Infection Control (KPC specific)- February 14

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Introduction: Growing Concern Over Klebsiella Pneumoniae Carbapenemase (KPC)

There have been 600 reported cases of antibiotic-resistant bacteria called Carbapenemase-producing Enterobacteriaceae (CPE) in England during the past year. These bacteria have developed resistance against carbapenems, the antibiotics which are usually used to treat serious infections. Drug-resistant CPE bacteria produce an enzyme (carbapenemase) which breaks down antibiotics and makes them ineffective.

There is rising concern about the drug-resistant “superbug” called Klebsiella pneumoniae Carbapenemase (KPC), which is reported to have caused sixteen deaths in Manchester during the past four years.

KPC causes urinary tract infections and pneumonia in patients with suppressed immune systems, such as frail elderly or severely ill patients. It is increasingly resistant to treatment with carbapenems (the only group of antibiotics which were effective against multidrug-resistant bacteria).

The KPC resistance mechanism first emerged in the United States and later spread to Israel and Greece. It is reported to have reached epidemic proportions in Italy.

Central Manchester Hospitals in the UK have reviewed their guidelines on antibiotics and the treatment of patients requiring bowel surgery or cancer treatment which compromises their immunity.

Local Context

In the UK, the problem may be spreading from the North West of England into the Midlands region. A Freedom of Information request reveals there have been two cases of KPC at New Cross Hospital in Wolverhampton in the past two years. Ten patients have been infected at the University Hospital of North Staffordshire.

Paduano, M. (2014). Warning over hospital superbug linked to 16 deaths. Birmingham: BBC Midlands Health News, March 7th 2014. Full Text Link.

See also:

Scientists warn over antibiotic-resistant superbug. Birmingham: BBC (Birmingham and Black Country) News, March 7th 2014. Full Text Link.

New Guidance

Only five patients were reported to Public Health England as having CPE in 2006; by 2013 this number exceeded 600. This number includes people who may only be carriers of CPE, and those with more serious infections.

Advice and assistance has been supplied by Public Health England:

Antibiotic resistance ‘toolkit’ launched. London: NHS Choices Behind the Headlines, March 7th 2013. Full Text Link.

This relates to:

PHE launches toolkit to manage hospital infections caused by antibiotic-resistant bacteria. London: Public Health England, March 6th 2014. Full Text Link.

What’s In the Public Health England Toolkit?

Public Health England has produced information leaflets for healthcare professionals to hand to people identified as being carriers or infected with CPE, and for people in contact with infected patients.

Public Health England has released their “toolkit” to address the problem of increasing outbreaks of hospital infections caused by antibiotic-resistant bacteria across England. This set of recommendations has been designed to provide plans and procedures to help health staff limit the spread of CPE in hospitals and into the community.

The toolkit focuses on the early detection of CPE. It offers advice on how to manage or treat CPE, and to control the spread of CPE in hospitals and residential care homes.

Public Health England’s full toolkit offering guidance for hospitals on the detection, management and control antibiotic-resistant bacterial infections caused by CPE may be accessed by selecting the following link:

Acute trust toolkit for the early detection, management and control of carbapenemase-producing Enterobacteriaceae. London: Public Health England, December 2013. Full Text Link.

NHS England’s 
Patient Safety Alert

NHS England has issued a (Level 2) patient safety alert about addressing the rising outbreaks of carbapenemase-producing Enterobacteriaceae:

Patient safety alert on addressing rising trends and outbreaks in carbapenemase-producing Enterobacteriaceae. London: NHS England, March 6th 2014. Full Text Link.

The Broad Policy Context

Volume Two of the Chief Medical Officer, Professor Dame Sally Davies’s first annual epidemiology and surveillance report made several recommendations, including:

1.  Antimicrobial resistance should be put on the national risk register and taken very seriously by politicians internationally, such as at the G8 and World Health Organization.

