Zavicefta (ceftazidime/avibactam) / Pfizer, AbbVie - LARVOL DELTA

Exploring mutational possibilities of KPC variants to reach high level resistance to cefiderocol. (PubMed, Sci Rep) - "All resistant clones shared a phenotype marked by cross-resistance to cefiderocol, ceftazidime, ceftazidime-avibactam, cefixime, and piperacillin, but restored susceptibility to carbapenems and most other β-lactams. Notably, ybiX has not previously been associated with cefiderocol resistance. These results underscore the importance of ongoing surveillance to detect emerging cefiderocol resistance in KPC-producing Enterobacterales."

Journal • Infectious Disease • Pneumonia

Ceftazidime-Avibactam Pharmacokinetic Comparative In Vivo/In Vitro Study in a Critically Ill Children Under High-Volume Continuous Venovenous Hemodiafiltration. (PubMed, Pharmacol Res Perspect) - "This report presents a comparative study of the pharmacokinetics of ceftazidime and avibactam, utilizing in vitro data derived from two experiments with continuous venovenous hemodiafiltration (CVVHDF) simulation and a comparison with a previously published in vivo case report. The results highlight the importance of therapeutic drug monitoring and the need for higher dosing or continuous infusion of ceftazidime-avibactam in critically ill children under crontinuous renal replacement therapy (CRRT)."

Clinical • Journal • PK/PD data • Preclinical

Beta-lactams and beta-lactamase inhibitors-current developments (PubMed, Inn Med (Heidelb)) - "These included MRSA-active cephalosporins (ceftaroline and ceftobiprole), new, broadly effective combinations of beta-lactams with beta-lactamase inhibitors, and cefiderocol, a new siderophore cephalosporin that uses the bacteria's own iron uptake systems of gram-negative bacteria to better reach the site of action through the outer membrane.In addition to cefiderocol, the most important active ingredients or fixed combinations already available on the German market include ceftazidime-avibactam, ceftolozane-tazobactam, and aztreonam-avibactam. Imipenem-relebactam and meropenem-vaborbactam are also available; Cefepim-enmetazobactam was recently added...However, interesting new combinations, such as ceftibutene-avibactam for oral use, are in development. Such combinations could also enable the oral treatment of infections by some carbapenemase producers in the future."

Journal • Review • Infectious Disease

Characterization of ertapenem-resistant Enterobacterales in Canadian hospitals: 17 years of the CANWARD study (2007-23). (PubMed, J Antimicrob Chemother) - "In Canada, ertapenem-resistant Enterobacterales remain uncommon (0.7%). CPE isolates demonstrated higher percent resistant values for multiple antimicrobial classes and harboured more antimicrobial resistance genes than non-CPE isolates. Continued monitoring for ertapenem-resistant Enterobacterales, particularly CPE, is important given their associated multidrug resistance to both established and newer agents."

Journal • Infectious Disease • Pneumonia

Ceftazidime-Avibactam in Critically Ill Patients: A Multicenter Observational Study. (PubMed, Antibiotics (Basel)) - "This study demonstrates that the mortality rate among ICU patients treated with this novel antimicrobial combination is consistent with findings from other studies involving heterogeneous populations. However, the rapid emergence of resistance underscores the need for vigilant surveillance and the implementation of robust antimicrobial stewardship strategies."

Journal • Observational data • Critical care • Infectious Disease • Transplantation

Ceftazidime-Avibactam Plus Aztreonam for the Treatment of Blood Stream Infection Caused by Klebsiella pneumoniae Resistant to All Beta-Lactame/Beta-Lactamase Inhibitor Combinations. (PubMed, Antibiotics (Basel)) - " Treatment with CAZ-AVI + ATM or DCT may offer similar clinical outcomes for patients suffering from BSI caused by K. pneumoniae strains resistant to all available BL/BLIs. However, larger studies are required to confirm the findings."

Journal • Critical care • Infectious Disease • Pneumonia • Respiratory Diseases • Septic Shock

Genomic Insights of Emerging Multidrug-Resistant OXA-48-Producing ST135 Proteus mirabilis. (PubMed, Antibiotics (Basel)) - "It exhibited a multidrug-resistant phenotype, being susceptible only to amikacin and ceftazidime/avibactam. The emergence of blaOXA-48 among P. mirabilis strains of the international clone ST135 in different geographical regions is worrying. Close monitoring of these strains is required in One Health settings."

Journal

Outbreak Caused by VIM-1- and VIM-4-Positive Proteus mirabilis in a Hospital in Zagreb. (PubMed, Pathogens) - "This study revealed an epidemic spread of carbapenemase-producing P. mirabilis in two wards in a psychiatric hospital. Due to the extensively resistant phenotype (XDR), therapeutic options were limited. This is the first report of carbapenemase-producing P. mirabilis in Croatia."

