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Year : 2016  |  Volume : 8  |  Issue : 1  |  Page : 41-50
Laboratory detection and clinical implication of oxacillinase-48 like carbapenemase: The hidden threat

Department of Clinical Microbiology, Christian Medical College, Vellore, Tamil Nadu, India

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Date of Web Publication11-Feb-2016


Carbapenemase producing Gram-negative pathogen is of great concern for physician. The challenging aspects are treatment option and infection control. Monitoring of respective carbapenemase resistance mechanism is necessary to prevent the outbreaks. Currently, the rapid emergence of oxacillinase (OXA-48) like is alarming. Increasing frequency of OXA-48 is seen than the classical carbapenemase (KPC, NDM, IMP, and VIM) across the world. The blaOXA-48 gene is commonly identified in Escherichia coli and Klebsiella pneumoniae. The transferrable plasmid of OXA-48 is associated with rapid spread and inter-species dissemination. In general, OXA-48-like enzymes weakly hydrolyzes both carbapenem and broad spectrum cephalosporins. Except OXA-163, which effectively hydrolyze cephalosporin. This poor hydrolytic profile obscures the detection of OXA-48-like. It may go undetected in routine diagnosis and complicates the treatment option. Co-production of OXA-48-like with CTX-M-15 and other carbapenemase (NDM, VIM) leads to the emergence of multidrug resistant strains.

Keywords: Carbapenemase, noscomial, OXA-48, OXA-48-like

How to cite this article:
Bakthavatchalam YD, Anandan S, Veeraraghavan B. Laboratory detection and clinical implication of oxacillinase-48 like carbapenemase: The hidden threat. J Global Infect Dis 2016;8:41-50

How to cite this URL:
Bakthavatchalam YD, Anandan S, Veeraraghavan B. Laboratory detection and clinical implication of oxacillinase-48 like carbapenemase: The hidden threat. J Global Infect Dis [serial online] 2016 [cited 2022 Jul 1];8:41-50. Available from:

   Introduction Top

The global spread of carbapenemase-producing Gram-negative pathogens is of special concern in healthcare and community settings. Invasive infection causing carbapenemase producers associated with significant mortality and morbidity. Carbapenemase confer resistance to most β-lactam antibiotics including carbapenem. [1] Moreover, frequent co-existence of other antibiotic resistant genes complicates the therapy and limits the treatment option. [2] The optimal treatment remains undefined. Accurate detection of carbapenemase producers is essential for infection control and management of antibiotic therapy.­ [3] The most representative carbapenemase is classified in three classes: Class A (KPC), Class B metallo β-lactamase (IMP, VIM, and NDM), and Class D oxacillinase (OXA-48). [4]

Certainly, OXA-48 a Class D β-lactamase are being increasingly reported with outbreaks and case reports across the world. [5] Horizontal transfer of mobile genetic elements carrying OXA-48-like gene results in rapid spread. [6] OXA-48-like enzyme weakly hydrolyzes both carbapenem and cephalosporin. Hence, elevated minimum inhibitory concentrations (MIC) to carbapenem and cephalosporin is not noticeable with OXA-48 like. [7] It may go undetected with routine diagnosis. Molecular characterization of OXA-48-like is warranted. Recently, many studies have reported OXA-48-like in Enterobacteriaceae, especially in Klebsiella spp. Identification of OXA-48 and its variant with short turnaround time promotes the time to active treatment.

The aim of this review is to summarize the characteristics of OXA-48, including hydrolytic activity, distribution of enzyme variants, plasmid-mediated rapid spread with a special reference to challenges in laboratory diagnosis and clinical implication.

Classification of carbapenemase

Carbapenemase identified in Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii are placed in three classes of β-lactamase as Ambler Class A, Class B metallo β-lactamase, and carbapenem hydrolyzing Class D oxacillinase. [8] Carbapenemase are classified into two major types based on the active site of the enzyme as serine carbapenemase (KPC and OXA type β-lactamase) and metallo-β-lactamase (IMP, VIM, and NDM). The spectrum of substrate for carbapenemase activity is varied [Table 1]. [9]

In the early 1990s, most of the identified carbapenemase are chromosomally encoded. Plasmid-mediated carbapenemase begins to emerge and creates the threat for rapid spread among Gram-negative pathogens. [10] Class A and Class B metallo-β-lactamase are described with well-defined set of characteristics. Notably, synergy test using the inhibitors of boronic acid derivatives (BA) and dipicolinic acid (DPA)/ethylene diamine tetra acetic acid (EDTA) were available to detect Class A and Class B carbapenemase. [11] However, OXA-48 is difficult to identify due to poor hydrolysis of substrates (carbapenem and cephalosporin). In contrast to other carbapenemase, elevated carbapenem MIC is not noticeable with OXA-48 unless co-produced with other β-lactamases. [12] Additionally, phenotypic method using specific inhibitor for OXA-48 is not currently available. [13] It is of great concern for clonal spread and inter-species dissemination. Hence, a phenotypic method for earlier detection of OXA-48 is essential.
Table 1: Substrate, hydrolysis and inhibitory profile of carbapenemase

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In Enterobacteriaceae, the most common carbapenemase producers are KPC, IMP, VIM and NDM. Comparatively OXA-48 and its variants are becoming widely distributed of late and commonly reported in Enterobacteriaceae. In contrast, so far only two studies have reported OXA-48 in A. baumannii and no single study with P. aeruginosa.[14]

Characteristics of oxacillinase-48

Carbapenem-hydrolyzing Class D β-lactamases are not inhibited by the inhibitor available in clinical use. This includes clavulanic acid, tazobactam and sulbactam. [15] Of the Class D carbapenemase, OXA-48 is of major concern due to its:

  1. Difficulty in detection,
  2. Association with treatment failure and
  3. High dissemination rate due to transferable plasmid.

Due to this property of OXA-48, susceptible or low-level resistance to cephalosporin and/or carbapenem is seen. Remarkably, enzyme kinetic analysis shows greater catalytic activity of OXA-48 to imipenem than meropenem. [16] OXA-48-like enzyme variants is plasmid coded and is associated with rapid spread in community settings. [17] Further, OXA-48 is frequently reported in clinically important noscomial pathogens E. coli and Klebsiella pneumoniae. The high level of OXA-48 resistance is associated with co-production of extended spectrum β-lactamase(ESBL). [18]

Variants of oxacillinase-48 like enzymes

A multi-drug resistant K. pneumoniae was isolated from a patient in Istanbul, Turkey and found a new OXA-type β-lactamase. [19] It was identified and named as OXA-48. Since 2001 with the appearance of first report on OXA-48, 11 enzyme variants were identified and reported across the world. This includes OXA-48, OXA-48b, OXA-54, OXA-162, OXA-163, OXA-181, OXA-199, OXA-204, OXA-232, OXA-242, and OXA-247. These enzyme variants differ by few amino acid substitution or deletion [Table 2]. OXA-48 and its variants were named and placed under the group as OXA-48-like variants. Most common host for production of OXA-48-like enzymes is Escherichia coli, K. pneumonia, Enterobacter cloacae, Serratia marcescens, Shewanella xiamenensis, Citrobacter freundii, Providencia rettgeri, Klebsiella oxytoca, Enterobacter sakazakii, and A. baumannii. [20]
Table 2: Variants of OXA-48-like enzyme and its deviation

