Dataset Information

Low Frequency of Ceftazidime-Avibactam Resistance among Enterobacteriaceae Isolates Carrying blaKPC Collected in U.S. Hospitals from 2012 to 2015.

ABSTRACT: Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae isolates have been increasingly reported worldwide, and therapeutic options to treat infections caused by these organisms are limited. We evaluated the activity of ceftazidime-avibactam and comparators against 456 Enterobacteriaceae isolates carrying blaKPC collected from 79 U.S. hospitals during 2012 to 2015. Overall, ceftazidime-avibactam (MIC50/90, 0.5/2 μg/ml; 99.3% susceptible) and tigecycline (MIC50/90, 0.5/1 μg/ml; 98.9% susceptible at ≤2 μg/ml) were the most active agents. Only 80.5% and 59.0% of isolates were susceptible to colistin and amikacin, respectively. All three isolates (0.7%) displaying resistance to ceftazidime-avibactam (K. pneumoniae; MICs, ≥16 μg/ml) were evaluated using whole-genome sequencing analysis and relative quantification of expression levels of porins and efflux pump. Two isolates carried metallo-β-lactamase genes, blaNDM-1 or blaVIM-4, among other β-lactam resistance mechanisms, and one displayed a premature stop codon in ompK35 and decreased expression of ompK36 Ceftazidime-avibactam was active against 100.0 and 99.3% of isolates carrying blaKPC-3 (n = 221) and blaKPC-2 (n = 145), respectively. Isolates carrying blaKPC were more commonly recovered from pneumonia (n = 155), urinary tract (n = 93), and skin/soft tissue (n = 74) infections. Ceftazidime-avibactam (97.8 to 100.0% susceptible) was consistently active against isolates from all infection sites. K. pneumoniae (83.3% of the collection) susceptibility rates were 99.2% for ceftazidime-avibactam, 98.9% for tigecycline, and 80.1% for colistin. Ceftazidime-avibactam susceptibility did not vary substantially when comparing isolates from intensive care unit (ICU) patients to those from non-ICU patients. Ceftazidime-avibactam was active against this large collection of isolates carrying blaKPC and represents a valuable addition to the armamentarium currently available for the treatment of infections caused by KPC-producing Enterobacteriaceae.

SUBMITTER: Castanheira M

PROVIDER: S-EPMC5328529 | biostudies-other | 2017 Mar

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:The activities of ceftazidime-avibactam, ceftolozane-tazobactam, and comparators were evaluated for 733 isolates displaying resistance to broad-spectrum cephalosporins and carrying extended-spectrum β-lactamase (ESBL) genes detected by whole-genome sequencing analysis. Isolates were collected during 2017 in U.S. hospitals. The ESBL producers were 486 Escherichia coli, 190 Klebsiella pneumoniae, and 42 Enterobacter cloacae isolates and isolates from 3 other species. The most common groups of ESBL-encoding genes were blaCTX-M-15-like (n = 491 isolates) and blaCTX-M-15 alone (n = 168) or plus blaOXA-1 (n = 260), followed by blaCTX-M-14-like (n = 162), which included blaCTX-M-27 and blaCTX-M-14 (104 and 51 isolates, respectively), and blaSHV-12 and blaSHV-7 (48 and 22 isolates, respectively). ESBL producers carried other β-lactamases, including 1 E. cloacae harboring blaKPC-3 All ESBL-producing isolates were susceptible to ceftazidime-avibactam, and 90.2/83.9% (CLSI/EUCAST breakpoints) were susceptible to ceftolozane-tazobactam. Tigecycline (98.1/95.8% susceptible) and colistin (99.2%) were comparators that displayed the greatest activity against these isolates. Ceftolozane-tazobactam inhibited 91.4/83.9% of isolates carrying blaCTX-M-15-like and 97.5/95.1% of isolates carrying blaCTX-M-14-like, and its activity was more limited against the 91 isolates carrying blaSHV (66.7/61.1% susceptible). Ceftolozane-tazobactam inhibited 95.5% of the E. coli isolates but only 83.0%, 64.3%, and 80.0% of K. pneumoniae, E. cloacae, and other species harboring ESBL-encoding genes (CLSI breakpoints), respectively. Outer membrane protein sequences for ceftolozane-tazobactam-nonsusceptible isolates did not exhibit significant differences compared to those in genetically related ceftolozane-tazobactam-susceptible isolates. Ceftazidime-avibactam was more active than other agents tested, including ceftolozane-tazobactam, and the activity of this combination was stable regardless of species or ESBL gene carried.