Journal • Infectious Disease • Psychiatry

Ceftazidime-Avibactam for the Treatment of Carbapenem-Resistant Organisms: A Prospective, Observational, Single-Center Study. (PubMed, Antibiotics (Basel)) - "In this cohort of critically ill patients, our results in terms of both clinical success and survival are in the upper range compared to those from mainly retrospective and some prospective studies. Although the benefits of ceftazidime-avibactam have been demonstrated in this and other studies, it must be prescribed cautiously to ensure it remains effective."

Journal • Observational data • Critical care • Infectious Disease • Pneumonia • Respiratory Diseases

Clinical Impact of New Delhi Metallo-Beta-Lactamase-Producing Enterobacterales in Critically Ill Patients: Are We Ready to Face the Challenge? (PubMed, J Clin Med) - "Six patients with invasive infection were treated with Cefiderocol and five with Ceftazidime/Avibactam and Aztreonam. In absence of early identification and appropriate treatment, patients may be at increased risk of colonization spread and potentially worse clinical outcomes. Early identification of the carbapenemase type is clinically relevant in critically ill patients with confirmed or suspected infection, as NDM production necessitates the use of specific agents for effective treatment."

Journal • Critical care • Infectious Disease

Gram-negative pathogens from Canadian hospitals: 17 years of results from the CANWARD study (2007-23). (PubMed, J Antimicrob Chemother) - "The CANWARD surveillance study has provided 17 years of reference antimicrobial susceptibility testing data."

Journal • Infectious Disease • Pneumonia

How do I manage Difficult-to-Treat Pseudomonas aeruginosa infections?: Key Questions for Today's Clinicians. (PubMed, Clin Microbiol Infect) - "Ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-cilastatin-relebactam and cefiderocol are newer options, but resistance and lack of relevant data from randomised clinical trials hampers knowledge of the best way to use them. Ceftolozane-tazobactam and ceftazidime-avibactam are initially preferred when susceptible because they enter the market first and there is more published evidence about them. Ceftolozane-tazobactam is preferred in P. aeruginosa pneumonia instead of ceftazidime-avibactam. Both can be equally used in other P. aeruginosa infection types. Imipenem-relebactam and cefiderocol may retain susceptibility when there is resistance to ceftolozane-tazobactam and ceftazidime-avibactam, and when metallo-beta-lactamases are not present. However, there are no head-to-head comparative studies to support a preference for one over the other. In the presence of metallo-beta-lactamases, cefiderocol is the preferred agent. Other options in this situation are..."

Journal • Review • Infectious Disease • Pneumonia • Respiratory Diseases

Current status and future prospects of antibacterial treatment for Carbapenem-resistant gram-negative bacterial infections in solid organ transplant recipients (PubMed, Zhonghua Yi Xue Za Zhi) - "The article provides an in-depth analysis of the efficacy, pharmacokinetic/pharmacodynamic (PK/PD) properties, and adverse effects of both commonly used antibiotics (such as tigecycline, polymyxins, and ceftazidime/avibactam) and the novel agents (including eravacycline and sulbactam/durlobactam), emphasizing the importance of combination therapy and personalized treatment approaches. Looking ahead, the review envisions a future where, guided by rapid and precise diagnostics, multidisciplinary management can optimize antimicrobial regimens for MDR infections in transplant recipients. The goal is to achieve individualized, effective treatment strategies, thereby improving outcomes in severe infections and advancing the management of CR-GNB infections in SOT patients in China."

Journal • Review • Immunology • Infectious Disease • Pneumonia • Respiratory Diseases • Solid Organ Transplantation • Transplantation

Molecular analysis and ceftazidime-avibactam susceptibilities of carbapenem-resistant Klebsiella pneumoniae: Seven year experience from blood cultures of liver transplant recipients in a university hospital. (PubMed, Diagn Microbiol Infect Dis) - "The presence of the OXA-48 resistance gene in CRKP isolates was closely associated with in vitro susceptibility to CZA, regardless of the diversity of the patient population."

Journal • Infectious Disease • Pneumonia • Septic Shock • Transplantation

Continuous infusion versus intermittent dosing of ceftazidime/avibactam in critically ill patients with Klebsiella pneumoniae OXA-48 or Pseudomonas aeruginosa infections: a single-center randomized open-label trial (ZAVICONT). Rationale and design. (PubMed, Front Pharmacol) - P4 | "This trial will provide evidence on optimal CZA administration regimen in critically ill ICU patients with severe infections due to MDR G-pathogens. clinicaltrials.gov, identifier NCT06811727."

Journal • Critical care • Infectious Disease • Pneumonia

Comparison of Effectiveness between Ceftazidime/Avibactam and Other Active Therapies for Oxacillinase-48-Producing Carbapenem-Resistant Klebsiella pneumoniae Bacteremia in Taiwan. (PubMed, Infect Dis Ther) - "Our findings revealed that CZA and other active therapies showed similar outcomes, but colistin-based regimens should be used cautiously."

Journal • Infectious Disease • Pneumonia

Model-informed individualized administration of ceftazidime-avibactam in critically ill patients: population pharmacokinetics studies and a parametric time-to-event analysis. (PubMed, J Antimicrob Chemother) - "The PopPK model for ceftazidime-avibactam was developed for critically ill Chinese adults. TTE analysis identified ceftazidime AUCss,24 h and MV as AKI risk factors. Renal function-guided dosing optimizes efficacy and safety."

