Clinical activity of ceftazidime/avibactam against MDR Enterobacteriaceae and Pseudomonas aeruginosa: pooled data from the ceftazidime/avibactam Phase III clinical trial programme

Stone, Gregory G.; Newell, Paul; Gasink, Leanne B.; Broadhurst, Helen; Wardman, Angela; Yates, Katrina; Chen, Zhangjing; Song, Jie; Chow, Joseph W.

doi:10.1093/jac/dky204

Cited by 69 publications

(52 citation statements)

References 14 publications

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“…This study is the largest evaluation of a cohort of patients treated with ceftazidime-avibactam for different types of infections due to GNB other than carbapenems-resistant Enterobacterales. In line with the pooled clinical cure rate observed in prior trials (85%) [19], about 90% of all assessed patients in our study were deemed an overall treatment success at the end of ceftazidime-avibactam treatment. Notably, this high clinical cure rate was observed despite our study population having a higher prevalence of infections caused by MDR, XDR, or PDR pathogens, underlying comorbidities and use of ceftazidime-avibactam as secondary therapy.…”

Section: Discussionsupporting

confidence: 88%

Clinical Experience with Ceftazidime-Avibactam for the Treatment of Infections due to Multidrug-Resistant Gram-Negative Bacteria Other than Carbapenem-Resistant Enterobacterales

et al. 2020

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Background: Experience in real clinical practice with ceftazidime-avibactam for the treatment of serious infections due to gram−negative bacteria (GNB) other than carbapenem-resistant Enterobacterales (CRE) is very limited. Methods: We carried out a retrospective multicenter study of patients hospitalized in 13 Italian hospitals who received ≥72 h of ceftazidime-avibactam for GNB other than CRE to assess the rates of clinical success, resistance development, and occurrence of adverse events. Results: Ceftazidime-avibactam was used to treat 41 patients with GNB infections other than CRE. Median age was 62 years and 68% of them were male. The main causative agents were P. aeruginosa (33/41; 80.5%) and extended spectrum beta lactamase (ESBL)-producing Enterobacterales (4/41, 9.8%). Four patients had polymicrobial infections. All strains were susceptible to ceftazidime-avibactam. The most common primary infection was nosocomial pneumonia (n = 20; 48.8%), primary bacteremia (n = 7; 17.1%), intra-abdominal infection (n = 4; 9.8%), and bone infection (n = 4; 9.8%). Ceftazidime-avibactam was mainly administered as a combination treatment (n = 33; 80.5%) and the median length of therapy was 13 days. Clinical success at the end of the follow-up period was 90.5%, and the only risk factor for treatment failure at multivariate analysis was receiving continuous renal replacement therapy during ceftazidime-avibactam. There was no association between clinical failures and type of primary infection, microbiological isolates, and monotherapy with ceftazidime-avibactam. Only one patient experienced recurrent infection 5 days after the end of treatment. Development of resistance to ceftazidime-avibactam was not detected in any case during the whole follow-up period. No adverse events related to ceftazidime-avibactam were observed in the study population. Conclusions: Ceftazidime-avibactam may be a valuable therapeutic option for serious infections due to GNB other than CRE.

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Section: Discussionsupporting

confidence: 88%

Clinical Experience with Ceftazidime-Avibactam for the Treatment of Infections due to Multidrug-Resistant Gram-Negative Bacteria Other than Carbapenem-Resistant Enterobacterales

et al. 2020

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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%

“…Various studies report that susceptibility to C/T in MDR P. aeruginosa isolates varies between 57.4% and 88.6% (Table 3) [14, [25][26][27] . In a phase 3 trial by Stone et al [24] , the proportion of CZA sensitivity in MDR P. aeruginosa isolates was 66.1% and the authors reported that CZA may be a good alternative to carbapenems. Other than the study of Stone et al [24] study, our literature search yielded no other studies on this subject.…”

Section: Discussionmentioning

confidence: 99%

“…In a phase 3 trial by Stone et al [24] , the proportion of CZA sensitivity in MDR P. aeruginosa isolates was 66.1% and the authors reported that CZA may be a good alternative to carbapenems. Other than the study of Stone et al [24] study, our literature search yielded no other studies on this subject. All isolates analyzed in our study were MDR and their susceptibility rates for C/T and CZA were 68.8% and 78.2%, respectively.…”

Section: Discussionmentioning

confidence: 99%

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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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“…113 In a pooled analysis from phase III studies of ceftazidime-avibactam, outcomes were similar in patients with MDR-Pseudomonas versus comparators. 114 However, when comparing antimicrobial activity of ceftolozanetazobactam to ceftazidime-avibactam against MDR-Pseudomonas, MICs are lower for ceftolozane-tazobactam. 115…”

Section: Mdr-pseudomonas Aeruginosamentioning

confidence: 99%

Difficult-to-Treat Antibiotic-Resistant Gram-Negative Pathogens in the Intensive Care Unit: Epidemiology, Outcomes, and Treatment

Strich

Kadri

2019

Semin Respir Crit Care Med

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Antibiotic resistance among gram-negative pathogens is a world-wide problem that poses a constant threat to patients in the intensive care unit and a therapeutic challenge for the intensivist. Furthermore, the substantial economic burden and increased mortality associated with infections due to highly resistant gram-negative pathogens exacerbate these challenges. Understanding the mechanisms, epidemiology, and risk factors for these infections is paramount to the successful control of outbreaks and for guiding therapy which often entails use of antibiotics with suboptimal efficacy and/or toxicity profiles. In this review we will discuss the global epidemiology, burden, risk factors, and treatment of highly resistant gram-negative infections as they apply to the intensive care population.

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Clinical activity of ceftazidime/avibactam against MDR Enterobacteriaceae and Pseudomonas aeruginosa: pooled data from the ceftazidime/avibactam Phase III clinical trial programme

Abstract: Ceftazidime/avibactam demonstrated similar clinical efficacy to predominantly carbapenem comparators against MDR Enterobacteriaceae and P. aeruginosa, and may be a suitable alternative to carbapenem-based therapies for cIAI, cUTI and NP/VAP caused by MDR Gram-negative pathogens.

Cited by 69 publications

References 14 publications

Clinical Experience with Ceftazidime-Avibactam for the Treatment of Infections due to Multidrug-Resistant Gram-Negative Bacteria Other than Carbapenem-Resistant Enterobacterales

Clinical Experience with Ceftazidime-Avibactam for the Treatment of Infections due to Multidrug-Resistant Gram-Negative Bacteria Other than Carbapenem-Resistant Enterobacterales

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

Difficult-to-Treat Antibiotic-Resistant Gram-Negative Pathogens in the Intensive Care Unit: Epidemiology, Outcomes, and Treatment

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