Carbapenem and colistin resistance in children with Enterobacteriaceae infections
Carbapenem and colistin resistance in children with Enterobacteriaceae infections
Background. Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging global public health threat. As a reserve agent, colistin has been the drug of choice for the treatment of infections caused by CRE. The aim of this study was to determine the risk factors of carbapenem and colistin-resistant Enterobacteriaceae infections and to investigate the outcomes. Methods. We conducted a retrospective study in a single university hospital between the years 2013 and 2017 including 150 patients with Enterobacteriaceae infections. Results. Of 150 Enterobacteriaceae infections, 62 (41%) were carbapenem and 23 (15%) were colistin-resistant. Colistin resistance rates among Enterobacteriaceae species increased from 4% in 2014 to 25% in 2017. The in-hospital mortality of the patients with colistin-resistant and with carbapenem-resistant infections were 39% (9/23) and 45% (28/62), respectively. Prior exposure to polyantibiotic therapy for Gram negative bacteria was found as a predictor of CRE (OR = 6.4; 95% CI 3.07-13.6; p = 0.001) infections. The median length of hospital stay prior to positive culture (OR = 1.02; 95%CI, 1.0-1.04; p = 0.003) and history of surgery during the admission (OR = 2.46; 95% CI 1.2-5.1; p = 0.005) were found as the predictors of CRE infections. Underlying necrotizing enterocolitis and/or short-bowel syndrome (OR=6.38; 95%CI 1.16-35; p = 0.033) and mechanical ventilation prior to index culture were found as predictors of colistin resistance (OR = 9.4; 95% CI 2-40.4; p = 0.004).Conclusions. Recognizing the risk factors of carbapenem and colistin resistant Enterobacteriaceae infections is essential in order to conserve carbapenem and colistin since there are no new antibiotics to treat multidrug-resistant Enterobacteriaceae infections.
___
- 1.Ben-Ami R, Rodríguez-Baño J, Arslan H, et al. A multinational survey of risk factors for infection with extended-spectrum beta-lactamase-producing enterobacteriaceae in nonhospitalized patients. Clin Infect Dis 2009; 49: 682-690.
- 2.Temkin E, Adler A, Lerner A, Carmeli Y. Carbapenem-resistant Enterobacteriaceae: biology, epidemiology and management. Ann NY Acad Sci 2014; 1323: 22-42.
- 3.Capone A, Giannella M, Fortini D, et al. High rate of colistin resistance among patients with carbapenem-resistant Klebsiella pneumoniae infection accounts for an excess of mortality. Clin Microbiol Infect 2013; 19: E23-E30.
- 4.Meletis G, Tzampaz E, Sianou E, Tzavaras I, Sofianou D. Colistin heteroresistance in carbapenemase-producing Klebsiella pneumoniae. J Antimicrob Chemother 2011; 66: 946-947.
- 5.Kontopidou F, Plachouras D, Papadomichelakis E, et al. Colonization and infection by colistin-resistant gram-negative bacteria in a cohort of critically ill patients. Clin Microbiol Infec 2011; 17: E9-E11.
- 6.Gupta N, Limbago BM, Patel JB, Kallen AJ. Carbapenem-resistant enterobacteriaceae: epidemiology and prevention. Clin Infect Dis 2011; 53: 60-67.
- 7.Ling ML, Tee YM, Tan SG, et al. Risk factors for acquisition of carbapenem resistant Enterobacteriaceae in an acute tertiary care hospital in Singapore. Antimicrob Resist Infect Control 2015; 4: 26.
- 8.Patel N, Harrington S, Dihmess A, et al. Clinical epidemiology of carbapenem-intermediate or-resistant Enterobacteriaceae. J Antimicrob Chemother 2011; 66: 1600-1608.
- 9.Carbapenem-Resistant Enterobacteriaceae (CRE) Control and Prevention Toolkit 2012 CER Toolkit Atlanta, GA: CDC, 2012. Available at: www.cdc.gov/hai/pdfs/cre/CRE-guidance-508.pdf [Updated 2015 November, cited 2017 May 15].
- 10.European Society of Clinical Microbiology and Infectious Diseases. European Committee on Antimicrobial Susceptibility Testing. Clinical breakpoints-bacteria(v7.1) [internet]. Switzerland: ESCMID, 2013. Available at: http:// www.eucast.org/clinical_breakpoints/ [Updated 2017 Dec 31, cited 2018 May 15].
- 11.Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 2008; 36: 309-332.
- 12.Patel G, Huprikar S, Factor SH, Jenkins SG, Calfee DP. Outcomes of carbapenem-resistant Klebsiella pneumoniae infection and the impact of antimicrobial and adjunctive therapies. Infect Control Hosp Epidemiol 2008; 29:1099-1106.
