Ceftazidime-avibactam (MIC 50/90 , 0.12/0.25 g/ml) inhibited 99.9% (20,698/20,709) of Enterobacteriaceae isolates at <8 g/ml. This compound was active against resistant subsets, including ceftazidime-nonsusceptible Enterobacter cloacae (MIC 50/90 , 0.25/ 0.5 g/ml) and extended-spectrum ␤-lactamase (ESBL) phenotype isolates. An ESBL phenotype was noted among 12.4% (1,696/ 13,692 isolates from targeted species) of the isolates, including 776 Escherichia coli (12.0% for this species; MIC 50/90 , 0.12/0.25 g/ml), 721 Klebsiella pneumoniae (16.3%; MIC 50/90 , 0.12/0.25 g/ml), 119 Klebsiella oxytoca (10.3%; MIC 50/90 , 0.06/0.25 g/ ml), and 80 Proteus mirabilis (4.9%; MIC 50/90 , 0.06/0.12 g/ml) isolates. The most common enzymes detected among ESBL phenotype isolates from 2013 (n ‫؍‬ 743) screened using a microarray-based assay were CTX-M-15-like (n ‫؍‬ 307), KPC (n ‫؍‬ 120), SHV ESBLs (n ‫؍‬ 118), and CTX-M-14-like (n ‫؍‬ 110). KPC producers were highly resistant to comparators, and ceftazidimeavibactam (MIC 50/90 , 0.5/2 g/ml) and tigecycline (MIC 50/90 , 0.5/1 g/ml; 98.3% susceptible) were the most active agents against these strains. Meropenem (MIC 50/90 , <0.06/<0.06 g/ml) and ceftazidime-avibactam (MIC 50/90 , 0.12/0.25 g/ml) were active against CTX-M-producing isolates. Other enzymes were also observed, and ceftazidime-avibactam displayed good activity against the isolates producing less common enzymes. Among 11 isolates displaying ceftazidime-avibactam MIC values of >8 g/ml, three were K. pneumoniae strains producing metallo-␤-lactamases (all ceftazidime-avibactam MICs, >32 g/ml), with two NDM-1 producers and one K. pneumoniae strain carrying the bla KPC-2 and bla VIM-4 genes. Therapeutic options for isolates producing ␤-lactamases may be limited, and ceftazidime-avibactam, which displayed good activity against strains, including those producing KPC enzymes, merits further study in infections where such organisms occur. E nterobacteriaceae species cause a variety of infection types and these organisms, including those producing extended-spectrum ␤-lactamases (ESBLs) and carbapenemases, have been implicated in severe health care-associated infections (HAIs) that are a leading cause of morbidity and mortality worldwide (1, 2). Among Gram-negative organisms associated with HAI in the United States, 15% of Klebsiella pneumoniae or Klebsiella oxytoca isolates and 2% of Escherichia coli isolates have been shown to be resistant to three or more antimicrobial classes and were categorized as multidrug resistant (MDR) (2). These isolates were the cause of central line-associated bloodstream infections, catheterassociated urinary tract infections, ventilator-associated pneumonia, and surgical site infections. Additionally, among hospitals reporting severe HAIs, 20% described the occurrence of carbapenem-resistant Klebsiella isolates that are usually MDR (2) and more recently, pandrug-resistant (PDR) isolates producing carbapenemases have been reported (3). Due to steadily increasing levels of antimicrobial resistance amo...

We evaluated doripenem-resistant Acinetobacter baumannii-Acinetobacter calcoaceticus complex (ACB; n ‫؍‬ 411) and Enterobacteriaceae (n ‫؍‬ 92) isolates collected from patients from 14 European and Mediterranean countries during 2009 to 2011 for the presence of carbapenemase-encoding genes and clonality. Following susceptibility testing, carbapenem-resistant (doripenem MIC, >2 g/ml) isolates were screened for carbapenemases. New ␤-lactamase genes were expressed in a common background and susceptibility was tested. Class 1 integrons were sequenced. Clonality was evaluated by pulsed-field gel electrophoresis and multilocus sequence typing (Pasteur scheme). Relative expression of ␤-lactam intrinsic resistance mechanisms was determined for carbapenemase-negative Enterobacteriaceae. ACB and Enterobacteriaceae displayed 58.9 and 0.9% doripenem resistance, respectively. bla OXA-23 , bla OXA-58 , and bla OXA-24/OXA-40 were detected among 277, 77, and 29 ACB, respectively (in 8, 6, and 5 countries). Ten Turkish isolates carried bla GES-11 or bla GES-22 . GES-22 (G243A and M169L mutations in GES-1) had an extendedspectrum ␤-lactamase profile. A total of 33 clusters of >2 ACB isolates were observed, and 227 isolates belonged to sequence type 2/international clone II. Other international clones were limited to Turkey and Israel. Doripenem-resistant Enterobacteriaceae increased significantly (0.7 to 1.6%), and 15 bla KPC-2 -and 22 bla KPC-3 -carrying isolates, mostly belonging to clonal complexes 11 and 258, were observed. Enterobacteriaceae isolates producing OXA-48 (n ‫؍‬ 16; in Turkey and Italy), VIM-1 (n ‫؍‬ 10; in Greece, Poland, and Spain), VIM-26 (n ‫؍‬ 1; in Greece), and IMP-19, VIM-4, and the novel VIM-35 (n ‫؍‬ 1 each from Poland) were detected. VIM-35 had one substitution compared to VIM-1 (A235T) and a similar susceptibility profile. One or more resistance mechanisms were identified in 4/6 carbapenemase-negative Enterobacteriaceae. This broad evaluation confirms results from country-specific surveys and shows a highly diverse population of carbapenemase-producing ACB and Enterobacteriaceae in Europe and Mediterranean countries.

The aim of the study was to characterize forty-eight Acinetobacter baumannii (ACB) isolates with confirmed tigecycline MIC values >2 mg/L observed in six Latin American (LATAM) hospitals (four countries) in 2011. During 2005-2011, 6,923 ACB isolates were collected as part of the SENTRY Program, and tigecycline susceptibility was quantified using the reference broth microdilution method. A total of 102/1881 ACB from LATAM hospitals displayed tigecycline minimum inhibitory concentration (MIC) values >2 mg/L, showing an increase from 4.3% in 2010 to 10.5% in 2011, which is considerably high when compared to other geographical regions. Forty-eight ACB from 2011 displaying elevated tigecycline MICs were typed by pulsed-field gel electrophoresis, which showed multiple clusters in Sao Paulo, Brazil, and a major clone in Guadalajara, Mexico. Eighteen unique isolates had the expression of adeA and adeF determined and results compared to a group of tigecycline-susceptible strains, which demonstrated that 18/18 strains had significantly increased expression of AdeABC and three isolates overexpressed AdeFGH. Sequencing of adeS and adeR revealed that 11 isolates displayed adeS mutations, and 5 isolates had mutations in adeR. Sequencing of trm showed frameshift mutations in eight isolates and insertion sequences leading to nonfunctional proteins in three isolates. TetX-encoding genes were not detected. We documented the recent increase of ACB displaying elevated tigecycline MICs in LATAM hospitals, dominantly due to the clonal expansion of isolates in Brazil and Mexico. Control of tigecycline usage in those countries and more strict infection control practices in the involved hospitals should be considered to reduce such outbreaks.

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