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- | Journal: Innovative β-lactam/β-lactamase inhibitor combinations for carbapenem-resistant Gram-negative bacteria. (Pubmed Central) - Apr 5, 2022
No abstract available
- || taniborbactam (VNRX-5133) / VenatoRx
Clinical, Journal, Combination therapy: Assessment of activity and resistance mechanisms to cefepime in combination with the novel β-lactamase inhibitors zidebactam, taniborbactam and enmetazobactam against a multicenter collection of carbapenemase-producing Enterobacterales. (Pubmed Central) - Mar 23, 2022
These results confirm the therapeutic potential of the new β-lactamase inhibitors, shedding light on the activity of cefepime and BLIs against CPE and resistance mechanisms. The cefepime/zidebactam and cefepime/taniborbactam combinations are particularly highlighted as promising alternatives to penicillin-based inhibitors for the treatment of CPE.
- | cefepime/zidebactam IV (WCK 5222) / Wockhardt
Journal: Molecular Characterization of WCK 5222 (Cefepime/Zidebactam)-Resistant Mutants Developed from a Carbapenem-Resistant Pseudomonas aeruginosa Clinical Isolate. (Pubmed Central) - Mar 18, 2022
Our results revealed that mutations in the zidebactam target protein PBP2 play a major role in the bacterial resistance to WCK 5222. We further demonstrated that the mutations reduced the affinities between PBP2 and zidebactam and resulted in functional resistance of PBP2 to zidebactam.
- | Preclinical, Journal: In vitro activity of cefiderocol, cefepime/zidebactam, cefepime/enmetazobactam, omadacycline, eravacycline, and other comparative agents against carbapenem-nonsusceptible Enterobacterales: Results from the Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART) in 2017-2020. (Pubmed Central) - Dec 16, 2021
The MICs of omadacycline were significantly higher than those of eravacycline and tigecycline. In summary, cefiderocol, ceftazidime/avibactam, and cefepime/zidebactam were more effective against CNS E. coli and K. pneumoniae, than other drugs; highlighting their potential as valuable therapeutics.
- || Clinical, Review, Journal: Role of new antibiotics in extended-spectrum β-lactamase-, AmpC- infections. (Pubmed Central) - Dec 16, 2021
New therapeutic agents against ESBL- and AmpC-producing Enterobacterales have distinctive specificities and limitations that require further investigations. Future randomized clinical trials are required to define the best strategy for their use in patients with serious infections due to ESBL- and/or AmpC- infections.
- ||||| cefepime/zidebactam IV (WCK 5222) / Wockhardt
Trial initiation date: Study of Cefepime-zidebactam (FEP-ZID) in Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP) (clinicaltrials.gov) - Nov 9, 2021
P3, N=504, Not yet recruiting, Sponsor: Wockhardt
Future randomized clinical trials are required to define the best strategy for their use in patients with serious infections due to ESBL- and/or AmpC- infections. Initiation date: Oct 2021 --> Jan 2022
- | cefepime/zidebactam IV (WCK 5222) / Wockhardt
Journal: Activity of β-lactam plus β-lactam-enhancer combination cefepime/zidebactam against Klebsiella pneumoniae harbouring defective OmpK35/36 porins and carbapenemases. (Pubmed Central) - Nov 4, 2021
Against these isolates, cefepime/zidebactam (1:1) showed a consistent activity (MICs ≤4 mg/L). In conclusion, cefepime/zidebactam overcomes enzymatic, and non-enzymatic carbapenem-impacting resistance mechanisms concurrently expressed in K. pneumoniae.
- | cefepime/zidebactam IV (WCK 5222) / Wockhardt
Preclinical, Journal: In vitro evolution of cefepime/zidebactam (WCK 5222) resistance in Pseudomonas aeruginosa: dynamics, mechanisms, fitness trade-off and impact on in vivo efficacy. (Pubmed Central) - Oct 30, 2021
In conclusion, cefepime/zidebactam overcomes enzymatic, and non-enzymatic carbapenem-impacting resistance mechanisms concurrently expressed in K. pneumoniae. Development of cefepime/zidebactam resistance in P. aeruginosa required multiple simultaneous mutations that were associated with a significant impairment of fitness and virulence.