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The kinetic properties of OXA-181, OXA-162, and OXA-204 appear broadly similar to OXA-48 in their hydrolytic profile. [21] OXA-181 is one of the most commonly encountered OXA-48-like variants in different geographic regions. OXA-181 weakly hydrolyses both carbapenem and cephalosporin and differs from OXA-48 at four amino acid substitution. In contrast, OXA-163 effectively hydrolyses cephalosporins (ceftazidime, cefotaxime, and cefepime) and aztreonam. [22] Interestingly, this property of OXA-163 is not detectable with OXA-48. Ideally OXA-163 appears similar to ESBL than carbapenemase in substrate profile. Unlike OXA-48, OXA-232 shows relatively lower hydrolytic activity against carbapenem. [23]

Plasmid as vehicle for spread of oxacillinase-48 like determinants

Initially, blaOXA-48 gene was reported in association with insertion sequence (IS)1999 in the upstream region. Later, blaOXA-48 gene is identified on self-transferrable IncL/M-type plasmid. [24] The transposon Tn1999 is located at the downstream of OXA-48 gene. The blaOXA-48 gene is a part of the transposon Tn1999, made of two copies of IS1999 as shown in [Figure 1]. [25] The most alarming finding is the transferable operon present in IncL/M-type. This plasmid is associated with high conjugation rate and accounts for rapid transfer and spread across the Gram-negative pathogens. [26]
Figure 1: Schematic representation of oxacillinase-48 and its transposons, (a) schematic representation of Tn1999 identifi ed with oxacillinase-48 gene, (b) schematic representation of Tn1999.2 identifi ed with oxacillinase-48 gene, (c) schematic representation of Tn1999.3 identified with oxacillinase-48 gene. Horizontal arrowsrepresent the orientation of gene and their transcription. Ä Indicate the interruption of an element/gene by insertion sequence

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Further variants of Tn1999 were identified with additional IS.Tn1999.2 contains IS1R element inserted into the upstream region of IS1999 seen in [Figure 1]. Similarly, an IS1R element located at the downstream of blaOXA-48 gene is called as Tn1999.3 as shown in [Figure 1]. [27] The hybrid promoter of combined IS1R/IS1999 element results in 2-fold greater hydrolysis of imipenem. Collectively, the presence of both increases the level of carbapenem resistance than possessing either one of the IS. [28]

Each OXA-48-like variants was identified on the plasmid with different ISs and arrangements. Modification in the genetic arrangements is described for the following enzyme variants such as OXA-181, OXA-204 and OXA-232 respectively. Unlike OXA-48, blaOXA-181 gene is inserted at the downstream region of ISEcp1and form the transposon Tn2013. [29] The presence of ISEcp1 facilitates the acquisition of ESBL genes such as CTX-M-15. [30] Co-production of OXA-181 with ESBLs makes the resistance profile broader with reliable detection. [31] However limits the therapeutic option; the blaOXA-204 gene is found on the IncA/C plasmid contains the transposon Tn2016 with the ISEcp1 was reported in K. pneumoniae from Tunisia. An additional element ISkpn15 inserted at the upstream of ISEcp1. Hybrid promoter was not identified in ISkpn15/ISEcp1 chimera. The promoter of ISEcp1 regulates the expression of blaOXA-204 gene. [32] IncA/C plasmid possess a wide host range and responsible for acquisition and spread of various β-lactamase genes. The notable among them include blaCMY and blaCTX-M genes. [33] In addition, blaNDM-1 and blaVIM-4 were also found on the plasmid scaffold. [34],[35] Further OXA-232 associates with ISEcp1 and found on non-conjugative plasmids, resulting in failure of transposase to mobilize blaOXA-232 gene either due to deletion or duplication in the upstream region of ISEcp1. [36]


The true prevalence of OXA-48 is relatively unknown due to the varying level of carbapenemase activity and difficult to detect with phenotypic methods. Outbreak of OXA-48 was reported initially from Turkey, United Kingdom and France. [37],[38],[39] Clinical cases of OXA-48 producing Enterobacteriaceae was reported widely from Lebanon, Belgium, United Kingdom, Tunisia, Morocco,Oman and Netherland. [40],[41],[42],[43],[44],[45],[46] Currently, Turkey, Middle East countries, and North African countries were considered a major reservoir of OXA-48. [47] Many outbreak and sporadic cases were reported in Turkey. [48],[49] The emergence of OXA-48 in hospital and community settings was reported sporadically in Senegal. [50] In Spain, noscomial outbreak of OXA-48 was reported with co-production of CTX-M-15. [51] Recently, an outbreak of OXA-48-like, being predominantly identified with OXA-48 from Netherland, Belgium and Germany. [52],[53],[54]

OXA-181 is the most common OXA-48-like variant reported across India. This includes two multicenter and two single center study reporting OXA-48-like. We reviewed 14 studies on OXA-48-like enzymes which include case reports, noscomial outbreaks and retrospective studies from France, Italy, Spain, the United States, North America, Argentina, Europe and America, New Zealand, Singapore, Japan, and India [Table 3].
Table 3: Outbreaks, surveillance and clinical case reports of OXA-48 across the world

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Interestingly, most of the OXA-48-like are reported in K. pneumoniae. The reviewed literature on OXA-48-like reveals ESBLs were the most common co-producing β-lactamase. Among ESBL, CTX-M-15 seems to be predominantly distributed CTX-M-1 group followed by CTX-M-14 belongs to CTX-M-9 cluster as shown in [Table 3]. Co-production of OXA-48 was also seen with other carbapenemase including NDM-1and VIM as shown in [Table 3]. [69] Next to NDM, OXA-48-like is the frequently reporting carbapenemase across India. Further co-production of OXA-48-like with NDM in countries with poor sanitation is worrisome.

Clinical implication

OXA-48 is of great clinical concern due to the difficulty in detection with reduced susceptibility to both carbapenem and broad-spectrum cephalosporin. The mortality remains high in patients infected with OXA-48-like producers. The challenging aspect of OXA-48 is that it may go undetected and classified as susceptible with imipenem and meropenem MIC of (≤1 μg/ml) as per Clinical and Laboratory Standards Institute (CLSI) and (≤2 μg/ml) as per European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines respectively. Accurate screening for the presence of OXA-48 is not possible with MIC determination alone. This OXA-48 remains as a hidden threat that obscures the laboratory diagnosis and complicates the treatment option. The plasmid that carries OXA-48 serves as a potential vehicle for dissemination of genes among clinical isolates and to the intestinal flora. [70] Currently, the plasmid that carries OXA-48 not often carries other antibiotic resistant genes. However recently co-production of OXA-48 with ESBL are being reported which is the cause for great concern.

In case of ESBL negative OXA-48 positive producers, broad spectrum cephalosporin is considered as potential treatment option except those with OXA-163 a potent hydrolyser of cephalosporinase. A neonate infected with OXA-48 producing K. pneumoniae was successfully treated with cefotaxime and amikacin from France. [71] A patient with central line infection of OXA-48 producing E. coli was recovered on ceftazidime and non-carbapenem combinational therapy. [72] However, the studies supporting the recommendation of broad spectrum cephalosporin in treating ESBL negative OXA-48 positive producers are limited.

Infection with ESBL positive and OXA-48 positive co-producers provide reliable identification but associates with wider range of resistance and limit the treatment option. Co-production of OXA-48 with CTX-M-15 and NDM serves as a vehicle for noscomial outbreaks as multidrug resistant pathogen as shown in [Table 3]. A better outcome was observed with triple combination of colistin, aminoglycoside with ceftazidime/cefepime in treating co-resistance of OXA-48 and ESBL. [73] Tigecycline and fosfomycin are also served as a treatment option but carries the risk for emergence of resistance. [74] The optimal treatment option for this multi-drug resistance pattern is unclear and there is a lack of evidence-based studies.