Project description:The International Network for Optimal Resistance Monitoring (INFORM) global surveillance program collected clinical isolates of Enterobacteriaceae (n = 7,665) and Pseudomonas aeruginosa (n = 1,794) from 26 medical centers in six Latin American countries from 2012 to 2015. The in vitro activity of ceftazidime-avibactam and comparators was determined for the isolates using the Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution method. Enterobacteriaceae were highly susceptible (99.7%) to ceftazidime-avibactam, including 99.9% of metallo-β-lactamase (MBL)-negative isolates; 87.4% of all P. aeruginosa isolates and 92.8% of MBL-negative isolates were susceptible to ceftazidime-avibactam. Susceptibility to ceftazidime-avibactam ranged from 99.4% to 100% for Enterobacteriaceae and from 79.1% to 94.7% for P. aeruginosa when isolates were analyzed by country of origin. Ceftazidime-avibactam inhibited 99.6% to 100% of Enterobacteriaceae isolates that carried serine β-lactamases, including extended-spectrum β-lactamases (ESBLs), AmpC cephalosporinases, and carbapenemases (KPC and OXA-48-like) as well as 99.7%, 99.6%, 99.5%, and 99.2% of MBL-negative isolates demonstrating ceftazidime-nonsusceptible, multidrug-resistant (MDR), meropenem-nonsusceptible, and colistin-resistant phenotypes, respectively. Among carbapenem-nonsusceptible isolates of P. aeruginosa (n = 750), 14.7% carried MBLs with or without additional acquired serine β-lactamases, while in the majority of isolates (70.0%), no acquired β-lactamase was identified. Ceftazidime-avibactam inhibited 89.5% of carbapenem-nonsusceptible P. aeruginosa isolates in which no acquired β-lactamase was detected. Overall, clinical isolates of Enterobacteriaceae collected in Latin America from 2012 to 2015 were highly susceptible to ceftazidime-avibactam, including isolates that exhibited resistance to ceftazidime, meropenem, colistin, or an MDR phenotype. Country-specific variations were noted in the susceptibility of P. aeruginosa isolates to ceftazidime-avibactam.

Project description:The in vitro activities of ceftazidime-avibactam and comparators against 9,149 isolates of Enterobacteriaceae and 2,038 isolates of Pseudomonas aeruginosa collected by 42 medical centers in nine countries in the Asia-Pacific region from 2012 to 2015 were determined as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance program. Antimicrobial susceptibility testing was conducted by Clinical and Laboratory Standards Institute (CLSI) broth microdilution, and isolate subset analysis was performed on the basis of the resistant phenotypes and β-lactamase content. Ceftazidime-avibactam demonstrated potent in vitro activity (MIC, ≤8 μg/ml) against all Enterobacteriaceae tested (99.0% susceptible) and was the most active against isolates that were metallo-β-lactamase (MBL) negative (99.8% susceptible). Against P. aeruginosa, 92.6% of all isolates and 96.1% of MBL-negative isolates were susceptible to ceftazidime-avibactam (MIC, ≤8 μg/ml). The rates of susceptibility to ceftazidime-avibactam ranged from 97.0% (Philippines) to 100% (Hong Kong, South Korea) for Enterobacteriaceae and from 83.1% (Thailand) to 100% (Hong Kong) among P. aeruginosa isolates, with lower susceptibilities being observed in countries where MBLs were more frequently encountered (Philippines, Thailand). Ceftazidime-avibactam inhibited 97.2 to 100% of Enterobacteriaceae isolates, per country, that carried serine β-lactamases, including extended-spectrum β-lactamases, AmpC cephalosporinases, and carbapenemases (KPC, GES, OXA-48-like). It also inhibited 91.3% of P. aeruginosa isolates that were carbapenem nonsusceptible in which no acquired β-lactamase was detected. Among MBL-negative Enterobacteriaceae isolates that were ceftazidime nonsusceptible, meropenem nonsusceptible, colistin resistant, and multidrug resistant, ceftazidime-avibactam inhibited 96.1, 87.7, 100, and 98.8% of isolates, respectively, and among MBL-negative P. aeruginosa isolates that were ceftazidime nonsusceptible, meropenem nonsusceptible, colistin resistant, and multidrug resistant, ceftazidime-avibactam inhibited 79.6, 83.6, 83.3, and 68.2% of isolates, respectively. Overall, clinical isolates of Enterobacteriaceae and P. aeruginosa collected in nine Asia-Pacific countries from 2012 to 2015 were highly susceptible to ceftazidime-avibactam.