- | cefepime/zidebactam IV (WCK 5222) / Wockhardt
Preclinical, Journal: Comparative in vivo activity of human-simulated plasma and epithelial lining fluid exposures of WCK 5222 (cefepime/zidebactam) against KPC- and OXA-48-like-producing Klebsiella pneumoniae in the neutropenic murine pneumonia model. (Pubmed Central) - Oct 29, 2021
Development of cefepime/zidebactam resistance in P. aeruginosa required multiple simultaneous mutations that were associated with a significant impairment of fitness and virulence. Clinically achievable WCK 5222 plasma and ELF exposures produced in vivo killing of carbapenem-resistant Enterobacterales in the neutropenic murine pneumonia model that is predictive of efficacy in humans.
- || Review, Journal: New β-Lactam-β-Lactamase Inhibitor Combinations. (Pubmed Central) - Oct 6, 2021
These drugs provide various levels of in vitro coverage of carbapenem-resistant Enterobacterales, with several drugs presenting in vitro activity against MBLs (cefepime-zidebactam, aztreonam-avibactam, meropenem-nacubactam, and cefepime-taniborbactam). Among these drugs, some also present in vitro activity against carbapenem-resistant P. aeruginosa (cefepime-zidebactam and cefepime-taniborbactam) and A. baumannii (cefepime-zidebactam and sulbactam-durlobactam).
- | cefepime/zidebactam IV (WCK 5222) / Wockhardt
Preclinical, Journal: In vitro activity of cefepime/zidebactam (WCK 5222) against recent Gram-negative isolates collected from high resistance settings of Greek hospitals. (Pubmed Central) - Sep 22, 2021
Other antibiotics including colistin showed limited activity against A. baumannii. The activity of cefepime/zidebactam against multi-drug-resistant isolates is attributable to zidebactam mediated novel β-lactam-enhancer mechanism.
- | Preclinical, Journal: In vitro activity of imipenem/relebactam, meropenem/vaborbactam, ceftazidime/avibactam, cefepime/zidebactam and other novel antibiotics against imipenem-non-susceptible Gram-negative bacilli from Taiwan. (Pubmed Central) - Aug 12, 2021
β-Lactam/BLI-BLE combinations were active in a higher proportion of INS-EC, INS-KP and INS-PA. The susceptibility of novel fluoroquinolones and tetracyclines was not superior to that of old ones.
- || Review, Journal: Is it time to move away from polymyxins?: evidence and alternatives. (Pubmed Central) - Aug 6, 2021
For the management of MBL infections, clinically used triple combination comprising ceftazidime-avibactam and aztreonam is hindered due to non-availability of antimicrobial susceptibility testing methods and lack of information on potential drug-drug interaction leading to PK changes impacting its safety and efficacy...With the recent evidence of suboptimal PK/PD particularly in lung environment, limited efficacy and increased nephrotoxicity associated with polymyxin use, the Clinical and Laboratory Standards Institute (CLSI) has revised both colistin and polymyxin B breakpoints...This change has questioned the dependency on polymyxins in treating XDR infections. In this context, recently approved cefiderocol and phase 3 stage combination drug cefepime-zidebactam assume greater significance due to their potential to act as polymyxin-supplanting therapies.
- |||||||||| cefepime/zidebactam IV (WCK 5222) / Wockhardt
New P3 trial: Study of Cefepime-zidebactam (FEP-ZID) in Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP) (clinicaltrials.gov) - Jul 28, 2021
P3, N=504, Not yet recruiting, Sponsor: Wockhardt
- | Journal: Treatment of extended-spectrum β-lactamases infections: what is the current role of new β-lactams/β-lactamase inhibitors? (Pubmed Central) - Jul 11, 2021
New BL/BLI have distinctive specificities and limitations that require further investigations. Future randomized clinical trials are required to define the best strategy for their administering for ESBL infections.
- | cefepime/zidebactam IV (WCK 5222) / Wockhardt
Journal: Activity of cefepime/zidebactam (WCK 5222) against 'problem' antibiotic-resistant Gram-negative bacteria sent to a national reference laboratory. (Pubmed Central) - Jul 11, 2021
Future randomized clinical trials are required to define the best strategy for their administering for ESBL infections. Assuming successful clinical trials, cefepime/zidebactam has scope to widely overcome critical resistances in both Enterobacterales and non-fermenters.
- | rifampicin / Generic mfg.
