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In vitro, in vivo and clinical studies comparing the efficacy of ceftazidime-avibactam monotherapy with ceftazidime-avibactam-containing combination regimens against carbapenem-resistant Enterobacterales and multidrug-resistant Pseudomonas aeruginosa isolates or infections: a scoping review

FRONTIERS IN MEDICINE (2023)

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Summary: This study investigated hospital-acquired bloodstream infections (HA-BSI) in 2600 adult patients from 333 ICUs in 52 countries. HA-BSI were frequently caused by Gram-negative, carbapenem-resistant, and difficult-to-treat pathogens. Antimicrobial resistance led to delays in adequate antimicrobial therapy, resulting in high mortality rates.

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Summary: This study investigated the characteristics and outcomes of carbapenem-resistant Pseudomonas aeruginosa (CRPA) infections and the distribution and clinical significance of carbapenemases. The results showed that carbapenemase-producing CRPA infections were associated with increased 30-day mortality, and the prevalence of carbapenemase genes varied by region. These findings highlight the therapeutic challenges posed by these carbapenem-resistant organisms.

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European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli (endorsed by European society of intensive care medicine)

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Article Infectious Diseases

A retrospective observational cohort study of the clinical epidemiology of bloodstream infections due to carbapenem-resistant Klebsiella pneumoniae in an OXA-48 endemic setting

Abdullah Tarik Aslan et al.

Summary: This study characterized the epidemiology and clinical outcomes of CRKP bloodstream infections in an OXA-48-predominant environment. Inappropriate therapy was associated with higher mortality and clinical failure. Appropriate regimens showed better outcomes for CRKP BSI with OXA-48 predominance.

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS (2022)

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INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS (2022)

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Impact of ceftazidime/avibactam versus best available therapy on mortality from infections caused by carbapenemase-producing Enterobacterales (CAVICOR study)

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Summary: The study found that ceftazidime/avibactam is an effective alternative for the treatment of carbapenemase-producing Enterobacterales (CPE) infections, especially in patients with certain high scores. Multivariate analysis showed that treatment with ceftazidime/avibactam was associated with survival, while high INCREMENT-CPE scores and SOFA scores were associated with higher mortality.

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Christopher J. L. Murray et al.

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LANCET (2022)

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Infectious Diseases Society of America 2022 Guidance on the Treatment of Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa)

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Characteristics and outcomes of carbapenemase harbouring carbapenem-resistant Klebsiella spp. bloodstream infections: a multicentre prospective cohort study in an OXA-48 endemic setting

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Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019

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Treatment strategies for OXA-48-like and NDM producing Klebsiella pneumoniae infections

Burcu Isler et al.

Summary: This article reviews the literature on the treatment of OXA-48-like and NDM-producing carbapenem-resistant Klebsiella pneumoniae (CRKP) and provides updated information on available antibiotic treatment strategies. The best treatment option for OXA-48 producers is ceftazidime-avibactam, followed by colistin. There is an unmet need for the treatment of NDM producers, but ceftazidime-avibactam and aztreonam combination or cefiderocol can be used if available.

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Safety of Ceftazidime-Avibactam in Combination with Aztreonam (COMBINE) in a Phase I, Open-Label Study in Healthy Adult Volunteers

Thomas P. Lodise et al.

Summary: This study evaluated the safety of the optimal ceftazidime-avibactam (CZA) with aztreonam (ATM) regimens identified in infection models of MBL-producing Enterobacterales. The results suggest that CZA-ATM administered as 2-h intermittent infusions is safe and caution should be exercised with the use of ATM continuous infusion at a high dose.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2022)

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Effect of ceftazidime/avibactam plus fosfomycin combination on 30 day mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae: results from a multicentre retrospective study

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Activity of aztreonam in combination with ceftazidime-avibactam against serine- and metallo-β-lactamase-producing Pseudomonas aeruginosa

Michelle Lee et al.

Summary: The combination of aztreonam and ceftazidime-avibactam shows promising results against SBL and MBL-producing Enterobacterales, although data on Pseudomonas aeruginosa are lacking. Subinhibitory concentrations of the two drugs produced synergy and restored bactericidal activity in most isolates tested, suggesting it may be a viable treatment option.

DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE (2021)

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Article Infectious Diseases

Ceftazidime/avibactam in the era of carbapenemase-producing Klebsiella pneumoniae: experience from a national registry study

I Karaiskos et al.

Summary: The study demonstrates that ceftazidime/avibactam is effective in treating infections caused by KPC-Kp, significantly reducing mortality rates. Additionally, ultimately fatal disease, rapidly fatal disease, and Charlson comorbidity index ≥ 2 were identified as independent predictors of death, while treatment with ceftazidime/avibactam-containing regimens was the only independent predictor of survival.

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY (2021)

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Article Immunology

Ceftazidime-Avibactam Use for Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae Infections: A Retrospective Observational Multicenter Study

Mario Tumbarello et al.

