Ceftazidime–avibactam treatment in bacteremia caused by OXA-48 carbapenemase-producing Klebsiella pneumoniae

Lima, Olalla; Sousa, Adrián; Longueira-Suárez, R.; Filgueira, A.; Taboada-Martínez, C.; Portela-Pino, C.; Nodar, Andrés; Vasallo-Vidal, F.; Martínez-Lamas, Lucía; Pérez-Landeiro, Antonio; Rubianes, M.; Pérez-Rodríguez, MT.

doi:10.1007/s10096-022-04482-9

Cited by 6 publications

(9 citation statements)

References 38 publications

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“…2 A). Most studies were 2020 onwards and were from China [ 22 , 26 , 30 , 31 , 33 , 39 , 41 , 43 ] and Spain [ 23 , 25 , 32 , 36 , 42 , 45 ] (Fig. 2 B and C).…”

Section: Resultsmentioning

confidence: 99%

“…Microbiological cure occurred in 58.33% ( n = 42/72) of patients in the CAZ-AVI group and 35.90% ( n = 14/39) of patients in the comparator group, which was in a single study (Table 2 ) [ 42 ]. Resistance to CAZ-AVI was observed in 2.89% ( n = 19/656, repeat susceptibility data not available) patients during the therapy, reported across five studies [ 24 , 28 , 29 , 36 , 44 ].…”

Section: Resultsmentioning

confidence: 99%

“…Sources of bacteremia were reported in six studies, but outcomes could not be differentiated by source. Overall, 10.80–99.30% of patients had bacteremia secondary to a pulmonary source sites [ 22 , 33 , 35 , 36 , 40 , 43 ].…”

Section: Resultsmentioning

confidence: 99%

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Ceftazidime-Avibactam in the Treatment of Patients with Bacteremia or Nosocomial Pneumonia: A Systematic Review and Meta-analysis

Shields,

Horcajada,

Kamat

et al. 2024

Infect Dis Ther

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Introduction Ceftazidime-avibactam (CAZ-AVI) is a combination of the third-generation cephalosporin ceftazidime and the novel, non-β-lactam β-lactamase inhibitor avibactam that is approved for the treatment of pediatric (≥ 3 months) and adult patients with complicated infections including hospital-acquired and ventilator-associated pneumonia (HAP/VAP), and bacteremia. This systematic literature review and meta-analysis (PROSPERO registration: CRD42022362856) aimed to provide a quantitative and qualitative synthesis to evaluate the effectiveness of CAZ-AVI in treating adult patients with bacteremia or nosocomial pneumonia caused by carbapenem-resistant Enterobacterales (non metallo-β-lactamase-producing strains) and multi-drug resistant (MDR) Pseudomonas aeruginosa infections. Methods The databases included in the search, until November 7, 2022, were Embase and PubMed. A total of 24 studies (retrospective: 22, prospective: 2) with separate outcomes for patients with bacteremia or pneumonia were included. Results The outcomes assessed were all-cause mortality, clinical cure, and microbiological cure. Qualitative (24 studies) and quantitative (8/24 studies) syntheses were performed. The quality of the studies was assessed using the MINORS checklist and the overall risk of bias was moderate to high. Conclusions In studies included in the meta-analysis, lower all-cause mortality for patients with bacteremia (OR = 0.30, 95% CI 0.19–0.46) and improved rates of clinical cure for patients with bacteremia (OR = 4.90, 95% CI 2.60–9.23) and nosocomial pneumonia (OR = 3.20, 95% CI 1.55–6.60) was observed in the CAZ-AVI group compared with the comparator group. Data provided here may be considered while using CAZ-AVI for the treatment of patients with difficult-to-treat infections. Systematic Review Registration PROSPERO CRD42022362856. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-024-00999-y.

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“…2 A). Most studies were 2020 onwards and were from China [ 22 , 26 , 30 , 31 , 33 , 39 , 41 , 43 ] and Spain [ 23 , 25 , 32 , 36 , 42 , 45 ] (Fig. 2 B and C).…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Ceftazidime-Avibactam in the Treatment of Patients with Bacteremia or Nosocomial Pneumonia: A Systematic Review and Meta-analysis

Shields,

Horcajada,

Kamat

et al. 2024

Infect Dis Ther

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“…In the past, some scholars have made retrospective studies on the efficacy of CAZ-AVI in the treatment of KP, but previous research focused mostly on bloodstream infections. [24][25][26][27] Cases included in this study covered pulmonary, abdominal, blood, and urinary tract infections, and the majority were pulmonary infections. In this study, the vast majority of KP strains were not screened for drug-resistance genes, and clinicians do not screen for drug-resistance genes in most clinical settings in China.…”

Section: Discussionmentioning

confidence: 99%

Clinical Efficacy and Safety Evaluation of Ceftazidime-Avibactam in the Treatment of Klebsiella pneumoniae Infection: A Retrospective Analysis from a Hospital in China