Project description:Plazomicin and comparator agents were tested by using the CLSI reference broth microdilution method against 4,825 clinical isolates collected during 2014 and 2015 in 70 U.S. hospitals as part of the ALERT (Antimicrobial Longitudinal Evaluation and Resistance Trends) program. Plazomicin (MIC50/MIC90, 0.5/2 ?g/ml) inhibited 99.2% of 4,362 Enterobacteriaceae at ?4 ?g/ml. Amikacin, gentamicin, and tobramycin inhibited 98.9%, 90.3%, and 90.3% of these isolates, respectively, by applying CLSI breakpoints. The activities of plazomicin were similar among Enterobacteriaceae species, with MIC50 values ranging from 0.25 to 1 ?g/ml, with the exception of Proteus mirabilis and indole-positive Proteeae that displayed MIC50 values of 2 ?g/ml. For 97 carbapenem-resistant Enterobacteriaceae (CRE), which included 87 isolates carrying blaKPC, plazomicin inhibited all but 1 isolate at ?2 ?g/ml (99.0% and 98.9%, respectively). Amikacin and gentamicin inhibited 64.9% and 56.7% of the CRE isolates at the respective CLSI breakpoints. Plazomicin inhibited 96.5 and 95.5% of the gentamicin-resistant isolates, 96.9 and 96.5% of the tobramycin-resistant isolates, and 64.3 and 90.0% of the amikacin-resistant isolates according to CLSI and EUCAST breakpoints, respectively. The activities of plazomicin against Pseudomonas aeruginosa (MIC50/MIC90, 4/16 ?g/ml) and Acinetobacter species (MIC50/MIC90, 2/16 ?g/ml) isolates were similar. Plazomicin was active against coagulase-negative staphylococci (MIC50/MIC90, 0.12/0.5 ?g/ml) and Staphylococcus aureus (MIC50/MIC90, 0.5/0.5 ?g/ml) but had limited activity against Enterococcus spp. (MIC50/MIC90, 16/64 ?g/ml) and Streptococcus pneumoniae (MIC50/MIC90, 32/64 ?g/ml). Plazomicin activity against the Enterobacteriaceae tested, including CRE and isolates carrying blaKPC from U.S. hospitals, supports the development plan for plazomicin to treat serious infections caused by resistant Enterobacteriaceae in patients with limited treatment options.

Project description:The activities of the novel β-lactam-β-lactamase inhibitor combination ceftazidime-avibactam and comparator agents were evaluated against a contemporary collection of clinically significant Gram-negative bacilli. Avibactam is a novel non-β-lactam β-lactamase inhibitor that inhibits Ambler class A, C, and some D enzymes. A total of 10,928 Gram-negative bacilli-8,640 Enterobacteriaceae, 1,967 Pseudomonas aeruginosa, and 321 Acinetobacter sp. isolates-were collected from 73 U.S. hospitals and tested for susceptibility by reference broth microdilution methods in a central monitoring laboratory (JMI Laboratories, North Liberty, IA, USA). Ceftazidime was combined with avibactam at a fixed concentration of 4 μg/ml. Overall, 99.8% of Enterobacteriaceae strains were inhibited at a ceftazidime-avibactam MIC of ≤4 μg/ml. Ceftazidime-avibactam was active against extended-spectrum β-lactamase (ESBL)-phenotype Escherichia coli and Klebsiella pneumoniae, meropenem-nonsusceptible (MIC≥2 μg/ml) K. pneumoniae, and ceftazidime-nonsusceptible Enterobacter cloacae. Among ESBL-phenotype K. pneumoniae strains, 61.1% were meropenem susceptible and 99.3% were inhibited at a ceftazidime-avibactam MIC of ≤4 μg/ml. Among P. aeruginosa strains, 96.9% were inhibited at a ceftazidime-avibactam MIC of ≤8 μg/ml, and susceptibility rates for meropenem, ceftazidime, and piperacillin-tazobactam were 82.0, 83.2, and 78.3%, respectively. Ceftazidime-avibactam was the most active compound tested against meropenem-nonsusceptible P. aeruginosa (MIC50/MIC90, 4/16 μg/ml; 87.3% inhibited at ≤8 μg/ml). Acinetobacter spp. (ceftazidime-avibactam MIC50/MIC90, 16/>32 μg/ml) showed high rates of resistance to most tested agents. In summary, ceftazidime-avibactam demonstrated potent activity against a large collection of contemporary Gram-negative bacilli isolated from patients in U.S. hospitals in 2012, including organisms that are resistant to most currently available agents, such as K. pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae and meropenem-nonsusceptible P. aeruginosa.