Journal: Susceptibility of Elizabethkingia spp. to commonly tested and novel antibiotics and concordance between broth microdilution and automated testing methods. (Pubmed Central) - Jul 7, 2021
Assuming successful clinical trials, cefepime/zidebactam has scope to widely overcome critical resistances in both Enterobacterales and non-fermenters. MDR, absence of standard interpretation criteria and poor intermethod concordance necessitate working guidelines to facilitate future research of emerging Elizabethkingia spp.
- | cefepime hydrochloride / Generic mfg.
Journal, Combination therapy: An update on cefepime and its future role in combination with novel β-lactamase inhibitors for MDR Enterobacterales and Pseudomonas aeruginosa. (Pubmed Central) - Jul 7, 2021
Cefepime/enmetazobactam has completed Phase III and cefepime/taniborbactam is in Phase III clinical studies, where they are being tested against carbapenems or piperacillin/tazobactam for the treatment of complicated urinary tract infections. While these combinations are promising, their role in the treatment of MDR Gram-negative infections can only be determined with further clinical studies.
- | cefepime/zidebactam IV (WCK 5222) / Wockhardt
Journal: Effective inhibition of PBPs by cefepime and zidebactam in the presence of VIM-1 drives potent bactericidal activity against MBL-expressing Pseudomonas aeruginosa. (Pubmed Central) - Jun 26, 2021
For the first time ever (to the best of our knowledge), this study demonstrates that in the presence of VIM-1 MBL, β-lactamase-labile cefepime and β-lactamase-stable zidebactam produce effective inhibition of respective target PBPs. For cefepime, this seems to be a result of a faster rate of PBP binding, which helps it overcome β-lactamase-mediated hydrolysis.
- | cefepime/zidebactam IV (WCK 5222) / Wockhardt
Journal: Activity of cefepime/zidebactam against MDR Escherichia coli isolates harbouring a novel mechanism of resistance based on four-amino-acid inserts in PBP3. (Pubmed Central) - Jun 26, 2021
coli isolates concurrently harbouring four-amino-acid inserts in PBP3 and NDM are an emerging therapeutic challenge. Assisted by the PBP2-binding action of zidebactam, the cefepime/zidebactam combination overcomes both target modification (PBP3 insert)- and carbapenemase (NDM)-mediated resistance mechanisms in E. coli.
- | cefepime/zidebactam IV (WCK 5222) / Wockhardt
Preclinical, Journal: In Vitro Activity of WCK 5222 (Cefepime-Zidebactam) against Worldwide Collected Gram-Negative Bacilli Not Susceptible to Carbapenems. (Pubmed Central) - Jun 22, 2021
The activity of cefepime-zidebactam against carbapenem-resistant Gram-negatives is ascribed to its β-lactam enhancer mechanism of action (i.e., zidebactam binding to PBP2 and its universal stability to both serine β-lactamases and MBLs). The results from this study support the continued development of cefepime-zidebactam as a potential therapy for infections caused by Enterobacterales, P. aeruginosa, and other non-fermentative Gram-negative bacilli where resistance to marketed antimicrobial agents is a limiting factor.
- | cefepime/zidebactam IV (WCK 5222) / Wockhardt, Zavicefta (ceftazidime/avibactam) / Pfizer, AbbVie
Preclinical, Journal: In Vitro Activity of Cefepime-Zidebactam, Ceftazidime-Avibactam and Other Comparators against Clinical Isolates of Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii: Results from China Antimicrobial Surveillance Network (CHINET) in 2018. (Pubmed Central) - Jun 22, 2021
Cefepime-zidebactam demonstrated limited activity (MIC, 16/32 mg/L) against the 515 A. baumannii (79.2% were carbapenem-resistant) isolates, and ceftazidime-avibactam were less active (MIC, 64/>64 mg/L). Cefepime-zidebactam was highly active against clinical isolates of Enterobacterales and P. aeruginosa, including bla-positive Enterobacterales and bla-positive Enterobacterales and carbapenem-resistant P. aeruginosa And ceftazidime-avibactam was highly active against bla-positive Enterobacterales and carbapenem-resistant P. aeruginosa.
- | cefepime/zidebactam IV (WCK 5222) / Wockhardt, Vabomere (meropenem/vaborbactam) / Melinta Therap
Journal: Emergence and Recovery of Ceftazidime-avibactam Resistance in blaKPC-33-Harboring Klebsiella pneumoniae Sequence Type 11 Isolates in China. (Pubmed Central) - Apr 28, 2021
The blaKPC-33-containing K. pneumoniae was susceptible to meropenem-vaborbactam, cefepime-zidebactam, tigecycline, and polymyxin B. The blaKPC-33 gene was located on a 77 551-bp transformable plasmid harboring qnrS1 and blaLAP-2. Detecting blaKPC-33-positive K. pneumoniae clinical strains is important for infection control.