Avibacatam, a non-β lactam β lactamase inhibitor selectively inhibits Class D OXA-48, Class A and Class C β-lactamase. It forms a stable complex with OXA-48 by establishing covalent bond. [75] The combination of avibactam with imipenem and cephalosporin (cefepime, ceftazidime, and cefotaxime) significantly reduces the MIC value of OXA-48 producers. [76] Interestingly, avibactam was identified with the broad coverage of OXA and other β-lactamase. Thus serves as an attractive treatment option.

In an in-vivo study, an infection is induced in murine model with OXA-48 producing K. pneumoniae. [77] The strains were susceptible to ceftazidime and imipenem as per MIC. However, the outcome was better with ceftazidime than with carbapenem treated group. A similar result was also revealed in experimental mice, in which peritonitis was induced with ESBL negative and OXA-48 producing K. pneumoniae.[78] Further clinical profile of OXA-48 producers does not concur with carbapenem MIC breakpoints ≤1 μg/ml (i.e., ≤1 μg/ml can be OXA-48 producers). Irrespective of carbapenem susceptibility, carbapenem is not reliable in treating patients infected with OXA-48 producers.

The optimal treatment remains unclear. In vitro susceptibility to colistin, tigecycline and aminoglycosides were promising. [79],[80] However, there is a limited proven clinical efficacy. Notably, emerging resistance to this antibiotic is already reported. [81],[82] Some studies have reported the better outcome with combinational therapy rather than with monotherapy. [83]

Appropriate therapy for OXA-48 is unpredictable and presents with multidrug resistant profile. Carbapenem MIC alone is not enough for treating patients with OXA-48 producers. Molecular characterization is essential to rule out the presence of OXA-48 producers that shows heterogeneous hydrolytic profile in phenotypic detection (MIC). Screening for OXA-48 in patient is necessary to prevent the noscomial outbreak prior to hospital admission. Rectal screening of the patient offers detection at the earliest and initiation of appropriate therapy. [84]

Laboratory detection of oxacillinase-48

Carbapenemase production is identified with the reduction in susceptibility to carbapenem. However, OXA-48-like exhibits low carbapenemase activity and makes it difficult to detect. At present, an OXA-48-like producer is not detectable with the well-defined phenotypic methods using β-lactam and β-lactamase inhibitor combination used to detect Class A and Class B carbapenemase. Further, a good inhibitor is not available for specific analysis of OXA-48-like enzyme. The most challenging part of OXA-48 detection is that it differs from other carbapenemase by exhibiting susceptibility to broad spectrum cephalosporins but remains resistant to carbapenem. However, the marker is not consistent to selectively identify OXA-48 as some may show resistance to both broad-spectrum cephalosporins and carbapenem equally. Most of the studies on carbapenemase detection are focused on Class A and Class B-metallo-β-lactamase. Very few studies are carried out for OXA-48-like detection.

Carbapenem minimum inhibitory concentrations and interpretative criteria

Resistance to carbapenem is reported on the basis of susceptibility testing. According to the CLSI guidelines (M100-S25), MIC breakpoints for imipenem and meropenem are susceptible (≤1 μg/ml) and resistant (>4 μg/ml). For ertapenem, the breakpoints are susceptible (≤0.5 μg/ml) and resistant (>2 μg/ml). The role of ertapenem with low MIC breakpoint in detecting OXA-48 remains to be assessed.

Modified Hodge test

Modified Hodge Test (MHT) or cloverleaf technique recommended by CLSI guidelines (M100-S25) is used extensively as a nonspecific screening test for routine diagnosis of carbapenemase producers. Carbapenemase producers inactivate the carbapenem and promote the growth of carbapenem susceptible indicator strain along the streak line toward carbapenem disk and results in a characteristic cloverleaf-like indentation. Comparable sensitivity but poor specificity was observed with MHT of 98% and 80% respectively with the longer turnaround time. [85] For OXA-48, MHT is found to be better with sensitivity and specificity of 96% and 84% respectively (unpublished data) contrast to the percentage described in CLSI. This may be due to the variation in the prevalence of OXA-48-like enzymes in different geographic regions. False negative results account for lack of specificity and low sensitivity. Unlike NDM, detection of OXA-48 seems to be better with MHT. [86]

Temocillin and minimum inhibitory concentrations

Temocillin, a semi synthetic β-lactam is identified as a suggestive marker to screen OXA-48-like determinants that confers high-level resistance. [87] Temocillin is stable against the hydrolysis of ESBL and AmpC enzymes. [88] However, high level of temocillin resistance is not only the characteristics of OXA-48-like producers but similar level of resistance is also observed with KPC and metallo-β-lactamase. Hence temocillin alone is not a diagnostic marker for OXA-48-like detection. [89] Temocillin with high-level MIC and nonsusceptibility to ceftazidime and other third generation cephalosporin gives the clue for the presence of OXA-48-like enzymes. Nonavailability of temocillin in many countries makes it impossible for screening. In CLSI or EUCAST guidelines breakpoint for temocillin is not available. Temocillin breakpoints are established by the British Society for Antimicrobial Therapy (BSAC), and it is the only available guideline to define temocillin MIC breakpoints as well zone diameter for interpretation of strains. According to BSAC, the breakpoints for temocillin are susceptible (≤32 μg/ml) and resistant (>32 μg/ml), and the zone diameter of ≥12 mm and ≤11 mm are defined as susceptible and resistant, respectively. [90]

Disc diffusion assay

Disc diffusion assay using temocillin, meropenem, BA, and/or DPA which is commercially available as KPC/MBL and OXA-48 Confirm Kit (Rosco Diagnostics) is used to discriminate OXA-48-like enzymes from other carbapenemase. If the synergy is not observed with meropenem and phenyl BA and/or DPA and temocillin with the zone diameter of <10 mm is identified as OXA-48 producers with the sensitivity and specificity of 100%. [91] Mastdiscs ID inhibitor combination disks are also useful for presumptive detection of OXA-48.

Chromogenic medium

Chromogenic medium enables rapid identification of carbapenem resistant pathogens either from clinical samples or from isolates. Although chromogenic media are a fairly rapid means of detecting CRO, its use is confined to rectal swab. Chrom ID OXA-48 is the only available chromogenic medium for selective identification of OXA-48 [Table 4]. Its exact composition is undisclosed; however,the media contains antibiotic for the inhibition of other microorganism and biochemical markers to differentiate species or groups of species using either chromogenic substrates or fermentable carbohydrates with a pH indicator. The sensitivity of chromogenic medium can be increased by incubating the plates for complete 24 h. In contrast to manufacturer's claims, false positives can occur. Confirmation of all positives with either disc diffusion assay or by molecular characterization is recommended.
Table 4: Comparison of chromogenic medium for the detection of carbapenem resistant organism

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Rapid diagnosis

Accurate and earlier detection of OXA-48-like determinants is necessary for better management of patient and infection control. The following rapid diagnostic methods tests are available for detection of carbapenemase producers.

Carba NP

Carba NP is a hydrolytic assay recommended by CLSI (M100-S25) guidelines as a confirmatory test for detection of carbapenemase that is simple and easy to perform. Hydrolysis of imipenem is indicated by the change in the pH of indicator phenol red and the color changes from red to yellow with the turnaround time <2 h. It has a sensitivity and specificity of 100% in detecting Class A and Class B metallo-β-lactamase. [95] However, the sensitivity of calorimetric microtube assay/Carba NP is shown to be 11% with OXA-48 according to CLSI guidelines (CLSI-2015). While in our experience we observed, Carba NP for OXA-48 detection shows sensitivity and specificity of 77% and 84% respectively (unpublished data). Indeed, suspected cause for low sensitivity with OXA-48-like enzymes is due to the presence of mucoid strains and/or weak carbapenemase activity. Further sensitivity of Carba NP with mucoid phenotypes may be improved by extending the incubation period from ½ to 1 h and reduction of inoculum size was preferred. [96] For weak carbapenemase producers, concentrated extract of cell suspension was recommended. [97]

Blue Carba is a variant of Carba NP in which bromothymol blue is used as an indicator instead of phenol red as in Carba NP assay. The main advantage of Blue Carba over Carba NP is the direct colony suspension approach without the need for lysis buffer. [98] The sensitivity and specificity of Blue Carba in detecting OXA-48 is yet to be established.