- 13.Hussein K, Sprecher H, Mashiach T, Oren I, Kassis I, Finkelstein R. Carbapenem resistance among Klebsiella pneumoniae isolates: risk factors, molecular characteristics, and susceptibility patterns. Infect Control Hosp Epidemiol 2009; 30: 666-671.
- 14.Schwaber MJ, Klarfeld-Lidji S, Navon-Venezia S, Schwartz D, Leavitt A, Carmeli Y. Predictors of carbapenem-resistant Klebsiella pneumoniae acquisition among hospitalized adults and effect of acquisition on mortality. Antimicrob Agents Chemother 2008; 52: 1028-1033.
- 15.Kritsotakis EI, Tsioutis C, Roumbelaki M, Christidou A, Gikas A. Antibiotic use and the risk of carbapenem-resistant extended-spectrum-β-lactamase-producing Klebsiella pneumoniae infection in hospitalized patients: results of a double case-control study. J Antimicrob Chemother 2011; 66: 1383-1391.
- 16.Bell BG, Schellevis F, Stobberingh E, Goossens H, Pringle M. A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance. BMC Infect Dis 2014; 14: 13.
- 17.Kofteridis DP, Valachis A, Dimopoulou D, et al. Risk factors for carbapenem-resistant Klebsiella pneumoniae infection/colonization: a case-case-control study. J Infect Chemother 2014; 20: 293-297.
- 18.Debby BD, Ganor O, Yasmin M, et al. Epidemiology of carbapenem resistant Klebsiella pneumoniae colonization in an intensive care unit. Eur J Clin Microbiol Infect Dis 2012; 31: 1811-1817.
- 19.World Health Organization (WHO). Global Guidelines on the Prevention of Surgical Site Infection. Geneva: WHO, 2016. Available at: www.who.int/gpsc/appendix4.pdf. [Updated Nov 2016; May 2018].
- 20.Hyle EP, Ferraro MJ, Silver M, Lee H, Hooper DC. Ertapenem-resistant Enterobacteriaceae: risk factors for acquisition and outcomes. Infect Control Hosp Epidemiol 2010; 31: 1242-1249.
- 21.Bhargava A, Hayakawa K, Silverman E, et al. Risk factors for colonization due to carbapenem-resistant Enterobacteriaceae among patients exposed to long-term acute care and acute care facilities. Infect Control Hosp Epidemiol 2014; 35: 398-405.
- 22.Candevir Ulu A, Kurtaran B, Inal AS, et al. Risk factors of carbapenem-resistant Klebsiella pneumoniae infection: a serious threat in ICUs. Med Sci Monit2015; 21: 219-224.
- 23.Zarkotou O, Pournaras S, Tselioti P, et al. Predictors of mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae and impact of appropriate antimicrobial treatment. Clin Microbiol Infect 2011; 17: 1798–-1803.
- 24.Humphries RM, Keledesis T, Dien Bard J, Ward KW, Bhattacharya D, Lewinski MA. Successful treatment of pan-resistant Klebsiella pneumoniae pneumonia and bacteraemia with a combination of high-dose tigecycline and colistin. J Med Microbiol 2010; 59: 1383-1386.
- 25.van Duin D, Kaye KS, Neuner EA, Bonomo RA. Carbapenem-resistant Enterobacteriaceae: a review of treatment and outcomes. Diagn Microbiol Infect Dis 2013; 75: 115-120.
- 26.de Maio Carrilho CMD, de Oliveira LM, Gaudereto J, et al. A prospective study of treatment of carbapenem-resistant Enterobacteriaceae infections and risk factors associated with outcome. BMC Infect Dis 2016; 16: 629.
- 27.European Society of Clinical Microbiology and Infectious Diseases. European Committee on Antimicrobial Susceptibility Testing (EUCAST). Recommendations for colistin (polymixin E) MIC testing-joint EUCAST and CLSI recommendation. internet]. Switzerland: ESCMID, 2016. Available at: http://www.eucast.org/ast_of_bacteria/guidance_documents/ [Updated 2016 March 22, cited 2018 May 5].
- 28.Dafopoulou K, Zarkotou O, Dimitroulia E, et al. Comparative evaluation of colistin susceptibility testing methods among carbapenem-nonsusceptible Klebsiella pneumoniae and Acinetobacter baumannii clinical isolates. Antimicrob Agents Chemother 2015; 59: 4625-4630.
- 29.Lee SY, Shin JH, Lee K, et al. Comparison of the vitex 2, microsan and etest methods with the agar dilution method in assessing colistin susceptibility of bloodstream isolates of Acinetobacter species from a Korean University Hospital. J Clin Microbiol 2013; 51: 1924-1926.