- | cefepime/zidebactam IV (WCK 5222) / Wockhardt
Preclinical, Journal: Comparative evaluation of the in vitro activities of WCK 5222 (cefepime/zidebactam) and combination antibiotic therapies against carbapenem-resistant Pseudomonas aeruginosa. (Pubmed Central) - Dec 18, 2020
WCK 5222 MICs ranged 2-32 mg/L and 97% were ≤16 mg/L while 105/146 (72%) combinations demonstrated inhibition below established susceptibility breakpoints. WCK 5222 monotherapy may be preferred over the combinations assessed for CRP infections.
- | cefepime/zidebactam IV (WCK 5222) / Wockhardt
Preclinical, Journal, Combination therapy: Evaluation of the in vitro activity of WCK 5222 (cefepime/zidebactam) and currently available combination therapies against single- and double-carbapenemase producing Enterobacteriaceae: Expanding the zone of hope. (Pubmed Central) - Nov 25, 2020
Thus, CZA+ATM may offer enhanced coverage over M/V+ATM of Enterobacteriaceae co-expressing MBL and SBL. With potent in vitro activity alone, further preclinical in vivo evaluations of WCK 5222 monotherapy are warranted.
- | Journal: Treatment of severe infections due to metallo-β-lactamases-producing Gram-negative bacteria. (Pubmed Central) - Nov 5, 2020
Other agents showing in vitro activity against MBL-GNB are currently in clinical development (e.g., cefepime/taniborbactam, LYS228, cefepime/zidebactam) that could be an important addition to our future armamentarium for severe MBL-GNB infections. Nonetheless, we should not discontinue our efforts to optimize the use of non-β-lactams agents, since they could remain an essential last-resort or alternative option in selected cases.
- || cefepime/zidebactam IV (WCK 5222) / Wockhardt, Zavicefta (ceftazidime/avibactam) / Pfizer, AbbVie
PK/PD data, Preclinical, Journal: Relevance of preclinical rodent pharmacokinetics in the selection of a companion antibiotic for combining with beta-lactamase inhibitor. (Pubmed Central) - Jul 22, 2020
The observed ratio for CL/V observed in rats agreed with corresponding human ratios for the pair wise comparison of the individual drugs in the combinations.6. Retrospectively, current pharmacokinetic findings suggest rat pharmacokinetic data may aid the combination of BLI with an appropriate antibiotic.
- | cefepime/zidebactam IV (WCK 5222) / Wockhardt
Journal: Activity of cefepime/zidebactam (WCK 5222) against Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii endemic to New York City medical centres. (Pubmed Central) - Jul 18, 2020
Cefepime/zidebactam demonstrated excellent activity against Enterobacteriaceae and P. aeruginosa, although activity was reduced in carbapenem-non-susceptible isolates. The activity against A. baumannii was reduced and studies examining the therapeutic efficacy in strains with high cefepime/zidebactam MICs are warranted.
- | cefepime/zidebactam IV (WCK 5222) / Wockhardt, meropenem / Generic mfg., Daewon Pharmaceutical
Preclinical, Journal: In Vivo Efficacy of WCK 5222 (Cefepime-Zidebactam) against Multidrug-Resistant Pseudomonas aeruginosa in the Neutropenic Murine Thigh Infection Model. (Pubmed Central) - May 19, 2020
WCK 5222 MICs ranged from 4 to 32 μg/ml. Substantial in vivo WCK 5222 activity was observed against all isolates, further enhancing the efficacy of zidebactam alone in 11/16 isolates (WCK 5222 mean reduction, -1.62 ± 0.58 log CFU/thigh), and a lack of activity was observed with cefepime monotherapy.