2.  Better surveillance data is required across the NHS and world-wide.

3.  The healthcare and pharmaceutical industries should work to preserve the efficacy of existing drugs and encourage the development of new antibiotics to fill the “discovery void” of the last 20 years.

4.  MRSA rates have fallen by 80% since 2003 through better hygiene. Similar approaches should be used when treating the next generation of healthcare associated infections, such as newer strains of harder-to-treat klebsiella.

Professor Dame Sally Davies (2013). Annual report of the Chief Medical Officer: Volume Two, 2011. Infections and the rise of antimicrobial resistance. London: Department of Health, March 2013. Full Text Link.

The Advisory Committee on Antimicrobial and Healthcare Associated Infections (ARHAI)’s fourth annual report includes ARHAI’s work plan for 2013 to 2014:

Wallace, J. (2013). Advisory committee on antimicrobial resistance and healthcare associated infections: 4th Annual Report, February 2012 – March 2013. London: Department of Health / Public Health England, November 12th 2013. Full Text Link.

A cross-government UK strategy was announced last year, by the Department of Health, to slow the development and spread of antimicrobial resistance. It has three strategic aims:

1.  Improving knowledge and understanding of antimicrobial resistance.

2.  Conservation and stewardship of the effectiveness of existing treatments.

3.  Stimulating the development of new antibiotics, diagnostics and novel therapies.

UK five-year Antimicrobial Resistance Strategy 2013 to 2018. London: Department of Health, September 10th 2013. Full Text Link.

The Big Picture

Laxminarayan, R. Duse, A. Wattal, C. [et al] (2013). Antibiotic resistance: the need for global solutions. Lancet Infectious Disorders. December 2013; 13(12): 1057-98.

Tzouvelekis, LS. Markogiannakis, A. Psichogiou, M. [et al] (2012). Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: an evolving crisis of global dimensions. Clinical Microbiology Reviews. October 2012; 25(4): 682-707. Full Text Link.

Nordmann, P. (2014). Carbapenemase-producing enterobacteriaceae: overview of a major public health challenge. Medecine et Maladies Infectieuses. February 2014; 44(2): 51-56. Review.

Nordmann, P. Dortet, L. Poirel, L. (2012). Carbapenem resistance in Enterobacteriaceae: here is the storm! Trends in Molecular Medicine. May 2012; 18(5): 263-72. Review.

Walsh, TR (2010). Emerging carbapenemases: a global perspective. International Journal of Antimicrobial Agents. November 2010; 36 Supplement 3: S8-14. Full Text Link.

van der Bij, AK. Pitout, JD. (2012). The role of international travel in the worldwide spread of multiresistant Enterobacteriaceae. Journal of Antimicrobial Chemotherapy. September 2012; 67(9): 2090-100. Review. Full Text Link.

Sandora, TJ. Goldmann, DA. (2012). Preventing lethal hospital outbreaks of antibiotic-resistant bacteria. The New England Journal of Medicine. December 6th 2012; 367(23): 2168-70. Full Text Link.

Patel, G. Bonomo, RA. (2013). "Stormy waters ahead": global emergence of carbapenemases. Frontiers in Microbiology. March 2013; 4: 48. Full Text Link.

KPC: Epidemiology

Gupta, N. Limbago, BM. Patel, JB. [et al]. (2011). Carbapenem-resistant Enterobacteriaceae: epidemiology and prevention. Clinical Infectious Diseases. July 1st 2011; 53(1): 60-7. Full Text Link.

Munoz-Price, LS. Poirel, L. Bonomo, RA. [et al] (2013). Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infectious Disorders. September 2013; 13(9): 785-96. Review.

Kothari, C. Gaind, R. Singh, LC. [et al] (2014). Community acquisition of β-lactamase producing Enterobacteriaceae in neonatal gut. BMC Microbiology. June 17th 2013; 13: 136. Full Text Link.

