Evaluation of the
            <i>In Vitro</i>
            Activity of Ceftazidime-Avibactam and Ceftolozane-Tazobactam against Meropenem-Resistant Pseudomonas aeruginosa Isolates

Buehrle, Deanna J; Shields, Ryan K.; Chen, Liang; Hao, Binghua; Press, Ellen G.; Alkrouk, Ammar; Potoski, Brian A.; Kreiswirth, Barry N.; Clancy, Cornelius J.; Nguyen, M. Hong

doi:10.1128/aac.02969-15

Cited by 90 publications

(54 citation statements)

References 24 publications

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“…All of the strains in our study were positive for carbapenemase production. Similar to results reported in the literature, we believe this may be responsible for the high C/T and CZA resistance rates in our study [21][22][23][24] . However, the inability to determine carbapenemase type or carbapenemase resistance genes was the major limitation of our study.…”

Section: Discussionsupporting

confidence: 92%

Investigation of Ceftalozan / tazobactam and Ceftazidim / avibaktam invitro activity against Karbapenemaz producing Pseudomonas aeruginosa strains

Aydemir¹,

Terzi²,

Köroğlu³

et al. 2019

mjima

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The emergence of multidrug-resistant (MDR) and extensively drug-resistant strains of Pseudomonas aeruginosa in recent years has become a major issue due to treatment difficulties as well as high morbidity and mortality rates. Treatment options for infections caused by these microorganisms are very limited. Ceftolozane/tazobactam (C/T) and ceftazidime/avibactam (CZA) are recently developed cephalosporin/betalactamase inhibitor combinations for the treatment of infections caused by MDR P. aeruginosa strains. The aim of this study was to investigate the in vitro efficacy of C/T and CZA against MDR P. aeruginosa strains and to compare the in vitro efficacy of these two drugs. Materials and Methods: Thirty-two MDR P. aeruginosa isolates were included in the study. Identification and antimicrobial susceptibilities of the strains were performed using a VITEK 2® automated system. The efficacy of CZA and C/T was determined by the gradient strip test (Liofilchem MIC strip test, Italy). Modified carbapenemase inactivation method was used to detect carbapenemase production in all strains. Results: Rates of antibiotic resistance in the isolates were 78% for amikacin, 96.8% for levofloxacin, 90.6% for ciprofloxacin, 71.8% for gentamicin, and 78% for netilmicin. Ceftazidime/avibactam resistance was detected in 7 (21.8%) of the isolates and C/T resistance in 10 (31.2%). All strains with resistance to CZA also had resistance to C/T. Three strains were resistant to C/T but susceptible to CZA. Carbapenemase production was positive in all strains. Conclusion: The results of this study indicate that CZA and C/T may be an alternative treatment for some of the carbapenem-resistant P. aeruginosa infections. Further in vitro and in vivo studies are needed to evaluate the effectiveness of these new treatment options against the increasing threat of MDR P. aeruginosa.

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Section: Discussionsupporting

confidence: 92%

Investigation of Ceftalozan / tazobactam and Ceftazidim / avibaktam invitro activity against Karbapenemaz producing Pseudomonas aeruginosa strains

Aydemir¹,

Terzi²,

Köroğlu³

et al. 2019

mjima

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“…While overall both drugs were active against >90% of the tested isolates, including 80% of the isolates resistant to piperacillin/tazobactam, ceftazidime, and cefepime, ceftolozane/tazobactam clearly demonstrated enhanced in vitro activity over ceftazidime/avibactam against this resistant subpopulation 60. For MDR P. aeruginosa , ceftolozane/tazobactam should, therefore, be considered the preferred choice owing to its enhanced stability over ceftazidime against multiple P. aeruginosa resistance mechanisms as well as sparing the enhanced β-lactamase inhibition offered by ceftazidime/avibactam for those infections with resistant Enterobacteriaceae where ceftazidime/avibactam demonstrates a broader spectrum of activity.…”

Section: Ceftazidime/avibactammentioning

confidence: 94%

Ceftolozane/tazobactam and ceftazidime/avibactam for the treatment of complicated intra-abdominal infections

Goodlet¹,

Nicolau²,

Nailor³

2016

TCRM

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Complicated intra-abdominal infections (cIAI) represent a large proportion of all hospital admissions and are a major cause of morbidity and mortality in the intensive care unit. Rising rates of multidrug resistant organisms (MDRO), including extended-spectrum β-lactamase producing Enterobacteriaceae and carbapenem-nonsusceptible Pseudomonas spp., for which there are few remaining active antimicrobial agents, pose an increased challenge to clinicians. Patients with frequent exposures to the health care system or multiple recurrent IAIs are at increased risk for MDRO; however, treatment options have traditionally been limited, in some cases necessitating the utilization of last-line agents with unfavorable side-effect profiles. Ceftolozane/tazobactam and ceftazidime/avibactam are two new cephalosporin and β-lactamase inhibitor combinations with recent US Food and Drug Administration approvals for the treatment of cIAI in combination with metronidazole. Ceftolozane/tazobactam has demonstrated excellent in vitro activity against MDR and extensively drug-resistant Pseudomonas spp., including carbapenem-nonsusceptible strains, while ceftazidime/avibactam effectively inhibits a broad range of β-lactamases, making it an excellent option for the treatment of carbapenem-resistant Enterobacteriaceae. Both agents were shown to be noninferior to meropenem for treatment of cIAI in Phase III trials; however, reduced responses in patients with renal impairment at baseline highlight the importance of routine serum creatinine monitoring and ongoing dose adjustments. This review highlights in vitro and in vivo data of these two agents and suggests their proper place in cIAI treatment to ensure adequate therapy in our most at-risk patients while sparing unnecessary use in patients without MDRO risk factors.

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“…To date, only one study has simultaneously evaluated the activities of C/T and CZA in vitro against Pseudomonas aeruginosa , and few studies have evaluated the effects of these antibiotics on multi-drug resistant (MDR) gram-negative bacteria [123]. This study aimed to examine the activities of C/T and CZA against β-lactam-resistant Enterobacteriaceae and P. aeruginosa clinical isolates.…”

mentioning

confidence: 99%

Susceptibility of Ceftolozane-Tazobactam and Ceftazidime-Avibactam Against a Collection of β-Lactam-Resistant Gram-Negative Bacteria

et al. 2017

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Evaluation of the In Vitro Activity of Ceftazidime-Avibactam and Ceftolozane-Tazobactam against Meropenem-Resistant Pseudomonas aeruginosa Isolates

Cited by 90 publications

References 24 publications

Investigation of Ceftalozan / tazobactam and Ceftazidim / avibaktam invitro activity against Karbapenemaz producing Pseudomonas aeruginosa strains

Investigation of Ceftalozan / tazobactam and Ceftazidim / avibaktam invitro activity against Karbapenemaz producing Pseudomonas aeruginosa strains

Ceftolozane/tazobactam and ceftazidime/avibactam for the treatment of complicated intra-abdominal infections

Susceptibility of Ceftolozane-Tazobactam and Ceftazidime-Avibactam Against a Collection of β-Lactam-Resistant Gram-Negative Bacteria

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