Dataset Information

Combination Therapy of Ceftazidime/Avibactam for the Treatment of Patients Infected with Carbapenem-Resistant Klebsiella pneumoniae: A Multicenter Retrospective Study.

ABSTRACT:

Introduction

This study aimed to evaluate the different efficacies between monotherapy and combination therapy with ceftazidime/avibactam (CAZ/AVI) in treating carbapenem-resistant Klebsiella pneumoniae (CRKP) infection.

Methods

We retrospectively analyzed observational multicenter data from 38 hospitals in China. Multivariate regression analysis was used to explore the association between combination therapy with CAZ/AVI and in-hospital mortality. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to validate our findings.

Results

A total of 132 eligible patients were divided into CAZ/AVI combination therapy (n = 43) and monotherapy (n = 89) cohorts. Multivariate logistic regression showed that there was no statistically significant relationship between combination therapy and a lower risk of in-hospital mortality [odds ratio (OR) 0.907, 95% confidence interval (CI) 0.329-2.498, p = 0.850]. In the subgroup of critical patients who were in the intensive care unit (ICU) (OR 0.943, 95% CI 0.221-4.033, p = 0.937) or with sequential organ failure assessment (SOFA) ≥ 3 (OR 0.733, 95% CI 0.191-2.808, p = 0.650), CAZ/AVI combination therapy was not a lower risk factor for in-hospital mortality. Moreover, in the subgroup of patients using CAZ/AVI plus tigecycline (accounting for 46.5% in the combination therapy) compared with CAZ/AVI monotherapy, there was no statistical difference between the two groups in in-hospital mortality, nor in the subgroup of patients with CRKP-associated pneumonia.

Conclusion

Combination therapy (or CAZ/AVI combined with tigecycline) and monotherapy with CAZ/AVI had similar prognoses in patients with only CRKP infection (or CRKP-associated pneumonia), as well as in critically ill patients. Larger randomized controlled trials are warranted to confirm these findings.

SUBMITTER: Lin J

PROVIDER: S-EPMC10505119 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Combination Therapy of Ceftazidime/Avibactam for the Treatment of Patients Infected with Carbapenem-Resistant Klebsiella pneumoniae: A Multicenter Retrospective Study.

Lin Jing J Zhang Li L Zhou Menglan M Tian Xiaotong X Chen Jialong J Lu Minya M Liu Zhengyin Z

Infectious diseases and therapy 20230801 8

<h4>Introduction</h4>This study aimed to evaluate the different efficacies between monotherapy and combination therapy with ceftazidime/avibactam (CAZ/AVI) in treating carbapenem-resistant Klebsiella pneumoniae (CRKP) infection.<h4>Methods</h4>We retrospectively analyzed observational multicenter data from 38 hospitals in China. Multivariate regression analysis was used to explore the association between combination therapy with CAZ/AVI and in-hospital mortality. Propensity score matching (PSM) ...[more]

PMID: 37653121

Similar Datasets

Project description:This research focused on evaluating the clinical results of patients suffering from pneumonia caused by carbapenem-resistant Klebsiella pneumoniae (CRKP), who received treatment with either ceftazidime-avibactam (CZA) alone or in combination with other antibiotics. From January 2020 to December 2023, we retrospectively analyzed CRKP-related pneumonia patients treated in two Chinese tertiary hospitals. Mortality was measured at 14 and 30 days as the primary outcome. Secondary outcomes included the 14-day microbiological cure rate and the 14-day clinical cure rate. Factors contributing to clinical failure were evaluated via both univariate analysis and multivariate logistic regression. To account for confounding factors, propensity score matching (PSM) was utilized. Among the 195 patients with CRKP infections, 103 (52.8 %) received CZA combination therapy, and 92 (47.2 %) patients received CZA monotherapy. The combination therapy group exhibited superior clinical and microbiological cure rates compared to the monotherapy group, with a 14-day clinical cure rate of 60.1 % vs. 45.7 % (P = 0.042) and a 14-day microbiological cure rate of 72.8 % vs. 58.6 % (P = 0.038), respectively. Combination therapy reduced mortality rates at 14 days (7.8 % vs. 17.4 %, P = 0.041), but not at 30 days (14.6 % vs. 25.0 %, P = 0.066). Even after using PSM, the group treated with the CZA combination continued to had a lower mortality rate at 14 days (5.9 % vs. 17.6 %, P = 0.039). The 14-day clinical cure rate for the combination therapy group was 63.2 %, and the 14-day microbial cure rate was 77.9 %. Both of these statistics were notably greater than those observed in the monotherapy group. Furthermore, the multivariate logistic regression model indicated a significant link between combination therapy and a decrease in clinical failure. Carbapenems were noted to be the most effective class of concomitant agents. Our findings indicate that patients with pneumonia due to CRKP benefit from combination treatment of CZA rather than monotherapy; administering carbapenem in combination with CZA in the early stages could provide considerable survival benefits.

