Emergence of OXA-48-Type Carbapenemase-Producing Enterobacteriaceae in German Hospitals

Pfeifer, Yvonne; Schlatterer, Kathrin; Engelmann, Elisabeth; Schiller, R.; Frangenberg, Hans Reiner; Stiewe, Doris; Holfelder, M.; Witte, Wolfgang; Nordmann, Patrice; Poirel, Laurent

doi:10.1128/aac.05315-11

Cited by 81 publications

(57 citation statements)

References 19 publications

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“…In the past decade, bla IMP-8 -producing K. pneumoniae isolates have been reported in Taiwan (8,9,14). Previous studies have reported that carbapenemases (bla KPC , bla , and bla OXA-162 ) could be found in R. planticola, R. ornithinolytica, and other Enterobacteriaceae (2,5,6,9,15). The carbapenemase genes in R. planticola in any specific country can be found in carbapenem-resistant Enterobacteriaceae, especially K. pneumoniae, in that country (Table 2).…”

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“…Bacteremia was the most common clinical manifestation in six of the 11 R. planticola infection cases in the literature (3). To date, there are isolates of Raoultella ornithinolytica and R. planticola which are resistant to carbapenem and carry different carbapenemases, including bla KPC , bla , and bla OXA-162 genes (2,5,6). However, bla IMP-8 -producing R. planticola has not been reported in the literature.…”

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First Report of bla _IMP-8 in Raoultella planticola

Tseng

Wang

Liang

et al. 2014

Antimicrob Agents Chemother

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Two carbapenem-resistant Raoultella planticola clinical isolates were isolated from patients with pneumonia and Port-A catheter-related bacteremia, respectively, in Taiwan. These isolates remained susceptible to fluoroquinolone, aminoglycoside, and colistin. Though the two isolates had the same antibiogram, plasmidic carbapenemase bla IMP-8 , class 1 integron cassette (dfrA12-orfF-aadA2), and qnrB2, they had different pulsed-field gel electrophoresis patterns, plasmid sizes, and outer membrane protein loss profiles. To our knowledge, this is the first report of bla IMP-8 found in R. planticola. Interestingly, bla IMP-8 is the most common carbapenemase found in Klebsiella pneumoniae in Taiwan. In the literature, carbapenemase genes in R. planticola in each country were also found in carbapenem-resistant Enterobacteriaceae in the same country. Raoultella planticola belongs to the Enterobacteriaceae family, is related to Klebsiella spp., and is mostly found in soil and water (1). Although the reports of R. planticola infection are limited, this bacterium has been reported in bloodstream infection, surgical site infection, and cystitis (2-4). Bacteremia was the most common clinical manifestation in six of the 11 R. planticola infection cases in the literature (3). To date, there are isolates of Raoultella ornithinolytica and R. planticola which are resistant to carbapenem and carry different carbapenemases, including bla KPC , bla , and bla OXA-162 genes (2, 5, 6). However, bla IMP-8 -producing R. planticola has not been reported in the literature.Among 411 carbapenem-resistant Enterobacteriaceae isolates collected from a nationwide surveillance study in Taiwan in 2012, two carbapenem-resistant R. planticola clinical isolates were identified from patients in the National Taiwan University Hospital. One was isolated from a sputum specimen; the other was from a blood specimen. The 16S rRNA gene sequencing confirmed identification of R. planticola initially with the Vitek 2 system (7). Case 1. A 77-year-old male patient was a case of non-small-cell lung cancer. He was admitted with pneumonia in February 2012. After admission, respiratory failure and shock developed. Chest roentgenography revealed bronchopneumonia in the right lower lung field. Sputum culture yielded carbapenem-resistant R. planticola (isolate 139), and the patient received levofloxacin and cefepime. Due to progressive leukocytosis, unstable hemodynamics, and increased O 2 demand, meropenem and colistin were prescribed instead of cefepime. The patient eventually died of pneumonia and shock.Case 2. A 57-year-old male patient had non-small-cell lung cancer with bilateral mediastinal lymph nodes and multiorgan metastasis. He received therapy with erlotinib and cisplatin. Port-A catheter-related bacteremia was suspected, and blood cultures grew Acinetobacter baumannii and carbapenem-resistant R. planticola (isolate 193). The patient received ceftazidime, levofloxacin, and gentamicin, and then the follow-up blood cultures were negative sterile 5 days later....

