Complex prosthetic joint infections due to carbapenemase-producing Klebsiella pneumoniae: a unique challenge in the era of untreatable infections☆

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SUMMARY

Objectives

Limited clinical experience exists regarding the management of prosthetic joint infection (PJI) due to multidrug-resistant (MDR) Gram-negative organisms. We review three cases of carbapenem-resistant Klebsiella pneumoniae (CRKP) complicating PJI.

Methods

This was a retrospective study of all patients at a tertiary care institution with CRKP complicating PJI between January 2007 and December 2010. Demographic data, procedures, organisms involved, length of stay, antibiotic treatments, and outcomes were collected. Antimicrobial susceptibility testing was performed on CRKP isolates, and the mechanism of resistance was ascertained by PCR.

Results

This analysis demonstrated that: (1) the CRKP possessed bla _KPC and were difficult to eradicate (persistent) in PJI; (2) multiple surgeries and antibiotic courses were undertaken and patients required a prolonged length of stay; (3) resistance to colistin and amikacin emerged on therapy; (4) the same strain of CRKP may be responsible for relapse of infection; (5) significant morbidity and mortality resulted.

Conclusions

These cases highlight the opportunistic and chronic nature of CRKP in PJIs and the need for aggressive medical and surgical treatment. Further investigations of the management of CRKP PJI and new drug therapies for infections due to MDR Gram-negative organisms are urgently needed.

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Most cited references 41

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Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study

Karthikeyan K Kumarasamy, Mark Toleman, Timothy R. Walsh … (2010)

Summary Background Gram-negative Enterobacteriaceae with resistance to carbapenem conferred by New Delhi metallo-β-lactamase 1 (NDM-1) are potentially a major global health problem. We investigated the prevalence of NDM-1, in multidrug-resistant Enterobacteriaceae in India, Pakistan, and the UK. Methods Enterobacteriaceae isolates were studied from two major centres in India—Chennai (south India), Haryana (north India)—and those referred to the UK's national reference laboratory. Antibiotic susceptibilities were assessed, and the presence of the carbapenem resistance gene bla NDM-1 was established by PCR. Isolates were typed by pulsed-field gel electrophoresis of XbaI-restricted genomic DNA. Plasmids were analysed by S1 nuclease digestion and PCR typing. Case data for UK patients were reviewed for evidence of travel and recent admission to hospitals in India or Pakistan. Findings We identified 44 isolates with NDM-1 in Chennai, 26 in Haryana, 37 in the UK, and 73 in other sites in India and Pakistan. NDM-1 was mostly found among Escherichia coli (36) and Klebsiella pneumoniae (111), which were highly resistant to all antibiotics except to tigecycline and colistin. K pneumoniae isolates from Haryana were clonal but NDM-1 producers from the UK and Chennai were clonally diverse. Most isolates carried the NDM-1 gene on plasmids: those from UK and Chennai were readily transferable whereas those from Haryana were not conjugative. Many of the UK NDM-1 positive patients had travelled to India or Pakistan within the past year, or had links with these countries. Interpretation The potential of NDM-1 to be a worldwide public health problem is great, and co-ordinated international surveillance is needed. Funding European Union, Wellcome Trust, and Wyeth.

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NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006-2007.

Alicia I. Hidron, Jonathan Edwards, Jean Patel … (2008)

