Zerbaxa (ceftolozane /tazobactam) / Merck (MSD) - LARVOL DELTA

Phenotypic screening for metallo-β-lactamases and extended-spectrum β-lactamases in Pseudomonas aeruginosa using the VITEK-2 AST-N443 and Phoenix NMIC-486 cards. (PubMed, Microbiol Spectr) - "However, these groups exhibit distinct susceptibility patterns to novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations, including ceftolozane/tazobactam (C/T), ceftazidime/avibactam (C/A), imipenem/relebactam (I/R), and meropenem/vaborbactam (M/V)...Antimicrobial susceptibility testing was performed using the VITEK-2 AST-N443 and Phoenix NMIC-486 cards on 135 whole-genome-sequenced international CRPA isolates resistant by disc diffusion to ceftazidime, cefepime, imipenem, and/or meropenem...Our study identifies reliable screening cut-offs for MBL- and ESBL-production in CRPA using standard VITEK 2 and Phoenix automated AST panels. This readily available approach may accelerate detection, support routine laboratory workflows, reduce unnecessary confirmatory testing, and facilitate earlier targeted therapy and infection-control interventions in laboratories using these systems worldwide without requiring additional specialized testing or infrastructure."

Journal • Infectious Disease

L2 β-lactamase contributes to ceftolozane-tazobactam resistance in Pseudomonas aeruginosa. (PubMed, Antimicrob Agents Chemother) - "The prevalence of non-susceptibility to ceftolozane-tazobactam (C/T) among Pseudomonas aeruginosa remains low, but novel mechanisms of C/T resistance are of concern. Interestingly, disruption of the gene blaL2 but not the truncated ampRL2 in PS2045 led to a decrease in C/T MIC. Thus, we report a novel mechanism of C/T resistance in P. aeruginosa partially mediated by an L2 β-lactamase independently of its canonical regulator, AmpRL2."

Journal

CLEMENT: Ceftolozane/Tazobactam Versus Meropenem for Febrile Neutropenia on Patients Colonized With or at Risk for Infection With Extended Spectrum Beta Lactamase - Producing Pathogens (clinicaltrials.gov) - P4 | N=55 | Recruiting | Sponsor: Beneficência Portuguesa de São Paulo | N=176 ➔ 55 | Trial completion date: Dec 2026 ➔ Dec 2027 | Trial primary completion date: Dec 2026 ➔ Aug 2027

Enrollment change • Head-to-Head • Trial completion date • Trial primary completion date • Febrile Neutropenia • Hematological Disorders • Infectious Disease • Neutropenia

Combining phages and ceftolozane/tazobactam against carbapenem-resistant Pseudomonas aeruginosa restricts the evolution of resistance in endotracheal tube biofilm. (ERS 2026) - "Conclusion Synergism between CT and PCKs in CRPA ETT biofilms is driven by a mutual delay in resistance emergence. Combined therapy restricted resistance evolution and prolonged the antibacterial efficacy of both approaches."

Respiratory Diseases

Ceftazidime-avibactam in elastomeric pump for vascular graft infection: a case report. (PubMed, Infez Med) - "A subsequent isolate of K. pneumoniae demonstrated resistance to both ertapenem and ceftolozane-tazobactam.Treatment was transitioned to daptomycin (500 mg daily) and ceftazidime-avibactam (2.5 g three times a day), with oral rifampin added for anti-biofilm activity.To facilitate early discharge per the patient's request, ceftazidime-avibactam was administered off-label via an elastomeric pump. This case demonstrates that continuous 12-hour infusion of ceftazidime-avibactam via elastomeric pumps is a feasible and safe strategy for managing complex CRE infections in the OPAT setting. Such tailored approaches can enhance patient quality of life and reduce hospital stays, though further prospective studies are needed."

Journal • Cardiomyopathy • Cardiovascular • Diabetes • Infectious Disease • Metabolic Disorders • Peripheral Arterial Disease • Pneumonia

In vivo efficacy of cefiderocol against ceftolozane/tazobactam- and ceftazidime/avibactam-resistant Pseudomonas aeruginosa carrying the AmpC E219K substitution. (PubMed, Antimicrob Agents Chemother) - "Cefiderocol failed to achieve stasis against a cefiderocol-resistant isolate. E219K impaired cefiderocol efficacy in vivo, supporting close monitoring of cefiderocol activity against isolates carrying this variant."

