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Local acquisition and nosocomial transmission of Klebsiella pneumoniae harbouring the blaNDM-1 gene in Australia

Alex Y C Tai, Rhonda L Stuart, Hannah E Sidjabat, Christopher N Lemoh, Benjamin A Rogers, Maryza Graham, David L Paterson and Tony M Korman
Med J Aust 2015; 202 (5): 270-271. || doi: 10.5694/mja14.01637
Published online: 16 March 2015

The emergence of carbapenem-resistant Enterobacteriaceae constitutes a critical global issue. Isolates harbouring the metallo-β-lactamase gene blaNDM-1 have few available treatment options. We report a case of an Australian adult with a locally acquired, community-onset blaNDM-1 Klebsiella pneumoniae infection and likely nosocomial transmission to another patient.

Clinical records

Patient A, a 68-year-old Australian-born woman living with her husband and son, had never travelled overseas and had no known contact with overseas visitors. Her past history included chronic bilateral lymphoedema with recurrent lower limb cellulitis, requiring multiple previous hospital admissions and home nursing care. She presented with septic shock and right leg erythema surrounding a 10 × 10 cm ulcer near the right lateral malleolus. Magnetic resonance imaging showed bony oedema and enhancement in the lateral malleolus, suggestive of osteomyelitis. Pseudomonas aeruginosa was isolated from blood cultures. A tissue biopsy from the overlying ulcer cultured P. aeruginosa, non-multiresistant methicillin-resistant Staphylococcus aureus (NORSA), and carbapenem-resistant Klebsiella pneumoniae, resistant to all first-line antimicrobials tested and susceptible to only colistin and fosfomycin.

She was given intravenous ceftazidime and vancomycin for treatment of P. aeruginosa and NORSA infection. After 6 weeks of treatment, the ulcer was not healing, and treatment for the carbapenemase-producing K. pneumoniae was commenced with intravenous colistin methanosulfonate (120 mg colistin base activity 12-hourly). Colistin was ceased after 3 weeks owing to acute kidney injury, and oral fosfomycin (3 g every 3 days) was administered for a further 6 weeks, in addition to oral ciprofloxacin and rifampicin for ongoing treatment of NORSA and P. aeruginosa infection. Since the cessation of her antibiotics, she has not required further antibiotic treatment of her ulcers.

Patient B, a 35-year-old Australian-born man with no history of overseas travel, was admitted with bilateral thigh cellulitis and septic shock. He had bilateral thigh debridement, with no evidence of necrotising fasciitis. Methicillin-susceptible S. aureus (MSSA) was isolated from multiple blood cultures. MSSA and Serratia liquefaciens were isolated from a thigh wound swab culture. Transthoracic echocardiogram revealed a left ventricular thrombus. He was commenced on intravenous flucloxacillin and ciprofloxacin. Two weeks after admission, further surgical samples from his thigh wounds cultured carbapenem-resistant K. pneumoniae, with similar antimicrobial susceptibility phenotype to Patient A. The isolate was deemed to be colonising the wound only, and no antimicrobials were commenced for treatment.

Both K. pneumoniae isolates demonstrated carbapenemase activity using the Carba NP assay.1 Molecular tests using polymerase chain reaction and sequencing for carbapenemase, extended-spectrum β-lactamase, plasmid-mediated AmpC β-lactamase and 16S ribosomal RNA methylase genes were performed as described elsewhere.2 The metallo-β-lactamase gene blaNDM-1 was detected in both isolates, in addition to blaCTX-M-15 and 16S ribosomal RNA methylases (armA and rmtB), which confer resistance to aminoglycosides, including amikacin. The relatedness of isolates was determined by semi-automated repetitive sequence-based polymerase chain reaction using a DiversiLab Klebsiella kit (bioMérieux). This analysis showed a > 95% genetic similarity between the two isolates. Further, the isolates were genetically distinct from two blaNDM-1-harbouring isolates that we isolated previously in patients with a history of overseas travel.

Patients A and B were admitted in December 2013 to a high dependency unit (HDU) — a four-bed area separated by curtains. They were one bed apart for 5 days before being moved adjacent to each other for 1 day, with Patient B occupying the bed cubicle space formerly occupied by Patient A for a further 5 days. The carbapenem-resistant K. pneumoniae was first identified in Patient A in the HDU, and 2 weeks later was isolated from Patient B.

After detection of the carbapenem-resistant K. pneumoniae, strict contact precautions were implemented. Environmental cleaning of the four-bed HDU and other rooms occupied by Patients A and B was undertaken with microfibre and steam cleaning, which has been shown to be an effective cleaning method.3 An exposure investigation was conducted, with environmental sampling and screening rectal swabs collected from all direct patient contacts of Patients A and B inoculated on chromogenic selective media. No other carbapenem-resistant organisms containing blaNDM-1 were isolated from clinical, screening or environmental samples.