Summary: The study found that there was no significant difference in 30-day mortality rates between patients treated with ceftazidime-avibactam alone and those treated with combination regimens for managing infections caused by carbapenem-resistant Enterobacteriaceae. Factors such as septic shock and neutropenia at infection onset were positively associated with mortality, while prolonged infusion of CAZ-AVI was negatively associated with mortality. Further research is needed to explore the potential survival benefits of prolonging CAZ-AVI infusions in certain types of infections.

CLINICAL INFECTIOUS DISEASES (2021)

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Article Infectious Diseases

Ceftazidime-avibactam, meropenen-vaborbactam, and imipenem-relebactam in combination with aztreonam against multidrug-resistant, metallo-β-lactamase-producing Klebsiella pneumoniae

Sofia Maraki et al.

Summary: The study evaluated the in vitro efficacy of different antibiotic combinations against multidrug-resistant Klebsiella pneumoniae, showing that certain combinations exhibited synergy. Further clinical studies are needed to confirm the efficacy of these antimicrobial combinations.

EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES (2021)

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Article Microbiology

Trends of Antimicrobial Resistance and Combination Susceptibility Testing of Multidrug-Resistant Pseudomonas aeruginosa Isolates from Cystic Fibrosis Patients: a 10-Year Update

Ijeoma N. Okoliegbe et al.

Summary: This study compared the in vitro activity of new antimicrobials with other antipseudomonal agents and found colistin to be one of the most active antimicrobials, while combinations with beta-lactam plus beta-lactamase inhibitors showed synergistic effects. The study also highlights the importance of effective fluoroquinolone stewardship for CF patients.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2021)

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Review Infectious Diseases

Systematic review and meta-analysis of in vitro efficacy of antibiotic combination therapy against carbapenem-resistant Gram-negative bacilli

Luigia Scudeller et al.

Summary: The efficacy of combination therapy for carbapenem-resistant Gram-negative bacilli (CR-GNB) infections remains controversial. In vitro studies suggest that combinations of polymyxins and carbapenems show high or moderate synergism against CR-GNB. Well-designed in vitro studies are crucial for guiding the selection of combination therapies in clinical trials and improving the armamentarium against carbapenem-resistant bacteria.

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS (2021)

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Article Infectious Diseases

Activity of ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam against carbapenemase-negative carbapenem-resistant Enterobacterales isolates from US hospitals

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Summary: Research on carbapenem-resistant Enterobacterales (CRE) without carbapenemase genes revealed complex resistance mechanisms, limited activity of most beta-lactam agents, and effective inhibition by ceftazidime/avibactam. Further studies are needed to understand the diverse resistance mechanisms and optimize treatment strategies for these isolates.

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS (2021)

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Time-Kill Evaluation of Antibiotic Combinations Containing Ceftazidime-Avibactam against Extensively Drug-Resistant Pseudomonas aeruginosa and Their Potential Role against Ceftazidime-Avibactam-Resistant Isolates

Maria M. Montero et al.

Summary: Ceftazidime-avibactam (CZA) has shown promise in treating Pseudomonas aeruginosa infections, particularly those that are extensively drug-resistant (XDR). Combination therapy with CZA and other antibiotics was more effective than monotherapy against XDR isolates, including those resistant to CZA. This study highlights the potential of CZA combinations in treating difficult-to-treat XDR P. aeruginosa infections.

MICROBIOLOGY SPECTRUM (2021)

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Article Infectious Diseases

Ceftazidime-Avibactam in Combination with In Vitro Non-susceptible Antimicrobials Versus Ceftazidime-Avibactam in Monotherapy in Critically Ill Patients with Carbapenem-Resistant Klebsiella Pneumoniae Infection: A Retrospective Cohort Study

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Jovan Borjan et al.

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS (2020)

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Meropenem-Vaborbactam versus Ceftazidime-Avibactam for Treatment of Carbapenem-Resistant Enterobacteriaceae Infections

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Ceftazidime-avibactam susceptible to resistant KPC-producing Enterobacterales bloodstream infections: an observational study

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Article Infectious Diseases

Ceftazidime-avibactam activity when tested against ceftazidime-nonsusceptible Citrobacter spp., Enterobacter spp., Serratia marcescens, and Pseudomonas aeruginosa from Unites States medical centers (2011-2014)

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Avibactam confers susceptibility to a large proportion of ceftazidime-resistant Pseudomonas aeruginosa isolates recovered from cystic fibrosis patients

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JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY (2015)

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Combination therapy for carbapenem-resistant Gram-negative bacteria

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Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance

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CLINICAL MICROBIOLOGY AND INFECTION (2012)

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CURRENT PHARMACEUTICAL DESIGN (2012)

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Review Microbiology

Antibacterial-Resistant Pseudomonas aeruginosa: Clinical Impact and Complex Regulation of Chromosomally Encoded Resistance Mechanisms

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CLINICAL MICROBIOLOGY REVIEWS (2009)

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Review Biochemistry & Molecular Biology

Pseudomonas aeruginosa hypoxic or anaerobic biofilm infections within cystic fibrosis airways

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TRENDS IN MICROBIOLOGY (2009)

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