ceftaroline/avibactam (ceftaroline fosamil/ NXL104) / AstraZeneca, Pfizer - LARVOL DELTA

Ceftaroline pharmacokinetics/pharmacodynamics in the hollow-fibre model of Mycobacterium abscessus lung disease. (PubMed, IJTLD Open) - "Ceftaroline-avibactam administered twice a day would be an adequate replacement for the four-times-a-day cefoxitin treatments for MAB-LD."

Journal • PK/PD data • Pulmonary Disease • Respiratory Diseases

Combinations comprising dual β-lactams and a β-lactamase inhibitor achieve optimal synergistic inhibition of Mycobacterium abscessus growth. (PubMed, Antimicrob Agents Chemother) - "Finally, triple combinations comprising dual β-lactam and one BLI, such as amoxicillin + ceftaroline + avibactam, achieved very high synergy, underscoring the complementary roles of dual β-lactams and BLIs. The evidence in this study necessitates a revised model that can more accurately explain the activities of β-lactams and BLIs and underscores the potential for optimizing β-lactam/BLI regimens against Mab."

Journal

Cerebrospinal fluid concentrations of ceftaroline and ceftazidime/avibactam in healthy volunteers: pharmacokinetics and probability of target attainment. (PubMed, Int J Antimicrob Agents) - "In healthy subjects, ceftaroline, ceftazidime and avibactam poorly distribute to CSF. Nonetheless, CSF exposure of both cephalosporins might be sufficient to cover certain, but not all, pathogens causative of CNS infections."

Journal • PK/PD data • Infectious Disease

Ceftaroline and Avibactam Removal by Continuous Renal Replacement Therapies: An in vitro Study. (PubMed, Blood Purif) - "Avibactam and ceftaroline are extensively removed through the polysulfone membrane, and a dose adjustment may be recommended for patients under CRRT to ensure pharmacodynamic target achievement."

Journal • Preclinical

Evaluation of the in vitro activity of ceftaroline, ceftazidime/avibactam and comparator antimicrobial agents against clinical isolates from paediatric patients in Kuwait: ATLAS data 2012-19. (PubMed, JAC Antimicrob Resist) - "Among 515 Enterobacterales isolates, 29.3% were ESBL-positive; susceptibility was highest to amikacin, ceftazidime/avibactam and meropenem (≥97.4%), regardless of ESBL status...All 269 MRSA and 180 MSSA isolates were susceptible to daptomycin, linezolid, teicoplanin, tigecycline and vancomycin...Ceftaroline was active against most Gram-positive isolates, including resistant phenotypes, and ESBL-negative Enterobacterales. These results indicate that novel antibiotics such as ceftazidime/avibactam and ceftaroline represent valuable treatment options for paediatric infections, including those caused by MDR organisms."

Journal • Preclinical • Infectious Disease • Influenza • Pediatrics • Pneumococcal Infections • Pneumonia • Respiratory Diseases

Microbiological, Clinical, and PK/PD Features of the New Anti-Gram-Negative Antibiotics: β-Lactam/β-Lactamase Inhibitors in Combination and Cefiderocol-An All-Inclusive Guide for Clinicians. (PubMed, Pharmaceuticals (Basel)) - "Considering the complexity of summarizing and integrating the emerging literature data of clinical outcomes, microbiological mechanisms, and pharmacokinetic/pharmacodynamic properties of the new BL/BLI and cefiderocol, we aimed to provide an overview of data on the following compounds: aztreonam/avibactam, cefepime/enmetazobactam, cefepime/taniborbactam, cefepime/zidebactam, cefiderocol, ceftaroline/avibactam, ceftolozane/tazobactam, ceftazidime/avibactam, imipenem/relebactam, meropenem/nacubactam and meropenem/vaborbactam. Each compound is described in a dedicated section by experts in infectious diseases, microbiology, and pharmacology, with tables providing at-a-glance information."

Journal • PK/PD data • Review • Infectious Disease

Innovative β-lactam/β-lactamase inhibitor combinations for carbapenem-resistant Gram-negative bacteria. (PubMed, Future Microbiol) - No abstract available

Journal • Infectious Disease

Role of new antibiotics in extended-spectrum β-lactamase-, AmpC- infections. (PubMed, Curr Opin Infect Dis) - "New therapeutic agents against ESBL- and AmpC-producing Enterobacterales have distinctive specificities and limitations that require further investigations. Future randomized clinical trials are required to define the best strategy for their use in patients with serious infections due to ESBL- and/or AmpC- infections."