Molecular based techniques

Phenotypic test identifies the carbapenemase producers in general without any specification over the class of carbapenemase. Molecular characterization is the only available tool for discriminating different carbapenemase encoding genes. Polymerase chain reaction (PCR)is considered as the gold standard for identification of OXA-48 and it should be followed by sequencing for the precise identification of enzyme variants of OXA-48-like. In addition to the conventional PCR, real-time PCR and microarray designed panels are also available for rapid detection of OXA-48-like [Table 5]. [99],[100],[101],[102] Matrix-assisted laser desorption ionization time-of-flight mass spectrometry is evaluated and available for detection of OXA-48, although its use in routine diagnosis is restricted due to the cost.
Table 5: Various commercially available molecular detection for OXA-48-like enzyme variants

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Xpert® Carba-R

Xpert® Carba-R is developed on the basis of real time PCR and the results are available with the turnaround time of 2 h. The panel of Xpert® Carba-R contains the sequences for targeting blaIMP , blaVIM , blaNDM , blaKPC , and blaOXA-48 genes. Of the 11 known variants of OXA-48-like, only four variants (blaOXA-48 , blaOXA-162 , blaOXA-163 ,and blaOXA-204 ) were designed to detect. [103] Incorporation of geographic-specific OXA-48-like variants in the proprietary panel may improve its sensitivity and broadens the detection of OXA-48-like enzymes across the world.

The Class A (KPC) and Class B (IMP, VIM, NDM) is considered important carbapenemases with focus of high priority. However, recently Class D carbapenemase OXA-48 is rapidly emerging and disseminating in Gram-negative pathogens. Interestingly, the self-conjugative plasmids that carry blaOXA -48 gene in composite transposons Tn1999 account for rapid spread as a single clone. As a consequence of low carbapenemase activity and poor hydrolyzes of broad spectrum cephalosporins complicates the identification. As a result, silent spread and outbreak occurs. Further surveillance studies are necessary to understand the dynamic of transmission, risk factors and reservoir of OXA-48 producers.

