Prevalence of Klebsiella pneumoniae strains producing carbapenemases and increase of resistance to colistin in an Italian teaching hospital from January 2012 To December 2014

BMC Infectious Diseases

Giorgio Palù¹  Stefania Stefani⁴  Monica Basso¹  Roberto Rinaldi²  Tiziana Tommasini³  Ettore De Canale³  Nicola Menegotto¹  Elisa Franchin¹  Alessandro Berto¹  Roberto Ghirardo¹  Elena Castellani¹  Erica Santacatterina¹  Andrea Bartolini¹  Saverio Giuseppe Parisi¹ 

[1] Department of Molecular Medicine, University of Padova, Via Gabelli 63, Padova, 35100, Italy;Infectious Diseases Unit, Padova Hospital, Padova, Italy;Microbiology and Virology Unit, Padova Hospital, Padova, Italy;Department of Biomedical and Biotecnological Sciences, University of Catania, Catania, Italy

关键词: Multilocus sequence typing;    Colistin resistance;    Rectal swabs;    Active surveillance;    Klebsiella pneumoniae carbapenemase producing;   

Others  :  1230331
DOI  :  10.1186/s12879-015-0996-7

 received in 2015-02-16, accepted in 2015-06-22,  发布年份 2015

【 摘 要 】

Background

The aim of this study was to characterize the spread of carbapenemase-producing Klebsiella pneumoniae (CPKP) in a tertiary level hospital using ongoing active surveillance with rectal swab cultures. Furthermore, this study analyzed the presence of CPKP in the clinical samples (CS) of a single patient as well as the evolution of Colistin-sensitive strains (CoS) to Colistin-resistant strains (CoR).

Methods

This study was performed from January 1, 2012 to December 31, 2014. In 2012, a survey was conducted in the Intensive Care Department. In autumn 2013, active monitoring was extended to the Surgery Department, and since mid-2014, the surveillance has included the Medical Department as well. Only the first isolated strain from each patient was included. Antimicrobial susceptibility testing was performed on CPKP isolates: Klebsiella pneumoniae carbapenemase, oxacillinase-48, Verona integron-encoded metallo-β-lactamase and New Delhi metallo-β-lactamase were detected using a validated in-house PCR method, and multilocus sequence typing (MLST) was used to investigate the clonal transmission of strains.

Results

A total of 15,104 patients were included in the study, and 496 consecutive non-replicated strains of CPKP were collected: 149 strains were collected in 2012 (39 [26.2 %] from surveillance rectal swabs [SRS]), 133 strains were collected in 2013 (70 [52.6 %] from SRS) and 214 strains were collected in 2014 (164 [76.6 %] from SRS). We observed a significant increase in the percentage of positive SRS cases in 2014 relative to 2013 and 2012 (p = 0.0001 and p = 0.0172, respectively) and in the proportion of CPKP first isolated by SRS relative to those identified by CS (p < 0.0001). Among all available samples, the number of CoR isolated from SRS was higher in 2013 and 2014 compared with 2012 (p = 0.0019 and p = 0.008, respectively). ST-258 and ST-512 were more prevalent in the tested specimens, and a new single locus variant (SLV) of ST-512 (ST-745) was isolated.

Conclusions

The results of this 3-year study of 15,104 patients highlight the clinical relevance of antimicrobial resistance as well as the drug-selection pressure of colistin therapy. The active surveillance in the three different departments increased the level of CPKP cases isolated by SRS.