Journal • Preclinical • Infectious Disease

Ceftolozane/Tazobactam Susceptibility in ESBL-Producing Enterobacterales: Insights from the SMART Program 2020-2022 in China. (PubMed, Infect Drug Resist) - "ESBL-E were defined as ceftriaxone-nonsusceptible (i.e, intermediate or resistant) and carbapenem-susceptible Enterobacterales (CSE), with species-specific adjustments for Morganella, Proteus, and Providencia; carbapenem-resistant isolates were analyzed separately. C/T susceptibility among ESBL-E was high in E. coli but substantially lower and more variable in K. pneumoniae and E. cloacae; the aggregate order-level susceptibility of 83.1% should not be relied upon to guide empiric therapy when Klebsiella or Enterobacter infection is suspected. Continued surveillance and susceptibility testing are essential to support evidence-based antimicrobial use."

Journal • Infectious Disease • Nephrology • Pneumonia

Ceftolozane/Tazobactam (C/T) and Ceftazidime/Avibactam (CZA) Non-susceptibility (NS) Among Hospitalized Adults with Pseudomonas aeruginosa (PSA) Isolated from Lower Respiratory Tract (LTR) Clinical Cultures: Index and Subsequent Episodes in the Kaiser Permanente Southern California (KPSC) System (IDWeek 2026) - No abstract available

Infectious Disease

Ceftolozane/Tazobactam Plus Metronidazole Versus Meropenem for Complicated Intra-abdominal Infections: A Systematic Review and Meta-Analysis (IDWeek 2026) - No abstract available

Retrospective data • Review • Infectious Disease

A Unique Cohort of Co-Infection-Free Difficult to Treat Pseudomonas aeruginosa Pneumonia: Mortality comparison of Aminoglycoside/ Fluoroquinolone/ Colistin Combination Based Regimen versus Ceftazidime/Avibactam or Ceftolozane/ Tazobactam. (IDWeek 2026) - No abstract available

Infectious Disease

Comparative effectiveness of ceftolozane/tazobactam relative to ceftazidime/avibactam for the treatment of adult, hospitalized patients with pneumonia due to multidrug-resistant Pseudomonas aeruginosa in U.S. Veterans Health Administration facilities. (PubMed, Antimicrob Agents Chemother) - "In this national VHA cohort, C/T and C/A demonstrated comparable clinical, microbiologic, and healthcare utilization outcomes. These findings support consideration of either C/T or C/A for MDR-PSA pneumonia when used at appropriate doses."

HEOR • Journal • Infectious Disease • Pneumonia • Respiratory Diseases

A Novel Real-Time SYBR Green PCR Assay for Integron Profiling in Pseudomonas aeruginosa: Unveiling the Resistance Nexus Between Food and Clinical Isolates. (PubMed, Pathogens) - "Phenotypic resistance was profiled against 16 antipseudomonal agents, with polymyxin and colistin resistance validated via reference broth microdilution...Absolute phenotypic resistance (100%) was recorded across both cohorts for meropenem, ceftazidime, aztreonam, tobramycin, polymyxins, and novel combination therapeutics (ceftazidime-avibactam and ceftolozane-tazobactam)... These findings reveal an overlapping, extreme resistome across the food-clinical interface and identify intI2 as a genetic tipping point for absolute pandrug resistance. The validated real-time assay provides a highly sensitive, proactive molecular surveillance framework capable of mapping high-risk mobile genetic platforms before they manifest as catastrophic empirical treatment failures."

Journal

Real-World Antibiotic Strategies for Multidrug-Resistant Pseudomonas aeruginosa: Evidence from the Italian SUSANA Multicentre Study. (PubMed, Antibiotics (Basel)) - "Ceftolozane-tazobactam (CT) (64.7%) and ceftazidime-avibactam (CZA) (20.2%) were the most prescribed agents. No independent association with improved survival was observed for combination therapy compared with monotherapy or for prolonged/continuous compared with standard infusion. These findings highlight the prognostic role of baseline clinical severity and support the need for prospective, randomized, pharmacokinetic/pharmacodynamic (PK/PD)-guided studies to identify patients who may benefit from these strategies."