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Conflicts of interest

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   References Top

Perez F, Van Duin D. Carbapenem-resistant Enterobacteriaceae: A menace to our most vulnerable patients. Cleve Clin J Med 2013;80:225-33.  Back to cited text no. 1
Temkin E, Adler A, Lerner A, Carmeli Y. Carbapenem-resistant Enterobacteriaceae: Biology, epidemiology, and management. Ann N Y Acad Sci 2014;1323:22-42.  Back to cited text no. 2
Miriagou V, Cornaglia G, Edelstein M, Galani I, Giske CG, Gniadkowski M, et al. Acquired carbapenemases in Gram-negative bacterial pathogens: Detection and surveillance issues. Clin Microbiol Infect 2010;16:112-22.  Back to cited text no. 3
Poirel L, Pitout JD, Nordmann P. Carbapenemases: Molecular diversity and clinical consequences. Future Microbiol 2007;2:501-12.  Back to cited text no. 4
Antunes NT, Lamoureaux TL, Toth M, Stewart NK, Frase H, Vakulenko SB. Class D β-lactamases: Are they all carbapenemases? Antimicrob Agents Chemother 2014;58:2119-25.  Back to cited text no. 5
Potron A, Poirel L, Rondinaud E, Nordmann P. Intercontinental spread of OXA-48 beta-lactamase-producing Enterobacteriaceae over a 11-year period, 2001 to 2011. Euro Surveill 2013;18. pii: 20549.  Back to cited text no. 6
Poirel L, Naas T, Nordmann P. Diversity, epidemiology, and genetics of class D beta-lactamases. Antimicrob Agents Chemother 2010;54:24-38.  Back to cited text no. 7
Nordmann P, Dortet L, Poirel L. Carbapenem resistance in Enterobacteriaceae: Here is the storm! Trends Mol Med 2012;18:263-72.  Back to cited text no. 8
Queenan AM, Bush K. Carbapenemases: The versatile beta-lactamases. Clin Microbiol Rev 2007;20:440-58.  Back to cited text no. 9
Göttig S, Gruber TM, Stecher B, Wichelhaus TA, Kempf VA. In vivo horizontal gene transfer of the carbapenemase OXA-48 during a nosocomial outbreak. Clin Infect Dis 2015;60:1808-15.  Back to cited text no. 10
Hrabák J, Chudácková E, Papagiannitsis CC. Detection of carbapenemases in Enterobacteriaceae: A challenge for diagnostic microbiological laboratories. Clin Microbiol Infect 2014;20:839-53.  Back to cited text no. 11
Djahmi N, Dunyach-Remy C, Pantel A, Dekhil M, Sotto A, Lavigne JP. Epidemiology of carbapenemase-producing Enterobacteriaceae and Acinetobacter baumannii in Mediterranean countries. Biomed Res Int 2014;2014:305784.  Back to cited text no. 12
Nordmann P, Gniadkowski M, Giske CG, Poirel L, Woodford N, Miriagou V; European Network on Carbapenemases. Identification and screening of carbapenemase-producing Enterobacteriaceae. Clin Microbiol Infect 2012;18:432-8.  Back to cited text no. 13
Mathlouthi N, Areig Z, Al Bayssari C, Bakour S, et al. Emergence of carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii clinical isolates collected from some Libyan hospitals. Microb Drug Resist 2015;21:335-41.  Back to cited text no. 14
Drawz SM, Bonomo RA. Three decades of beta-lactamase inhibitors. Clin Microbiol Rev 2010;23:160-201.  Back to cited text no. 15
Docquier JD, Calderone V, De Luca F, Benvenuti M, Giuliani F, Bellucci L, et al. Crystal structure of the OXA-48 beta-lactamase reveals mechanistic diversity among class D carbapenemases. Chem Biol 2009;16:540-7.  Back to cited text no. 16
Potron A, Kalpoe J, Poirel L, Nordmann P. European dissemination of a single OXA-48-producing Klebsiella pneumoniae clone. Clin Microbiol Infect 2011;17:E24-6.  Back to cited text no. 17
Nordmann P, Naas T, Poirel L. Global spread of Carbapenemase-producing Enterobacteriaceae. Emerg Infect Dis 2011;17:1791-8.  Back to cited text no. 18
Poirel L, Héritier C, Tolün V, Nordmann P. Emergence of oxacillinase-mediated resistance to imipenem in Klebsiella pneumoniae. Antimicrob Agents Chemother 2004;48:15-22.  Back to cited text no. 19
Evans BA, Amyes SG. OXA β-lactamases. Clin Microbiol Rev 2014;27: 241-63.  Back to cited text no. 20
Oueslati S, Nordmann P, Poirel L. Heterogeneous hydrolytic features for OXA-48-like β-lactamases. J Antimicrob Chemother 2015;70:1059-63.  Back to cited text no. 21
Abdelaziz MO, Bonura C, Aleo A, El-Domany RA, Fasciana T, Mammina C. OXA-163-producing Klebsiella pneumoniae in Cairo, Egypt, in 2009 and 2010. J Clin Microbiol 2012;50:2489-91.  Back to cited text no. 22
Teo JW, Kurup A, Lin RT, Hsien KT. Emergence of clinical Klebsiella pneumoniae producing OXA-232 carbapenemase in Singapore. New Microbes New Infect 2013;1:13-5.  Back to cited text no. 23
Berger S, Alauzet C, Aissa N, Hénard S, Rabaud C, Bonnet R, et al. Characterization of a new blaOXA-48-carrying plasmid in Enterobacteriaceae. Antimicrob Agents Chemother 2013;57:4064-7.  Back to cited text no. 24
Aubert D, Naas T, Héritier C, Poirel L, Nordmann P. Functional characterization of IS1999, an IS4 family element involved in mobilization and expression of beta-lactam resistance genes. J Bacteriol 2006;188:6506-14.  Back to cited text no. 25
Poirel L, Bonnin RA, Nordmann P. Genetic features of the widespread plasmid coding for the carbapenemase OXA-48. Antimicrob Agents Chemother 2012;56:559-62.  Back to cited text no. 26
Giani T, Conte V, Di Pilato V, Aschbacher R, Weber C, Larcher C, et al.Escherichia coli from Italy producing OXA-48 carbapenemase encoded by a novel Tn1999 transposon derivative. Antimicrob Agents Chemother 2012;56:2211-3.  Back to cited text no. 27
Carrër A, Poirel L, Eraksoy H, Cagatay AA, Badur S, Nordmann P. Spread of OXA-48-positive carbapenem-resistant Klebsiella pneumoniae isolates in Istanbul, Turkey. Antimicrob Agents Chemother 2008;52:2950-4.  Back to cited text no. 28
Potron A, Nordmann P, Lafeuille E, Al Maskari Z, Al Rashdi F, Poirel L. Characterization of OXA-181, a carbapenem-hydrolyzing class D beta-lactamase from Klebsiella pneumoniae. Antimicrob Agents Chemother 2011;55:4896-9.  Back to cited text no. 29
Poirel L, Naas T, Nordmann P. Genetic support of extended-spectrum beta-lactamases. Clin Microbiol Infect 2008;14 Suppl 1:75-81.  Back to cited text no. 30
Dimou V, Dhanji H, Pike R, Livermore DM, Woodford N. Characterization of Enterobacteriaceae producing OXA-48-like carbapenemases in the UK. J Antimicrob Chemother 2012;67:1660-5.  Back to cited text no. 31
Potron A, Nordmann P, Poirel L. Characterization of OXA-204, a carbapenem-hydrolyzing class D β-lactamase from Klebsiella pneumoniae. Antimicrob Agents Chemother 2013;57:633-6.  Back to cited text no. 32
Seiffert SN, Marschall J, Perreten V, Carattoli A, Furrer H, Endimiani A. Emergence of Klebsiella pneumoniae co-producing NDM-1, OXA-48, CTX-M-15, CMY-16, QnrA and ArmA in Switzerland. Int J Antimicrob Agents 2014;44:260-2.  Back to cited text no. 33
Carattoli A. Resistance plasmid families in Enterobacteriaceae. Antimicrob Agents Chemother 2009;53:2227-38.  Back to cited text no. 34
Carattoli A, Villa L, Poirel L, Bonnin RA, Nordmann P. Evolution of IncA/C blaCMY-2-carrying plasmids by acquisition of the blaNDM-1 carbapenemase gene. Antimicrob Agents Chemother 2012;56:783-6.  Back to cited text no. 35
Potron A, Rondinaud E, Poirel L, Belmonte O, Boyer S, Camiade S, et al. Genetic and biochemical characterisation of OXA-232, a carbapenem-hydrolysing class D β-lactamase from Enterobacteriaceae. Int J Antimicrob Agents 2013;41:325-9.  Back to cited text no. 36
Nazik H, Aydin S, Albayrak R, Bilgi EA, Yildiz I, Kuvat N,et al.Detection and spread of oxa-48-producing Klebsiella oxytoca isolates in Istanbul, Turkey. Southeast Asian J Trop Med Public Health 2014;45:123-9.  Back to cited text no. 37
Thomas CP, Moore LS, Elamin N, Doumith M, Zhang J, Maharjan S, et al. Early (2008-2010) hospital outbreak of Klebsiella pneumoniae producing OXA-48 carbapenemase in the UK. Int J Antimicrob Agents 2013;42:531-6.  Back to cited text no. 38