Clinical • Journal • Infectious Disease

Selection and characterization of mutational resistance to aztreonam/avibactam in β-lactamase-producing Enterobacterales. (PubMed, J Antimicrob Chemother) - "The risk of mutational resistance to aztreonam/avibactam appears smaller than for ceftazidime/avibactam, where Asp179Tyr arises readily in KPC enzymes, conferring frank resistance. Asn346 substitutions in AmpC enzymes may remain a risk, having been repeatedly selected with multiple avibactam combinations in vitro."

Journal

Global trends of antimicrobial susceptibility to ceftaroline and ceftazidime-avibactam: a surveillance study from the ATLAS program (2012-2016). (PubMed, Antimicrob Resist Infect Control) - "The addition of avibactam improves the activity of ceftazidime against Enterobacteriaceae and P. aeruginosa. The global antimicrobial susceptibilities to ceftaroline and ceftazidime-avibactam were, in general, stable from 2012 to 2016, but a marked reduction in the susceptibilities of specific species and CR-P. aeruginosa to ceftazidime-avibactam was observed."

Clinical • Journal • Complement-mediated Rare Disorders • Infectious Disease • Pneumonia • Respiratory Diseases

Treatment of extended-spectrum β-lactamases infections: what is the current role of new β-lactams/β-lactamase inhibitors? (PubMed, Curr Opin Infect Dis) - "New BL/BLI have distinctive specificities and limitations that require further investigations. Future randomized clinical trials are required to define the best strategy for their administering for ESBL infections."

Journal

New cephalosporins for the treatment of pneumonia in internal medicine wards. (PubMed, J Thorac Dis) - "The overcoming prevalence of resistant gram-negative and positive bacteria (e.g., methicillin-resistant Staphylococcus aureus, penicillin and ceftriaxone-resistant Streptococcus pneumoniae, extended-spectrum β-lactamases and carbapenemases producing Enterobacteriaceae) has made the most of the first-line agents ineffective for treating lower respiratory tract infections. A broad-spectrum of activity, favourable pulmonary penetration, harmlessness and avoiding in some cases a combination therapy, characterise new cephalosporins such as ceftolozane/tazobactam, ceftobiprole, ceftazidime/avibactam and ceftaroline...The "universal pneumonia antibiotic strategy" is no longer acceptable for treating lung infections. Antimicrobial therapy should be individualized considering local antimicrobial resistance and epidemiology, the stage of the illness and potential host factors predisposing to a high risk for specific pathogens."

Journal • Review • Complement-mediated Rare Disorders • Infectious Disease • Pneumonia • Respiratory Diseases

Characterizing the role of porin mutations in susceptibility of beta lactamase producing Klebsiella pneumoniae isolates to ceftaroline and ceftaroline-avibactam. (PubMed, Int J Infect Dis) - "Outer membrane porins play a key role in the transport of ceftaroline inKlebsiella pneumoniae but it remains effective in isolates with altered permeability due to common porin mutations. The addition of avibactam substantially enhances the potency of ceftaroline providing an effective remedy to the problem of omnipresent beta lactamases in these bacteria."

Journal • Infectious Disease • Pneumonia • Respiratory Diseases

ERRATUM TO: In Vitro Activities of Ceftaroline/Avibactam, Ceftazidime/Avibactam, and Other Comparators Against Pathogens From Various Complicated Infections in China. (PubMed, Clin Infect Dis) - No abstract available

Journal • Preclinical

In Vitro Activities of Ceftaroline/Avibactam, Ceftazidime/Avibactam, and Other Comparators Against Pathogens From Various Complicated Infections in China. (PubMed, Clin Infect Dis) - "The highest overall susceptibility levels for all Enterobacteriaceae during the study period were observed for CPA, CZA, doripenem (DOR), meropenem (MEM), and amikacin (AMK), which were all >90%. The addition of 4 mg/L avibactam greatly increased the activities of CPT and CAZ against most Enterobacteriaceae and P. aeruginosa isolates, whereas no significant changes were observed in Acinetobacter spp. or any of the gram-positive strains."

Journal • Preclinical