【 授权许可】

   
2015 Parisi et al.

【 图 表 】

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【 参考文献 】

• [1]Munoz-Price LS, Poirel L, Bonomo RA, Schwaber MJ, Daikos GL, Cormican M et al.. Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect Dis. 2013; 13:785-789.
• [2]Nordmann P, Naas T, Poirel L. Global spread of Carbapenemase-producing Enterobacteriaceae. Emerg Infect Dis. 2011; 17:1791-1798.
• [3]Doumith M, Ellington MJ, Livermore DM, Woodford N. Molecular mechanisms disrupting porin expression in ertapenem-resistant Klebsiella and Enterobacter spp. clinical isolates from the UK. J Antimicrob Chemother. 2009; 63:659-667.
• [4]Giani T, D’Andrea MM, Pecile P, Borgianni L, Nicoletti P, Tonelli F et al.. Emergence in Italy of Klebsiella pneumoniae sequence type 258 producing KPC-3 Carbapenemase. J Clin Microbiol. 2009; 47:3793-3794.
• [5]Mezzatesta ML, Gona F, Caio C, Petrolito V, Sciortino D, Sciacca A et al.. Outbreak of KPC-3-producing, and colistin-resistant, Klebsiella pneumoniae infections in two Sicilian hospitals. Clin Microbiol Infect. 2011; 17:1444-1447.
• [6]Ah Y, Kim AJ, Lee JY. Colistin resistance in Klebsiella pneumoniae. Int J Antimicrob Agents. 2014; 44:8-15.
• [7]Tzouvelekis LS, Markogiannakis A, Piperaki E, Souli M, Daikos GL. Treating infections caused by carbapenemase-producing Enterobacteriaceae. Clin Microbiol Infect. 2014; 20:862-872.
• [8]Monaco M, Giani T, Raffone M, Arena F, Garcia-Fernandez A, Pollini S et al.. Colistin resistance superimposed to endemic carbapenem-resistant Klebsiella pneumoniae: a rapidly evolving problem in Italy, November 2013 to April 2014. Euro Surveill. 2014; 19:20939.
• [9]Antoniadou A, Kontopidou F, Poulakou G, Koratzanis E, Galani I, Papadomichelakis E et al.. Colistin-resistant isolates of Klebsiella pneumoniae emerging in intensive care unit patients: first report of a multiclonal cluster. J Antimicrob Chemother. 2007; 59:786-790.
• [10]Marchaim D, Chopra T, Pogue JM, Perez F, Hujer AM, Rudin S et al.. Outbreak of colistin-resistant, carbapenem-resistant Klebsiella pneumoniae in metropolitan Detroit, Michigan. Antimicrob Agents Chemother. 2011; 55:593-599.
• [11]Cannatelli A, D’Andrea MM, Giani T, Di Pilato V, Arena F, Ambretti S et al.. In vivo emergence of colistin resistance in Klebsiella pneumoniae producing KPC-type carbapenemases mediated by insertional inactivation of the PhoQ/PhoP mgrB regulator. Antimicrob Agents Chemother. 2013; 57:5521-5526.
• [12]Poirel L, Jayol A, Bontron S, Villegas MV, Ozdamar M, Türkoglu S et al.. The mgrB gene as a key target for acquired resistance to colistin in Klebsiella pneumoniae. J Antimicrob Chemother. 2015; 70:75-78.
• [13]Munoz-Price LS, Quinn JP. Deconstructing the infection control bundles for the containment of carbapenem-resistant Enterobacteriaceae. Curr Opin Infect Dis. 2013; 26:378-8.
• [14]Karaiskos I, Giamarellou H. Multidrug-resistant and extensively drug-resistant Gram-negative pathogens: current and emerging therapeutic approaches. Expert Opin Pharmacother. 2014; 15:1351-1370.
• [15]The European Committee on antimicrobial susceptibility testing subcommittee for detection of resistance mechanisms and specific resistances of clinical and/or epidemiological importance: version 1.0. December 2013. http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Resistance_mechanisms/EUCAST_detection_of_resistance_mechanisms_v1.0_20131211.pdf. Accessed 20 Jan 2015.
• [16]Sbrana F, Malacarne P, Viaggi B, Costanzo S, Leonetti P, Leonildi A et al.. Carbapenem-sparing antibiotic regimens for infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae in intensive care unit. Clin Infect Dis. 2013; 56:697-700.
• [17]The European Committee on antimicrobial susceptibility testing clinical breakpoints tables v 4.0.http://www.eucast.org/ast_of_bacteria. Accessed 20 Jan 2015 /