Cuzon G, Ouanich J, Gondret R, Naas T, Nordmann P. Outbreak of OXA-48-positive carbapenem-resistant Klebsiella pneumoniae isolates in France. Antimicrob Agents Chemother 2011;55:2420-3.  Back to cited text no. 39
Matar GM, Cuzon G, Araj GF, Naas T, Corkill J, Kattar MM, et al. Oxacillinase-mediated resistance to carbapenems in Klebsiella pneumoniae from Lebanon. Clin Microbiol Infect 2008;14:887-8.  Back to cited text no. 40
Cuzon G, Naas T, Bogaerts P, Glupczynski Y, Huang TD, Nordmann P. Plasmid-encoded carbapenem-hydrolyzing beta-lactamase OXA-48 in an imipenem-susceptible Klebsiellapneumoniae strain from Belgium. Antimicrob Agents Chemother 2008;52:3463-4.  Back to cited text no. 41
Livermore DM. Has the era of untreatable infections arrived? J Antimicrob Chemother 2009;64 Suppl 1:i29-36.  Back to cited text no. 42
Cuzon G, Naas T, Lesenne A, Benhamou M, Nordmann P. Plasmid-mediated carbapenem-hydrolysing OXA-48 beta-lactamase in Klebsiellapneumoniae from Tunisia. Int J Antimicrob Agents 2010;36:91-3.  Back to cited text no. 43
Benouda A, Touzani O, Khairallah MT, Araj GF, Matar GM. First detection of oxacillinase-mediated resistance to carbapenems in Klebsiellapneumoniae from Morocco. Ann Trop Med Parasitol 2010;104:327-30.  Back to cited text no. 44
Dortet L, Poirel L, Al Yaqoubi F, Nordmann P. NDM-1, OXA-48 and OXA-181 carbapenemase-producing Enterobacteriaceae in Sultanate of Oman. Clin Microbiol Infect 2012;18:E144-8.  Back to cited text no. 45
Kalpoe JS, Al Naiemi N, Poirel L, Nordmann P. Detection of an Ambler class D OXA-48-type β-lactamase in a Klebsiellapneumoniae strain in The Netherlands. J Med Microbiol 2011;60:677-8.  Back to cited text no. 46
Poirel L, Potron A, Nordmann P. OXA-48-like carbapenemases: The phantom menace. J Antimicrob Chemother 2012;67:1597-606.  Back to cited text no. 47
Aktas Z, Kayacan CB, Schneider I, Can B, Midilli K, Bauernfeind A. Carbapenem-hydrolyzing oxacillinase, OXA-48, persists in Klebsiella pneumoniae in Istanbul, Turkey. Chemotherapy 2008;54:101-6.  Back to cited text no. 48
Gülmez D, Woodford N, Palepou MF, Mushtaq S, Metan G, Yakupogullari Y, et al. Carbapenem-resistant Escherichia coli and Klebsiella pneumoniae isolates from Turkey with OXA-48-like carbapenemases and outer membrane protein loss. Int J Antimicrob Agents 2008;31:523-6.  Back to cited text no. 49
Moquet O, Bouchiat C, Kinana A, Seck A, Arouna O, Bercion R, et al. Class D OXA-48 carbapenemase in multidrug-resistant enterobacteria, Senegal. Emerg Infect Dis 2011;17:143-4.  Back to cited text no. 50
Pitart C, Solé M, Roca I, Fàbrega A, Vila J, Marco F. First outbreak of a plasmid-mediated carbapenem-hydrolyzing OXA-48 beta-lactamase in Klebsiella pneumoniae in Spain. Antimicrob Agents Chemother 2011;55:4398-401.  Back to cited text no. 51
Dautzenberg MJ, Ossewaarde JM, de Kraker ME, van der Zee A, van Burgh S, de Greeff SC, et al. Successful control of a hospital-wide outbreak of OXA-48 producing Enterobacteriaceae in the Netherlands, 2009 to 2011. Euro Surveill 2014;19. pii: 20723.  Back to cited text no. 52
Glupczynski Y, Huang TD, Bouchahrouf W, Rezende de Castro R, Bauraing C, Gérard M, et al. Rapid emergence and spread of OXA-48-producing carbapenem-resistant Enterobacteriaceae isolates in Belgian hospitals. Int J Antimicrob Agents 2012;39:168-72.  Back to cited text no. 53
Pfeifer Y, Schlatterer K, Engelmann E, Schiller RA, Frangenberg HR, Stiewe D, et al. Emergence of OXA-48-type carbapenemase-producing Enterobacteriaceae in German hospitals. Antimicrob Agents Chemother 2012;56:2125-8.  Back to cited text no. 54
Liapis E, Pantel A, Robert J, Nicolas-Chanoine MH, Cavalié L, van der Mee-Marquet N, et al. Molecular epidemiology of OXA-48-producing Klebsiella pneumoniae in France. Clin Microbiol Infect 2014;20:O1121-3.  Back to cited text no. 55
Kocsis E, Savio C, Piccoli M, Cornaglia G, Mazzariol A. Klebsiella pneumoniae harbouring OXA-48 carbapenemase in a Libyan refugee in Italy. Clin Microbiol Infect 2013;19:E409-11.  Back to cited text no. 56
Paño-Pardo JR, Ruiz-Carrascoso G, Navarro-San Francisco C, Gómez-Gil R, Mora-Rillo M, Romero-Gómez MP, et al. Infections caused by OXA-48-producing Klebsiella pneumoniae in a tertiary hospital in Spain in the setting of a prolonged, hospital-wide outbreak. J Antimicrob Chemother 2013;68:89-96.  Back to cited text no. 57
Doi Y, O′Hara JA, Lando JF, Querry AM, Townsend BM, Pasculle AW, et al. Co-production of NDM-1 and OXA-232 by Klebsiella pneumoniae. Emerg Infect Dis 2014;20:163-5.  Back to cited text no. 58
Lascols C, Peirano G, Hackel M, Laupland KB, Pitout JD. Surveillance and molecular epidemiology of Klebsiella pneumoniae isolates that produce carbapenemases: First report of OXA-48-like enzymes in North America. Antimicrob Agents Chemother 2013;57:130-6.  Back to cited text no. 59
Gomez S, Pasteran F, Faccone D, Bettiol M, Veliz O, De Belder D, et al. Intrapatient emergence of OXA-247: A novel carbapenemase found in a patient previously infected with OXA-163-producing Klebsiella pneumoniae. Clin Microbiol Infect 2013;19:E233-5.  Back to cited text no. 60
Castanheira M, Mendes RE, Woosley LN, Jones RN. Trends in carbapenemase-producing Escherichia coli and Klebsiella spp. from Europe and the Americas: Report from the SENTRY antimicrobial surveillance programme (2007-09). J Antimicrob Chemother 2011;66:1409-11.  Back to cited text no. 61
Williamson DA, Heffernan H, Sidjabat H, Roberts SA, Paterson DL, Smith M, et al. Intercontinental transfer of OXA-181-producing Klebsiella pneumoniae into New Zealand. J Antimicrob Chemother 2011;66:2888-90.  Back to cited text no. 62
Balm MN, Ngan G, Jureen R, Lin RT, Teo JW. OXA-181-producing Klebsiella pneumoniae establishing in Singapore. BMC Infect Dis 2013;13:58.  Back to cited text no. 63
Kayama S, Koba Y, Shigemoto N, Kuwahara R, Kakuhama T, Kimura K, et al. Imipenem-susceptible, meropenem-resistant Klebsiellapneumoniae producing OXA-181 in Japan. Antimicrob Agents Chemother 2015;59:1379-80.  Back to cited text no. 64
Castanheira M, Deshpande LM, Mathai D, Bell JM, Jones RN, Mendes RE. Early dissemination of NDM-1- and OXA-181-producing Enterobacteriaceae in Indian hospitals: Report from the SENTRY Antimicrobial Surveillance Program, 2006-2007. Antimicrob Agents Chemother 2011;55:1274-8.  Back to cited text no. 65
Lascols C, Hackel M, Marshall SH, Hujer AM, Bouchillon S, Badal R, et al. Increasing prevalence and dissemination of NDM-1 metallo-β-lactamase in India: Data from the SMART study (2009). J Antimicrob Chemother 2011;66:1992-7.  Back to cited text no. 66
Khajuria A, Praharaj AK, Kumar M, Grover N. Emergence of Escherichia coli, Co-Producing NDM-1 and OXA-48 Carbapenemases, in Urinary Isolates, at a Tertiary Care Centre at Central India. J Clin Diagn Res 2014;8:DC01-4.  Back to cited text no. 67
Shanthi M, Sekar U, K A, Bramhne HG. OXA-181 Beta Lactamase is not a Major Mediator of Carbapenem Resistance in Enterobacteriaceae. J Clin Diagn Res 2013;7:1986-8.  Back to cited text no. 68
Shibl A, Al-Agamy M, Memish Z, Senok A, Khader SA, Assiri A. The emergence of OXA-48- and NDM-1-positive Klebsiellapneumoniae in Riyadh, Saudi Arabia. Int J Infect Dis 2013;17:e1130-3.  Back to cited text no. 69
Nordmann P, Poirel L. Strategies for identification of carbapenemase-producing Enterobacteriaceae. J Antimicrob Chemother 2013;68:487-9.  Back to cited text no. 70
Levast M, Poirel L, Carrër A, Deiber M, Decroisette E, Mallaval FO, et al. Transfer of OXA-48-positive carbapenem-resistant Klebsiellapneumoniae from Turkey to France. J Antimicrob Chemother 2011;66:944-5.  Back to cited text no. 71
