy 2011;57:77-84.
16.
Hou PF, Chen XY, Yan GF, Wang YP, Ying CM: Study of the correlation of imipenem resistance with efflux pumps AdeABC, AdeIJK, AdeDE and AbeM in clinical isolates of Acinetobacter baumannii. Chemotherapy 2012;58:152-158.
17.
Lemos EV, Hoz FP, Alvis N, Einarson TR, Quevedo E, Castaneda C, Leon Y, Amado C, Canon O, Kawai K: Impact of carbapenem resistance on clinical and economic outcomes among patients with Acinetobacter baumannii infection in Colombia. Clin Microbiol Infect 2013, DOI: 10.1111/1469-0691.12251.
18.
Alp E, Kalin G, Coskun R, Sungur M, Guven M, Doganay M: Economic burden of ventilator-associated pneumonia in a developing country. J Hosp Infect 2012;81:128-130.
19.
Garza-González E, Llaca-Díaz JM, Bosques-Padilla FJ, González GM: Prevalence of multidrug-resistant bacteria at a tertiary-care teaching hospital in Mexico: special focus on Acinetobacter baumannii. Chemotherapy 2010;56:275-279.
20.
Morfín-Otero R, Alcántar-Curiel MD, Rocha MJ, Alpuche-Aranda CM, Santos-Preciado JI, Gayosso-Vázquez C, Araiza-Navarro JR, Flores-Vaca M, Esparza-Ahumada S, González-Díaz E, Pérez-Gómez HR, Rodríguez-Noriega E: Acinetobacter baumannii infections in a tertiary care hospital in Mexico over the past 13 years. Chemotherapy 2013;59:57-65.
21.
Shakoor S, Khan E, Zafar A, Hasan R: In vitro activity of tigecycline and other tetracyclines against carbapenem-resistant Acinetobacter species: report from a tertiary care centre in Karachi, Pakistan. Chemotherapy 2010;56:184-189.
22.
Montero A, Ariza J, Corbella X, Domenech A, Cabellos C, Ayats J, Tubau F, Borraz C, Gudiol F: Antibiotic combinations for serious infections caused by carbapenem-resistant Acinetobacter baumannii in a mouse pneumonia model. J Antimicrob Chemother 2004;54:1085-1091.
23.
Karageorgepolis DE, Falagas ME: Current control and treatment of multidrug-resistant Acinetobacter baumannii infections. Lancet Infect Dis 2008;8:751-762.
24.
Falagas ME, Kasiakou SK: Colistin: the revival of polymyxins for the management of multidrug-resistant Gram-negative bacterial infections. Clin Infect Dis 2005;40:1333-1341.
25.
Lee CH, Tang YF, Su LH, Chien CC, Liu JW: Antimicrobial effects of varied combinations of meropenem, sulbactam, and colistin on a multidrug-resistant Acinetobacter baumannii isolate that caused meningitis and bacteremia. Microb Drug Resist 2008;14:233-237.
26.
Paul M, Bishara J, Levcovich A, Chowers M, Goldberg E, Singer P, Lev S, Leon P, Raskin M, Yahav D, Leibovici L: Effectiveness and safety of colistin: prospective comparative cohort study. J Antimicrob Chemother 2010;65:1019-1027.
27.
Betrosian AP, Frantzeskaki F, Xanthaki A, Douzinas EE: Efficacy and safety of high-dose ampicillin/sulbactam vs. colistin as monotherapy for the treatment of multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia. J Infect 2008;56:432-436.
28.
Çikman A, Ceylan MR, Parlak M, Karahocagil MK, Berktas M: Evaluation of colistin-ampicillin/sulbactam combination efficacy in imipenem-resistant Acinetobacter baumannii strains (in Turkish). Mikrobiyol Bul 2013;47:147-151.
29.
Mutlu Yilmaz E, Sunbul M, Aksoy A, Yilmaz H, Guney AK, Guvenc T: Efficacy of tigecycline/colistin combination in a pneumonia model caused by extensively drug-resistant Acinetobacter baumannii. Int J Antimicrob Agents 2012;40:332-336.
30.
Kalin G, Alp E, Akin A, Coskun R, Doganay M: Comparison of colistin and colistin/sulbactam for the treatment of multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia. Infection 2013, DOI: 10.1007/s15010-013-0495-y.
31.
Deveci A, Coban AY, Acicbe O, Tanyel E, Yaman G, Durupinar B: In vitro effects of sulbactam combinations with different antibiotic groups against clinical Acinetobacter baumannii isolates. J Chemother 2012;24:247-252.
32.
Sheng W, Wang J, Li S, Lin Y, Cheng A, Cen Y, Chang S: Comparative in vitro antimicrobial activities of antimicrobial combinations against carbapenem-resistant Acinetobacter species: Acinetobacter baumannii versus Acinetobacter genospecies 3 and 13TU. Diagn Microbiol Infect Dis 2011;70:380-386.
33.
Pongpech P, Amornnopparattanakul S, Panapakdee S, Fungwithaya S, Nannha P, Dhiraputra C, Leelarrasamee A: Antibacterial activity of carbapenem-based combinations against multidrug-resistant Acinetobacter baumannii. J Med Assoc Thai 2010;93:161-171.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.