Skip to main content
Top
Published in: BMC Infectious Diseases 1/2016

Open Access 01-12-2016 | Research article

A prospective study of treatment of carbapenem-resistant Enterobacteriaceae infections and risk factors associated with outcome

Authors: Claudia M. D. de Maio Carrilho, Larissa Marques de Oliveira, Juliana Gaudereto, Jamile S. Perozin, Mariana Ragassi Urbano, Carlos H. Camargo, Cintia M. C. Grion, Anna Sara S. Levin, Silvia F. Costa

Published in: BMC Infectious Diseases | Issue 1/2016

Login to get access

Abstract

Background

To describe the clinical and microbiological data of carbapenem-resistant Enterobacteriaceae (CRE) infections, the treatment used, hospital- and infection-related mortality, and risk factors for death.

Methods

A prospective cohort conducted from March 2011 to December 2012. Clinical, demographic, and microbiological data such as in vitro sensitivity, clonality, carbapenemase gene mortality related to infection, and overall mortality were evaluated. Data were analyzed using Epi Info version 7.0 (CDC, Atlanta, GA, USA) and SPSS (Chicago, IL, USA).

Results

One hundred and twenty-seven patients were evaluated. Pneumonia, 52 (42 %), and urinary tract infections (UTI), 51 (40.2 %), were the most frequent sites of infection. The isolates were polyclonal; the BlaKPC gene was found in 75.6 % of isolates, and 27 % of isolates were resistant to colistin. Mortality related to infection was 34.6 %, and was higher among patients with pneumonia (61.4 %). Combination therapy was used in 98 (77.2 %), and monotherapy in 22.8 %; 96.5 % of them were UTI patients. Shock, age, and dialysis were independent risk factors for death. There was no difference in infection-related death comparing colistin-susceptible and colistin-resistant infections (p = 0.46); neither in survival rate comparing the use of combination therapy with two drugs or more than two drugs (p = 0.32).