- || cefepime/zidebactam IV (WCK 5222) / Wockhardt
PK/PD data, Preclinical, Journal: A Novel β-lactam Enhancer Zidebactam Augments the In vivo Pharmacodynamic Activity of Cefepime in Neutropenic Mouse Lung A. baumannii Infection Model. (Pubmed Central) - Mar 14, 2020
WCK 5222 is a combination of cefepime and the high-affinity PBP2-binding β-lactam enhancer zidebactam...Thus, zidebactam mediated improvement in cefepime's bactericidal effect observed in time-kill studies manifested in vivo through lowering of cefepime's pharmacodynamic requirement. This is a first ever study demonstrating β-lactam enhancer role of zidebactam that helps augment in vivo activity of cefepime by reducing the magnitude of its pharmacodynamically relevant exposures against A. baumannii.
- || Clinical, Review, Journal: Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections. (Pubmed Central) - Feb 24, 2020
A section is devoted to reviewing upcoming active drugs such as imipenem-relebactam, cefepime-zidebactam, cefiderocol, and murepavadin. Finally, other therapeutic strategies, such as use of vaccines, antibodies, bacteriocins, anti-quorum sensing, and bacteriophages, are described as future options.
- cefepime/zidebactam IV (WCK 5222) / Wockhardt
Complementary inhibition of penicillin binding proteins by cefepime and zidebactam in presence of VIM-1 results in potent in vitro and in vivo bactericidal action against metallo-β-lactamase producing Pseudomonas aeruginosa () - Feb 4, 2020 - Abstract #ECCMID2020ECCMID_5135;
Finally, other therapeutic strategies, such as use of vaccines, antibodies, bacteriocins, anti-quorum sensing, and bacteriophages, are described as future options. The results show that cefepime and zidebactam effectively bind to respective target PBPs in the presence of MBL; presumably, as a result of cefepime faster rate of PBP binding which helps evade β-lactamase mediated hydrolysis.
- The role of non-tuberculous mycobacteria in patients with cystic fibrosis (Arena 5) - Feb 4, 2020 - Abstract #ECCMID2020ECCMID_3952;
The mean age was higher in patients with positive culture for NTM compared to those with negative culture. We can conclude that this type of infection is related to the exposure time, which increases with the age of the patients.
- || cefepime/zidebactam IV (WCK 5222) / Wockhardt
Clinical, PK/PD data, Journal: Single-Center Evaluation of the Pharmacokinetics of WCK 5222 (Cefepime-Zidebactam Combination) in Subjects with Renal Impairment. (Pubmed Central) - Jan 29, 2020
P1
Our findings suggest that dose adjustments for WCK 5222 will be required according to the degree of renal impairment. Overall, WCK 5222 (FEP-ZID) was found to be safe and well tolerated in subjects with normal and impaired renal function.
- | cefepime/zidebactam IV (WCK 5222) / Wockhardt
Preclinical, Journal: In Vivo Efficacy of Humanized WCK 5222 (Cefepime-Zidebactam) Exposures Against Carbapenem-Resistant Acinetobacter baumannii in the Neutropenic Thigh Model. (Pubmed Central) - Jan 17, 2020
Five of six isolates examined expressed OXA-23 or OXA-24. WCK 5222, despite showing MICs 16 - 64 mg/L, produced remarkable in vivo activity; human-simulated exposure showed a decline in bacterial burden for all isolates [mean reduction -2.09 ± 1.01 log CFU/thigh], while lack of activity was observed with cefepime and zidebactam monotherapies.
- | Journal: New Drugs for Multidrug-Resistant Gram-Negative Organisms: Time for Stewardship. (Pubmed Central) - Nov 29, 2019
Murepavadin is shown to be specifically active against CR- and colistin-resistant P. aeruginosa strains. Despite successful development of novel antibiotics, strict implementation of an antibiotic stewardship policy in combination with the use of well-established phenotypic tests and novel multiplex PCR methods for detection of the most commonly encountered β-lactamases/carbapenemases in hospitals is important for prescribing effective antibiotics against CRE and decreasing the resistance burden due to CRE.
- | cefepime/zidebactam IV (WCK 5222) / Wockhardt
Preclinical, Journal: Efficacy of human-simulated bronchopulmonary exposures of cefepime, zidebactam and the combination (WCK 5222) against MDR Pseudomonas aeruginosa in a neutropenic murine pneumonia model. (Pubmed Central) - Oct 25, 2019
Human-simulated bronchopulmonary exposure of WCK 5222 is effective against MDR P. aeruginosa at MIC ≤16 mg/L in a murine pneumonia model. These data support the clinical development of WCK 5222 for pseudomonal lung infections.
