Ceftazidime–Avibactam Improves Outcomes in High-Risk Neutropenic Patients with Klebsiella pneumoniae Carbapenemase-Producing Enterobacterales Bacteremia

Herrera, Fabián; Torres, Diego; Laborde, Ana; Jordán, Rosana; Mañez, Noelia; Berruezo, Lorena; Lambert, Sandra; Suchowiercha, Nadia; Costantini, Patricia; Nenna, Andrea; Pereyra, María Laura; Benso, José; González Ibañez, María Luz; Eusebio, María José; Barcán, Laura; Baldoni, Nadia; Tula, Lucas; Roccia Rossi, Inés; Luck, Martín; Soto, Vanesa; Fernández, Verónica; Carena, Alberto Ángel

doi:10.3390/microorganisms12010195

Cited by 4 publications

(1 citation statement)

References 43 publications

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“…It is anticipated to be a promising empirical carbapenem-sparing regimen for the patients with hematological malignancy in febrile neutropenia in the future [109,110]. One retrospective study shows that CAZ/AVI may be considered the preferred therapeutic option for KPC-producing Enterobacteriaceae blood stream infections in high-risk neutropenic patients [111].…”

Section: Novel Beta-lactam/beta-lactamase Inhibitorsmentioning

confidence: 99%

Systematic Review of Beta-Lactam vs. Beta-Lactam plus Aminoglycoside Combination Therapy in Neutropenic Cancer Patients

Ishikawa,

Nakamura,

Kawai

et al. 2024

Cancers

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We performed a systematic review of studies that compared beta-lactams vs. beta-lactams plus aminoglycosides for the treatment of febrile neutropenia in cancer patients. Method: We searched CENTRAL, MEDLINE, and Embase for studies published up to October 2023, and randomized controlled trials (RCTs) that compared anti-Pseudomonas aeruginosa beta-lactam monotherapy with any combination of an anti-Pseudomonas aeruginosa beta-lactam and an aminoglycoside were included. Result: The all-cause mortality rate of combination therapy showed no significant differences compared with that of monotherapy (RR 0.99, 95% CI 0.84 to 1.16, high certainty of evidence). Infection-related mortality rates showed that combination therapy had a small positive impact compared with the intervention with monotherapy (RR 0.83, 95% CI 0.66 to 1.05, high certainty of evidence). Regarding treatment failure, combination therapy showed no significant differences compared with monotherapy (RR 0.99, 95% CI 0.94 to 1.03, low certainty of evidence). In the sensitivity analysis, the treatment failure data published between 2010 and 2019 showed better outcomes in the same beta-lactam group (RR 1.10 [95% CI, 1.01–1.19]). Renal failure was more frequent with combination therapy of any daily dosing regimen (RR 0.46, 95% CI 0.36 to 0.60, high certainty of evidence). Conclusion: We found combining aminoglycosides with a narrow-spectrum beta-lactam did not spare the use of broad-spectrum antibiotics. Few studies included antibiotic-resistant bacteria and a detailed investigation of aminoglycoside serum levels, and studies that combined the same beta-lactams showed only a minimal impact with the combination therapy. In the future, studies that include the profile of antibiotic-resistant bacteria and the monitoring of serum aminoglycoside levels will be required.

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Section: Novel Beta-lactam/beta-lactamase Inhibitorsmentioning

confidence: 99%

Systematic Review of Beta-Lactam vs. Beta-Lactam plus Aminoglycoside Combination Therapy in Neutropenic Cancer Patients

Ishikawa,

Nakamura,

Kawai

et al. 2024

Cancers

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Clinical impact of ceftazidime/avibactam on the treatment of suspected or proven infections in a large cohort of patients with haematological malignancies: a multicentre observational real-world study

