Antibiotic treatment of infections due to carbapenem-resistant enterobacteriaceae: Systematic evaluation of the available evidence

Antimicrobial Agents and Chemotherapy

Volumn 58, Issue 2, 2014, Pages 654-663

  Falagas, Matthew E ^a,b,c   Lourida, Panagiota ^a   Poulikakos, Panagiotis ^a,b   Rafailidis, Petros I ^a   Tansarli, Giannoula S ^a  

^a ALFA INSTITUTE OF BIOMEDICAL SCIENCES AIBS   (Greece)

^b MITERA HOSPITAL   (Greece)

^c TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMIKACIN; AMOXICILLIN; AZTREONAM; CARBAPENEM; CARBAPENEMASE; CEFEPIME; CEFTAZIDIME; CIPROFLOXACIN; COLISTIN; DOXYCYCLINE; ERTAPENEM; FOSFOMYCIN; GENTAMICIN; IMIPENEM; LINEZOLID; MEROPENEM; NITROCEFIN; PIPERACILLIN PLUS TAZOBACTAM; POLYMYXIN B; SULTAMICILLIN; TIGECYCLINE; VANCOMYCIN;

ANTIBIOTIC RESISTANCE; ANTIBIOTIC THERAPY; ARTICLE; BACTEREMIA; BILIARY TRACT INFECTION; BLOODSTREAM INFECTION; CATHETER INFECTION; CRITICALLY ILL PATIENT; DISEASE SEVERITY; DRUG EFFICACY; DRUG TREATMENT FAILURE; ENTEROBACTERIACEAE; EVALUATION STUDY; HEPATITIS; HOSPITAL INFECTION; HUMAN; INFECTION; INTENSIVE CARE UNIT; KLEBSIELLA; MENINGITIS; MONOTHERAPY; MORTALITY; NONHUMAN; PERITONITIS; PNEUMONIA; PRIORITY JOURNAL; SEPTIC SHOCK; SOFT TISSUE INFECTION; SURGICAL INFECTION; SYSTEMATIC REVIEW; URINARY TRACT INFECTION; UROSEPSIS; VENTILATOR ASSOCIATED PNEUMONIA; WOUND INFECTION;

ANTI-BACTERIAL AGENTS; BACTEREMIA; BETA-LACTAM RESISTANCE; CARBAPENEMS; COLISTIN; CRITICAL ILLNESS; DRUG THERAPY, COMBINATION; ENTEROBACTERIACEAE; HUMANS; MINOCYCLINE; PNEUMONIA, BACTERIAL; SURVIVAL ANALYSIS; URINARY TRACT INFECTIONS;

EID: 84893435097     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.01222-13     Document Type: Article

References (60)