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First Report of bla _IMP-8 in Raoultella planticola

Tseng

Wang

Liang

et al. 2014

Antimicrob Agents Chemother

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“…OXA-48 carbapenemase is an Ambler class D ␤-lactamase that was first identified in 2001 from a multidrug-resistant Klebsiella pneumoniae isolate from Turkey (7). Many sporadic cases have been reported, first in Turkey and then in many other European countries and Israel (8)(9)(10)(11)(12)(13). OXA-48 is now considered an endemic carbapenemase in Enterobacteriaceae, at least in Turkey and in North African countries such as Morocco, Algeria, and Tunisia, and a source of outbreak situations in France, Belgium, Spain, and the Netherlands (14)(15)(16)(17)(18)(19)(20).…”

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Derepressed Transfer Properties Leading to the Efficient Spread of the Plasmid Encoding Carbapenemase OXA-48

Potron

Poirel

Nordmann

2014

Antimicrob Agents Chemother

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The current emergence of the carbapenemase OXA-48 among Enterobacteriaceae is related to the spread of a single IncL/M-type plasmid, pOXA-48a. This plasmid harbors the bla OXA-48 gene within a composite transposon, Tn1999, which is inserted into the tir gene, encoding a transfer inhibition protein. We showed that the insertion of Tn1999 into the tir gene was involved in a higher transfer frequency of plasmid pOXA-48a. This may likely be the key factor for the successful dissemination of this plasmid. P lasmids belonging to the IncL/M incompatibility group are commonly identified among environmental and clinical enterobacterial isolates (1-3). They have been increasingly identified as a source of multidrug resistance. Indeed, IncL/M-type plasmids are the main plasmids responsible for the dissemination of specific extended-spectrum ␤-lactamase genes such as the bla CTX-M-3 gene and have also been shown to harbor carbapenemase genes such as the bla NDM-1 and bla OXA-48 genes (4-6). OXA-48 carbapenemase is an Ambler class D ␤-lactamase that was first identified in 2001 from a multidrug-resistant Klebsiella pneumoniae isolate from Turkey (7). Many sporadic cases have been reported, first in Turkey and then in many other European countries and Israel (8-13). OXA-48 is now considered an endemic carbapenemase in Enterobacteriaceae, at least in Turkey and in North African countries such as Morocco, Algeria, and Tunisia, and a source of outbreak situations in France, Belgium, Spain, and the Netherlands (14-20). The spread of OXA-48 producers and of KPC producers represents the most important source of multidrug resistance in Europe and the United States. The spread of the bla OXA-48 gene is linked mostly to the dissemination of the single 62-kb IncL/Mtype plasmid pOXA-48a (20). Most of the OXA-48-positive Enterobacteriaceae harbor this specific plasmid, which is spreading among various enterobacterial species (20). Sequence analysis of plasmid pOXA-48a showed that the bla OXA-48 gene is bracketed by two copies of IS1999, giving rise to a composite transposon named Tn1999 (8, 21). Tn1999 is inserted into the tir gene, encoding a transfer inhibition protein, which is therefore not functional (6). Interestingly, a gene similar to this tir gene has been shown to inhibit plasmid RP4 conjugal transfer (22). Therefore, the aim of this study was to evaluate whether the disruption of the tir gene consecutive to the Tn1999 insertion in pOXA-48a could play a role in the dissemination of this plasmid and, consequently, of the bla OXA-48 gene. MATERIALS AND METHODSBacterial strains, plasmids, and culture conditions. Clinical strains K. pneumoniae 11978 (bla ) and K. pneumoniae 601 (bla NDM-1 ) were previously described (7,23). Escherichia coli TOP10(pOXA-48a) and E. coli TOP10(pNDM-OM), harboring the natural plasmids of K. pneumoniae 11978 and K. pneumoniae 601, respectively, were obtained by mating-out assays. Nalidixic acid-resistant E. coli JM109, nalidixic acidresistant Enterobacter cloacae SB, and rifampin-resistant E. coli TOP1...