Discussion

The metallo-β-lactamase gene blaNDM-1 was first described in a patient hospitalised in Sweden after travel to India in 20084 and subsequently identified in a series of patients in the United Kingdom, many of whom had travelled to the Indian subcontinent.5 There have been documented cases of infection with imported blaNDM-1-containing bacteria in Australia.6-10 These carbapenem-resistant bacteria are challenging to treat, as available treatment options are often limited to infrequently used drugs such as colistin, fosfomycin and tigecycline.

The case of Patient A has significant public health ramifications as the first detection of carbapenem-resistant blaNDM-1-harbouring K. pneumoniae infection locally acquired in Australia, independent of international travel or documented contact with a traveller. The case suggests that there may be more cases of blaNDM-1-harbouring bacteria in our community than previously suspected. We hypothesise that this carbapenem-resistant Enterobacteriaceae isolate was acquired after transmission from an unidentified carrier of blaNDM-1, possibly during previous hospital admissions or receipt of home nursing care.

The transmission from Patient A to Patient B may have occurred via a number of mechanisms. First, environmental contamination may have contributed, given that both patients shared the same bed area at different times. We previously reported an outbreak of carbapenem-resistant Enterobacteriaceae harbouring the metallo-β-lactamase gene blaIMP-4, associated with contaminated sinks in an intensive care unit; in that case, no carbapenem-resistant organisms containing blaNDM-1 were isolated from environmental samples.11 The second possible contributing factor for transmission is lapses in infection control practices by health care staff, which emphasises the importance of adhering to standard precautions such as hand hygiene.12

These cases highlight the evolving Australian epidemiology of multidrug-resistant organisms, particularly bacteria harbouring blaNDM-1. Such resistance is no longer exclusively associated with obvious international travel. There is an increasing need for effective antimicrobial stewardship and infection control measures to prevent potential future nosocomial spread of these organisms. In addition, further research and surveillance is needed in monitoring these local isolates to identify potential risk factors for local acquisition and any reservoirs within the Australian health system and community.

  • Alex Y C Tai1
  • Rhonda L Stuart1
  • Hannah E Sidjabat2
  • Christopher N Lemoh1
  • Benjamin A Rogers1,2
  • Maryza Graham1
  • David L Paterson2,3
  • Tony M Korman1

  • 1 Monash Infectious Diseases, Melbourne, VIC.
  • 2 University of Queensland, Brisbane, QLD.
  • 3 Royal Brisbane and Women's Hospital, Brisbane, QLD.

Correspondence: alakaytai@gmail.com

Competing interests:

No relevant disclosures.

  • 1. Lee LY, Korman TM, Graham M. Rapid time to results and high sensitivity of the CarbaNP test on early cultures. J Clin Microbiol 2014; 52: 4023-4026.
  • 2. Sidjabat H, Nimmo GR, Walsh TR, et al. Carbapenem resistance in Klebsiella pneumoniae due to the New Delhi metallo-β-lactamase. Clin Infect Dis 2011; 52: 481-484.
  • 3. Gillespie E, Wilson J, Lovegrove A, et al. Environment cleaning without chemicals in clinical settings. Am J Infect Control 2013; 41: 461-463.
  • 4. Yong D, Toleman MA, Giske CG, et al. Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother 2009; 53: 5046-5054.
  • 5. Kumarasamy KK, Toleman MA, Walsh TR, et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis 2010; 10: 597-602.
  • 6. Blyth CC, Pereira L, Goire N. New Delhi metallo-beta-lactamase-producing enterobacteriaceae in an Australian child who had not travelled overseas [letter]. Med J Aust 2014; 200: 386. <MJA full text>
  • 7. Chua KYL, Grayson ML, Burgess AN, et al. The growing burden of multidrug-resistant infections among returned Australian travellers. Med J Aust 2014; 200: 116-118. <MJA full text>
  • 8. Poirel L, Lagrutta E, Taylor P, et al. Emergence of metallo-beta-lactamase NDM-1-producing multidrug-resistant Escherichia coli in Australia. Antimicrob Agents Chemother 2010; 54: 4914-4916.
  • 9. Rogers BA, Sidjabat HE, Silvey A, et al. Treatment options for New Delhi metallo-beta-lactamase-harboring enterobacteriaceae. Microb Drug Resist 2013; 19: 100-103.
  • 10. Fernando GA, Collignon PJ, Bell JM. A risk for returned travellers: the “post-antibiotic era” [letter]. Med J Aust 2010; 193: 59. <MJA full text>
  • 11. Kotsanas D, Wijesooriya WR, Korman TM, et al. “Down the drain”: carbapenem-resistant bacteria in intensive care unit patients and handwashing sinks. Med J Aust 2013; 198: 267-269. <MJA full text>
  • 12. Australian Commission on Safety and Quality in Health Care. Recommendations for the control of multi-drug resistant gram-negatives: carbapenem resistant Enterobacteriaceae. Sydney: ACSQHC, 2013. http://www.safetyandquality.gov.au/wp-content/uploads/2013/12/MRGN-Guide-Enterobacteriaceae-PDF-1.89MB.pdf (accessed Jan 2015).

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