1. Nordmann P, Cuzon G, Naas T. 2009. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect. Dis. 9:228-236. http://dx.doi.org/10.1016/S1473-3099(09)70054-4.
2. Vardakas KZ, Tansarli GS, Rafailidis PI, Falagas ME. 2012. Carbapenems versus alternative antibiotics for the treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum beta-lactamases: a systematic review and meta-analysis. J. Antimicrob. Chemother. 67:2793-2803. http://dx.doi.org/10.1093/jac/dks301.
3. CDC, CfDCaP. 2013. Vital signs: carbapenem-resistant enterobacteriaceae. MMWR Morb. Mortal. Wkly. Rep. 62:165-170.
4. Falagas ME, Kasiakou SK. 2005. Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections. Clin. Infect. Dis. 40:1333-1341. http://dx.doi.org/10.1086/429323.
5. Falagas ME, Kopterides P. 2007. Old antibiotics for infections in critically ill patients. Curr. Opin. Crit. Care 13:592-597. http://dx.doi.org/ 10.1097/MCC.0b013e32827851d7.
6. Ben-David D, Kordevani R, Keller N, Tal I, Marzel A, Gal-Mor O, Maor Y, Rahav G. 2012. Outcome of carbapenem resistant Klebsiella pneumoniae bloodstream infections. Clin. Microbiol. Infect. 18:54-60. http://dx.doi.org/10.1111/j. 1469-0691.2011.03478.x.
7. Chang HJ, Hsu PC, Yang CC, Kuo AJ, Chia JH, Wu TL, Lee MH. 2011. Risk factors and outcomes of carbapenem-nonsusceptible Escherichia coli bacteremia: a matched case-control study. J. Microbiol. Immunol. Infect. 44:125-130. http://dx.doi.org/10.1016/j.jmii.2010.06.001.
8. Patel G, Huprikar S, Factor SH, Jenkins SG, Calfee DP. 2008. Outcomes of carbapenem-resistant Klebsiella pneumoniae infection and the impact of antimicrobial and adjunctive therapies. Infect. Control Hosp. Epidemiol. 29:1099-1106. http://dx.doi.org/10.1086/592412.
9. Alexander BT, Marschall J, Tibbetts RJ, Neuner EA, Dunne WM, Jr, Ritchie DJ. 2012. Treatment and clinical outcomes of urinary tract infections caused by KPC-producing Enterobacteriaceae in a retrospective cohort. Clin. Ther. 34:1314-1323. http://dx.doi.org/10.1016/j.clinthera.2012.05.002.
10. Bergamasco MD, Barroso Barbosa M, de Oliveira Garcia D, Cipullo R, Moreira JC, Baia C, Barbosa V, Abboud CS. 2012. Infection with Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae in solid organ transplantation. Transpl. Infect. Dis. 14:198-205. http://dx.doi.org/10.1111/j. 1399-3062.2011.00688.x.
11. Capone A, Giannella M, Fortini D, Giordano A, Meledandri M, Ballardini M, Venditti M, Bordi E, Capozzi D, Balice MP, Tarasi A, Parisi G, Lappa A, Carattoli A, Petrosillo N. 2013. High rate of colistin resistance among patients with carbapenem-resistant Klebsiella pneumoniae infection accounts for an excess of mortality. Clin. Microbiol. Infect. 19: E23-E30. http://dx.doi.org/10. 1111/1469-0691.12070.
12. Daikos GL, Petrikkos P, Psichogiou M, Kosmidis C, Vryonis E, Skoutelis A, Georgousi K, Tzouvelekis LS, Tassios PT, Bamia C, Petrikkos G. 2009. Prospective observational study of the impact of VIM-1 metallobeta-lactamase on the outcome of patients with Klebsiella pneumoniae bloodstream infections. Antimicrob. Agents Chemother. 53:1868-1873. http://dx.doi.org/10.1128/AAC.00782- 08.
13. Huang SR, Liu MF, Lin CF, Shi ZY. 28 November 2012. Molecular surveillance and clinical outcomes of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae infections. J. Microbiol. Immunol. Infect. http://dx.doi.org/10.1016/j.jmii.2012.08.029.