• [18]Frasson I, Biasolo MA, Bartolini A, Cavallaro A, Richter SN, Palù G. Rapid detection of blaVIM-1-37 and blaKPC1/2-12 alleles from clinical samples by multiplex PCR-based assays. Int J Antimicrob Agents. 2013; 42:68-71.
• [19]K. pneumoniae MLST database. (http://bigsdb.web.pasteur.fr/klebsiella/klebsiella.html. Last accessed January 20, 2015)
• [20]Gagliotti C, Cappelli V, Carretto E, Marchi M, Pan A, Ragni P et al.. Control of carbapenemase-producing Klebsiella pneumoniae: a region-wide intervention. Euro Surveill. 2014; 19:20943.
• [21]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.
• [22]Bogdanovich T, Adams-Haduch JM, Tian GB, Nguyen MH, Kwak EJ, Muto CA et al.. Colistin-resistant, Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae belonging to the international epidemic clone ST258. Clin Infect Dis. 2011; 53:373-376.
• [23]Chen S, Hu F, Zhang X, Xu X, Liu Y, Zhu D et al.. Independent emergence of colistin-resistant Enterobacteriaceae clinical isolates without colistin treatment. J Clin Microbiol. 2011; 49:4022-4023.
• [24]Arduino SM, Quiroga MP, Ramírez MS, Merkier AK, Errecalde L, Di Martino A et al.. Transposons and integrons in colistin-resistant clones of Klebsiella pneumoniae and Acinetobacter baumannii with epidemic or sporadic behavior. J Med Microbiol. 2012; 61:1417-1420.
• [25]Borer A, Saidel-Odes L, Eskira S, Nativ R, Riesenberg K, Livshiz-Riven I et al.. Risk factors for developing clinical infection with carbapenem-resistant Klebsiella pneumoniae in hospital patients initially only colonized with carbapenem-resistant K pneumoniae. Am J Infect Control. 2012; 40:421-425.
• [26]Shilo S, Assous MV, Lachish T, Kopuit P, Bdolah-Abram T, Yinnon AM et al.. Risk factors for bacteriuria with carbapenem-resistant Klebsiella pneumoniae and its impact on mortality: a case–control study. Infection. 2013; 41:503-509.
• [27]Capone A, Giannella M, Fortini D, Giordano A, Meledandri M, Ballardini M 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.
• [28]Gasink LB, Edelstein PH, Lautenbach E, Synnestvedt M, Fishman NO. Risk factors and clinical impact of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae. Infect Control Hosp Epidemiol. 2009; 30:1180-1185.
• [29]Perez F, Endimiani A, Ray AJ, Decker BK, Wallace CJ, Hujer KM et al.. Carbapenem resistant Acinetobacter baumannii and Klebsiella pneumoniae across a hospital system: impact of post-acute care facilities on dissemination. J Antimicrob Chemother. 2010; 65:1807-1818.
• [30]Olaitan AO, Diene SM, Kempf M, Berrazeg M, Bakour S, Gupta SK et al.. Worldwide emergence of colistin resistance in Klebsiella pneumoniae from healthy humans and patients in Lao PDR, Thailand, Israel, Nigeria and France owing to inactivation of the PhoP/PhoQ regulator mgrB: an epidemiological and molecular study. Int J Antimicrob Agents. 2014; 44:500-507.
• [31]Garcia-Alvarez L, Dawson S, Cookson B, Hawkey P. Working across the veterinary and human health sectors. J Antimicrob Chemother. 2012; 67 Suppl 1:i37-i49.
• [32]Kontopidou F, Plachouras D, Papadomichelakis E, Koukos G, Galani I, Poulakou G et al.. Colonization and infection by colistin-resistant Gram-negative bacteria in a cohort of critically ill patients. Clin Microbiol Infect. 2011; 17:E9-E11.
• [33]Zarkotou O, Pournaras S, Voulgari E, Chrysos G, Prekates A, Voutsinas D. Risk factors and outcomes associated with acquisition of colistin-resistant KPC-producing Klebsiella pneumoniae: a matched case–control study. J Clin Microbiol. 2010; 48:2271-2274.
• [34]Poudyal A, Howden BP, Bell JM, Gao W, Owen RJ, Turnidge JD, et al. In vitro pharmacodynamics of colistin against multidrug-resistant Klebsiella pneumoniae. J Antimocrob Chemother 2008;62:1311-8.