Goren MG, Chmelnitsky I, Carmeli Y, Navon-Venezia S. Plasmid-encoded OXA-48 carbapenemase in Escherichia coli from Israel. J Antimicrob Chemother 2011;66:672-3.  Back to cited text no. 72
Balkan II, Aygün G, Aydin S, Mutcali SI, Kara Z, Kuskucu M, et al. Blood stream infections due to OXA-48-like carbapenemase-producing Enterobacteriaceae: Treatment and survival. Int J Infect Dis 2014;26:51-6.  Back to cited text no. 73
Yamamoto M, Pop-Vicas AE. Treatment for infections with carbapenem-resistant Enterobacteriaceae: What options do we still have? Crit Care 2014;18:229.  Back to cited text no. 74
Ehmann DE, Jahic H, Ross PL, Gu RF, Hu J, Kern G, et al. Avibactam is a covalent, reversible, non-β-lactam β-lactamase inhibitor. Proc Natl Acad Sci U S A 2012;109:11663-8.  Back to cited text no. 75
Aktas Z, Kayacan C, Oncul O. In vitro activity of avibactam (NXL104) in combination with β-lactams against Gram-negative bacteria, including OXA-48 β-lactamase-producing Klebsiella pneumoniae. Int J Antimicrob Agents 2012;39:86-9.  Back to cited text no. 76
Wiskirchen DE, Nordmann P, Crandon JL, Nicolau DP. Efficacy of humanized carbapenem exposures against New Delhi metallo-β-lactamase (NDM-1)-producing enterobacteriaceae in a murine infection model. Antimicrob Agents Chemother 2013;57:3936-40.  Back to cited text no. 77
Mimoz O, Grégoire N, Poirel L, Marliat M, Couet W, Nordmann P. Broad-spectrum β-lactam antibiotics for treating experimental peritonitis in mice due to Klebsiella pneumoniae producing the carbapenemase OXA-48. Antimicrob Agents Chemother 2012;56:2759-60.  Back to cited text no. 78
Falagas ME, Lourida P, Poulikakos P, Rafailidis PI, Tansarli GS. Antibiotic treatment of infections due to carbapenem-resistant Enterobacteriaceae: Systematic evaluation of the available evidence. Antimicrob Agents Chemother 2014;58:654-63.  Back to cited text no. 79
Livermore DM, Warner M, Mushtaq S, Doumith M, Zhang J, Woodford N. What remains against carbapenem-resistant Enterobacteriaceae? Evaluation of chloramphenicol, ciprofloxacin, colistin, fosfomycin, minocycline, nitrofurantoin, temocillin and tigecycline. Int J Antimicrob Agents 2011;37:415-9.  Back to cited text no. 80
Zarkotou O, Pournaras S, Voulgari E, Chrysos G, Prekates A, Voutsinas D, et al. Risk factors and outcomes associated with acquisition of colistin-resistant KPC-producing Klebsiella pneumoniae: A matched case-control study. J Clin Microbiol 2010;48:2271-4.  Back to cited text no. 81
Anthony KB, Fishman NO, Linkin DR, Gasink LB, Edelstein PH, Lautenbach E. Clinical and microbiological outcomes of serious infections with multidrug-resistant gram-negative organisms treated with tigecycline. Clin Infect Dis 2008;46:567-70.  Back to cited text no. 82
Tumbarello M, Viale P, Viscoli C, Trecarichi EM, Tumietto F, Marchese A, et al. Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: Importance of combination therapy. Clin Infect Dis 2012;55:943-50.  Back to cited text no. 83
Arana DM, Saez D, García-Hierro P, Bautista V, Fernández-Romero S, Ángel de la Cal M, et al. Concurrent interspecies and clonal dissemination of OXA-48 carbapenemase. Clin Microbiol Infect 2015;21:148.e1-4.  Back to cited text no. 84
Vasoo S, Cunningham SA, Kohner PC, Simner PJ, Mandrekar JN, Lolans K, et al. Comparison of a novel, rapid chromogenic biochemical assay, the Carba NP test, with the modified Hodge test for detection of carbapenemase-producing Gram-negative bacilli. J Clin Microbiol 2013;51:3097-101.  Back to cited text no. 85
Girlich D, Poirel L, Nordmann P. Value of the modified Hodge test for detection of emerging carbapenemases in Enterobacteriaceae. J Clin Microbiol 2012;50:477-9.  Back to cited text no. 86
Hartl R, Widhalm S, Kerschner H, Apfalter P. Temocillin and meropenem to discriminate resistance mechanisms leading to decreased carbapenem susceptibility with focus on OXA-48 in Enterobacteriaceae. Clin Microbiol Infect 2013;19:E230-2.  Back to cited text no. 87
Livermore DM, Tulkens PM. Temocillin revived. J Antimicrob Chemother 2009;63:243-5.  Back to cited text no. 88
Woodford N, Pike R, Meunier D, Loy R, Hill R, Hopkins KL. In vitro activity of temocillin against multidrug-resistant clinical isolates of Escherichia coli, Klebsiella spp. and Enterobacter spp. and evaluation of high-level temocillin resistance as a diagnostic marker for OXA-48 carbapenemase. J Antimicrob Chemother 2014;69:564-7.  Back to cited text no. 89
Andrews JM, Jevons G, Walker R, Ashby J, Fraise AP. Temocillin susceptibility by BSAC methodology. J Antimicrob Chemother 2007;60:185-7.  Back to cited text no. 90
Van Dijk K, Voets GM, Scharringa J, Voskuil S, Fluit AC, Rottier WC, et al. A disc diffusion assay for detection of class A, B and OXA-48 carbapenemases in Enterobacteriaceae using phenyl boronic acid, dipicolinic acid and temocillin. Clin Microbiol Infect 2014;20:345-9.  Back to cited text no. 91
Cohen Stuart J, Voets G, Rottier W, Voskuil S, Scharringa J, Van Dijk K, et al. Evaluation of the Oxoid Brilliance™ CRE Agar for the detection of carbapenemase-producing Enterobacteriaceae. Eur J Clin Microbiol Infect Dis 2013;32:1445-9.  Back to cited text no. 92
Vrioni G, Daniil I, Voulgari E, Ranellou K, Koumaki V, Ghirardi S, et al. Comparative evaluation of a prototype chromogenic medium (ChromID CARBA) for detecting carbapenemase-producing Enterobacteriaceae in surveillance rectal swabs. J Clin Microbiol 2012;50:1841-6.  Back to cited text no. 93
Girlich D, Anglade C, Zambardi G, Nordmann P. Comparative evaluation of a novel chromogenic medium (chromID OXA-48) for detection of OXA-48 producing Enterobacteriaceae. Diagn Microbiol Infect Dis 2013;77:296-300.  Back to cited text no. 94
Dortet L, Poirel L, Nordmann P. Rapid identification of carbapenemase types in Enterobacteriaceae and Pseudomonas spp. by using a biochemical test. Antimicrob Agents Chemother 2012;56:6437-40.  Back to cited text no. 95
Dortet L, Poirel L, Nordmann P. Further proofs of concept for the Carba NP test. Antimicrob Agents Chemother 2014;58:1269.  Back to cited text no. 96
Tijet N, Boyd D, Patel SN, Mulvey MR, Melano RG. Evaluation of the Carba NP test for rapid detection of carbapenemase-producing Enterobacteriaceae and Pseudomonasaeruginosa. Antimicrob Agents Chemother 2013;57:4578-80.  Back to cited text no. 97
Pires J, Novais A, Peixe L. Blue-carba, an easy biochemical test for detection of diverse carbapenemase producers directly from bacterial cultures. J Clin Microbiol 2013;51:4281-3.  Back to cited text no. 98
Kaase M, Szabados F, Wassill L, Gatermann SG. Detection of carbapenemases in Enterobacteriaceae by a commercial multiplex PCR. J Clin Microbiol 2012;50:3115-8.  Back to cited text no. 99
Nijhuis R, Samuelsen O, Savelkoul P, van Zwet A. Evaluation of a new real-time PCR assay (Check-Direct CPE) for rapid detection of KPC, OXA-48, VIM, and NDM carbapenemases using spiked rectal swabs. Diagn Microbiol Infect Dis 2013;77:316-20.  Back to cited text no. 100
Naas T, Cuzon G, Bogaerts P, Glupczynski Y, Nordmann P. Evaluation of a DNA microarray (Check-MDR CT102) for rapid detection of TEM, SHV, and CTX-M extended-spectrum β-lactamases and of KPC, OXA-48, VIM, IMP, and NDM-1 carbapenemases. J Clin Microbiol 2011;49:1608-13.  Back to cited text no. 101
Sauget M, Cabrolier N, Manzoni M, Bertrand X, Hocquet D. Rapid, sensitive and specific detection of OXA-48-like-producing Enterobacteriaceae by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. J Microbiol Methods 2014;105:88-91.  Back to cited text no. 102
Lafeuille E, Laouira S, Sougakoff W, Soulier-Escrihuela O, Leconte J, Garrec H, et al. Detection of OXA-48-like carbapenemase genes by the Xpert® Carba-R test: Room for improvement. Int J Antimicrob Agents 2015;45:441-2.  Back to cited text no. 103