Xu,

Luo,

Huang

et al. 2023

IDR

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Background: Ceftazidime-avibactam (CAZ-AVI) is a new cephalosporin/β-lactamase inhibitor combination that received clinical approval in China in 2019. This study aims to investigate the efficacy and safety of CAZ-AVI in the treatment of Klebsiella pneumoniae (KP) infection in a hospital, and differences in efficacy among various infection sites and between monotherapy and combination therapy, providing valuable insights for its further application. Methods: Patients who used CAZ-AVI between January 2019 and April 2023 were identified through the hospital information system. Demographic information, details of the infection site, KP strain's drug sensitivity report, treatment duration, combination therapies, adverse drug reactions (ADR), and 28-day survival were recorded. Clinical and microbiological efficacies were analyzed using SPSS 23.0 software to compare different infection sites and combination therapies. Results:The overall effective clinical response (CR) rate of CAZ-AVI against KP infection was 62.13%, with a favorable microbial response (MR) rate was 65.68% and a 28-day survival rate was 63.91%. No significant difference occurred in effective CR and 28-day survival rate among different infection sites (P = 0.709 and 0.862, respectively). The favorable MR rate for abdominal infections was slightly lower than that for other sites of infection (P = 0.021). No significant differences in effective CR, favorable MR, and 28-day survival between monotherapy and combination therapy were present (P values were 0.649, 0.123, and 0.280, respectively). The incidence of ADR was 1.78%, including increased creatinine, elevated transaminase, hematuria, and thrombocytopenia. Conclusion: CAZ-AVI demonstrates good clinical efficacy and safety in the treatment of KP infections. The clinical efficacy of CAZ-AVI was similar across different infection sites, and combination therapy did not show an advantage over monotherapy. Further studies are warranted. It should be noted that CAZ-AVI may induce thrombocytopenia and hematuria.

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“…15 Compared with best available therapy, CAZ-AVI treatment was associated with a greater clinical success in CRKP bacteremia. 16 However, within a short time when CAZ/AVI was introduced into clinic, some cases of CRKP resistance were reported. 17,18 The fourth-generation cephalosporin cefepime is a broad-spectrum antibiotic frequently used in clinical practice but is easily degraded by many existing β-lactamases.…”

Section: Introductionmentioning

confidence: 99%

In vitro Activity of Cefepime/Avibactam Against Carbapenem Resistant Klebsiella pneumoniae and Integrative Metabolomics-Proteomics Approach for Resistance Mechanism: A Single-Center Study

Wen,

Luo,

Chen

et al. 2023

IDR

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We aimed to evaluate the in vitro antibacterial effects of combination of cefepime/avibactam against carbapenem-resistant Klebsiella pneumonia (CRKP) and explore the resistance mechanism of FEP/AVI. Patients and Methods: This study explored the in vitro antibacterial activities of ceftazidime/avibactam (CAZ/AVI) and cefepime/ avibactam (FEP/AVI) against 40 and 76 CRKP clinical isolates. Proteomics and metabolomics were employed to investigate the resistance mechanisms of CRKP to FEP/AVI. Results: FEP/AVI (MIC 50 /MIC 90 0.5/4-64/4 μg/mL, resistance rate 17.1%) showed better antibacterial activity against CRKP than CAZ/AVI (MIC 50 /MIC 90 4/4-128/4 μg/mL, resistance rate 20%) in vitro. Bioinformatics analysis showed that the differentially expressed proteins (DEPs) were enriched in alanine, aspartate and glutamate metabolism, and ribosome. Remarkably, transcriptional and translational activity-related pathways were inhibited in FEP/AVI resistant CRKP. Overlap analysis suggested that H-NS might play an important role in resistance to FEP/AVI in CRKP. The mRNA levels of DEPs-related genes (adhE, gltB, purA, ftsI and hns) showed the same trends as DEPs in FEP/AVI susceptible and resistant strains. FEP/AVI resistant isolates demonstrated stronger biofilm formation capacity than susceptible isolates. Metabolomics results showed that disturbed metabolites were mainly lipids, and adenine was decreased in FEP/AVI resistant CRKP. Conclusion: These results indicated that H-NS, GltB and SpoT may directly or indirectly promote biofilm formation of CRKP and led to FEP/AVI resistance, but inhibited ribosomal function. Our study provides a mechanistic insight into the acquisition of resistance to FEP/AVI in Klebsiella pneumoniae.

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Ceftazidime–avibactam treatment in bacteremia caused by OXA-48 carbapenemase-producing Klebsiella pneumoniae

Cited by 6 publications

References 38 publications

Ceftazidime-Avibactam in the Treatment of Patients with Bacteremia or Nosocomial Pneumonia: A Systematic Review and Meta-analysis

Ceftazidime-Avibactam in the Treatment of Patients with Bacteremia or Nosocomial Pneumonia: A Systematic Review and Meta-analysis

Clinical Efficacy and Safety Evaluation of Ceftazidime-Avibactam in the Treatment of Klebsiella pneumoniae Infection: A Retrospective Analysis from a Hospital in China

In vitro Activity of Cefepime/Avibactam Against Carbapenem Resistant Klebsiella pneumoniae and Integrative Metabolomics-Proteomics Approach for Resistance Mechanism: A Single-Center Study

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