Ceftazidime-Avibactam To Treat Life-Threatening Infections by Carbapenem-Resistant Pathogens in Critically Ill Mechanically Ventilated Patients

Tsolaki, Vasiliki; Mantzarlis, Konstantinos; Mpakalis, Athanasios; Malli, Ergina; Tsimpoukas, Fotios; Tsirogianni, A.; Papagiannitsis, Costas C.; Zygoulis, Paris; Papadonta, Maria-Eirini; Petinaki, Efthimia; Makris, Demosthènes; Zakynthinos, Epaminondas

doi:10.1128/aac.02320-19

Cited by 69 publications

(59 citation statements)

References 26 publications

(35 reference statements)

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“…Consistent with previous reports [17,32], we were unable to detect adverse drug events related to ceftazidime-avibactam treatment, even when the drug was administered for a relatively prolonged period of time (median of 13 days (range 2-49 days)). However, due to the retrospective nature of our data we are limited to that information reported in the medical records.…”

Section: Discussionsupporting

confidence: 89%

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: 89%

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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“…Clinical cure at the test-of-cure visit was achieved by 68.8% of CAZ-AVI recipients in the clinically modi ed intent-to-treat population, and by 77.4% in the clinically evaluable population from data of phase III REPROVE trial (40). Recently, a study from Tsolaki et al showed that patients with CAZ-AVI had improved clinical cure rates (80.5%), microbiological eradication (94.3%) and 28-day survival rates (85.4%) than those with other available antibiotic agents (41). It is hypothesized that these variations are primarily due to all the patients in the present study having HAP/VAP, higher Charlson's comorbidity scores, more complicated risk factors for multisite infections and a greater risk of mortality.…”

Section: Discussionmentioning

confidence: 99%

Ceftazidime-avibactam Versus Tigecycline for the Treatment of Carbapenem-resistant Klebsiella Pneumoniae-induced Pneumonia in Critically Ill Patients

Shi¹,

Hu²,

Liu³

et al. 2021

Preprint

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Background: To assess the safety patterns and outcomes of ceftazidime-avibactam (CAZ-AVI) versus tigecycline (TGC) for the treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) pneumonia defined as either hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP).Methods: Clinical and microbiological cure rates, 28-day survival rates, and safety evaluation were compared between patients treated with CAZ-AVI versus those treated with TGC in a retrospective study. Conventional multivariate logistic regression analysis and three propensity score (PS) analyses were performed to control for confounding variables.Results: A total of 105 cases were included in the study; 62 patients (59%) received TGC, and 43 patients (41%) received CAZ-AVI. Clinical cure rates and microbiological cure success of CAZ-AVI were superior to TGC [51.2% versus 29.0%(P=0.022) and74.4% versus 33.9%（P<0.001）, respectively]. There were no significant differences between the two groups with regard to 28-day survival rates (66.1% versus 69.8%, P=0.695). In analyses of conventional multivariate logistic regression and propensity score (PS) analysis, patients in the CAZ-AVI group were more likely to have achieved clinical cure and microbiological success compared with patients in the TGC group. However, the difference between the two groups with regard to 28-day survival rates were not significant. In terms of safety evaluation, generally, the CAZ-AVI group had a lower incidence of adverse reactions when compared with the TGC group.Conclusions: CAZ-AVI may be a suitable alternative to TGC for the treatment of HAP or VAP caused by CRKP in critically ill patients.

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“…However, this PD target is significantly lower than the suggested ß-Lactam targets of 100% fT> MIC or 100% fT> MICx4 in critically ill patients. Nevertheless, this standard dosage regimen of ceftazidime-avibactam has resulted in superior clinical success and survival than other treatment regimens to treat life-threatening infections by carbapenemresistant pathogens (42,43).…”

Section: Ceftzidime-avibactammentioning

confidence: 99%

Minireview on Novel Anti-infectious Treatment Options and Optimized Drug Regimens for Sepsis

Hites

2021

Front. Med.

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Sepsis, a life-threatening organ dysfunction caused by a dysregulated response to infection is a major public health concern, as it is a leading cause of mortality and critical illness worldwide. Antibiotics are one of the cornerstones of the treatment of sepsis; administering appropriate antibiotics in a rapid fashion to obtain adequate drug concentrations at the site of the infection can improve survival of patients. Nevertheless, it is a challenge for clinicians to do so. Indeed, clinicians today are regularly confronted with infections due to very resistant pathogens, and standard dosage regimens of antibiotics often do not provide adequate antibiotic concentrations at the site of the infection. We provide a narrative minireview of different anti-infectious treatments currently available and suggestions on how to deliver optimized dosage regimens to septic patients. Particular emphasis will be made on newly available anti-infectious therapies.

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Ceftazidime-Avibactam To Treat Life-Threatening Infections by Carbapenem-Resistant Pathogens in Critically Ill Mechanically Ventilated Patients

Cited by 69 publications

References 26 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

Ceftazidime-avibactam Versus Tigecycline for the Treatment of Carbapenem-resistant Klebsiella Pneumoniae-induced Pneumonia in Critically Ill Patients

Minireview on Novel Anti-infectious Treatment Options and Optimized Drug Regimens for Sepsis

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