Evaluation of ceftazidime/avibactam for serious infections due to multidrug-resistant and extensively drug-resistant Pseudomonas aeruginosa

Rodríguez‐Núñez, Olga; Ripa, Marco; Morata, Laura; Calle, C. de la; Cardozo, Celia; Fehér, Csaba; Pellicé, Martina; Valcárcel, Andrea; Puerta‐Alcalde, Pedro; Marco, Francesc; García-Vidal, Carolina; Rı́o, Ana del; Soriano, Álex; Martı́nez-Martı́nez, José A.

doi:10.1016/j.jgar.2018.07.010

Cited by 47 publications

(36 citation statements)

References 19 publications

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“…Ceftazidime-avibactam is a new β-lactam/β-lactamase inhibitor currently approved by the European Medicines Agency for the treatment of complicated intra-abdominal infections [5,6], complicated urinary tract infections [7], hospital-acquired pneumonia (including ventilator-associated pneumonia), and more generally, for aerobic gram-negative infections with limited treatment options [8]. In real-life experiences, high rates of favorable response to ceftazidime-avibactam treatment are reported in patients with infections due to carbapenem−resistant Enterobacterales (CRE), with an overall success rate of about 70% [9][10][11][12][13][14][15], whereas post-marketing experience regarding the use of ceftazidime-avibactam for infections due to MDR-GNB other than CRE remains scarce [16][17][18] Moreover, information regarding features associated with clinical failures and the emergence of resistance in this group of patients are even scarcer. For this reason, in this multicenter study we describe our experience about the use of ceftazidime-avibactam for the treatment of infections due to MDR-GNB other than CRE in 13 Italian hospitals.…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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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“…In addition, avibactam not only inhibits ESBLs, but also effectively inhibits class A carbapenemases such as AmpC beta-lactamases and Klebsiella pneumoniae carbapenemase (KPC) [7,14,15] . Avibactam has in vitro activity against Ambler class A, C, and some class D serine betalactamases, but not against metallo-beta-lactamases [1,4] . Studies have revealed that C/T and CZA are more effective against MDR infections than other cephalosporins and beta-lactamase inhibitors [11,14] .…”

Section: Discussionmentioning

confidence: 97%

“…Similar to the current study comparing the efficacy of C/T and CZA against MDR P. aeruginosa strains, there are a few other studies in the literature that compare the efficacy of these two drugs [6,7,22,23] . In some of these studies, C/T-resistant P. aeruginosa isolates were found to be susceptible to CZA, while most demonstrated that C/T had greater in vitro inhibitory activity than CZA (Table 3) [1,7] . In a large study investigating 309 resistant (to ceftazidime, cefepime, meropenem, imipenem and/ or piperacillin-tazobactam) P. aeruginosa isolates, Humphries et al [7] reported 52.4% and 27.6% C/T and CZA susceptibility in beta-lactam and carbapenem-resistant strains, respectively.…”

Section: 1%mentioning

confidence: 99%

“…The recent emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) P. aeruginosa strains has become a serious problem due to treatment difficulties and high morbidity and mortality rates. Many of these solates show reduced sensitivity to antipseudomonal drugs, including beta-lactam antibiotics [1] . The alternative treatment options are limited and comprise usage of newly developed antibiotics or combination of certain antibiotics to benefit from their synergistic effect [2] .…”

Section: Introductionmentioning

confidence: 99%

“…Ceftolozane/tazobactam (C/T) and ceftazidime/avibactam (CZA) are Food and Drug Administration (FDA)-approved cephalosporin/beta-lactamase inhibitor combinations. They are recently developed for the treatment of infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, including MDR P. aeruginosa strains and other Gram-negative bacteria [1,3,4] . The introduction of these new antimicrobial agents was promising for the treatment of drug-resistant infections, and the clinical importance of these antibiotics is steadily increasing [1] .…”

Section: Introductionmentioning

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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Approach to the Treatment of Patients with Serious Multidrug‐Resistant Pseudomonas aeruginosa Infections

2020

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Multidrug resistance(MDR) among Pseudomonas aeruginosa (PSA) isolates presents a significant clinical challenge and can substantially complicate the approach to selection of optimal antibiotic therapy. This review addresses major considerations in antibiotic selection for patients with suspected or documented serious MDR‐PSA infections. Common mechanisms contributing to MDR among clinical PSA isolates are summarized. Empiric and definitive therapy considerations are addressed including the potential role of combination therapy. Newer agents with in vitro activity against MDR‐PSA (e.g., ceftolozane‐tazobactam, ceftazidime‐avibactam, imipenem‐relebactam, and cefiderocol) and their potential roles in clinical settings are discussed. Although these newer agents are promising options for the treatment of MDR‐PSA, clinical data remain generally limited. Future studies are needed to determine optimal agents for the empiric and definitive treatment of MDR‐PSA.

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Evaluation of ceftazidime/avibactam for serious infections due to multidrug-resistant and extensively drug-resistant Pseudomonas aeruginosa

Cited by 47 publications

References 19 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

Approach to the Treatment of Patients with Serious Multidrug‐Resistant Pseudomonas aeruginosa Infections

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