Project description:This study aimed to assess the in vitro efficacy of ceftazidime-avibactam (CZA) in combination with various antimicrobial agents against carbapenem-resistant Klebsiella pneumoniae (CRKP). We selected 59 clinical CRKP isolates containing distinct drug resistance mechanisms. The minimum inhibitory concentrations (MICs) of meropenem (MEM), colistin (COL), eravacycline (ERA), amikacin (AK), fosfomycin (FOS), and aztreonam (ATM), both individually and in combination with CZA, were tested using the checkerboard method. The interactions of antimicrobial agent combinations were assessed by fractional inhibitory concentration index (FICI) and susceptible breakpoint index (SBPI). The time-kill curve assay was employed to dynamically evaluate the effects of these drugs alone and in combination format. In the checkerboard assay, the combination of CZA+MEM showed the highest level of synergistic effect against both KPC-producing and carbapenemase-non-producing isolates, with synergy rates of 91.3% and 100%, respectively. Following closely was the combination of FOS+CZA . For metallo-beta-lactamases (MBLs) producing strains, ATM+CZA displayed complete synergy, while the combination of MEM+CZA showed a synergy rate of only 57.14% for NDM-producing strains and 91.67% for IMP-producing strains. In the time-kill assay, MEM+CZA also demonstrated significant synergistic effects against the two KPC-2-producing isolates (Y070 and L70), the two carbapenemase-non-producing isolates (Y083 and L093), and the NDM-1-producing strain L13, with reductions in log10 CFU/mL exceeding 10 compared to the control. Against the IMP-producing strain Y047, ATM+CZA exhibited the highest synergistic effect, resulting in a log10 CFU/mL reduction of 10.43 compared to the control. The combination of CZA and MEM exhibited good synergistic effects against KPC-producing and non-enzyme-producing strains, followed by the FOS+CZA combination. Among MBL-producing strains, ATM+CZA demonstrated the most pronounced synergistic effect. However, the combinations of CZA with ERA, AK, and COL show irrelevant effects against the tested clinical isolates.ImportanceOur study confirmed the efficacy of the combination CZA+MEM against KPC-producing and non-carbapenemase-producing strains. For metalloenzyme-producing strains, CZA+ATM demonstrated the most significant synergy. Additionally, CZA exhibited a notable synergy effect when combined with FOS. These combination therapies present promising new options for the treatment of CRKP infection.

Project description:BackgroundCarbapenem-resistant Klebsiella pneumoniae (CRKP) infections in patients with cirrhosis represent a significant therapeutic challenge as they are associated with poor outcomes due to high rates of treatment failure, and frequently induce liver decompensation.AimsTo evaluate treatment failure and in-hospital mortality in two cohorts of patients with cirrhosis and with CRKP infections treated with antibiotic regimens including or excluding Ceftazidime-avibactam.MethodsData from hospitalized patients with liver cirrhosis and CRKP infections were extracted and retrospectively analyzed.ResultsDuring the study period, 39 cirrhotic patients with confirmed invasive CRKP infections were enrolled. Overall, the median age was 60 years with a median MELD score of 16 points. Urinary tract infections were diagnosed in 46%, followed by pneumonia in 23%, and primary bacteremia in 18% of patients. Treatment failure was reported in 10 patients (26%), while in-hospital mortality in 15 patients (38%). A monotherapy was used in 8 patients (20.5%), while a combination therapy was required in 31 patients (79.5%). Ceftazidime-avibactam therapy was associated with lower rates of treatment failure (7% vs. 38%, P = 0.032) independent of severity of liver disease (Child Class) and mono or combination antibiotic therapy. Acute kidney injury, hepatorenal syndrome, and acute-on-chronic liver failure were the consequences more frequently observed in patients with treatment failure. In-hospital mortality was associated with treatment failure, and Ceftazidime-avibactam therapy improved in-hospital survival (log rank test: P = 0.035) adjusted for Child class and mono or combination therapy.ConclusionTreatment including ceftazidime-avibactam was associated with a lower rate of treatment failure in cirrhotic patients with CRKP infections. Considering the favorable efficacy and outcomes of ceftazidime-avibactam, this drug should be considered for the treatment of these severe infections in patients with liver cirrhosis, though further investigation is required.

Dataset Information

Combination Therapy of Ceftazidime/Avibactam for the Treatment of Patients Infected with Carbapenem-Resistant Klebsiella pneumoniae: A Multicenter Retrospective Study.

Introduction

Methods

Results

Conclusion

Publications

Combination Therapy of Ceftazidime/Avibactam for the Treatment of Patients Infected with Carbapenem-Resistant Klebsiella pneumoniae: A Multicenter Retrospective Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets