Determination of Disk Diffusion and MIC Quality Control Guidelines for High-Dose Cefepime-Tazobactam (WCK 4282), a Novel Antibacterial Combination Consisting of a β-Lactamase Inhibitor and a Fourth-Generation Cephalosporin

Riedel, Stefan; Huband, Michael D.; Sader, Hélio S.; Flamm, Robert K.; Jones, Ronald N.

doi:10.1128/jcm.00788-17

Cited by 3 publications

(4 citation statements)

References 6 publications

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“…An MIC QC range of Ն64 g/ml was previously established for cefepime against E. coli NCTC 13353, and all cefepime MIC replicates in this study were determined to be Ͼ128 g/ml. This strain has been recommended previously as a routine QC strain for testing cefepimetazobactam (35,36) and likewise serves as an appropriate control to assess the functionality of enmetazobactam in combination with cefepime. It is, therefore, recommended as a routine QC strain to assess cefepime-enmetazobactam performance in broth microdilution and disk diffusion assays.…”

Section: Discussionmentioning

confidence: 99%

Development of Broth Microdilution MIC and Disk Diffusion Antimicrobial Susceptibility Test Quality Control Ranges for the Combination of Cefepime and the Novel β-Lactamase Inhibitor Enmetazobactam

Belley¹,

Huband

Fedler

et al. 2019

J Clin Microbiol

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Third-generation cephalosporin resistance among Enterobacteriaceae, mediated by the spread of extended-spectrum ␤-lactamases (ESBLs), is a very serious medical concern with limited therapeutic options. Enmetazobactam (formerly AAI101) is a novel penicillanic sulfone ␤-lactamase inhibitor active against a wide range of ESBLs. The combination of enmetazobactam and cefepime has entered phase 3 development in patients with complicated urinary tract infections. Using the Clinical and Laboratory Standards Institute (CLSI) M23 tier 2 study design, broth microdilution MIC and disk diffusion quality control (QC) ranges were determined for cefepime-enmetazobactam. Enmetazobactam was tested at a fixed concentration of 8 g/ml in the MIC assay, and a cefepime-enmetazobactam disk mass of 30/20 g was used in the disk diffusion assay. Escherichia coli ATCC 25922, E. coli ATCC 35218, E. coli NCTC 13353, Klebsiella pneumoniae ATCC 700603, and Pseudomonas aeruginosa ATCC 27853 were chosen as reference strains. The CTX-M-15-producing E. coli NCTC 13353 isolate is recommended for routine testing to control for inhibition of ESBL activity by enmetazobactam. Broth microdilution MIC QC ranges spanned 3 to 4 doubling dilutions and contained 99.6% to 100.0% of obtained MIC values for the five reference strains. Disk diffusion yielded inhibition zone diameter QC ranges that spanned 7 mm and encompassed 97.1% to 100.0% of the obtained values. Quality control ranges were approved by the CLSI in 2017 (broth microdilution MIC) and 2019 (disk diffusion). The established QC ranges will ensure that appropriate assay performance criteria are attained using CLSI reference methodology when determining the susceptibility of clinical isolates to cefepime-enmetazobactam.

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Section: Discussionmentioning

confidence: 99%

Development of Broth Microdilution MIC and Disk Diffusion Antimicrobial Susceptibility Test Quality Control Ranges for the Combination of Cefepime and the Novel β-Lactamase Inhibitor Enmetazobactam

Belley¹,

Huband

Fedler

et al. 2019

J Clin Microbiol

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“…The agar disk diffusion technique was used to test the bacteria's susceptibility to a panel of 16 antibiotics from various classes, including the including Ampicillin(Am), Amoxillin+clavulanic acid (AMC), Piperacillin-tazobactam (TZP), Ceftriaxone (CRO), Ceftazidime (CAZ), Cefepime(FEB), Cefoxitin(CFM), Cefotaxime (CTX), Meropenem(MRP), Imipenem(IMI), Gentamicin(CN), Tetracyclin (TE),Trimethoprim/ Sulphamethoxazole (SXT), Chloramphenicol(C), Ciprofloxacin(CIP) and Colistin(CS) were tested using the agar disk diffusion method [15,16]. Using sterile swabs, pure cultures of known bacteria were suspended and then dispersed on Muller Hinton agar (Oxoid, UK) media using a 0.85 % saline to 0.5 McFarland turbidity criteria.…”

Section: Antibiotics-susceptibility Patternsmentioning

confidence: 99%

Molecular Detection of Plasmid-mediated colistin-resistance genes in Multi-drug resistant Escherichia coli isolated from human and poultry in Duhok city, Iraq