Tumbarello,

Giuliano,

Criscuolo

et al. 2024

Journal of Antimicrobial Chemotherapy

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Objectives To evaluate clinical impact of ceftazidime/avibactam on treating infections due to MDR Gram-negative bacteria in patients with haematological malignancies (HMs). Methods We conducted a retrospective, observational study at 17 Italian haematological wards that included patients with HMs receiving ceftazidime/avibactam for the treatment of suspected or proven infections. The primary endpoint was all-cause mortality 30 days after infection onset. Secondary endpoints included the development of in vitro ceftazidime/avibactam resistance, adverse reactions and infection relapse. Results Of 198 patients enrolled, 66 had fever of unknown origin and 132 had microbiologically proven infections (MPIs). Enterobacterales were responsible for 98 MPIs, with KPC producers accounting for 75% of these, and carbapenem-resistant Pseudomonas aeruginosa caused 25% of MPIs. The overall 30-day mortality rate was 17.7%. Infection relapse occurred in four patients with MPI. Patients who died within 30 days of infection onset tended to have pre-existing cerebrovascular diseases, a Charlson Comorbidity Index > 4 and septic shock at infection onset and had received inadequate initial antibiotic therapy. Thirty-day mortality was independently associated with septic shock at infection onset and inappropriate initial antibiotic therapy. Conclusions Our study provides further evidence about the effectiveness of ceftazidime/avibactam in treating infections in patients with HMs.

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Ceftazidime-Avibactam for the Treatment of Febrile Neutropenia in HSCT Recipients and Acute Leukemia Patients Post Induction Chemotherapy

Frem,

Khazzeka,

Allaw

et al. 2024

Preprint

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Background Febrile neutropenia is a common and major complication in patients with acute leukemia or those undergoing hematopoietic stem cell transplantation (HSCT). Understanding patient characteristics and patterns of susceptibility in febrile neutropenia is essential to provide the appropriate antimicrobial therapy. First-line agents should have Pseudomonas coverage, but with the increase in multi-drug resistant organisms, ceftazidime-avibactam has emerged as a new therapy in febrile neutropenia. Methods This is a retrospective case-control study of a total of 300 admissions (143 patients) between January 2009 and December 2017. Patients with hematologic neoplasms and patients that underwent HSCT who satisfied the definition of febrile neutropenia and treated with ceftazidime-avibactam (CAZAVI) were included in the study. A bivariate regression model to explore independent predictors of septic shock and mortality was constructed. Results Patients who received ceftazidime-avibactam (CAZAVI) were more likely to have a microbiologically documented infection (59.0% vs. 28.3%). Almost all complications were significantly more frequent in the CAZAVI group, with sepsis being the most common, occurring in 59.0% of patients in the CAZAVI arm. Our multivariable logistic regression analysis showed that receiving CAZAVI was an independent risk factor for both sepsis and mortality (aOR 6.33 [95% CI 2.81–14.30] and 7.82 [2.63–23.26], respectively). Conclusion Knowing the most common organisms isolated during a neutropenic fever episode as well as the patterns of resistance, compounded with an understanding of the risk factors for morbidity and mortality in such a vulnerable population, is key to providing them with appropriate prophylactic and therapeutic management. In addition, more studies should be done on the effectiveness of ceftazidime-avibactam in treating febrile neutropenia in the population at hand.

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Ceftazidime–Avibactam Improves Outcomes in High-Risk Neutropenic Patients with Klebsiella pneumoniae Carbapenemase-Producing Enterobacterales Bacteremia

Cited by 4 publications

References 43 publications

Systematic Review of Beta-Lactam vs. Beta-Lactam plus Aminoglycoside Combination Therapy in Neutropenic Cancer Patients

Systematic Review of Beta-Lactam vs. Beta-Lactam plus Aminoglycoside Combination Therapy in Neutropenic Cancer Patients

Clinical impact of ceftazidime/avibactam on the treatment of suspected or proven infections in a large cohort of patients with haematological malignancies: a multicentre observational real-world study

Ceftazidime-Avibactam for the Treatment of Febrile Neutropenia in HSCT Recipients and Acute Leukemia Patients Post Induction Chemotherapy

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