Incidence rates of carbapenemase-producing Enterobacteriaceae clinical isolates in France: a prospective nationwide study in 2011-12

An interregional surveillance program was conducted in the northwestern part of France to determine the prevalence of carbapenem-nonsusceptible Enterobacteriaceae (CNSE) isolates and their susceptibility to ceftazidime-avibactam and aztreonamavibactam combinations. Nonduplicate CNSE clinical isolates were prospectively collected from six hospitals between June 2012 and November 2013. MICs of ceftazidime and aztreonam, alone or combined with a fixed concentration of avibactam (4 g/ml), and those of carbapenems (comparator agents) were determined. MICs of ertapenem in combination with phenylalanine arginine-naphthylamide dihydrochloride (PA␤N) were also determined to assess active efflux. Genes encoding carbapenemases, plasmid-mediated AmpC enzymes, extended-spectrum ␤-lactamases (ESBLs), and major outer membrane proteins (OMPs) were amplified and sequenced. OMPs were also extracted for SDS-PAGE analysis. Among the 139 CNSE isolates, mainly Enterobacter spp. and Klebsiella pneumoniae, 123 (88.4%) were ertapenem nonsusceptible, 12 (8.6%) exhibited reduced susceptibility to all carbapenems, and 4 Proteeae isolates (2.9%) were resistant to imipenem. Carbapenemase production was detected in only two isolates (producing OXA-48 and IMI-3). In contrast, OMP deficiency, in association with AmpCs and/or ESBLs (mainly CTX-M-9, SHV-12, and CTX-M-15), was largely identified among CNSE isolates. The ceftazidime-avibactam and aztreonamavibactam combinations exhibited potent activity against CNSE isolates (MIC 50 /MIC 90 , 1/1 g/ml and 0.5/0.5 g/ml, respectively) compared to that of ceftazidime and aztreonam alone (MIC 50 /MIC 90 , 512/512 g/ml and 128/512 g/ml, respectively). This study reveals the in vitro activity of ceftazidime-avibactam and aztreonam-avibactam combinations against a large collection of porin-deficient enterobacterial isolates that are representative of the CNSE recovered in the northern part of France.

Section: Discussionsupporting

confidence: 93%

Molecular Characterization of Carbapenem-Nonsusceptible Enterobacterial Isolates Collected during a Prospective Interregional Survey in France and Susceptibility to the Novel Ceftazidime-Avibactam and Aztreonam-Avibactam Combinations

Dupont

Gaillot

Goetgheluck

et al. 2016

“…Also included are 13 isolates carrying MBLs and serine carbapenemases: VIM-1 and KPC-2 (n ϭ 4), IMP-4 and KPC-2 (n ϭ 2), VIM-4 and OXA-48 (n ϭ 2), VIM-31 and OXA-48 (n ϭ 1), NDM-1 and OXA-48 (n ϭ 3), and NDM-1 and OXA-232 (n ϭ 1). have been performed, and the frequency of noncarbapenemasemediated mechanisms among carbapenem-nonsusceptible Enterobacteriaceae has been found to be 77.2 to 98.6% (13,(32)(33)(34). These estimates exceeded the proportion observed here, but that is likely because those collections included ertapenem-nonsusceptible isolates, against which meropenem can retain some activity, whereas that was not the case in the present work (35).…”

contrasting

confidence: 64%

In Vitro Susceptibility to Ceftazidime-Avibactam of Carbapenem-Nonsusceptible Enterobacteriaceae Isolates Collected during the INFORM Global Surveillance Study (2012 to 2014)

Jonge

Karlowsky²,

Kazmierczak³

et al. 2016

143

bThe activity of ceftazidime-avibactam was assessed against 961 isolates of meropenem-nonsusceptible Enterobacteriaceae. Most meropenem-nonsusceptible metallo-␤-lactamase (MBL)-negative isolates (97.7%) were susceptible to ceftazidime-avibactam. Isolates that carried KPC or OXA-48-like ␤-lactamases, both alone and in combination with extended-spectrum ␤-lactamases (ESBLs) and/or AmpC ␤-lactamases, were 98.7% and 98.5% susceptible to ceftazidime-avibactam, respectively. Meropenem-nonsusceptible, carbapenemase-negative isolates demonstrated 94.7% susceptibility to ceftazidimeavibactam. Ceftazidime-avibactam activity was compromised only in isolates for which carbapenem resistance was mediated through metallo-␤-lactamases.

