Fetroja (cefiderocol) / Shionogi - LARVOL DELTA

The Therapeutic Potential of Cefiderocol in the Treatment of Multidrug-Resistant Gram-Negative Bacteria: A Narrative Review. (PubMed, J Clin Med) - "Clinical studies have shown CFDC to be an effective drug with few adverse effects. When used CFDC appropriately within antibiotic stewardship guidelines, this drug is an effective, well-tolerated targeted treatment option for patients with severe clinical conditions."

Journal • Review • Infectious Disease

Activity of aztreonam-avibactam, cefiderocol, and cefepime-taniborbactam against a global collection of genetically characterized metallo-β-lactamase-producing Enterobacterales. (PubMed, Antimicrob Agents Chemother) - "Tigecycline and colistin inhibited 94.1% and 76.6% of the isolates (FDA and EUCAST breakpoints, respectively). MBL-producing organisms are still considered an unmet medical need. Aztreonam-avibactam was active against this large collection of MBL-producing isolates that had elevated MIC values for many comparator agents."

Journal

Susceptibilities of cefiderocol, meropenem-xeruborbactam, cefepime-taniborbactam, aztreonam-avibactam, and sulbactam-durlobactam against imipenem-non-susceptible Gram-negative bacilli in Taiwan. (PubMed, Int J Infect Dis) - " Cefiderocol was highly effective, whereas novel β-lactam/β-lactamase inhibitors activity varied by species and carbapenemase types. PBP3 alterations reduced FTB and AZA activity in INS-EC."

Journal • Infectious Disease • Pneumonia

Interpretive agreement of susceptibility between broth microdilution and disk diffusion methods for cefiderocol, using criteria from the Clinical and Laboratory Standards Institute, European Committee on Antimicrobial Susceptibility Testing, and the Food and Drug Administration. (PubMed, J Clin Microbiol) - "This study compares the categorical agreement between broth microdilution and DD method interpretations for Gram-negative bacilli across multiple guidelines and highlights the potential for misclassification. It also provides susceptibility data for Burkholderia cepacia and Elizabethkingia anophelis, for which established interpretive criteria are currently lacking."

Journal • Infectious Disease • Pneumonia

Current Management Strategies of Difficult-to-Treat Resistant Pseudomonas aeruginosa Infections. (PubMed, Infect Dis Clin North Am) - "Although new active therapeutic options such as ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam and cefiderocol are currently available, lack of randomized control trials, drug access limitations, and emerging resistance have a negative impact on the management of these infections. This review discusses the mechanisms of resistance, molecular epidemiology, clinical management, and current and future therapeutic strategies for DTR P aeruginosa infections."

Journal • Review • Infectious Disease

Deciphering the emergence of mutations in Pseudomonas aeruginosa after ceftolozane/tazobactam treatment and evaluating therapeutic alternatives. (PubMed, BMC Microbiol) - "Ceftolozane/tazobactam resistance development was associated mainly with chromosomal mutations in the ampC gene but also with mutations in its regulatory genes. Knowledge about these mutations and gene polymorphisms is essential for interpreting resistance phenotypes from genomic data."

Journal

Real-world use of cefiderocol as monotherapy or combination therapy for the treatment of Gram-negative bacterial infections: the multicentre retrospective CEFI-BAC study. (PubMed, Int J Infect Dis) - "Real-world experience supports the role of cefiderocol as a valuable option for GNBIs, with no clinical advantage of combination therapy over monotherapy. Notably, NDM-producing infections and use of cefiderocol as salvage therapy are associated with poor outcomes, highlighting the need for optimised treatment strategies."

Journal • Monotherapy • Real-world evidence • Retrospective data • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Genomic diversity and adaptive resistance mechanisms in Pseudomonas aeruginosa from bronchiectasis. (PubMed, mSystems) - "Notably, mucoid isolates exhibited significantly higher cefiderocol MICs compared to non-mucoid isolates (P = 0.0073), along with enhanced biofilm formation (P < 0.0001) but reduced virulence in the Galleria mellonella infection model...Notably, we uncover a novel resistance mechanism involving synergistic interactions between alginate production and mutations in iron-uptake regulators, particularly pirR. These findings underscore the complex evolutionary pressures shaping P. aeruginosa persistence in NCFB and provide valuable insights into its resistance and virulence balance, offering potential targets for more effective therapeutic interventions."

Journal • Bronchiectasis • Genetic Disorders • Immunology • Infectious Disease • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

blaKPC-2 amplification and a novel mrcA mutation drive Cefiderocol heteroresistance in ST11 CRKP. (PubMed, Int J Antimicrob Agents) - "This mechanism may lead to underestimated resistance in standard testing and an increased risk of treatment failure. Monitoring resistance gene expression and mutations could improve FDC applications and identify HR phenotypes."

Journal • Infectious Disease • Pneumonia

Case Report of Treatment of Polymicrobial Bacteremia Caused by Carbapenem-Resistant Klebsiella pneumoniae, and Bacillus Species in an Immunocompetent Patient With Meropenem-Vaborbactam. (PubMed, J Pharm Pract) - "The Infectious Disease Society of America (IDSA) recommends meropenem-vaborbactam, ceftazidime-avibactam, or imipenem-cilastatin-relebactam as preferred options with cefiderocol as an alternative, all of which are also alternative options for CTX-M Enterobacterales...This case report illustrates the treatment course of CTX-M and KPC-producing Klebsiella pneumoniae, and Bacillus species bacteremia that included cefiderocol, followed by vancomycin and meropenem-vaborbactam, and then meropenem-vaborbactam monotherapy...In our report, an immunocompetent patient developed a polymicrobial bloodstream infection caused by an MDR Klebsiella pneumoniae, and Bacillus species, which was successfully treated with meropenem-vaborbactam. This unusual infection and treatment course also serves to promote awareness of another treatment option for invasive Bacillus species infection and furthermore encourages providers to request testing & sensitivities to consolidate therapy,..."

Journal • Infectious Disease • Pneumonia

One-year surveillance of last-resort antimicrobial resistance patterns in carbapenemase-producing Klebsiella pneumoniae strains isolated in a Romanian tertiary care hospital: a prospective study. (PubMed, Germs) - "Strains presenting a minimum inhibitory concentration to meropenem of >0.125 μg/mL underwent phenotypic enzyme production testing, followed by synergistic testing to identify antimicrobial salvage therapy options...Forty-six strains were resistant to cefiderocol (35.7%), 108 (83.7%) to ceftazidime/avibactam, 127 (98.4%) to ceftolozane/tazobactam, 116 (90.0%) to imipenem/relebactam and 127 (98.4%) to aztreonam. The association of aztreonam with ceftazidime/avibactam demonstrated a synergistic effect in 127 (98.5%) strains, while aztreonam with imipenem/relebactam was efficient in vitro against 103 (79.8%) strains. Antimicrobial resistance remains a concerning phenomenon among Enterobacterales, especially when considering the increasing resistance rates even against salvage therapy antimicrobials."

Journal • Infectious Disease • Pneumonia

Multidrug-resistant Acinetobacter baumannii meningitis and cerebellar abscess: case report and therapeutic considerations. (PubMed, Germs) - "Initial empirical therapy consisted of meropenem and vancomycin, subsequently adjusted according to the susceptibility profile to cefiderocol, intravenous and intrathecal colistin, combined with ampicillin/sulbactam and minocycline. Intrathecal administration of colistin, in combination with systemic multidrug therapy, proved decisive in controlling the infection. An interdisciplinary approach and individualized antimicrobial regimens are essential to achieving a favorable prognosis in such complex cases."

Journal • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Infectious Disease • Mood Disorders • Pain

Emergence of mutH V76G among longitudinal carbapenem resistant Klebsiella pneumoniae causing long-term colonization and recurrent infection disrupts DNA mismatch repair and results in a hypermutator phenotype. (PubMed, bioRxiv) - "Clinical mutH V76G isolates and CRISPR-engineered mutH V76G mutants were hypermutators based on rifampin mutational frequencies...Both clinical and lab-engineered mutH V76G mutant strains rapidly acquire resistance or reduced susceptibility to new antibiotics like ceftazidime-avibactam, meropenem-vaborbactam and cefiderocol, due to mutations in carbapenemase ( bla KPC-3 ), porin ( ompK36 ) and other genes. mutH V76G -driven hypermutation also enhances horizontal transfer of resistance plasmids and improves K. pneumoniae fitness during mouse infections. This study is important for understanding K. pneumoniae hypermutation as a potent mediator of antibiotic resistance and other phenotypes relevant to human infections."

