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Year : 2013  |  Volume : 31  |  Issue : 2  |  Page : 200--201

Carbapenemase producing Proteus: Any therapeutic suggestions?

Sumit Rai, Devendra Kumar Niranjan, Narendra Pal Singh, Iqbal Rajinder Kaur 
 Department of Microbiology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Dilshad Garden, New Delhi, India

Correspondence Address:
Sumit Rai
Department of Microbiology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Dilshad Garden, New Delhi

How to cite this article:
Rai S, Niranjan DK, Singh NP, Kaur IR. Carbapenemase producing Proteus: Any therapeutic suggestions?.Indian J Med Microbiol 2013;31:200-201

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Rai S, Niranjan DK, Singh NP, Kaur IR. Carbapenemase producing Proteus: Any therapeutic suggestions?. Indian J Med Microbiol [serial online] 2013 [cited 2020 Nov 28 ];31:200-201
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Dear Editor,

There has been an upsurge and rampant global spread of carbapenem resistant Enterobacteriaceae (CRE) members in the recent decade with a recent emergence of novel enzymes like blaNDM . [1] Multiple phenotypic and genotypic tests have been used for detection of this novel gene and drugs like polymyxins have been suggested as the only alternative for such isolates. [2],[3],[4] This gene has been detected in Escherichia coli and Klebsiella pneumoniae from India and also in Acinetobacter baumannii from a recent study done at our department. [3] However, this phenotype has also been observed in Proteus spp which is the matter of present concern.

The bacteriology laboratory of our department had processed 7196 non repeat clinical isolates of family Enterobacteriaceae from April 2010 to Dec 2011. Among these isolates, WHONET antibiogram data demonstrated 516 (7.2%) to be CRE isolates. Presence of carbapenem resistance was confirmed prospectively using an array of multiple phenotypic tests. [2] These isolates were most sensitive to polymyxin B (95%) followed by colistin (86%), tigecycline (53%) and chloramphenicol (43%) and were resistant to all other classes of antimicrobials. [4] However there was a subset of 45 carbapenem resistant Proteus isolates which were difficult to assess for carbapenemase activity by the Modified Hodge Test due to occasional swarming in 22 isolates. These were established as carbapenemases producers using the imipenem ethylenediametetraacetic acid (EDTA) disc synergy test and imipenem/EDTA combined disc test. [2] The critical issue is that unlike other members of family Enterobacteriaceae, Proteus spp. are inherently resistant to nitrofurantoin, polymyxins and also that high minimum inhibitory concentrations along with drug safety issues for tigecycline does not allow concrete conclusions to be drawn for its safe use, [5] which are the reasons why these drugs are neither tested nor reported for Proteus spp. However according to our data, only piperacillin + tazobactam seemed to have in vitro efficacy (73% sensitive) but its clinical usefulness is questionable as in vivo activity of beta lactam/beta lactamase inhibitor (BL/BLI) combinations has not been evaluated for carbapenemase producing Enterobacteriaceae isolates. This is the reason why we invite a debate over the in vivo efficacy of piperacillin + tazobactam and other treatment options for carbapenemase producing Proteus isolates. Our data demonstrates ampicillin/sulbactam as the next possible BL/BLI combination after piperacillin/tazobactam against carbapenem resistant Proteus [Figure 1]. It may however seem that sulbactam and tazobactam based BL/BLI combinations may be more effective; susceptibility testing for cefoperazone/sulbactam and cefepime/tazobactam are not performed due to non - availability of breakpoint zones by Clinical Laboratory Standards Institute (CLSI) and hence their in vivo activity against CRE in not known.{Figure 1}


1Yong D, Toleman MA, Giske CG, Cho HS, Sundman K, Lee K, 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;53:5046-54.
2Rai S, Manchanda V, Singh NP, Kaur IR. Zinc-dependent carbapenemases in clinical isolates of family Enterobacteriaceae. Indian J Med Microbiol 2011;29:275-9.
3Manchanda V, Rai S, Gupta S, Rautela RS, Chopra R, Rawat DS, et al. Development of TaqMan real-time polymerase chain reaction for the detection of the newly emerging form of carbapenem resistance gene in clinical isolates of Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii. Indian J Med Microbiol 2011;29:249-53.
4Kumaraswamy KK, Toleman MA, Walsh TR, Bagaria J, Butt F, Balakrishnan R, et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan and the UK: A molecular, iological and epidemiological study. Lancet Infect Dis 2012;10:597-602.
5Kelesidis T, Karageorgopoulos DE, Kelesidis I, Falagas ME. Tigecycline for the treatment of multidrug-resistant Enterobacteriaceae: A systematic review of the evidence from microbiological and clinical studies. J Antimicrob Chemother 2008;62:895-904.