Project description:Enterobacteriaceae producing the Ambler class D OXA-48 carbapenemase, combined with additional resistance mechanisms, such as permeability defects or cocarriage of class A, B, or C β-lactamases, can become highly resistant to most β-lactams currently in use, including carbapenems. A total of 45,872 Enterobacteriaceae clinical isolates collected in 39 countries as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance study in 2012 to 2015 were tested for susceptibility to β-lactams and comparator agents using the Clinical and Laboratory Standards Institute broth microdilution methodology and screened for the presence of β-lactamases. The blaOXA-48 and blaOXA-48-like genes were detected in 333 isolates across 14 species of Enterobacteriaceae collected in 20 countries across the globe. Few agents tested were effective in vitro against the overall collection of OXA-48-producers (n = 265), with tigecycline (MIC90, 2 µg/ml; 92.5% susceptible), ceftazidime-avibactam (MIC90, 4 µg/ml; 92.5% susceptible), and aztreonam-avibactam (MIC90, 0.5 µg/ml; 99.6% of isolates with MIC ≤8 µg/ml) demonstrating the greatest activity. Similarly, colistin (MIC90, 1 µg/ml; 94.2% susceptible), tigecycline (MIC90, 2 µg/ml; 92.6% susceptible), ceftazidime-avibactam (MIC90, >128 µg/ml; 89.7% susceptible), and aztreonam-avibactam (MIC90, 4 µg/ml; 100% of isolates with MIC ≤8 µg/ml) were most active against OXA-48-like-positive isolates (n = 68). The in vitro activity of ceftazidime-avibactam was improved against the subset of metallo-β-lactamase (MBL)-negative, OXA-48- and OXA-48-like-positive isolates (99.2% and 100% susceptible, respectively). The data reported here support the continued investigation of ceftazidime-avibactam and aztreonam-avibactam for the treatment of infections caused by carbapenem-resistant Enterobacteriaceae carrying OXA-48 and OXA-48-like β-lactamases in combination with serine- or metallo-β-lactamases.

Project description:The activities of meropenem-vaborbactam and comparators against 152 (1.1%) carbapenem-resistant Enterobacterales (CRE) isolates identified among 13,929 Enterobacterales isolates collected from U.S. hospitals during 2016 to 2018 were evaluated. CRE rates were higher in the Middle Atlantic census division (3.5%) than in the other divisions (range, 0.0% for the West North Central division to 1.4% for the West South Central division). Among the CRE isolates, 134 carried carbapenemase genes, and these included 72 isolates carrying blaKPC-3, 51 isolates carrying blaKPC-2, 4 isolates carrying blaNDM-1, 3 isolates carrying blaSME-4, 2 isolates carrying blaVIM-1, 1 isolate carrying blaOXA-232, and 1 isolate carrying blaKPC-4 Meropenem-vaborbactam was active against 95.4% of the CRE isolates and 94.8% of the carbapenem-producing Enterobacterales (CPE) isolates when applying the CLSI breakpoints. All isolates producing serine carbapenemases were inhibited by meropenem-vaborbactam at ≤8 mg/liter. One Citrobacter freundii isolate carrying blaKPC-3 had a meropenem-vaborbactam MIC of 8 mg/liter and was resistant according to CLSI breakpoints (the isolate was susceptible when the EUCAST criterion of an MIC of ≤8 mg/liter for susceptible was applied), had disrupted OmpC and OmpF sequences, and overexpressed AcrAB-TolC. All carbapenemase-negative CRE isolates (n = 18) were inhibited by meropenem-vaborbactam at ≤4 mg/liter, and the MIC values of this combination ranged from 0.25 to 4 mg/liter. Among 7 isolates carrying metallo-β-lactamases and/or oxacillinases with carbapenemase activity, meropenem-vaborbactam susceptibility was 14.3% and 57.1% when applying CLSI and EUCAST breakpoints, respectively. CRE isolates were resistant to many comparator agents, and the most active agents were tigecycline, colistin, and amikacin (to which 63.2% to 96.7% of the isolates were susceptible). Understanding the epidemiology of CRE isolates in U.S. hospitals and the resistance mechanisms among these isolates is important to form guidelines for the treatment of infections caused by these organisms, which have high mortality rates.

Dataset Information

Low Frequency of Ceftazidime-Avibactam Resistance among Enterobacteriaceae Isolates Carrying blaKPC Collected in U.S. Hospitals from 2012 to 2015.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets