scholarly journals Comparison of In Vitro Antimicrobial Efficacy of The Ceftolozane-Tazobactam and Ceftazidime-Avibactam Combinations Against Carbapenem-Resistant Enterobacteriaceae Strains Isolated From Various Clinical Specimens.

2021 ◽  
Author(s):  
Mustafa GÜZEL ◽  
Duygu ÖCAL ◽  
İlke TOKER ÖNDER ◽  
Doğan AKDOĞAN ◽  
Gül BAHAR ERDEM ◽  
...  
Keyword(s):  
Antimicrobial Efficacy ◽  
Clinical Specimens ◽  
Carbapenem Resistant ◽  
Carbapenem Resistant Enterobacteriaceae

scholarly journals 621. In vitro Ceftazidime: Avibactam Resistance in Carbapenem-Resistant Enterobacteriaceae Isolates

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S288-S289
Author(s):  
Maymonah Belal ◽  
Lori Villasis ◽  
Elizabeth Diago-Navarro ◽  
Michael Motley ◽  
Allen Young; Eric Spitzer ◽  
...  
Keyword(s):  
Resistant Isolate ◽  
Ventilator Associated Pneumonia ◽  
Repeated Testing ◽  
Klebsiella Species ◽  
Carbapenem Resistant ◽  
Strain Collection ◽  
Enterobacter Species ◽  
Resistant Strains ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract Background Ceftazidime–avibactam (CAZ-AVI) is a new antibiotic with activity against many Carbapenem-resistant Enterobacteriaceae (CRE). Although CAZ-AVI resistance in CRE has been reported, it is not consistently assessed. Our study aimed to assess the prevalence of CAZ-AVI resistance in CRE isolated from patients with and without prior exposure to CAZ-AVI. Methods We tested 116 CRE isolates for CAZ-AVI resistance by Kirby–Bauer (KB) disk diffusion susceptibility. Resistant isolates were verified by repeat KB and E-test performed by the Stony Brook Hospital laboratory. The blaKPC gene of resistant strains was amplified by PCR and sequenced. Patient data were used to determine whether patients were colonized or infected, and whether they were exposed to CAZ-AVI. Results Of the 116 CRE isolates from 86 patients (96 encounters), 50% were Klebsiella species, 23.2% were Enterobacter species, 10.3% Escherichia coli and 16.5% other CRE. They were recovered from colonized (37%) and infected (63%) patients of which 18% were treated with CAZ-AVI during their hospitalizations (median duration of therapy, 6 days). Two CRE isolates (1.7%) were found to be resistant on repeated testing. One isolate was K. pneumoniae derived from the sputum of a patient diagnosed with ventilator-associated pneumonia who received 40 days of CAZ-AVI therapy prior to isolation of the resistant isolate (KB diameter 20 mm, MIC > 512 μg/mL by E-Test). Sequencing of the strain’s blaKPC3 gene revealed a previously described Ambler-position D179Y mutation that has been shown to convey resistance. The second CAZ-AVI-resistant K. pneumoniae (KB diameter 19 mm, MIC 64 μg/mL by E-test) was isolated from the urine of a colonized patient naïve to CAZ-AVI therapy. The strain’s blaKPC10 gene had no mutations. Conclusion In our strain collection, the rate of resistance to CAZ-AVI remains low <2%. Although we found one mutation (D179Y) previously linked to CAZ-AVI resistance we also discovered one K. pneumoniae isolate with in vitro resistance to CAZ-AVI that did not exhibit any blaKPC mutations conveying CAZ-AVI resistance. Interestingly, this strain was derived from a patient with no prior CAZ-AVI exposure. Whole-genome sequencing will be performed to identify other genes or mutations that may confer resistance. Disclosures All authors: No reported disclosures.

scholarly journals Unusual Escherichia coli PBP 3 Insertion Sequence Identified from a Collection of Carbapenem-Resistant Enterobacteriaceae Tested In Vitro with a Combination of Ceftazidime-, Ceftaroline-, or Aztreonam-Avibactam

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Yunliang Zhang ◽  
Ankita Kashikar ◽  
C. Adam Brown ◽  
Gerald Denys ◽  
Karen Bush
Keyword(s):  
Escherichia Coli ◽  
Health Care ◽  
Gene Duplication ◽  
Insertion Sequence ◽  
Penicillin Binding Protein ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Health Care Centers ◽  
Carbapenem Resistant Enterobacteriaceae

ABSTRACT Carbapenemase-producing Enterobacteriaceae isolates (n = 110) from health care centers in central Indiana (from 2010 to 2013) were tested for susceptibility to combinations of avibactam (4 μg/ml) with ceftazidime, ceftaroline, or aztreonam. MIC50/MIC90 values were 1/2 μg/ml (ceftazidime-avibactam), 0.5/2 μg/ml (ceftaroline-avibactam), and 0.25/0.5 μg/ml (aztreonam-avibactam.) A β-lactam MIC of 8 μg/ml was reported for the three combinations against one Escherichia coli isolate with an unusual TIPY insertion following Tyr344 in penicillin-binding protein 3 (PBP 3) as the result of gene duplication.

scholarly journals Bactericidal Efficacy of Meropenem in Combination with Cefmetazole against IMP-producing Carbapenem-Resistant Enterobacteriaceae

2019 ◽  
Author(s):  
Ryuichiro Abe ◽  
Hideharu Hagiya ◽  
Yukihiro Akeda ◽  
Norihisa Yamamoto ◽  
Yoshikazu Ishii ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Animal Studies ◽  
Bactericidal Effect ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Enterobacter Hormaechei ◽  
Time Kill ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract Objective: Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to public and clinical health because of their high levels of resistance to various antibiotics. We assessed the efficacy of combination therapy with meropenem (MEM) and cefmetazole (CMZ) against Imipenemase (IMP)-producing CRE, using the checkerboard method and time-killing assay on 13 Enterobacteriaceae isolates harboring blaIMP-1 (4 Enterobacter hormaechei, 5 Escherichia coli, and 4 Klebsiella pneumoniae isolates) and 13 isolates harboring blaIMP-6 (8 E. coli and 5 K. pneumoniae isolates). Results: Minimum inhibitory concentrations (MICs) of MEM and CMZ ranged from 2 to 64 and 64 to 2048 μg/mL, respectively. Checkerboard method demonstrated the synergy of the MEM/CMZ combination in all the tested IMP-producing CRE isolates, and the time-kill assay indicated a bactericidal effect for both blaIMP-1 and blaIMP-6 positive CRE when MEM/CMZ combination was used. In vitro, the MEM/CMZ combination was potentially effective against IMP-1- or IMP-6-producing CRE. Further investigations including in vivo animal studies and clinical studies are warranted to corroborate the clinical utility of the novel combination therapy.

scholarly journals Effects of KPC Variant and Porin Genotype on the In Vitro Activity of Meropenem-Vaborbactam against Carbapenem-Resistant Enterobacteriaceae

2019 ◽  
Vol 63 (3) ◽  
Author(s):  
William R. Wilson ◽  
Ellen G. Kline ◽  
Chelsea E. Jones ◽  
Kristin T. Morder ◽  
Roberta T. Mettus ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Disk Diffusion ◽  
Broth Microdilution ◽  
Wild Type ◽  
Content Type ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Strip Testing ◽  
Carbapenem Resistant Enterobacteriaceae

ABSTRACT Meropenem-vaborbactam is a new agent with the potential to treat carbapenem-resistant Enterobacteriaceae (CRE) infections. We describe the in vitro activity of meropenem-vaborbactam against representative CRE genotypes and laboratory-engineered Escherichia coli isolates harboring mutant blaKPC genes associated with ceftazidime-avibactam resistance. We also compared disk diffusion and gradient strip testing methods to standard broth microdilution methods. Against 120 CRE isolates, median ceftazidime-avibactam and meropenem-vaborbactam MICs were 1 and 0.03 µg/ml, respectively. Ninety-eight percent (117/120) of isolates were susceptible to meropenem-vaborbactam (MICs ≤ 4 µg/ml). Against Klebsiella pneumoniae isolates harboring mutant blaKPC, the addition of vaborbactam lowered the meropenem MICs in 78% of isolates (14/18); 100% were susceptible to meropenem-vaborbactam. Median meropenem-vaborbactam MICs were higher against K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates with mutant ompK36 porin genes (n = 26) than against those with wild-type ompK36 porin genes (n = 54) (0.25 versus 0.03 µg/ml; P < 0.0001). Against E. coli TOP10 isolates with plasmid constructs containing wild-type blaKPC or mutant blaKPC, the addition of vaborbactam at 8 µg/ml lowered the meropenem MICs 2- to 512-fold, resulting in meropenem-vaborbactam MICs of 0.03 µg/ml. The rates of categorical agreement with broth microdilution for disk diffusion or gradient strips ranged from 90 to 95%. Essential agreement rates were higher for research-use-only (RUO) gradient strips manufactured by bioMérieux (82%) than for those manufactured by Liofilchem (48%) (P < 0.0001). Taken together, our data highlight the potent in vitro activity of meropenem-vaborbactam against CRE, including isolates resistant to ceftazidime-avibactam. Vaborbactam inhibited both wild-type and variant KPC enzymes. On the other hand, KPC-producing K. pneumoniae isolates with ompK36 mutations displayed higher meropenem-vaborbactam MICs than isolates with wild-type ompK36. The results of susceptibility testing with RUO bioMérieux gradient strips most closely aligned with those of broth microdilution methods.

scholarly journals 685. An In Vitro Investigation of WCK 5222 (Cefepime/Zidebactam) and Currently Available Combination Antibiotic Regimens Against Enterobacteriaceae That Co-express Serine-β-Lactamase (SBL) and Metallo-β-Lactamase (MBL) Enzymes

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S311-S312
Author(s):  
Lindsay M Avery ◽  
Elias M Mullane ◽  
David P Nicolau
Keyword(s):  
In Vivo Evaluation ◽  
Carbapenem Resistant ◽  
Gradient Diffusion ◽  
In Vitro Investigation ◽  
Point Of Intersection ◽  
Combination Regimens ◽  
Concentration Indices ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract Background Carbapenem-resistant Enterobacteriaceae (CRE) that simultaneously harbor SBLs and MBLs may demonstrate pan-drug resistance. Current therapeutic options include combinations of aztreonam (ATM), which is resistant to hydrolysis by MBLs, plus ceftazidime/avibactam (CZA) or meropenem/vaborbactam (M/V) for coverage of relevant SBLs. However, these selections add a level of complexity to clinical management compared with administration of a single antibiotic as monotherapy. Methods Minimum inhibitory concentrations (MICs) of WCK 5222 (cefepime/zidebactam), ATM, CZA, and M/V were determined with Liofilchem MIC Test Strips against SBL- and MBL-positive CRE (N = 15). The gradient diffusion strip (GDS) cross method was used to assess the activities of CZA+ATM and M/V+ATM. Additive interactions as defined by fractional inhibitory concentration indices ≤ 1 would be predicted based upon the known genotypic profiles; thus, the relative activities of the combination regimens were compared with the “zone of hope” (ZOH) test. The size of the ZOH (the zone of inhibited growth) was quantitated by multiplying the observed length of inhibited growth (in mm) adjacent to each GDS from the point of intersection. The Mann–Whitney rank-sum test was used to assess differences. Results All isolates (N = 15) contained one MBL and ≥1 SBL, and were resistant to ATM, CZA, and M/V with the exception of one isolate intermediate to M/V (MIC=8 mg/L). The WCK 5222 MIC50 (range) was 1 (0.19–2) mg/L. The median (interquartile range) ZOH product for CZA+ATM and M/V+ATM was 75.4 (62.8–93.7) and 23.5 (14.1–60.4), respectively (P = 0.002). In strains that produced OXA-type carbapenemases (n = 6), the median ZOH product for CZA+ATM and M/V+ATM was 78.1 and 20.7, respectively (P = 0.004). In the remaining 9 strains with a single carbapenemase (i.e., the MBL),the median ZOH product for CZA+ATM and M/V+ATM was 73.8 and 25.6, respectively (P = 0.052). Conclusion WCK 5222 displayed potent in vitro activity against SBL- and MBL-positive CRE, warranting further pre-clinical in vivo evaluation as a monotherapy option. When considering the co-expression of SBL and MBL, CZA+ATM appears to offer enhanced coverage compared with M/V+ATM. Disclosures All authors: No reported disclosures.

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