Editor,
Multi-drug-resistant Gram-negative pathogens are increasingly isolated at hospitals around the world. We report two cases of colonisation and infection with Enterobacter cloacae strains producing New Delhi Metallo-β-lactamase 1 (NDM-1), not previously reported in Northern Ireland.
Case 1: A 6 year-old-boy on holiday in India suffered electrical burns to 60% of his body. On day 10 he was airlifted back to the regional paediatric ICU. On day 20 both a swab of burns on his left leg and the tip of a femoral line removed that day, grew multi-resistant E. cloacae. Both E. cloacae isolates were retested at the Health Protection Agency (HPA) Antibiotic Resistance Monitoring and Reference Laboratory (ARMRL) which found carbapenem resistance in the leg isolate (Table 1). This isolate was positive by PCR for blaNDM-1 encoding NDM-1 β-lactamase. The femoral line isolate lacked NDM-1 enzyme, but had an extended-spectrum β-lactamase (ESBL). Pulsed-field gel electrophoresis showed that these E. cloacae were distinct strains. Thankfully, the patient did not require antimicrobial treatment for these E. cloacae strains, and was discharged on day 91.
Table 1.
Final antibiotic susceptibility patterns and additional tests of multi-resistant E. cloacae and P. aeruginosa strains
| Antibiotic susceptibility testing | Case 1 | Case 2 | ||
|---|---|---|---|---|
| E. cloacae | E. cloacae | P. aeruginosa | E. cloacae | |
| Tip femoral line | Left leg swab | Bone Sample | Bone Sample | |
| Ciprofloxacin | R | R | R | R |
| Piperacillin/tazobactam | R | R | R | R |
| Meropenem | S | R | R | R |
| Colistin | S | S | S | S |
| Tigecycline | S | I | R | I |
| Aztreonam | R | R | S | R |
| Fosfomycin | I | I | R | S |
| Imipenem-EDTA Test* | - | + | + | + |
| ESBL Test | + | - | - | |
| blaNDM-1 gene | - | + | - | + |
| blaVIM gene | - | - | + | - |
R Resistant
S Susceptible
I Intermediate, all as graded against European Committee on Antimicrobial Susceptibility Testing and British Society for Antimicrobial Chemotherapy breakpoints
* Screening test for metallo-β-lactamase
+ Positive
- Negative
Case 2: A 46 year-old man presented with a wound infection a month after external fixation of a fracture of the 4th and 5th metatarsals of the right foot following a road traffic accident in India. Bone samples taken during debridement in theatre on day 7 grew Pseudomonas aeruginosa and E. cloacae, both multi-resistant. At ARMRL the P. aeruginosa was positive by PCR for the blaVIM carbapenemase gene whilst the E. cloacae was positive for blaNDM-1. On day 50, his antibiotics were changed from colistin and tigecycline to intravenous colistin, aztreonam and fosfomycin on the basis of susceptibility results from ARMRL (Table 1). On day 92, he was discharged following completion of 6 weeks of antibiotic therapy for osteomyelitis and made a full recovery.
NDM-1 is a metallo-β-lactamase (MBL). These have one or more divalent cations, generally zinc, at their active site.1 Other MBLs include the IMP and VIM types. MBLs hydrolyse carbapenems and all other β-lactams except aztreonam, to which many producers are also resistant for other reasons. They are inhibited by chelators of divalent cations such as ethylenediaminetetraacetic acid (EDTA) but not by clavulanate or tazobactam.1 MBLs are challenging to detect and molecular methods for identifying individual types of MBLs remain the province of reference laboratories.
Referrals to the HPA indicate that the numbers of carbapenemase-producing isolates in the United Kingdom are rising sharply, with NDM-1 often associated with prior medical exposure in India or Pakistan.2 Most organisms with NDM-1 are resistant to almost all antibiotics except colistin and, less consistently, to tigecycline and fosfomycin, making it important to prevent transmission to other patients.3
These cases indicate import of NDM-1 into Northern Ireland and underscore the need for vigilance to the risk of multi-drug-resistant organisms being introduced via transfers of patients who have received medical care abroad. Infection control measures need to be implemented promptly to limit spread of these organisms as there are few, if any therapeutic options available.
Acknowledgments
We would like to thank Dr Neil Woodford at ARMRL, clinical and laboratory staff in the Belfast Trust, Northern Ireland.
References
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