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“…The MICs of ceftazidime and meropenem were determined by the broth dilution method (22). The group included 113 isolates producing KPC-(n ϭ 21), VIM-(n ϭ 44), NDM-(n ϭ 24), IMP-(n ϭ 4), and OXA-48-type (n ϭ 19) carbapenemases and one isolate coproducing VIM and IMP metallo-␤-lactamases (23)(24)(25)(26)(27)(28)(29). The remaining 48 isolates were non-carbapenemase producers (Table 1) (21,30).…”

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Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry Meropenem Hydrolysis Assay with NH ₄ HCO ₃ , a Reliable Tool for Direct Detection of Carbapenemase Activity

et al. 2015

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A comparison of a matrix-assisted laser desorption ionization-time of flight mass spectrometric (MALDI-TOF MS) meropenem hydrolysis assay with the Carba NP test showed that both methods exhibited low sensitivity (approximately 76%), mainly due to the false-negative results obtained with OXA-48-type producers. The addition of NH 4 HCO 3 to the reaction buffer for the MALDI-TOF MS assay dramatically improved its sensitivity (98%). Automatic interpretation of the MALDI-TOF MS assay, using the MBT STAR-BL software, generally agreed with the results obtained after manual analysis. For the Carba NP test, spectrophotometric analysis found six additional carbapenemase producers. Nosocomial infections caused by carbapenem-resistant Enterobacteriaceae and Pseudomonas spp. are now emerging worldwide and are difficult to treat (1). Previous data have shown that strict epidemiological intervention based on the rapid detection of carbapenemase production can prevent the spread of those bacteria (2). Therefore, the introduction of rapid and sensitive methodologies for the detection of carbapenemase-producing bacteria is of utmost importance. Recently, two new highly sensitive and rapid methods for the direct detection of carbapenemase activity were developed. In 2011, two research groups demonstrated that matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) can detect carbapenemase activity, based on mass spectral profiles obtained from carbapenem molecules (3, 4). The second method, the Carba NP test, is a biochemical method used in the detection of carbapenemase activity in Enterobacteriaceae, Pseudomonas spp., and Acinetobacter species (5-7). This test is based on a decrease in pH resulting from the hydrolysis of the ␤-lactam ring of carbapenem molecules, which is detected using phenol red as a pH indicator.The aim of this study was to validate the efficiency of a MALDI-TOF MS meropenem hydrolysis assay and the Carba NP test for the detection of carbapenemase producers. The performances of both methods were compared with that of a recently published modification of the MALDI-TOF MS assay (MALDI-TOF BIC) in an effort to increase the reliability of detecting OXA-48 producers (8). Furthermore, the automatic interpretation of all methods was evaluated.The methods were tested against a group of 124 Enterobacteriaceae and 37 Pseudomonas aeruginosa isolates from collections of the Faculty of Medicine and University Hospital in Plzen (Czech Republic), the National Medicines Institute in Warsaw (Poland), the Robert Koch Institute in Wernigerode (Germany), and the University Hospital in Larissa (Greece). The isolates were previously characterized, as described below. All isolates were tested for extended-spectrum ␤-lactamase (ESBL) and AmpC expression by the ESBL double-disk synergy test (DDST) with cefotaxime, ceftazidime, aztreonam, and amoxicillin-clavulanate disks in the absence and presence of cloxacillin (250 g/ml) (9). Susceptibility to carbapenems was determined by using imipenem, merope...

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Emergence of OXA-48-Type Carbapenemase-Producing Enterobacteriaceae in German Hospitals

Cited by 81 publications

References 19 publications

First Report of bla _IMP-8 in Raoultella planticola

First Report of bla _IMP-8 in Raoultella planticola

Derepressed Transfer Properties Leading to the Efficient Spread of the Plasmid Encoding Carbapenemase OXA-48

Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry Meropenem Hydrolysis Assay with NH ₄ HCO ₃ , a Reliable Tool for Direct Detection of Carbapenemase Activity

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Emergence of OXA-48-Type Carbapenemase-Producing Enterobacteriaceae in German Hospitals

Cited by 81 publications

References 19 publications

First Report of bla IMP-8 in Raoultella planticola

First Report of bla IMP-8 in Raoultella planticola

Derepressed Transfer Properties Leading to the Efficient Spread of the Plasmid Encoding Carbapenemase OXA-48

Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry Meropenem Hydrolysis Assay with NH 4 HCO 3 , a Reliable Tool for Direct Detection of Carbapenemase Activity

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First Report of bla _IMP-8 in Raoultella planticola

First Report of bla _IMP-8 in Raoultella planticola

Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry Meropenem Hydrolysis Assay with NH ₄ HCO ₃ , a Reliable Tool for Direct Detection of Carbapenemase Activity