14. Maltezou HC, Giakkoupi P, Maragos A, Bolikas M, Raftopoulos V, Papahatzaki H, Vrouhos G, Liakou V, Vatopoulos AC. 2009. Outbreak of infections due to KPC-2-producing Klebsiella pneumoniae in a hospital in Crete (Greece). J. Infect. 58:213-219. http://dx.doi.org/10.1016/j.jinf.2009.01.010.
15. Michalopoulos A, Virtzili S, Rafailidis P, Chalevelakis G, Damala M, Falagas ME. 2010. Intravenous fosfomycin for the treatment of nosocomial infections caused by carbapenem-resistant Klebsiella pneumoniae in critically ill patients: a prospective evaluation. Clin. Microbiol. Infect. 16: 184-186. http://dx.doi.org/10.1111/j.1469-0691.2009.02921.x.
16. Mouloudi E, Protonotariou E, Zagorianou A, Iosifidis E, Karapanagiotou A, Giasnetsova T, Tsioka A, Roilides E, Sofianou D, Gritsi-Gerogianni N. 2010. Bloodstream infections caused by metallo-betalactamase/ Klebsiella pneumoniae carbapenemase-producing K. pneumoniae among intensive care unit patients in Greece: risk factors for infection and impact of type of resistance on outcomes. Infect. Control Hosp. Epidemiol. 31:1250-1256. http://dx.doi.org/10.1086/ 657135.
17. Navarro-San Francisco C, Mora-Rillo M, Romero-Gomez MP, Moreno-Ramos F, Rico-Nieto A, Ruiz-Carrascoso G, Gomez-Gil R, Arribas-Lopez JR, Mingorance J, Pano-Pardo JR. 2013. Bacteraemia due to OXA-48-carbapenemase-producing Enterobacteriaceae: a major clinical challenge. Clin. Microbiol. Infect. 19:E72-E79. http://dx.doi.org/10.1111/1469-0691.12091.
18. Nguyen M, Eschenauer GA, Bryan M, O'Neil K, Furuya EY, Della-Latta P, Kubin CJ. 2010. Carbapenem-resistant Klebsiella pneumoniae bacteremia: factors correlated with clinical and microbiologic outcomes. Diagn. Microbiol. Infect. Dis. 67:180-184. http://dx.doi.org/10.1016/j.diagmicrobio.2010.02.001.
19. Qureshi ZA, Paterson DL, Potoski BA, Kilayko MC, Sandovsky G, Sordillo E, Polsky B, Adams-Haduch JM, Doi Y. 2012. Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens. Antimicrob. Agents Chemother. 56:2108-2113. http://dx.doi.org/10.1128/ AAC.06268-11.
20. Rihani DS, Wallace MR, Sieger BE, Waite RA, Fox M, Brown SA, Deryke CA. 2012. Over-treatment of carbapenemase-producing Enterobacteriaceae. Scand. J. Infect. Dis. 44:325-329. http://dx.doi.org/10.3109/00365548.2011.638318.
21. Sanchez-Romero I, Asensio A, Oteo J, Munoz-Algarra M, Isidoro B, Vindel A, Alvarez-Avello J, Balandin-Moreno B, Cuevas O, Fernandez-Romero S, Azanedo L, Saez D, Campos J. 2012. Nosocomial outbreak of VIM-1-producing Klebsiella pneumoniae isolates of multilocus sequence type 15: molecular basis, clinical risk factors, and outcome. Antimicrob. Agents Chemother. 56:420-427. http://dx.doi.org/10.1128/AAC.05036-11.
22. Souli M, Galani I, Antoniadou A, Papadomichelakis E, Poulakou G, Panagea T, Vourli S, Zerva L, Armaganidis A, Kanellakopoulou K, Giamarellou H. 2010. An outbreak of infection due to beta-lactamase Klebsiella pneumoniae carbapenemase 2-producing K. pneumoniae in a Greek University Hospital: molecular characterization, epidemiology, and outcomes. Clin. Infect. Dis. 50:364-373. http://dx.doi.org/10.1086/649865.
23. Souli M, Kontopidou FV, Papadomichelakis E, Galani I, Armaganidis A, Giamarellou H. 2008. Clinical experience of serious infections caused by Enterobacteriaceae producing VIM-1 metallo-beta-lactamase in a Greek University Hospital. Clin. Infect. Dis. 46:847-854. http://dx.doi.org/10.1086/528719.