said,

yassin

2024

Egyptian Journal of Veterinary Sciences

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HE plasmid-borne colistin resistance gene mcr-types were formerly recognized as plasmidmediated colistin mechanism among clinical and animal samples Escherichia coli from China and thereafter reported worldwide. The study investigated for screening of plasmid-mediated colistin and carbapenems resistant genes in Escherichia coli isolates from human and poultry origin. After isolation and identification of isolates from clinical specimens and poultry cloacal swab, disc diffusion and broth microdilution method were determined antibiotic susceptibility patterns, phenotypic Extended-Spectrum Beta-lactamase enzymes (ESBL)-production test and phenotypic colistin resistance. Molecular detection by PCR was applied to targeted carbapenems-resistance genes (KPC-2, OXA-48 and NDM-1) and colistin-resistant genes (mcr-1, mcr-2 and mcr-3). The majority of isolates were higher resistance to commonly used antibiotic categories with Multi-Drug Resistance (63 %) and (93 %) of clinical and poultry E coli isolate, respectively. Using broth microdilution (16%) of isolates displayed phenotypic colistin resistance. Human isolates had higher NDM-1 gene (33.3%), while, higher OXA-48 gene (22.2%) was in poultry isolates, and no KPC-2 gene was identified. Only isolates from poultry contained the mcr-1 gene (27.7%), while mcr-2 gene was present only in human isolates (4.7%) and mcr-3 gene in both human (33.3%) and poultry (22.2%) isolates. Negative mcr-1, 2, and 3 isolates expressed high rates of ESBLproduction. The coexistence of (mcr-3 + NDM-1) was frequent, including 10 isolates, and one isolate carried (mcr-2+mcr-3+NDM-1) combination from urine samples. Data of colistin resistance among clinical and poultry isolates in this region is scarce. Identification of colistin and carbapenems-resistance genes via plasmids among those isolates menace and approaches pan-resistance and failure treatment.

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“…Cefepime-tazobactam (FEP-TAZ) consists of 2 g cefepime plus 2 g tazobactam that is administered every 8 h via a 90-min infusion as a therapeutic option for the treatment of Gram-negative bacterial infections prevalent in hospital settings, such as complicated urinary tract infections, nosocomial pneumonia, and complicated intraabdominal infections (1)(2)(3)(4)(5)(6)(7). Both cefepime and tazobactam have been extensively evaluated.…”

mentioning

confidence: 99%

“…The dosing of cefepime at 1 g every 12 h (q12h) is considered a low dose, and the dosing of cefepime at 2 g every 8 h (q8h) is considered a high dose (7). Cefepime-tazobactam combines an AmpC-stable cephalosporin with an established inhibitor which is active against extended-spectrum ␤-lactamases (ESBLs) (1)(2)(3)(4)(5)(6)(7). Cefepime-tazobactam is active against Pseudomonas aeruginosa and Enterobacteriaceae strains, including ESBL screening-positive-phenotype Escherichia coli strains and ceftazidime-nonsusceptible Enterobacter spp.…”

mentioning

confidence: 99%

Single-Center Investigation of the Pharmacokinetics of WCK 4282 (Cefepime-Tazobactam Combination) in Renal Impairment

Preston

Mamikonyan²,

Mastim

et al. 2019

Antimicrob Agents Chemother

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WCK 4282 is a combination product of cefepime (FEP) and tazobactam (TAZ) in a 1:1 ratio currently under development for the treatment of multidrug-resistant Gram-negative bacterial infections. We investigated the effect of renal impairment on the pharmacokinetics (PK) and safety of WCK 4282 in 48 subjects with various degrees of renal function. Subjects were categorized on the basis of their Cockcroft-Gault equation-estimated creatinine clearance (CLCR). We enrolled 6 subjects each into those with mild (CLCR, 60 to <90 ml/min), moderate (CLCR, 30 to <60 ml/min), or severe (CLCR, <30 ml/min) renal impairment and those with end-stage renal disease (ESRD) requiring hemodialysis and 24 healthy control subjects (CLCR, ≥90 ml/min). Healthy subjects and subjects with mild and moderate renal impairment received a single 90-min infusion of 4 g of WCK 4282 (2 g FEP and 2 g TAZ). Subjects with severe renal impairment and ESRD received 2 g of WCK 4282 (1 g FEP and 1 g TAZ) over 90 min. The plasma exposure of FEP-TAZ increased as renal function decreased. In subjects with mild, moderate, and severe renal impairment and ESRD, the mean exposure (area under the plasma concentration versus time curve from time zero extrapolated to infinity) of FEP and TAZ increased by 1.3- and 1.2-fold, 2.3- and 2.3-fold, 4.7- and 4.0-fold, and 8.5- and 11.6-fold, respectively. The urinary recovery of FEP and TAZ decreased with increasing renal impairment. There were no adverse events reported during the study. The findings suggest that dose adjustments for WCK 4282 will be required according to the degree of renal impairment. A single infusion of WCK 4282 was found to be safe and well tolerated in subjects with normal and impaired renal function. (This study has been registered at ClinicalTrials.gov under identifier NCT02709382.)

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Determination of Disk Diffusion and MIC Quality Control Guidelines for High-Dose Cefepime-Tazobactam (WCK 4282), a Novel Antibacterial Combination Consisting of a β-Lactamase Inhibitor and a Fourth-Generation Cephalosporin

Cited by 3 publications

References 6 publications

Development of Broth Microdilution MIC and Disk Diffusion Antimicrobial Susceptibility Test Quality Control Ranges for the Combination of Cefepime and the Novel β-Lactamase Inhibitor Enmetazobactam

Development of Broth Microdilution MIC and Disk Diffusion Antimicrobial Susceptibility Test Quality Control Ranges for the Combination of Cefepime and the Novel β-Lactamase Inhibitor Enmetazobactam

Molecular Detection of Plasmid-mediated colistin-resistance genes in Multi-drug resistant Escherichia coli isolated from human and poultry in Duhok city, Iraq

Single-Center Investigation of the Pharmacokinetics of WCK 4282 (Cefepime-Tazobactam Combination) in Renal Impairment

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