Journal • Mismatch repair • Infectious Disease • Pneumonia

In vitro activity of cefiderocol and sulbactam-durlobactam against carbapenem-resistant Acinetobacter baumannii clinical isolates collected between 2019 and 2024. (PubMed, Infect Dis (Lond)) - "Among the 159 carbapenem-resistant Acinetobacter baumannii isolates, 72.9% (n = 116) carried the blaOXA-23 gene, 10.7% (n = 17) harboured blaOXA-24/40, and 16.4% (n = 26) did not possess any of the carbapenemase genes included in the testing panel. Cefiderocol and sulbactam-durlobactam exhibited strong in vitro activity against carbapenem-resistant A. baumannii isolates from a single University Hospital and may represent valuable treatment options for patients with limited therapeutic alternatives."

Journal • Preclinical • Infectious Disease

Sphingobacterium spp. as intrinsic producers of SPI Ambler class B metallo-β-lactamases. (PubMed, J Antimicrob Chemother) - "S. spiritivorum was the most prevalent species of Sphingobacterium identified in clinical samples. All S. spiritivorum-like species produced a chromosomally encoded SPI-like MBL that might be challenging for the treatment of infections caused by this bacterial species."

Journal • Infectious Disease

Molecular Characterization of KPC-2 and CMY AmpC Beta Lactamases in Ceftazidime-Avibactam Resistant Klebsiella pneumoniae in a Tertiary Care Hospital. (PubMed, Cureus) - "Introduction Multidrug-resistant (MDR) Klebsiella pneumoniae poses significant treatment challenges, particularly in intensive care settings. Sanger sequencing confirmed 99.3% similarity with bla CMY-2. Conclusion CMY AmpC β-lactamase emerged as the predominant mechanism of CZA resistance in K. pneumoniae, highlighting the need for routine AmpC screening, prudent use of alternatives such as cefiderocol, tigecycline, or fosfomycin, and sustained genomic surveillance to guide therapy and infection control."

Journal • Critical care • Infectious Disease • Pneumonia

A DDI Study to Investigate PK and Safety of Cefiderocol in Combination With Xeruborbactam in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=60 | Completed | Sponsor: Qpex Biopharma, Inc. | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease

Empirical and targeted antimicrobial therapy in patients with febrile neutropenia and haematological malignancy or after haematopoietic cell transplantation: recommendations from the 10th European Conference on Infections in Leukaemia. (PubMed, Lancet Infect Dis) - "Treatment options include β-lactam plus aminoglycoside combinations, carbapenem with or without BLI, anti-pseudomonal cephalosporin and BLI combinations, or cefiderocol, individualised by local epidemiology and patient factors. Antimicrobial stewardship is recommended, including antimicrobial de-escalation once resistant Gram-negative bacteria infection is excluded; and antibiotic discontinuation regardless of neutrophil count, in patients who are afebrile and stable after completing the intended course. We provide treatment strategies for resistant Gram-negative bacteria infections."

Journal • Review • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Transplantation

Cefiderocol Resistance in Pseudomonas aeruginosa ST175: A Case Report with Genomic Analysis. (PubMed, Antibiotics (Basel)) - "Cefiderocol resistance can emerge rapidly in vivo during treatment of infections caused by P. aeruginosa ST175. Continuous surveillance, molecular characterization of resistance mechanisms, and cautious use of cefiderocol-preferably in combination regimens-are warranted to preserve its clinical utility."