24. Trevino M, Navarro D, Barbeito G, Garcia-Riestra C, Crespo C, Regueiro BJ. 2011. Molecular and epidemiological analysis of nosocomial carbapenem-resistant Klebsiella spp. using repetitive extragenic palindromic-polymerase chain reaction and matrix-assisted laser desorption/ ionization-time of flight. Microb. Drug Resist. 17:433-442. http://dx.doi.org/ 10.1089/mdr.2010.0182.
25. Tumbarello M, Viale P, Viscoli C, Trecarichi EM, Tumietto F, Marchese A, Spanu T, Ambretti S, Ginocchio F, Cristini F, Losito AR, Tedeschi S, Cauda R, Bassetti M. 2012. Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemaseproducing K. pneumoniae: importance of combination therapy. Clin. Infect. Dis. 55:943-950. http://dx.doi.org/10.1093/ cid/cis588.
26. Weisenberg SA, Morgan DJ, Espinal-Witter R, Larone DH. 2009. Clinical outcomes of patients with Klebsiella pneumoniae carbapenemaseproducing K. pneumoniae after treatment with imipenem or meropenem. Diagn. Microbiol. Infect. Dis. 64:233-235. http://dx.doi.org/10.1016/j.diagmicrobio.2009.02.004.
27. Yan JJ, Lee NY, Chen HM, Wang MC, Ko WC, Tsai LH, Wu JJ. 2013. Bloodstream infections caused by IMP-8-producing Enterobacteriaceae isolates: the need for clinical laboratory detection of metallo-betalactamases? Eur. J. Clin. Microbiol. Infect. Dis. 32:345-352. http://dx.doi.org/10.1007/s10096-012- 1748-x.
28. Zarkotou O, Pournaras S, Tselioti P, Dragoumanos V, Pitiriga V, Ranellou K, Prekates A, Themeli-Digalaki K, Tsakris A. 2011. Predictors of mortality in patients with bloodstream infections caused by KPCproducing Klebsiella pneumoniae and impact of appropriate antimicrobial treatment. Clin. Microbiol. Infect. 17:1798-1803. http://dx.doi.org/10.1111/j.1469-0691.2011.03514.x.
29. Jernigan MG, Press EG, Nguyen MH, Clancy CJ, Shields RK. 2012. The combination of doripenem and colistin is bactericidal and synergistic against colistin-resistant, carbapenemase-producing Klebsiella pneumoniae. Antimicrob. Agents Chemother. 56:3395-3398. http://dx.doi.org/10.1128/AAC.06364-11.
30. American Thoracic Society, Infectious Diseases Society of America 2005. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am. J. Respir. Crit. Care Med. 171:388-416. http://dx.doi.org/10.1164/rccm.200405-644ST.
31. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R. 2013. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 39:165-228. http://dx.doi.org/10.1007/s00134-012-2769-8.
32. Tansarli GS, Rafailidis PI, Kapaskelis A, Falagas ME. 2012. Frequency of the off-label use of antibiotics in clinical practice: a systematic review. Expert Rev. Anti Infect. Ther. 10:1383-1392. http://dx.doi.org/10.1586/eri.12. 137.
33. FDA. 2010. FDA drug safety communication: increased risk of death with Tygacil (tigecycline) compared to other antibiotics used to treat similar infections. FDA, Rockville, MD. http://www.fda.gov/drugs/drugsafety/ucm224370. htm.
34. Prasad P, Sun J, Danner RL, Natanson C. 2012. Excess deaths associated with tigecycline after approval based on noninferiority trials. Clin. Infect. Dis. 54:1699-1709. http://dx.doi.org/10.1093/cid/cis270.
35. Yahav D, Lador A, Paul M, Leibovici L. 2011. Efficacy and safety of tigecycline: a systematic review and meta-analysis. J. Antimicrob. Chemother. 66:1963-1971. http://dx.doi.org/10.1093/jac/dkr242.
36. Vardakas KZ, Rafailidis PI, Falagas ME. 2012. Effectiveness and safety of tigecycline: focus on use for approved indications. Clin. Infect. Dis. 54: 1672-1674. http://dx.doi.org/10.1093/cid/cis239.
37. Paul M, Benuri-Silbiger I, Soares-Weiser K, Leibovici L. 2004. Beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials. BMJ 328:668. http://dx.doi.org/10.1136/bmj.38028.520995.63.
38. Vardakas KZ, Tansarli GS, Bliziotis IA, Falagas ME. 2013. Lactam plus aminoglycoside or fluoroquinolone combination versus beta-lactam monotherapy for Pseudomonas aeruginosa infections: a meta-analysis. Int. J. Antimicrob. Agents 41:301-310. http://dx.doi.org/10.1016/j.ijantimicag.2012.12.006.
39. Lee J, Patel G, Huprikar S, Calfee DP, Jenkins SG. 2009. Decreased susceptibility to polymyxin B during treatment for carbapenem-resistant Klebsiella pneumoniae infection. J. Clin. Microbiol. 47:1611-1612. http://dx.doi.org/10.1128/JCM.02466-08.
40. Souli M, Galani I, Boukovalas S, Gourgoulis MG, Chryssouli Z, Kanellakopoulou K, Panagea T, Giamarellou H. 2011. In vitro interactions of antimicrobial combinations with fosfomycin against KPC-2-producing Klebsiella pneumoniae and protection of resistance development. Antimicrob. Agents Chemother. 55:2395-2397. http://dx.doi.org/10.1128/AAC.01086-10.
41. Bliziotis IA, Samonis G, Vardakas KZ, Chrysanthopoulou S, Falagas ME. 2005. Effect of aminoglycoside and beta-lactam combination therapy versus beta-lactam monotherapy on the emergence of antimicrobial resistance: a meta-analysis of randomized, controlled trials. Clin. Infect. Dis. 41:149-158. http://dx.doi.org/10.1086/430912.
42. Elemam A, Rahimian J, Doymaz M. 2010. In vitro evaluation of antibiotic synergy for polymyxin B-resistant carbapenemase-producing Klebsiella pneumoniae. J. Clin. Microbiol. 48:3558-3562. http://dx.doi.org/10.1128/JCM.01106-10.
43. Pournaras S, Vrioni G, Neou E, Dendrinos J, Dimitroulia E, Poulou A, Tsakris A. 2011. Activity of tigecycline alone and in combination with colistin and meropenem against Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae strains by time-kill assay. Int. J. Antimicrob. Agents 37:244-247. http://dx.doi.org/10.1016/j.ijantimicag.2010.10.031.
44. Samonis G, Maraki S, Karageorgopoulos DE, Vouloumanou EK, Falagas ME. 2012. Synergy of fosfomycin with carbapenems, colistin, netilmicin, and tigecycline against multidrug-resistant Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa clinical isolates. Eur. J. Clin. Microbiol. Infect. Dis. 31:695-701. http://dx.doi.org/10.1007/s10096-011-1360-5.
45. Falagas ME, Karageorgopoulos DE, Nordmann P. 2011. Therapeutic options for infections with Enterobacteriaceae producing carbapenemhydrolyzing enzymes. Future Microbiol. 6:653-666. http://dx.doi.org/10.2217/fmb.11.49.
46. Castanheira M, Sader HS, Jones RN. 2010. Antimicrobial susceptibility patterns of KPC-producing or CTX-M-producing Enterobacteriaceae. Microb. Drug Resist. 16:61-65. http://dx.doi.org/10.1089/mdr.2009.0031.
47. Falagas ME, Tansarli GS, Ikawa K, Vardakas KZ. 2013. Clinical outcomes with extended or continuous versus short-term intravenous infusion of carbapenems and piperacillin/tazobactam: a systematic review and meta-analysis. Clin. Infect. Dis. 56:272-282. http://dx.doi.org/10.1093/cid/cis857.
48. Freeman CD, Nicolau DP, Belliveau PP, Nightingale CH. 1997. Oncedaily dosing of aminoglycosides: review and recommendations for clinical practice. J. Antimicrob. Chemother. 39:677-686. http://dx.doi.org/10.1093/jac/39.6.677.
49. Bulik CC, Nicolau DP. 2011. Double-carbapenem therapy for carbapenemase-producing Klebsiella pneumoniae. Antimicrob. Agents Chemother. 55:3002-3004. http://dx.doi.org/10.1128/AAC.01420-10.