- | cefepime/zidebactam IV (WCK 5222) / Wockhardt, meropenem / Generic Mfg., Daewon Pharmaceutical
Preclinical, Journal: Assessment of the In Vivo Efficacy of WCK 5222 (Cefepime-Zidebactam) Against Carbapenem-Resistant Acinetobacter baumannii in the Neutropenic Murine Lung Infection Model. (Pubmed Central) - Oct 11, 2019
In control animals and those that received cefepime or zidebactam alone, mean bacterial growth at 24-h was >2 log CFU/lung compared with 0-h controls (6.32±0.33 log CFU/lung). WCK 5222 produced a decline in bacterial burden for all isolates (mean reduction, -3.34±0.85 log CFU/lung) and demonstrated remarkable potency.
- | cefepime/zidebactam IV (WCK 5222) / Wockhardt
PK/PD data, Preclinical, Journal: WCK 5222 (Cefepime/Zidebactam) Pharmacodynamic Target Analysis against Metallo-β-lactamase producing Enterobacteriaceae in the Neutropenic Mouse Pneumonia Model. (Pubmed Central) - Oct 9, 2019
A 1-log kill endpoint was demonstrated for the group of organisms at approximately 31% T>MIC. These target exposures for stasis and 1-log kill are much lower than previously observed cephalosporin monotherapy PK/PD targets.
- | cefepime/zidebactam IV (WCK 5222) / Wockhardt
Clinical, Journal: Plasma and Intrapulmonary Concentrations of Cefepime and Zidebactam following Intravenous Administration of WCK 5222 to Healthy Adult Subjects. (Pubmed Central) - Sep 26, 2019
The AM to total plasma ratios were 0.27 and 0.10, respectively. The observed plasma, ELF and AM concentrations of cefepime and zidebactam support studies of WCK 5222 for treatment of pneumonia caused by susceptible pathogens.
- Zerbaxa (ceftolozane /tazobactam) / Merck (MSD), cefepime/zidebactam IV (WCK 5222) / Wockhardt, Zavicefta (ceftazidime + avibactam) / Pfizer, Allergan
Comparison of Cefepime-Zidebactam (WCK 5222), Ceftazidime-Avibactam, and Ceftolozane-Tazobactam Tested against Gram-Negative Organisms Causing Pneumonia in United States Hospitals in 2018 () - Aug 26, 2019 - Abstract #IDWeek2019IDWeek_2609;
The only other compounds active against XM were co-trimoxazole (MIC50/90, ≤0.12/2 mg/L; 95.7%S) and levofloxacin (MIC50/90, 1/2 mg/L; 70.7%S). FEP-ZID inhibited 71.0% and 98.9% of A. baumannii isolates at ≤8 and ≤64 mg/L, respectively.Conclusion : FEP-ZID showed potent in vitro activity against GNB causing pneumonia in US hospitals and may represent a valuable therapeutic option for these difficult-to-treat infections
- cefepime/zidebactam IV (WCK 5222) / Wockhardt
Antimicrobial Activity of the Novel β-Lactam Enhancer Combination Cefepime-Zidebactam (WCK-5222) Tested against Gram-Negative Bacteria Isolated in United States Medical Centers from Patients with Bloodstream Infections () - Aug 26, 2019 - Abstract #IDWeek2019IDWeek_2135;
maltophilia displayed low S rates to most comparators.Conclusion : FEP-ZID demonstrated potent activity against a large collection GNB from BSI, including isolates resistant to other BL inhibitor combinations and/or carbapenems. These results support further clinical development of FEP-ZID.
- cefepime/zidebactam IV (WCK 5222) / Wockhardt
WCK 5222 (Cefepime/Zidebactam): An In Vitro Assessment of Activity Compared with Current Dual-Antibiotic Options against Multidrug-Resistant Pseudomonas aeruginosa () - Aug 26, 2019 - Abstract #IDWeek2019IDWeek_1522;
In total, β-lactam susceptibility was restored in 14% (13/94) of combinations compared with 78% (14/18) of WCK 5222 MICs ≤ 8 mg/L.Conclusion : In a selection of MDR-PSA isolates that included carbapenem- and C/T-resistant strains, WCK 5222 MICs ≤ 8 mg/L (cefepime-susceptible) were observed more frequently than restoration of susceptibility in select β-lactams in combination with FOF or AMK. WCK 5222 monotherapy may offer enhanced coverage of MDR-PSA over empirically-selected combination therapies.