To describe the frequency of selected antimicrobial resistance patterns among pathogens causing device-associated and procedure-associated healthcare-associated infections (HAIs) reported by hospitals in the National Healthcare Safety Network (NHSN). Data are included on HAIs (ie, central line-associated bloodstream infections, catheter-associated urinary tract infections, ventilator-associated pneumonia, and surgical site infections) reported to the Patient Safety Component of the NHSN between January 2006 and October 2007. The results of antimicrobial susceptibility testing of up to 3 pathogenic isolates per HAI by a hospital were evaluated to define antimicrobial-resistance in the pathogenic isolates. The pooled mean proportions of pathogenic isolates interpreted as resistant to selected antimicrobial agents were calculated by type of HAI and overall. The incidence rates of specific device-associated infections were calculated for selected antimicrobial-resistant pathogens according to type of patient care area; the variability in the reported rates is described. Overall, 463 hospitals reported 1 or more HAIs: 412 (89%) were general acute care hospitals, and 309 (67%) had 200-1,000 beds. There were 28,502 HAIs reported among 25,384 patients. The 10 most common pathogens (accounting for 84% of any HAIs) were coagulase-negative staphylococci (15%), Staphylococcus aureus (15%), Enterococcus species (12%), Candida species (11%), Escherichia coli (10%), Pseudomonas aeruginosa (8%), Klebsiella pneumoniae (6%), Enterobacter species (5%), Acinetobacter baumannii (3%), and Klebsiella oxytoca (2%). The pooled mean proportion of pathogenic isolates resistant to antimicrobial agents varied significantly across types of HAI for some pathogen-antimicrobial combinations. As many as 16% of all HAIs were associated with the following multidrug-resistant pathogens: methicillin-resistant S. aureus (8% of HAIs), vancomycin-resistant Enterococcus faecium (4%), carbapenem-resistant P. aeruginosa (2%), extended-spectrum cephalosporin-resistant K. pneumoniae (1%), extended-spectrum cephalosporin-resistant E. coli (0.5%), and carbapenem-resistant A. baumannii, K. pneumoniae, K. oxytoca, and E. coli (0.5%). Nationwide, the majority of units reported no HAIs due to these antimicrobial-resistant pathogens.

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Carbapenem-resistant Enterobacteriaceae: epidemiology and prevention.

Neil Gupta, Brandi M. Limbago, Jean B Patel … (2011)

Over the past 10 years, dissemination of Klebsiella pneumoniae carbapenemase (KPC) has led to an increase in the prevalence of carbapenem-resistant Enterobacteriaceae (CRE) in the United States. Infections caused by CRE have limited treatment options and have been associated with high mortality rates. In the previous year, other carbapenemase subtypes, including New Delhi metallo-β-lactamase, have been identified among Enterobacteriaceae in the United States. Like KPC, these enzymes are frequently found on mobile genetic elements and have the potential to spread widely. As a result, preventing both CRE transmission and CRE infections have become important public health objectives. This review describes the current epidemiology of CRE in the United States and highlights important prevention strategies. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

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Author and article information

Journal

Journal ID (nlm-journal-id): 9610933

Journal ID (pubmed-jr-id): 20844

Journal ID (nlm-ta): Int J Infect Dis

Journal ID (iso-abbrev): Int. J. Infect. Dis.

Title: International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases

ISSN (Print): 1201-9712

ISSN (Electronic): 1878-3511

Publication date Nihms-submitted: 16 January 2015

Publication date (Electronic): 09 May 2014

Publication date (Print): August 2014

Publication date PMC-release: 01 August 2015

Volume: 25

Pages: 73-78

Affiliations

[a ]Division of Infectious Disease, Spectrum Health Medical Group, 230 Michigan Ave, NE, Grand Rapids, MI 49503, USA

[b ]Section of Bone and Joint Infections, Department of Infectious Diseases, Cleveland Clinic Foundation, Cleveland, Ohio, USA

[c ]Division of Infectious Diseases, UNC School of Medicine, Chapel Hill, North Carolina, USA

[d ]Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland Clinic Foundation, Cleveland, Ohio, USA

[e ]Research Services, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA

[f ]Medicine Services, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA

[g ]Department of Medicine, Case Western Reserve School of Medicine, Cleveland, Ohio, USA

[h ]Department of Pharmacology, Case Western Reserve School of Medicine, Cleveland, Ohio, USA

[i ]Department of Molecular Biology and Microbiology, Case Western Reserve School of Medicine, Cleveland, Ohio, USA

[j ]Department of Orthopedic Surgery and Rheumatologic Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA

Author notes

[* ]Corresponding author. Tel.: +1 616 774 2822; fax: +1 616 391 8665. Jorgelina.deSanctis@ 123456spectrumhealth.org , camiodio@ 123456gmail.com (J. de Sanctis)

Article

Manuscript ID: NIHMS655630

DOI: 10.1016/j.ijid.2014.01.028

PMC ID: 4336167

PubMed ID: 24813874

SO-VID: e7f85b76-72d6-43b3-adfd-b456f75a854c

License:

This is an open access article under the CC BY-NC-SA license ( http://creativecommons.org/licenses/by-nc-sa/3.0/).