Jain, R. Walk, ST. Aronoff, DM. [et al] (2013). Emergence of Carbapenemase producing Klebsiella Pneumoniae of Sequence type 258 in Michigan, USA. Infectious Disease Reports. January 22nd 2013; 5(1): e5. Review. Full Text Link.

Giani, T. Pini, B. Arena, F. [et al] (2013). Epidemic diffusion of KPC carbapenemase-producing Klebsiella pneumoniae in Italy: results of the first countrywide survey, 15 May to 30 June 2011. Euro Surveillance: European Communicable Disease Bulletin. May 30th 2013;18(22). Full Text Link.

Cantón, R. Akóva, M. Carmeli, Y. [et al]; European Network on Carbapenemases (2012). Rapid evolution and spread of carbapenemases among Enterobacteriaceae in Europe. Clinical Microbiology and Infection. May 2012;18(5): 413-31. Full Text Link.

van der Bij, AK. Pitout, JD. (2012). The role of international travel in the worldwide spread of multiresistant Enterobacteriaceae. Journal of Antimicrobial Chemotherapy. September 2012; 67(9): 2090-100. Review. Full Text Link.

KPC: Genetic Testing
& Research

Tzouvelekis, LS. Markogiannakis, A. Psichogiou, M. [et al] (2012). Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: an evolving crisis of global dimensions. Clinical Microbiology Reviews. October 2012; 25(4): 682-707. Full Text Link.

Ramos, PI. Picão, RC. Almeida, LG. [et al] (2014). Comparative analysis of the complete genome of KPC-2-producing Klebsiella pneumoniae Kp13 reveals remarkable genome plasticity and a wide repertoire of virulence and resistance mechanisms. BMC Genomics. January 22nd 2014; 15: 54. Full Text Link.

KPC: Microbiology (Miscellaneous)

Tzouvelekis, LS. Markogiannakis, A. Psichogiou, M. [et al] (2012). Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: an evolving crisis of global dimensions. Clinical Microbiology Reviews. October 2012; 25(4): 682-707. Full Text Link.

Nordmann, P. Dortet, L. Poirel, L. (2012). Carbapenem resistance in Enterobacteriaceae: here is the storm! Trends in Molecular Medicine. May 2012; 18(5): 263-72. Review.

Jain, R. Walk, ST. Aronoff, DM. [et al] (2013). Emergence of Carbapenemase producing Klebsiella Pneumoniae of Sequence type 258 in Michigan, USA. Infectious Disease Reports. January 22nd 2013; 5(1): e5. Review. Full Text Link.

Arnold, RS. Thom, KA. Sharma, S. [et al] (2011). Emergence of Klebsiella pneumoniae carbapenemase-producing bacteria. Southern Medical Journal. January 2011; 104(1): 40-5. Review. Full Text Link.

Rapp, RP. Urban, C. (2012). Klebsiella pneumoniae carbapenemases in Enterobacteriaceae: history, evolution, and microbiology concerns. Pharmacotherapy. May 2012; 32(5): 399-407.

KPC: Screening / Detection

Kothari, C. Gaind, R. Singh, LC. [et al] (2014). Community acquisition of β-lactamase producing Enterobacteriaceae in neonatal gut. BMC Microbiology. June 17th 2013; 13: 136. Full Text Link.

Carbonne, A. Thiolet, JM. Fournier, S. [et al] (2010). Control of a multi-hospital outbreak of KPC-producing Klebsiella pneumoniae type 2 in France, September to October 2009. Euro Surveillance: European Communicable Disease Bulletin. December 2nd 2010; 15(48). Full Text Link.

Alrabaa, SF. Nguyen, P. Sanderson, R. [et al] (2013). Early identification and control of carbapenemase-producing Klebsiella pneumoniae, originating from contaminated endoscopic equipment. American Journal of Infection Control. June 2013; 41(6): 562-4.

Bracco, S. Migliavacca, R. Pini, B. [et al] (2013). Evaluation of brilliance CRE agar for the detection of carbapenem-resistant gram-negative bacteria. New Microbiologica. April 2013; 36(2): 181-6. Full Text Link.