50. Hong JH, Clancy CJ, Cheng S, Shields RK, Chen L, Doi Y, Zhao Y, Perlin DS, Kreiswirth BN, Nguyen MH. 2013. Characterization of porin expression in Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae identifies isolates most susceptible to the combination of colistin and carbapenems. Antimicrob. Agents Chemother. 57:2147-2153. http://dx.doi.org/10.1128/AAC.02411- 12.
51. Lee GC, Burgess DS. 2012. Treatment of Klebsiella pneumoniae carbapenemase (KPC) infections: a review of published case series and case reports. Ann. Clin. Microbiol. Antimicrob. 11:32. http://dx.doi.org/10.1186/ 1476-0711-11-32.
52. Garonzik SM, Li J, Thamlikitkul V, Paterson DL, Shoham S, Jacob J, Silveira FP, Forrest A, Nation RL. 2011. Population pharmacokinetics of colistin methanesulfonate and formed colistin in critically ill patients from a multicenter study provide dosing suggestions for various categories of patients. Antimicrob. Agents Chemother. 55:3284-3294. http://dx.doi.org/10.1128/AAC. 01733-10.
53. Meletis G, Tzampaz E, Sianou E, Tzavaras I, Sofianou D. 2011. Colistin heteroresistance in carbapenemase-producing Klebsiella pneumoniae. J. Antimicrob. Chemother. 66:946-947. http://dx.doi.org/10.1093/jac/dkr007.
54. Kontopoulou K, Protonotariou E, Vasilakos K, Kriti M, Koteli A, Antoniadou E, Sofianou D. 2010. Hospital outbreak caused by Klebsiella pneumoniae producing KPC-2 beta-lactamase resistant to colistin. J. Hosp. Infect. 76:70-73. http://dx.doi.org/10.1016/j.jhin.2010.03.021.
55. Mammina C, Bonura C, Di Bernardo F, Aleo A, Fasciana T, Sodano C, Saporito MA, Verde MS, Tetamo R, Palma DM. 16 August 2012. Ongoing spread of colistin-resistant Klebsiella pneumoniae in different wards of an acute general hospital, Italy, June to December 2011. Euro urveill. 17(33):pii20248.
56. Marchaim D, Chopra T, Pogue JM, Perez F, Hujer AM, Rudin S, Endimiani A, Navon-Venezia S, Hothi J, Slim J, Blunden C, Shango M, Lephart PR, Salimnia H, Reid D, Moshos J, Hafeez W, Bheemreddy S, Chen TY, Dhar S, Bonomo RA, Kaye KS. 2011. Outbreak of colistinresistant, carbapenem-resistant Klebsiella pneumoniae in metropolitan Detroit, Michigan. Antimicrob. Agents Chemother. 55:593-599. http://dx.doi.org/10.1128/AAC.01020-10.
57. Valencia R, Arroyo LA, Conde M, Aldana JM, Torres MJ, Fernandez-Cuenca F, Garnacho-Montero J, Cisneros JM, Ortiz C, Pachon J, Aznar J. 2009. Nosocomial outbreak of infection with pan-drug-resistant Acinetobacter baumannii in a tertiary care university hospital. Infect. Control Hosp. Epidemiol. 30:257-263. http://dx.doi.org/10.1086/595977.
58. Karageorgopoulos DE, Kelesidis T, Kelesidis I, Falagas ME. 2008. Tigecycline for the treatment of multidrug-resistant (including carbapenemresistant) Acinetobacter infections: a review of the scientific evidence. J. Antimicrob. Chemother. 62:45-55. http://dx.doi.org/10.1093/jac/ dkn165.
59. Matthaiou DK, Michalopoulos A, Rafailidis PI, Karageorgopoulos DE, Papaioannou V, Ntani G, Samonis G, Falagas ME. 2008. Risk factors associated with the isolation of colistin-resistant gram-negative bacteria: a matched case-control study. Crit. Care Med. 36:807-811. http://dx.doi.org/10.1097/CCM. 0B013E3181652FAE.
60. Sun Y, Cai Y, Liu X, Bai N, Liang B, Wang R. 2013. The emergence of clinical resistance to tigecycline. Int. J. Antimicrob. Agents 41:110-116. http://dx.doi.org/10.1016/j.ijantimicag.2012.09.005.