Journal • PK/PD data • Acute Kidney Injury • Infectious Disease • Nephrology • Renal Disease • CRP

Cost-effectiveness Analysis Comparing Ceftazidime/Avibactam With Standard of Care in the Treatment of Hospital and Ventilator-Acquired Pneumonia in the Philippines. (PubMed, Value Health Reg Issues) - "CAZ-AVI is expected to be a highly cost-effective second-line treatment compared with colistin + high-dose meropenem from the societal perspective in the Philippines."

HEOR • Journal • Infectious Disease • Pneumonia • Respiratory Diseases

Comparison of risk factors and mortality of candidemia by Candida auris versus Candida non-auris in intensive care units. (PubMed, Infect Dis (Lond)) - "Compared to the C. albicans group, the C. auris group had more frequent ceftazidime avibactam use (OR:6.72, 95%CI: 1.29-34.98, p = 0.024) and tracheostomy (OR:4.13, 95%CI: 1.70-10.02, p = 0.002), longer colistin (OR:1.07, 95%CI: 1.01-1.13, p = 0.021) and urinary catheter use (OR:1.02, 95%CI: 1.01-1.03, p = 0.023). The necessity of broad-spectrum antibiotics and indwelling catheters should be routinely reassessed to reduce C. auris candidemia. Lower mortality was linked to microbiologic response; thus, fungal eradication should be prioritised in clinical practice."

Journal • Chronic Obstructive Pulmonary Disease • Critical care • Immunology • Pulmonary Disease • Respiratory Diseases • Thrombocytopenia

Recurrent invasive liver abscess syndrome induced by Klebsiella pneumoniae with emerging drug resistance: a case report and literature review. (PubMed, Front Med (Lausanne)) - "Treatment escalated from meropenem to ceftazidime-avibactam plus tigecycline, resulting in clinical improvement and discharge after 48 days. This case highlights the critical challenge of emerging resistance in hvKp during prolonged therapy, emphasizing the need for early molecular surveillance, multidisciplinary collaboration, and optimized antibiotic stewardship to mitigate treatment failure in ILAS."

Journal • CNS Disorders • Gene Therapies • Hepatology • Infectious Disease • Nephrology • Pneumonia

High transconjugation efficiency of fusion plasmid pNDM_KPC in carbapenem-resistant Citrobacter freundii and its formation driven by IS26-mediated integration. (PubMed, Microbiol Spectr) - "Synergy effect and bactericidal activity were observed on aztreonam plus ceftazidime/avibactam or meropenem/vaborbactam or imipenem/relebactam. Furthermore, we identify the IS26 element downstream of the intI site as a potential recombination hotspot driving plasmid fusion. These insights deepen our understanding of carbapenemase gene transmission and call for global attention to the fusion plasmid-mediated resistance spread."

Journal • Infectious Disease • Pneumonia

Carriage and infections by multi-carbapenemases producing Enterobacterales. (PubMed, Diagn Microbiol Infect Dis) - "Clinical features of patients with MCP-EB are common in the hospital population with chronic diseases and showed high mortality rates both in infected and carriers-only patients. Aztreonam/avibactam and cefiderocol could be promising treatment options against MCP-EB infections."

Journal • Cardiovascular • Chronic Kidney Disease • Infectious Disease • Nephrology • Pneumonia • Renal Disease • Respiratory Diseases

Development of blood culture time-to-positivity as a pharmacodynamic indicator for monitoring antibiotic therapy against MDR Gram-negative bacteria. (PubMed, J Antimicrob Chemother) - "Tpos is a simple, reproducible marker of serum antibiotic activity against ESBL- and carbapenemase-producing K. pneumoniae. With further clinical validation, Tpos could be developed as a complementary surrogate marker for early detection of inadequate antimicrobial therapy in patients receiving antibiotic therapy for bloodstream infections caused by MDR Gram-negative bacteria."

Journal • PK/PD data • Infectious Disease • Pneumonia

Synergistic cefiderocol-containing antibiotic combinations active against highly drug-resistant Acinetobacter baumannii patient isolates with diverse resistance mechanisms. (PubMed, J Antimicrob Chemother) - "Several cefiderocol-containing combinations show strong in vitro synergy against XDR and PDR A. baumannii. These combinations, especially cefiderocol-ceftazidime/avibactam and cefiderocol-sulbactam/durlobactam, may enhance treatment of highly resistant A. baumannii strains and warrant further clinical investigation."

Journal

Investigation of EDTA-CarbaNP-direct test for the detection of metallo-β-lactamases in Pseudomonas aeruginosa. (PubMed, Diagn Microbiol Infect Dis) - "The positivity of CNPdt in CR-Pa is limited, but EDTA-CNPdt detected 100 % of MBL-producing isolates when CNPdt was positive. This test can be used for MBL detection and prediction of CZA resistance in CNPdt positive isolates."

Journal • Infectious Disease