Nordmann, P. Gniadkowski, M. Giske, CG. [et al] (2012). Identification and screening of carbapenemase-producing Enterobacteriaceae. Clinical Microbiology and Infection. May 2012; 18(5): 432-Review. Full Text Link.

Picão, RC. Jones, RN. Mendes, RE. [et al] (2014). Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae testing susceptible to cefepime by reference methods. Journal of Clinical Microbiology. July 2013; 51(7): 2388-90. Full Text Link.

Tofteland, S. Naseer, U. Lislevand, JH. [et al] (2013). A long-term low-frequency hospital outbreak of KPC-producing Klebsiella pneumoniae involving Intergenus plasmid diffusion and a persisting environmental reservoir. PLoS One. 2013; 8(3) :e59015. Full Text Link.

Gaibani, P. Colombo, R. Arghittu, M. [et al] (2014). Successful containment and infection control of a Carbapenem-resistant Klebsiella pneumoniae outbreak in an Italian hospital. New Microbiol. January 2014; 37(1): 87-90. Full Text Link.

KPC & Specific Conditions

Di Carlo, P. Gulotta, G. Casuccio, A. [et al] (2014). KPC - 3 Klebsiella pneumoniae ST258 clone infection in postoperative abdominal surgery patients in an intensive care setting: analysis of a case series of 30 patients. BMC Anesthesiology. July 3rd 2013; 13(1): 13. Full Text Link.

Ceccarelli, G. Falcone, M. Giordano, A. [et al] (2013). Successful ertapenem-doripenem combination treatment of bacteremic ventilator-associated pneumonia due to colistin-resistant KPC-producing Klebsiella pneumoniae. Antimicrobial Agents and Chemotherapy. June 2013; 57(6): 2900-1. Full Text Link.

Du, X. Fu, Y. Yu, Y. (2013). Tigecycline treatment of infection caused by KPC-producing Escherichia coli in a pediatric patient. Annals of Clinical Microbiology and Antimicrobials. August 13th 2013; 12: 19. Full Text Link.

KPC: Surveillance

Carbapenem resistance. London [Online]: Public Health England, December 2013. Full Text Link. Possible also of interest, there is: The British Society for Antimicrobial Chemotherapy’s Bacteraemia Resistance Surveillance Programme. [Online]: British Society for Antimicrobial Chemotherapy (BSAC) Resistance Surveillance Project, 2014. Full Text Link.

Giani, T. Pini, B. Arena, F. [et al] (2013). Epidemic diffusion of KPC carbapenemase-producing Klebsiella pneumoniae in Italy: results of the first countrywide survey, 15 May to 30 June 2011. Euro Surveillance: European Communicable Disease Bulletin. May 30th 2013;18(22). Full Text Link.

Di Carlo, P. Gulotta, G. Casuccio, A. [et al] (2014). KPC - 3 Klebsiella pneumoniae ST258 clone infection in postoperative abdominal surgery patients in an intensive care setting: analysis of a case series of 30 patients. BMC Anesthesiology. July 3rd 2013; 13(1): 13. Full Text Link.

Tofteland, S. Naseer, U. Lislevand, JH. [et al] (2013). A long-term low-frequency hospital outbreak of KPC-producing Klebsiella pneumoniae involving Intergenus plasmid diffusion and a persisting environmental reservoir. PLoS One. 2013; 8(3) :e59015. Full Text Link.

KPC: Transmission Prevention

Gupta, N. Limbago, BM. Patel, JB. [et al]. (2011). Carbapenem-resistant Enterobacteriaceae: epidemiology and prevention. Clinical Infectious Diseases. July 1st 2011; 53(1): 60-7. Full Text Link.

Carbonne, A. Thiolet, JM. Fournier, S. [et al] (2010). Control of a multi-hospital outbreak of KPC-producing Klebsiella pneumoniae type 2 in France, September to October 2009. Euro Surveillance: European Communicable Disease Bulletin. December 2nd 2010; 15(48). Full Text Link.