“…OXA-48 prevalence is also increasing in other European countries, such as France, Germany, Belgium, and the United Kingdom, where increasing numbers of outbreaks have been described (1,(17)(18)(19)(20)(21). However, OXA-48 is rarely identified in North America (22).…”

Section: Bacterial Isolates and Carbapenemase Typesmentioning

confidence: 99%

Prospective Multicenter Study of Carbapenemase-Producing Enterobacteriaceae from 83 Hospitals in Spain Reveals High In Vitro Susceptibility to Colistin and Meropenem

Oteo

Ortega

Bartolomé

et al. 2015

129

hospitals (about 40,000 hospital beds) prospectively collected nonduplicate Enterobacteriaceae using the screening cutoff recommended by EUCAST. Carbapenemase characterization was performed by phenotypic methods and confirmed by PCR and sequencing. Multilocus sequencing types (MLST) were determined for Klebsiella pneumoniae and Escherichia coli. A total of 702 Enterobacteriaceae isolates met the inclusion criteria; 379 (54%) were CPE. OXA-48 (71.5%) and VIM-1 (25.3%) were the most frequent carbapenemases, and K. pneumoniae (74.4%), Enterobacter cloacae (10.3%), and E. coli (8.4%) were the species most affected. Susceptibility to colistin, amikacin, and meropenem was 95.5%, 81.3%, and 74.7%, respectively. The most prevalent sequence types (STs) were ST11 and ST405 for K. pneumoniae and ST131 for E. coli. Forty-five (54.1%) of the hospitals had at least one CPE case. For K. pneumoniae, ST11/OXA-48, ST15/OXA-48, ST405/ OXA-48, and ST11/VIM-1 were detected in two or more Spanish provinces. ST11 isolates carried four carbapenemases (VIM-1, OXA-48, KPC-2, and OXA-245), but ST405 isolates carried OXA-48 only. A wide interregional spread of CPE in Spain was observed, mainly due to a few successful clones of OXA-48-producing K. pneumoniae (e.g., ST11 and ST405). The dissemination of OXA-48-producing E. coli is a new finding of public health concern. According to the susceptibilities determined in vitro, most of the CPE (94.5%) had three or more options for antibiotic treatment. C arbapenemase-producing Enterobacteriaceae (CPE), mainly Klebsiella pneumoniae, are an emerging threat to public and individual health worldwide. These microorganisms are often resistant to almost all available antibiotics (1, 2), so there are few alternative treatment options. The most common carbapenemases are KPC (class A); VIM, IMP, and NDM (class B); and the OXA-48 types (class D). However, the extent to which health care systems have been affected and the carbapenemase types that are predominant differ substantially from country to country (3).A multicenter study performed in Spain in 2009 revealed 43 (0.04%) cases of CPE, which were mostly VIM-1 and IMP-22 (4). After that, we reported a rapid increase in the number of cases of CPE, mainly OXA-48-producing K. pneumoniae, in this country from 2010 to 2012 (5-7).Because previous studies (5, 6) were based on voluntary reports without taking into account key important issues, in this paper, we present data on the impact of CPE as obtained from a prospective, multicenter, and population-based study. We show that carbapenemase production in this country is widely and irregularly distributed; however, the rates of susceptibility to meropenem and colistin were still high.(The preliminary results of this study were presented in part at the 24th European Congress of Clinical Microbiology and Infectious Diseases Annual Meeting, 10 to 13 May 2014 in Barcelona, Spain,).