cefiderocol and Klebsiella-Infections

OXA-48 and NDM are amongst the most prevalent carbapenemase types associated with. We reviewed studies looking at the antibiotic treatment and outcome of OXA-48-like and/or NDM-producing CRKP.. The best available treatment option for OXA-48 producers is ceftazidime-avibactam, where available and when the price permits its use. Colistin remains as the second-line option if

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Aztreonam; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Cefiderocol; Colistin; Drug Combinations; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests

In this study, we aimed to clarify the evolutionary trajectory of a Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) population during β-lactam antibiotic therapy. Five KPC-Kp isolates were collected from a single patient. Whole-genome sequencing and a comparative genomics analysis were performed on the isolates and all

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Bacterial Proteins; beta-Lactamases; Cefiderocol; Ceftazidime; Drug Combinations; Humans; Klebsiella; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Moxalactam

Ceftazidime/avibactam and cefiderocol are two of the latest antibiotics with activity against a wide variety of Gram-negatives, including carbapenem-resistant Enterobacterales. We sought to describe the phenotypic and genotypic characteristics of ceftazidime/avibactam- and cefiderocol-resistant KPC-Klebsiella pneumoniae (KPC-Kp) detected during an outbreak in 2020 in the medical ICU of our hospital.. We collected 11 KPC-Kp isolates (6 clinical; 5 surveillance samples) resistant to ceftazidime/avibactam and cefiderocol from four ICU patients (November 2020 to January 2021), without prior exposure to these agents. All patients had a decontamination regimen as part of the standard ICU infection prevention protocol. Additionally, one ceftazidime/avibactam- and cefiderocol-resistant KPC-Kp (June 2019) was retrospectively recovered. Antibiotic susceptibility was determined by broth microdilution. β-Lactamases were characterized and confirmed. WGS was also performed.. All KPC-Kp isolates (ceftazidime/avibactam MIC  ≥16/4 mg/L; cefiderocol MIC ≥4 mg/L) were KPC + CTX-M-15 producers and belonged to the ST307 high-risk-clone (ST307-HRC). KPC-62 (L168Q) was detected in all isolates involved in the 2020 outbreak, contained in January 2021. KPC-31 (D179Y) was identified in the KPC-Kp from 2019. Cloning experiments demonstrated that both blaKPC-62 and blaKPC-31 were responsible for ceftazidime/avibactam resistance (MIC >16 mg/L) and an increased cefiderocol MIC. Additionally, mutations in OmpA and EnvZ/OmpR porin proteins (in KPC-62-Kp) and in PBP2 (in KPC-31-Kp) were found and may be involved in cefiderocol resistance.. The emergence of resistance to both ceftazidime/avibactam and cefiderocol in KPC-Kp-HRCs, together with the diversification of novel KPC enzymes displaying different antibiotic resistance phenotypes, is an epidemiological and clinical risk.

Topics: Bacterial Proteins; Cefiderocol; Ceftazidime; Hospitals, University; Humans; Klebsiella Infections; Klebsiella pneumoniae; Retrospective Studies; Spain

Klebsiella pneumoniae AR 0047 from the CDC and FDA Antibiotic Resistance Isolate Bank is resistant to cefiderocol, a siderophore-conjugated cephalosporin. Genomics analysis and genetic complementation revealed that a frameshift mutation in

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefiderocol; Cephalosporins; Escherichia coli; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Porins

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; Cefiderocol; Cephalosporins; Drug Combinations; Humans; Klebsiella Infections; Klebsiella pneumoniae; Lactams; Microbial Sensitivity Tests

In February 2022, a critically ill patient colonized with a carbapenem-resistant K. pneumoniae producing KPC-3 and VIM-1 carbapenemases was hospitalized for SARS-CoV-2 in the intensive care unit of Policlinico Umberto I hospital in Rome, Italy. During 95 days of hospitalization, ceftazidime/avibactam, meropenem/vaborbactam, and cefiderocol were administered consecutively to treat 3 respiratory tract infections sustained by different bacterial agents. Those therapies altered the resistome of K. pneumoniae sequence type 512 colonizing or infecting the patient during the hospitalization period. In vivo evolution of the K. pneumoniae sequence type 512 resistome occurred through plasmid loss, outer membrane porin alteration, and a nonsense mutation in the cirA siderophore gene, resulting in high levels of cefiderocol resistance. Cross-selection can occur between K. pneumoniae and treatments prescribed for other infective agents. K. pneumoniae can stably colonize a patient, and antimicrobial-selective pressure can promote progressive K. pneumoniae resistome evolution, indicating a substantial public health threat.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cefiderocol; Ceftazidime; Humans; Italy; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests

To assess the in vitro activity of cefiderocol (CFDC) against a collection of both ceftazidime-avibactam (CZA) susceptible and resistant KPC-producing Enterobacterales (KPC-EB) isolates. Secondly, to assess its synergistic activity in combination with different antibiotics.. One hundred KPC-EB isolates were tested: 60 CZA susceptible and 40 CZA resistant. Among them, 17 pairs of CZA susceptible and resistant KPC-producing Klebsiella pneumoniae (KPC-Kp) isolates were collected from 17 distinct patients before and after CZA treatment, respectively. CFDC susceptibility was evaluated by both broth microdilution (lyophilized panels; Sensititre; Thermo Fisher) and disk diffusion testing. Results were interpreted using EUCAST breakpoints. Synergistic activity of CFDC in combination with CZA, meropenem-vaborbactam, imipenem, and amikacin against six characterized KPC-Kp strains, before and after acquisition of CZA resistance, was evaluated using gradient diffusion strip crossing method.. CFDC resistance rate was significantly higher in CZA resistant EB subset than in the susceptible one (p < 0.001): 82.5% vs 6.7%. MIC50 and MIC90 values were 0.25 and 2 mg/L, 8 and 64 mg/L in CZA-susceptible and CZA-resistant subset, respectively. KPC-Kp isolates harboring KPC-D179Y or KPC-Δ242-GT-243 variants showed CFDC MICs ranging from 4 to 64 mg/L. CFDC showed in vitro synergistic effect mostly with CZA, against both CZA susceptible and resistant isolates, resulting in a synergy rate of 66.7%.. CZA resistance mechanisms in KPC-EB impair the in vitro activity of CFDC, often leading to co-resistance. CFDC in combination with the new β-lactamases inhibitors might represent a strategy to enhance its activity.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Bacterial Proteins; beta-Lactamases; Cefiderocol; Ceftazidime; Cephalosporins; Drug Combinations; Drug Resistance, Bacterial; Drug Synergism; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cefiderocol; Cephalosporins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefiderocol; Cephalosporins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Mutation; Siderophores

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cefiderocol; Cephalosporins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

Topics: Bacteremia; Cefiderocol; Cephalosporins; Humans; Klebsiella Infections; Klebsiella pneumoniae

By serially exposing an NDM-producing Klebsiella pneumoniae clinical strain to cefiderocol, we obtained a mutant with cefiderocol MIC of >128 μg/ml. The mutant contained an early stop codon in the iron transporter gene

Topics: Amino Acid Sequence; Amino Acid Substitution; Anti-Bacterial Agents; beta-Lactamases; Cation Transport Proteins; Cefiderocol; Cephalosporins; Codon, Nonsense; Drug Resistance, Multiple, Bacterial; Frameshift Mutation; High-Throughput Nucleotide Sequencing; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Siderophores

Cefiderocol is a newly approved siderophore cephalosporin that demonstrates expanded

Topics: Adolescent; Anti-Bacterial Agents; Azabicyclo Compounds; Bacteremia; beta-Lactamases; Cefiderocol; Ceftazidime; Cephalosporins; Drug Combinations; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Osteomyelitis; Polymyxin B; Pseudomonas aeruginosa; Pseudomonas Infections; Siderophores

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Cefiderocol; Cephalosporins; Compassionate Use Trials; Critical Illness; Drug Resistance, Multiple, Bacterial; Humans; Influenza, Human; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Pneumonia; Treatment Outcome

Cefiderocol (S-649266), a novel siderophore cephalosporin, shows potent activity against carbapenem-resistant Gram-negative bacilli. In this study, we evaluated the efficacy of cefiderocol against carbapenem-resistant Gram-negative bacilli (

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; beta-Lactam Resistance; Cefiderocol; Cephalosporins; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Klebsiella Infections; Klebsiella pneumoniae; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Rats; Rats, Sprague-Dawley; Respiratory Tract Infections