Alrabaa, SF. Nguyen, P. Sanderson, R. [et al] (2013). Early identification and control of carbapenemase-producing Klebsiella pneumoniae, originating from contaminated endoscopic equipment. American Journal of Infection Control. June 2013; 41(6): 562-4.

Tofteland, S. Naseer, U. Lislevand, JH. [et al] (2013). A long-term low-frequency hospital outbreak of KPC-producing Klebsiella pneumoniae involving Intergenus plasmid diffusion and a persisting environmental reservoir. PLoS One. 2013; 8(3) :e59015. Full Text Link.

Sandora, TJ. Goldmann, DA. (2012). Preventing lethal hospital outbreaks of antibiotic-resistant bacteria. The New England Journal of Medicine. December 6th 2012; 367(23): 2168-70. Full Text Link.

Gaibani, P. Colombo, R. Arghittu, M. [et al] (2014). Successful containment and infection control of a Carbapenem-resistant Klebsiella pneumoniae outbreak in an Italian hospital. New Microbiol. January 2014; 37(1): 87-90. Full Text Link.

KPC: Treatment Options

Tzouvelekis, LS. Markogiannakis, A. Psichogiou, M. [et al] (2012). Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: an evolving crisis of global dimensions. Clinical Microbiology Reviews. October 2012; 25(4): 682-707. Full Text Link.

Di Carlo, P. Gulotta, G. Casuccio, A. [et al] (2014). KPC - 3 Klebsiella pneumoniae ST258 clone infection in postoperative abdominal surgery patients in an intensive care setting: analysis of a case series of 30 patients. BMC Anesthesiology. July 3rd 2013; 13(1): 13. Full Text Link.

Arnold, RS. Thom, KA. Sharma, S. [et al] (2011). Emergence of Klebsiella pneumoniae carbapenemase-producing bacteria. Southern Medical Journal. January 2011; 104(1): 40-5. Review. Full Text Link.

Livermore, DM. (2009). Has the era of untreatable infections arrived? Journal of Antimicrobial Chemotherapy. September 2009; 64 Supplement 1: i29-36. Review. Full Text Link.

Lee, GC. Burgess, DS. (2013). Polymyxins and Doripenem combination against KPC-producing Klebsiella pneumoniae. Journal of Clinical Medicine Research. April 2013; 5(2): 97-100. Full Text Link.

Ceccarelli, G. Falcone, M. Giordano, A. [et al] (2013). Successful ertapenem-doripenem combination treatment of bacteremic ventilator-associated pneumonia due to colistin-resistant KPC-producing Klebsiella pneumoniae. Antimicrobial Agents and Chemotherapy. June 2013; 57(6): 2900-1. Full Text Link.

Tascini, C. Tagliaferri, E. Giani, T. [et al] (2014). Synergistic activity of colistin plus rifampin against colistin-resistant KPC-producing Klebsiella pneumoniae. Antimicrobial Agents and Chemotherapy. August 2013; 57(8): 3990-3. Full Text Link.

Du, X. Fu, Y. Yu, Y. (2013). Tigecycline treatment of infection caused by KPC-producing Escherichia coli in a pediatric patient. Annals of Clinical Microbiology and Antimicrobials. August 13th 2013; 12: 19. Full Text Link.

Falagas, ME. Karageorgopoulos, DE. Nordmann, P. [et al] (2011). Therapeutic options for infections with Enterobacteriaceae producing carbapenem-hydrolyzing enzymes. Future Microbiology. June 2011; 6(6): 653-66. Review.

Lee, GC. Burgess, DS. (2012). Treatment of Klebsiella pneumoniae carbapenemase (KPC) infections: a review of published case series and case reports. Annals of Clinical Microbiology and Antimicrobials. December 13th 2012; 11: 32. Full Text Link.