Conclusions

CRE infection mortality was higher among patients with pneumonia. Infections caused by colistin-resistant isolates did not increase mortality. The use of more than two drugs on combination therapy did not show a protective effect on outcome. The isolates were polyclonal, and the blaKPC gene was the only carbapenemase found. Shock, dialysis, and age over 60 years were independent risk factors for death.
Literature
1.
go back to reference Adler A, Carmeli Y. Dissemination of the Klebsiella pneumoniae carbapenemase in the health care settings: tracking the trails of an elusive offender. MBio. 2011;2(6):10,1128;mBio.00280,11 Adler A, Carmeli Y. Dissemination of the Klebsiella pneumoniae carbapenemase in the health care settings: tracking the trails of an elusive offender. MBio. 2011;2(6):10,1128;mBio.00280,11
2.
go back to reference Nordmann P, Cuzon G, Naas T. The real threat of Klebsiella pneumonia carbapenemase-producing bacteria. Lancet Infect Dis. 2009;9(4):228–36.CrossRefPubMed Nordmann P, Cuzon G, Naas T. The real threat of Klebsiella pneumonia carbapenemase-producing bacteria. Lancet Infect Dis. 2009;9(4):228–36.CrossRefPubMed
3.
go back to reference Munoz-Price LS, Poirel L, Bonomo RA, et al. Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect Dis. 2013;13:785–96.CrossRefPubMedPubMedCentral Munoz-Price LS, Poirel L, Bonomo RA, et al. Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect Dis. 2013;13:785–96.CrossRefPubMedPubMedCentral
4.
go back to reference Daikos GL, Tsaousi S, Tzouvelekis S, et al. Carbapenemase-producing Klebsiella pneumoniae bloodstream infections: lowering mortality by antibiotic combination schemes and the role of carbapenems. Antimicrob Agents Chemother. 2014;58(4):2322–8.CrossRefPubMedPubMedCentral Daikos GL, Tsaousi S, Tzouvelekis S, et al. Carbapenemase-producing Klebsiella pneumoniae bloodstream infections: lowering mortality by antibiotic combination schemes and the role of carbapenems. Antimicrob Agents Chemother. 2014;58(4):2322–8.CrossRefPubMedPubMedCentral
5.
6.
go back to reference Marchaim D, Chopra T, Perez F, et al. Outcomes and genetic relatedness of carbapenem-resistant enterobacteriaceae at Detroit Medical Center. Infect Control Hosp Epidemiol. 2011;32(9):861–71.CrossRefPubMedPubMedCentral Marchaim D, Chopra T, Perez F, et al. Outcomes and genetic relatedness of carbapenem-resistant enterobacteriaceae at Detroit Medical Center. Infect Control Hosp Epidemiol. 2011;32(9):861–71.CrossRefPubMedPubMedCentral
7.
go back to reference Mezzatesta ML, Gona F, Caio C, et al. Outbreak of KPC-3-producing and colistin-resistant, Klebsiella pneumoniae infections in two Sicilian Hospitals. Clin Microbiol Infect. 2011;17(9):1444–7.CrossRefPubMed Mezzatesta ML, Gona F, Caio C, et al. Outbreak of KPC-3-producing and colistin-resistant, Klebsiella pneumoniae infections in two Sicilian Hospitals. Clin Microbiol Infect. 2011;17(9):1444–7.CrossRefPubMed
8.
go back to reference Correa L, Martino MDV, Siqueira I, et al. A hospital-based matched case-control study to identify clinical outcome and risk factors associated with carbapenem-resistant Klebsiella pneumoniae infection. BMC Infect Dis. 2013;13:80.CrossRefPubMedPubMedCentral Correa L, Martino MDV, Siqueira I, et al. A hospital-based matched case-control study to identify clinical outcome and risk factors associated with carbapenem-resistant Klebsiella pneumoniae infection. BMC Infect Dis. 2013;13:80.CrossRefPubMedPubMedCentral
9.
go back to reference Kontopidou F, Giamarellou H, Katerelos P, et al. Infections caused by carbapenem-resistant Klebsiella pneumoniae among patients in intensive care in Greece: a multi-centre study on clinical outcome and therapeutic options. Clin Microbiol Infect. 2014;20(2):117–23.CrossRef Kontopidou F, Giamarellou H, Katerelos P, et al. Infections caused by carbapenem-resistant Klebsiella pneumoniae among patients in intensive care in Greece: a multi-centre study on clinical outcome and therapeutic options. Clin Microbiol Infect. 2014;20(2):117–23.CrossRef
10.
go back to reference Grundmann H, Livermore DM, Giske CK, et al. Carbapenem non- susceptible Enterobacteriaceae in Europe: conclusions from a meeting of a national experts. Euro Surveill. 2010;15(46):1-13. Grundmann H, Livermore DM, Giske CK, et al. Carbapenem non- susceptible Enterobacteriaceae in Europe: conclusions from a meeting of a national experts. Euro Surveill. 2010;15(46):1-13.
11.
go back to reference de Oliveira MS, de Assis DB, Freire MP, et al. Treatment of KPC-producing Enterobacteriacea: suboptimal efficacy of polymyxins. Clin Microbiol Infect. 2015;21(2):179.e1–7.CrossRef de Oliveira MS, de Assis DB, Freire MP, et al. Treatment of KPC-producing Enterobacteriacea: suboptimal efficacy of polymyxins. Clin Microbiol Infect. 2015;21(2):179.e1–7.CrossRef
12.
go back to reference 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:E23–30.CrossRefPubMed 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:E23–30.CrossRefPubMed
13.
go back to reference Humphries RM, Keledesis T, Bard JD, et al. Successful treatment of pan-resistant Klebsiella pneumoniae pneumonia and bacteraemia with a combination of high dose tigecycline and colistin. J Med Microbiol. 2010;59:1383–6.CrossRefPubMed Humphries RM, Keledesis T, Bard JD, et al. Successful treatment of pan-resistant Klebsiella pneumoniae pneumonia and bacteraemia with a combination of high dose tigecycline and colistin. J Med Microbiol. 2010;59:1383–6.CrossRefPubMed
14.
go back to reference van Duin D, Kaye KS, Neuner EA, Bonomo RA. Carbapenem-resistant Enterobacteriaceae: a review of treatment and outcomes. Diagn Microbiol Infect Dis. 2013;75(2):115–20.CrossRefPubMedPubMedCentral van Duin D, Kaye KS, Neuner EA, Bonomo RA. Carbapenem-resistant Enterobacteriaceae: a review of treatment and outcomes. Diagn Microbiol Infect Dis. 2013;75(2):115–20.CrossRefPubMedPubMedCentral
15.