Journal • Real-world evidence • Infectious Disease • Pneumonia • Respiratory Diseases • Septic Shock

A Ten-Year Trend of Antimicrobial Resistance in Pseudomonas aeruginosa From United States Medical Centers: Results From the INFORM Surveillance Program (2015-2024). (PubMed, Open Forum Infect Dis) - "Ceftazidime-avibactam, ceftolozane-tazobactam, and imipenem-relebactam were active against 97.0%-97.9% of isolates overall. Piperacillin-tazobactam and ceftazidime activities decreased slightly during the study period, whereas the activities of meropenem, levofloxacin, and tobramycin improved since 2017."

Journal • Infectious Disease • Pneumonia • Respiratory Diseases

Real-world use of novel β-lactams in immunologically vulnerable patients: insights from an Italian retrospective cohort. (PubMed, JAC Antimicrob Resist) - "Adult patients receiving NBLs (cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/relebactam or meropenem/vaborbactam) were included. In a real-world Italian cohort spanning 5 years, NBLs were widely used in immunologically vulnerable patients, a population often underrepresented in pivotal antibiotic trials, with K. pneumoniae carbapenemase-producing K. pneumoniae and P. aeruginosa as predominant pathogens. Unadjusted comparisons showed similar clinical outcomes despite greater baseline severity among non-vulnerable patients, a hypothesis-generating finding warranting confirmation in adjusted, prospective studies."

Journal • Real-world evidence • Retrospective data • Hematological Disorders • Human Immunodeficiency Virus • Immunology • Infectious Disease • Pneumonia • Rheumatology • Solid Organ Transplantation • Transplantation

Clinical Outcomes and Healthcare Resource Utilization Results Among Hospitalized Adults with Cystic Fibrosis Treated with Ceftolozane/Tazobactam: A SPECTRA Real-World Subgroup Analysis. (PubMed, Antibiotics (Basel)) - " In this SPECTRA subgroup analysis, C/T was associated with favorable real-world clinical outcomes among hospitalized adults with CF treated for an index infection. Interpretation is limited by the retrospective design, heterogeneous infection indications/sites, and limited interpretability of microbiologic endpoints in CF."

Clinical data • HEOR • Journal • Real-world evidence • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Comparison of Ceftolozane-Tazobactam Versus Meropenem Regimens in Treating Bloodstream Infections Caused by Extended-Spectrum β-Lactamase-Producing Enterobacterales: Real-World Data from a Greek Tertiary Center. (PubMed, J Clin Med) - "These observational data support further prospective evaluation of C/T as a potential carbapenem-sparing option. Prospective randomized controlled trials are required to confirm these findings before clinical practice algorithms are modified."

Journal • Real-world evidence • Infectious Disease • Pneumonia • Septic Shock

Carbapenem resistance and susceptibility to Ceftazidima/avibactam and Ceftolozane/tazobactam in Pseudomonas aeruginosa and Enterobacterales in a reference laboratory in Lima, Peru: A cross-sectional study. (PubMed, PLoS One) - "Meropenem resistance in P. aeruginosa reached 33% overall and 60% in respiratory specimens...Ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T) were highly active (>89%) against non-carbapenemase-producing P. aeruginosa, but <1% effective against producers...Among Enterobacterales, carbapenemase production was frequent in carbapenem-resistant isolates, with metallo-β-lactamases predominating. The limited activity of CZA against MBL producers underscores the urgent need for novel β-lactam/β-lactamase inhibitor combinations to address MBL-producing Enterobacterales."

Journal • Observational data • Retrospective data • Infectious Disease • Pneumonia

Activity of Aztreonam-avibactam and Ceftazidime-Avibactam against Enterobacterales and Pseudomonas aeruginosa causing infections in patients hospitalized in hematology, oncology, and transplant units from United States medical centres (2019-2024). (PubMed, Diagn Microbiol Infect Dis) - "Aztreonam-avibactam, ceftazidime-avibactam, and meropenem-vaborbactam were highly active against Enterobacterales (99.9-99.4% susceptible), including MDR isolates (99.6-98.1% susceptible), but only aztreonam-avibactam exhibited good activity against CRE (95.8% susceptible). The most active agents against P. aeruginosa were ceftazidime-avibactam (95.7% susceptible), ceftolozane-tazobactam (94.8% susceptible), and tobramycin (91.5% susceptible). Piperacillin-tazobactam and meropenem were active against 81.4% and 82.5% of P. aeruginosa, respectively, and aztreonam-avibactam inhibited 78.6% of P. aeruginosa at ≤8 mg/L."