Correspondence Address:
Balaji Veeraraghavan
Department of Clinical Microbiology, Christian Medical College, Vellore, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0974-777X.176149

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Detection of OXA-48 Gene in Carbapenem-Resistant Escherichia coli and Klebsiella pneumoniae from Urine Samples

Sushma Gurung, Sonali Kafle, Binod Dhungel, Nabaraj Adhikari, Upendra Thapa Shrestha, Bipin Adhikari, Megha Raj Banjara, Komal Raj Rijal, Prakash Ghimire
Infection and Drug Resistance. 2020; Volume 13: 2311
[Pubmed] | [DOI]
17 Evaluation of the synergy of ceftazidime/avibactam in combination with colistin, doripenem, levofloxacin, tigecycline, and tobramycin against OXA-48 producing Enterobacterales
Emel Mataraci Kara, Mesut Yilmaz, Ayse Istanbullu Tosun, Berna Özbek Çelik
Journal of Chemotherapy. 2020; 32(4): 171
[Pubmed] | [DOI]
18 In Vitro Synergistic Effect and Mutant Prevention Concentrations of Cefepime Alone or in Combination with Sulbactam Against OXA-48-positive Klebsiella pneumoniae Isolates
Emel Mataraci-Kara, Mesut Yilmaz, Berna Özbek-Çelik
Current Microbiology. 2020; 77(9): 2137
[Pubmed] | [DOI]
19 An African perspective on the prevalence, fate and effects of carbapenem resistance genes in hospital effluents and wastewater treatment plant (WWTP) final effluents: A critical review
Kingsley Ehi Ebomah, Anthony Ifeanyi Okoh
Heliyon. 2020; 6(5): e03899
[Pubmed] | [DOI]
20 Development of a new spectrophotometric assay for rapid detection and differentiation of KPC, MBL and OXA-48 carbapenemase-producing Klebsiella pneumoniae clinical isolates
John G. Routsias, Dimitris Tsakogiannis, Magda Katsiki, Dionysia Marinou, Maria Mavrouli, Georgia Vrioni, Athanasios Tsakris
International Journal of Antimicrobial Agents. 2020; 56(6): 106211
[Pubmed] | [DOI]
21 Evaluating the antimicrobial resistance patterns and molecular frequency of blaoxa-48 and blaGES-2 genes in Pseudomonas aeruginosa and Acinetobacter baumannii strains isolated from burn wound infection in Tehran, Iran
F. Tarafdar, B. Jafari, T. Azimi
New Microbes and New Infections. 2020; 37: 100686
[Pubmed] | [DOI]
22 Gastrointestinal Carriage of Vancomycin-Resistant Enterococci and Carbapenem-Resistant Gram-Negative Bacteria in an Endemic Setting: Prevalence, Risk Factors, and Outcomes
Alexandra Vasilakopoulou, Polyxeni Karakosta, Sophia Vourli, Aikaterini Tarpatzi, Paraskevi Varda, Maria Kostoula, Anastasia Antoniadou, Spyros Pournaras
Frontiers in Public Health. 2020; 8
[Pubmed] | [DOI]
23 Rising Threat of OXA-48 and other Carbapenemase Encoding Genes among Carbapenem Resistant Enterobacteriaceae in India
Satyajeet K. Pawar, Shivaji T. Mohite, Kailash D. Datkhile, Madhavi N. Patil, Satish V. Kakade
Journal of Pure and Applied Microbiology. 2020; 14(3): 1917
[Pubmed] | [DOI]
24 Evaluation of Two Methods for the Detection of Third Generation Cephalosporins Resistant Enterobacterales Directly From Positive Blood Cultures
Clarisse Durand, Agathe Boudet, Jean-Philippe Lavigne, Alix Pantel
Frontiers in Cellular and Infection Microbiology. 2020; 10
[Pubmed] | [DOI]
25 Molecular Mechanisms, Epidemiology, and Clinical Importance of ß-Lactam Resistance in Enterobacteriaceae
Giulia De Angelis, Paola Del Giacomo, Brunella Posteraro, Maurizio Sanguinetti, Mario Tumbarello
International Journal of Molecular Sciences. 2020; 21(14): 5090
[Pubmed] | [DOI]
26 Managing All the Genotypic Knowledge: Approach to a Septic Patient Colonized by Different Enterobacteriales with Unique Carbapenemases
Stacy C. Park, Alexander M. Wailan, Katie E. Barry, Kasi Vegesana, Joanne Carroll, Amy J. Mathers, William R. Miller, Jose M. Munita
Antimicrobial Agents and Chemotherapy. 2019; 63(8)
[Pubmed] | [DOI]
27 Diversity of Carbapenemase-Producing Escherichia coli Isolates in France in 2012-2013
Lauraine Gauthier, Laurent Dortet, Garance Cotellon, Elodie Creton, Gaëlle Cuzon, Valérie Ponties, Rémy A. Bonnin, Thierry Naas
Antimicrobial Agents and Chemotherapy. 2018; 62(8)
[Pubmed] | [DOI]
28 Treatment of Infections by OXA-48-Producing Enterobacteriaceae
Adam Stewart, Patrick Harris, Andrew Henderson, David Paterson
Antimicrobial Agents and Chemotherapy. 2018; 62(11)
[Pubmed] | [DOI]
29 Rapid Detection of the Commonly Encountered Carbapenemases (New Delhi Metallo-ß-Lactamase, OXA-48/181) Directly from Various Clinical Samples using Multiplex Real-Time Polymerase Chain Reaction Assay
Mubin Kazi, Rukhsar Khot, Anjali Shetty, Camilla Rodrigues
Indian Journal of Medical Microbiology. 2018; 36(3): 369
[Pubmed] | [DOI]
30 Newer ß-Lactam/ß-Lactamase Inhibitor for Multidrug-Resistant Gram-Negative Infections: Challenges, Implications and Surveillance Strategy for India
Balaji Veeraraghavan, Agila Kumari Pragasam, Yamuna Devi Bakthavatchalam, Shalini Anandan, V Ramasubramanian, Subramanian Swaminathan, Ram Gopalakrishnan, Rajeev Soman, OC Abraham, Vinod C Ohri, Kamini Walia
Indian Journal of Medical Microbiology. 2018; 36(3): 334
[Pubmed] | [DOI]
31 Detection of Carbapenemase-producing Enterobacteriaceae using Chromogenic Medium, ChromidID OXA-48, in Critical Care Patients of Kasr Al-Ainy Hospital in Egypt
Basma A. El Awady, Mera Anan, Hamida Gohar, Mohamed Saleh
Journal of Pure and Applied Microbiology. 2017; 11(4): 1655
[Pubmed] | [DOI]
32 Evaluation of Genotypic and Phenotypic Methods to Detect Carbapenemase Production in Gram-Negative Bacilli
Allison R McMullen, Melanie L Yarbrough, Meghan A Wallace, Angela Shupe, Carey-Ann D Burnham
Clinical Chemistry. 2017; 63(3): 723
[Pubmed] | [DOI]
33 New mechanisms, new worries
Marc Sprenger, Keiji Fukuda
Science. 2016; 351(6279): 1263
[Pubmed] | [DOI]


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