go back to reference Lee GC, Burgess DS. Treatment of Klebsiella pneumoniae carbapenemase (KPC) infections: a review of published case series and case reports. Ann Clin Microbiol Antimicrob. 2012;11:32–40.CrossRefPubMedPubMedCentral Lee GC, Burgess DS. Treatment of Klebsiella pneumoniae carbapenemase (KPC) infections: a review of published case series and case reports. Ann Clin Microbiol Antimicrob. 2012;11:32–40.CrossRefPubMedPubMedCentral
16.
go back to reference Horan T, 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;36:309–32.CrossRefPubMed Horan T, 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;36:309–32.CrossRefPubMed
17.
go back to reference Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;31(4):1250–6.CrossRefPubMed Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;31(4):1250–6.CrossRefPubMed
18.
go back to reference Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373–83.CrossRefPubMed Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373–83.CrossRefPubMed
19.
go back to reference Institute CLS. Performance Standards for Antimicrobial Susceptibility Testing; Nineteenth Informational Supplement, M100-S20. CLSI: Wayne (PA); 2012. Institute CLS. Performance Standards for Antimicrobial Susceptibility Testing; Nineteenth Informational Supplement, M100-S20. CLSI: Wayne (PA); 2012.
20.
go back to reference European Committee on Antimicrobial Susceptibility Testing (Eucast). 2012. European Committee on Antimicrobial Susceptibility Testing (Eucast). 2012.
21.
go back to reference Bradford PA, Bratu C, Urban M, et al. Emergence of carbapenem-resistant Klebsiella species possessing the class A carbapenem-hydrolyzing KPC-2 and inhibitor-resistant TEM-30 beta-lactases in New York City. Clin Infect Dis. 2004;39:55–60.CrossRefPubMed Bradford PA, Bratu C, Urban M, et al. Emergence of carbapenem-resistant Klebsiella species possessing the class A carbapenem-hydrolyzing KPC-2 and inhibitor-resistant TEM-30 beta-lactases in New York City. Clin Infect Dis. 2004;39:55–60.CrossRefPubMed
22.
go back to reference Chen Y, Zhou Z, Jiang Y, Yu Y. Emergence of NDM-1-producing Acinetobacter baumannii in China. J Antimicrob Chemother. 2011;66:1255–9.CrossRefPubMed Chen Y, Zhou Z, Jiang Y, Yu Y. Emergence of NDM-1-producing Acinetobacter baumannii in China. J Antimicrob Chemother. 2011;66:1255–9.CrossRefPubMed
23.
go back to reference Monteiro J, Widen RH, Pignatari ACC. Rapid detection of carbapenemase genes by multiplex real time PCR. J Antimicrob Chemother. 2012;67:907–9.CrossRef Monteiro J, Widen RH, Pignatari ACC. Rapid detection of carbapenemase genes by multiplex real time PCR. J Antimicrob Chemother. 2012;67:907–9.CrossRef
24.
go back to reference Pfaller MA. Chromosomal restriction fragment analysis by pulsed-field gel electrophoresis. In: Isemberg HD, editor. Clinical microbiology procedures handbook. Washington: American Society for Microbiology; 1993. Pfaller MA. Chromosomal restriction fragment analysis by pulsed-field gel electrophoresis. In: Isemberg HD, editor. Clinical microbiology procedures handbook. Washington: American Society for Microbiology; 1993.
25.
go back to reference Qureshi ZA, Paterson DL, Potoski BA, et al. Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens. Antimicrob Agents Chemother. 2012;56(4):2108–13.CrossRefPubMedPubMedCentral Qureshi ZA, Paterson DL, Potoski BA, et al. Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens. Antimicrob Agents Chemother. 2012;56(4):2108–13.CrossRefPubMedPubMedCentral
26.
go back to reference Souli M, Galani I, Antoniadou A, et al. An outbreak of infection due to β-lactamase Klebsiella pneumoniae carbapenemase 2-producing K. pneumoniae in a Greek university hospital. Clin Infect Dis. 2010;50:364–73.CrossRefPubMed Souli M, Galani I, Antoniadou A, et al. An outbreak of infection due to β-lactamase Klebsiella pneumoniae carbapenemase 2-producing K. pneumoniae in a Greek university hospital. Clin Infect Dis. 2010;50:364–73.CrossRefPubMed
27.
go back to reference Tumbarello M, Trecarichi EM, De Rosa FG, et al. Infections caused by KPC-producing Klebsiella pneumoniae: differences in therapy and mortality in a multicenter study. J Antimicrob Chemother. 2015;70(7):2133–43.CrossRefPubMed Tumbarello M, Trecarichi EM, De Rosa FG, et al. Infections caused by KPC-producing Klebsiella pneumoniae: differences in therapy and mortality in a multicenter study. J Antimicrob Chemother. 2015;70(7):2133–43.CrossRefPubMed
28.
go back to reference 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;17:1798–803.CrossRefPubMed 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;17:1798–803.CrossRefPubMed
29.
go back to reference Ceccarelli G, Falconi M, Giordano A. Successful ertapenem-doripenem combination treatment of bacteremic ventilator-associated pneumonia due to colistin resistant KPC-producing K. pneumoniae. Antimicrob Agents Chemother. 2013;57(6):2900–1.CrossRefPubMedPubMedCentral Ceccarelli G, Falconi M, Giordano A. Successful ertapenem-doripenem combination treatment of bacteremic ventilator-associated pneumonia due to colistin resistant KPC-producing K. pneumoniae. Antimicrob Agents Chemother. 2013;57(6):2900–1.CrossRefPubMedPubMedCentral
30.
go back to reference Cicora F, Mos F, Paz M, Allende NG, Roberti J. Infections with blaKPC-2-producing Klebsiella pneumoniae in renal transplant patients: a retrospective study. Transplant Proc. 2013;45(9):3389–93.CrossRefPubMed Cicora F, Mos F, Paz M, Allende NG, Roberti J. Infections with blaKPC-2-producing Klebsiella pneumoniae in renal transplant patients: a retrospective study. Transplant Proc. 2013;45(9):3389–93.CrossRefPubMed
Metadata
Title
A prospective study of treatment of carbapenem-resistant Enterobacteriaceae infections and risk factors associated with outcome
Authors
Claudia M. D. de Maio Carrilho
Larissa Marques de Oliveira
Juliana Gaudereto
Jamile S. Perozin
Mariana Ragassi Urbano
Carlos H. Camargo
Cintia M. C. Grion
Anna Sara S. Levin
Silvia F. Costa
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2016
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-016-1979-z

Other articles of this Issue 1/2016

BMC Infectious Diseases 1/2016 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.