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

Antimicrobial Activity of Aztreonam-Avibactam and Other β-Lactamase Inhibitor Combinations Tested Against Enterobacterales Isolates from Pediatric Patients from United States Medical Centers (2019-2023). (PubMed, Antibiotics (Basel)) - "Susceptibility to imipenem-relebactam varied from 97.1% (ceftriaxone-nonsusceptible) to 100.0% (ESBL producers). Ceftolozane-tazobactam showed good activity against ESBL producers (91.8% susceptible), but limited activity against ceftriaxone-nonsusceptible (75.8% susceptible) and MDR isolates (80.9% susceptible)...ESBL-producing Enterobacterales, mainly CTX-M, remain an important cause of infection in children. Aztreonam-avibactam, ceftazidime-avibactam, and meropenem-vaborbactam were highly active against isolates from both pediatric and adult population."

Journal • Infectious Disease • Nephrology • Pediatrics • Pneumonia • Respiratory Diseases

Enhancing the Time-to-Positivity Paradigm for Guidance of Antimicrobial Therapy: A Model-Based Approach. (PubMed, Comput Chem Eng) - "We evaluate this approach through in vitro studies using ceftazidime/avibactam against Acinetobacter baumannii and cefiderocol/avibactam against Pseudomonas aeruginosa. To our knowledge, this represents the first enhancement of the TTP assay. With further development, enhanced TTP could become a powerful tool for optimizing antimicrobial therapy in clinical settings."

Journal • Critical care • Infectious Disease

Cefiderocol Comparative Resistance and Clinical Predictors in CRE-BSI: Data from an OXA-48-Endemic Region with Rising OXA-48/NDM Coproducers. (PubMed, Antibiotics (Basel)) - "Susceptibility to cefiderocol, CAZ-AVI, and colistin was determined according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2023 criteria. Cefiderocol demonstrated potent in vitro activity against CRE-BSI isolates, with resistance confined to distinct high-risk clinical settings. This pre-implementation study provides baseline microbiological and epidemiological data from an OXA-48 endemic region with rising NDM prevalence, underscoring the importance of early surveillance and stewardship strategies before cefiderocol becomes clinically available."

Journal • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Infectious Disease • Oncology • Transplantation

Use of Aztreonam-Avibactam with Rapid Eravacycline Step-Down Therapy for a Tibial Septic Non-Union by NDM-Producing Enterobacter cloacae. (PubMed, Antibiotics (Basel)) - "Cultures grew Enterobacter cloacae complex resistant to meropenem, ceftazidime-avibactam, meropenem-vaborbactam, and cefiderocol, as well as Candida parapsilosis...The patient was treated with ATM-AVI plus micafungin, achieving clinical stability within three days...At eight-week follow-up, the patient remained clinically improved without relapse or adverse effects. This case highlights ATM-AVI as a critical therapy for NDM-producing orthopedic infections involving hardware and supports eravacycline as a feasible step-down option in outpatient management."

Journal • Infectious Disease • Musculoskeletal Diseases • Orthopedics

In Vitro Activity of Cefiderocol Against Multi-Drug-Resistant Gram-Negative Clinical Isolates in Romania. (PubMed, Antibiotics (Basel)) - " The presence of NDM-producing isolates with complete resistance to cefiderocol in our study highlights the risk that resistance may spread rapidly once the drug becomes widely used. Cefiderocol may be an effective option for treating MDR bacterial infections, but strict microbiological monitoring remains essential."

Journal • Preclinical • Infectious Disease • Pneumonia

β-Lactam/β-Lactamase Inhibitor Combinations in Sepsis-Associated Acute Kidney Injury and Renal Replacement Therapy. (PubMed, Antibiotics (Basel)) - "This review summarizes PK/PD features, extracorporeal clearance, and practical dosing considerations about ceftolozane-tazobactam, ceftazidime-avibactam, aztreonam-avibactam, cefiderocol, meropenem-vaborbactam, imipenem-relebactam, and newer agents including sulbactam-durlobactam, cefepime-enmetazobactam, and cefepime-taniborbactam. Full-dose initiation during the first 24-48 h, followed by careful adjustment, appears prudent. Therapeutic drug monitoring should be used when available, and institution-specific protocols should be integrated into stewardship programs to improve efficacy and minimize resistance."

Journal • Review • Acute Kidney Injury • Infectious Disease • Nephrology • Pediatrics • Renal Disease • Septic Shock