Journal • Hematological Disorders • Infectious Disease • Nephrology • Oncology • Pneumonia • Respiratory Diseases • Transplantation

Treatment of central nervous system infections caused by Pseudomonas aeruginosa with difficult-to-treat resistance: a narrative review. (PubMed, Front Med (Lausanne)) - "The continuous emergence of novel antimicrobial agents, especially new β-lactam antimicrobials, has provided more therapeutic alternatives for DTR-PA infections. This paper mainly discusses the pharmacokinetic/pharmacodynamic studies and clinical research of traditional antimicrobial agents (ceftolozane-tazobactam, ceftazidime-avibactam, aztreonam-avibactam, and cefiderocol) and novel antimicrobial agents (aminoglycosides, polymyxins, and fosfomycin) in the treatment of DTR-PA-CNSI, to evaluate their feasibility and the selection of therapeutic regimens for DTR-PA-CNSI and provide new strategies for clinical medication."

Journal • Review • Infectious Disease

In vitro activity of cefiderocol against highly resistant Gram-negative pathogens collected in the SENTRY Surveillance Program between 2020 and 2024. (PubMed, J Glob Antimicrob Resist) - "Cefiderocol showed potent in vitro activity against contemporary isolates of Gram-negative bacteria displaying challenging resistance phenotypes."

Journal • Preclinical • Infectious Disease

In vivo emergence of ceftazidime/avibactam resistance in Pseudomonas aeruginosa driven by OXA-1381, a novel W157L Ω-loop variant of OXA-2. (PubMed, Antimicrob Agents Chemother) - "Cloning experiments demonstrated that OXA-1381 is an extended-spectrum variant conferring increased resistance to ceftazidime/avibactam and ceftolozane/tazobactam but decreased resistance to carbapenems. Kinetic analyses revealed a marked increase in the affinity and catalytic efficiency of OXA-1381 against ceftazidime and ceftolozane, while showing reduced hydrolytic activity against meropenem, consistent with the observed phenotypic trade-off...The findings document the in vivo evolution of ceftazidime/avibactam resistance in an ESBL-producing P. aeruginosa background, mediated by structural modification of a narrow-spectrum OXA-2 enzyme. In addition, they highlight the potential of integron-borne genes encoding "silent" β-lactamases to evolve under antibiotic pressure and compromise the activity of last-line agents."

Journal • Preclinical

Implementation of automated alerts for last-resort antibiotics with indication review by infectious diseases specialists: impact on antibiotic prescription quality and costs. (PubMed, Infection) - "Implementation of automated last-resort antibiotic alerts, followed by an indication review by ID specialists, proved to be a valuable tool with respect to prescription quality and economic benefits. Generalisability of this approach should be investigated in non-tertiary care settings. Moreover, future studies should address potential effects on clinical outcomes and antimicrobial resistance patterns."

Journal • Infectious Disease

Whole genome sequencing of ceftolozane/tazobactam-resistant, XDR Pseudomonas aeruginosa ST773 in hospitalized critically ill infants and young children with ventilator-associated pneumonia. (PubMed, Front Cell Infect Microbiol) - "Five isolates (11.9%) exhibited an extensively drug-resistant (XDR) phenotype and were resistant to both ceftazidime-avibactam and ceftolozane-tazobactam. These findings highlight the clinical significance of this sequence type and raise concerns about its potential impact in the NICU and PICU settings. Continuous genomic surveillance, along with improved antimicrobial stewardship and stricter infection control practices, remains essential to limit its spread."

Journal • Critical care • Infectious Disease • Pediatrics • Pneumonia • Respiratory Diseases

Genetic Determinants of Nonsusceptibility to Novel β-Lactam/β-Lactamase Inhibitors in Non-Metallo-β-Lactamase-Producing Pseudomonas aeruginosa. (PubMed, J Glob Antimicrob Resist) - "Reduced susceptibility to BL/BLI agents among non-MBL-producing isolates appeared to be associated with chromosomal adaptations involving altered AmpC regulation, OprD dysfunction, and efflux-associated mechanisms. These findings highlight the importance of genomic surveillance beyond carbapenemase detection as the clinical use of these agents expands."

Journal