- cefepime/zidebactam IV (WCK 5222) / Wockhardt
Efficacy of Human-Simulated Bronchopulmonary Exposures of Cefepime and Zidebactam (WCK 5222) Against Multidrug Resistant (MDR) Pseudomonas aeruginosa (PSA) in a Neutropenic Murine Pneumonia Model () - Aug 26, 2019 - Abstract #IDWeek2019IDWeek_1475;
All isolates showed growth or stasis on FEP.Conclusion : Human-simulated bronchopulmonary exposures of WCK5222 is effective against MDR PSA at MIC up to 16 mg/L in a neutropenic murine model. These data support the clinical development of WCK5222 for the treatment of pseudomonal lung infections, but further studies of PSA with high WCK5222 MIC are necessary to delineate the susceptibility breakpoint.
- cefepime/zidebactam IV (WCK 5222) / Wockhardt
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 () - Aug 26, 2019 - Abstract #IDWeek2019IDWeek_1466;
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.
- cefepime/zidebactam IV (WCK 5222) / Wockhardt
Cefepime time above MIC PK/PD target determination when combined with the novel beta-lactam enhancer zidebactam in a murine pneumonia model against carbapenemase-producing Enterobacteriaceae including those with metallo-beta-lactamase enzymes () - Apr 5, 2019 - Abstract #ECCMID2019ECCMID_2900;
Interestingly, we found comparatively low T>MIC targets for cefepime when combined with zidebactam for stasis and 1-log kill endpoints. For example, the stasis target for cefepime/zidebactam was a cefepime T>MIC of 20% (95% CI [2.8%, 27.9%]).
- cefepime/zidebactam IV (WCK 5222) / Wockhardt
Selection of EUCAST disk potency for WCK 5222 (cefepime-zidebactam, FEP-ZID) susceptibility testing against Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii () - Apr 5, 2019 - Abstract #ECCMID2019ECCMID_2727;
The FEP-ZID 30-30 µg disk could reliably distinguish between the S and R organisms based on potential FEP-ZID MIC breakpoints of either ≤16, or ≤32 or ≤64mg/L for P. aeruginosa, either ≤32 or ≤64mg/L for A. baumannii and ≤8mg/L for Enterobacterales. The 30-30µg disk was accepted by the EUCAST development laboratory for these potential breakpoints.
- cefepime/zidebactam IV (WCK 5222) / Wockhardt, meropenem / Generic mfg., Daewon Pharmaceutical
Cefepime-zidebactam (WCK-5222) activity when tested against Gram-negative organisms isolated from patients hospitalised in Europe and the Asia-Pacific region in 2018 () - Apr 5, 2019 - Abstract #ECCMID2019ECCMID_1468;
Cefepime-zidebactam demonstrated potent in vitro activity against gram-negative bacilli isolates collected in European and APAC medical centres in 2018, including multidrug-resistant Enterobacteriaceae, meropenem-nonsusceptible P. aeruginosa, and S. maltophilia. These in vitro results support further development of cefepime-zidebactam for treatment of systemic gram-negative infections.
- cefepime/zidebactam IV (WCK 5222) / Wockhardt, meropenem / Generic mfg., Daewon Pharmaceutical
Antimicrobial activity of cefepime-zidebactam (WCK-5222) against clinical isolates of carbapenem-resistant Enterobacteriaceae collected worldwide in 2018 () - Apr 5, 2019 - Abstract #ECCMID2019ECCMID_1389;
Cefepime-zidebactam demonstrated potent in vitro activity against contemporary (2018) CRE isolates collected worldwide. Antimicrobial agents currently available for clinical use exhibited limited activity against CRE, emphasizing the urgent need for novel agents to treat infections caused by these multidrug-resistant organisms.
- | cefepime/zidebactam IV (WCK 5222) / Wockhardt
Journal: Activity of Cefepime-Zidebactam against Multidrug-Resistant (MDR) Gram-Negative Pathogens. (Pubmed Central) - Mar 28, 2019
Notably, it inhibited isolates producing carbapenemases of Ambler classes A, B, and D, and P. aeruginosa isolates with multiple resistance mechanisms including combinations of upregulated efflux, diminished or non-functional OprD porins, and AmpC overproduction. Its clinical role will be determined initially by the breakpoints assigned to it, comparison studies with other investigational β-lactamase inhibitor combinations, and ultimately by the developing body of therapeutic outcome data.