Asunto(s)
Antibacterianos , Cefepima , Combinación Piperacilina y Tazobactam , Sepsis , Humanos , Cefepima/administración & dosificación , Antibacterianos/efectos adversos , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Combinación Piperacilina y Tazobactam/administración & dosificación , Combinación Piperacilina y Tazobactam/uso terapéutico , Sepsis/tratamiento farmacológico , Cefalosporinas/uso terapéutico , Cefalosporinas/efectos adversosRESUMEN
BACKGROUND: There are multiple antibiotic regimens for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) in clinical practice. We conducted this meta-analysis to compare the efficacy and safety of cefiderocol-based regimens and colistin-based regimens in the treatment of CRAB infections. METHODS: Two authors independently searched the PubMed, Web of Science, Embase, and Cochrane databases from their establishment to April 15, 2024, to search for randomized controlled trials (RCTs) or cohort studies, and compared the clinical efficacy and safety of cefiderocol-based regimens and colistin-based regimens in the treatment of CRAB infections. The Newcastle Ottawa Scale (NOS) checklist was used to evaluate the quality of the included studies. The primary outcome was all-cause mortality, and subgroup analysis was conducted on the basis of the site of infection and the risk of bias in the studies. Trial sequential analysis (TSA) was then conducted. RESULTS: Six observational studies were included, with 251 cases in the cefiderocol-based group and 372 cases in the colistin-based group. Compared to the colistin-based group, the cefiderocol-based group had lower all-cause mortality (RR = 0.71, 95% CI: 0.54-0.92, P = 0.01) and 30-day mortality (RR = 0.64, 95% CI: 0.43-0.95, P = 0.03). However, for the 14-day and 28-day mortality rates, there was no statistically significant difference between two groups. According to the subgroup analysis, among patients with bloodstream infection (BSI), the cefiderocol-based group had lower all-cause mortality, but it did not reduce the mortality of ventilator-associated pneumonia (VAP) patients. The result of TSA showed that our conclusions are reliable. There was no significant statistical difference in the microbiological cure rate, clinical cure rate, or duration of hospitalization. In addition, the cefiderocol-based group did not have an increased incidence of acute kidney injury (AKI). CONCLUSIONS: Compared with the colistin-based regimens, the cefiderocol-based regimens were significantly associated with a lower risk of mortality in CRAB-infected patients, especially for patients with BSI. However, they did not show any advantages in terms of the clinical cure rate or microbiological cure rate, nor did they reduce the incidence of AKI. PROSPERO REGISTRATION NUMBER: CRD42023487213.
Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Antibacterianos , Carbapenémicos , Cefiderocol , Colistina , Colistina/uso terapéutico , Colistina/farmacología , Acinetobacter baumannii/efectos de los fármacos , Humanos , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/mortalidad , Infecciones por Acinetobacter/microbiología , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Carbapenémicos/uso terapéutico , Carbapenémicos/farmacología , Cefalosporinas/uso terapéutico , Farmacorresistencia Bacteriana Múltiple , Resultado del TratamientoRESUMEN
Antimicrobial resistance is currently recognized as an urgent concern against public health in worldwide. Carbapenem-resistant (CR) Gram-negative bacteria, such as Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii are listed as critical pathogens which are widely spread and can cause severe and often deadly infections in WHO guidance. Cefiderocol (Fetroja®), a novel and first siderophore cephalosporin, was approved for the infections caused by these problematic CR Gram-negative bacteria in Japan on November 30, 2023. Cefiderocol has unique mechanisms to be incorporated into bacterial cells using bacterial iron transportation system and to be highly stable against most ß-lactamases, which lead to promising antibacterial activity against these Gram-negative bacteria including CR strains in vitro. In CREDIBLE-CR Ph3 trial, cefiderocol showed the good efficacy and safety for patients with CR Gram-negative bacteria. In APEKS-cUTI and APEKS-NP trials, cefiderocol showed non-inferiority and suggested superiority to imipenem/cilastatin in complicated urinary tract infection (cUTI) patients, and non-inferiority to high dose of meropemen in pneumonia patients, respectively. Cefiderocol is expected to be an optimal treatment for CR Gram-negative infections with limited treatment options and would be an important drug to combat the threat of CR bacteria.
Asunto(s)
Antibacterianos , Carbapenémicos , Cefiderocol , Cefalosporinas , Infecciones por Bacterias Gramnegativas , Sideróforos , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Cefiderocol/farmacología , Cefiderocol/uso terapéutico , Cefalosporinas/farmacología , Cefalosporinas/uso terapéutico , Farmacorresistencia Bacteriana , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Sideróforos/farmacologíaRESUMEN
BACKGROUND: Antibiotic resistance among Gram-negative bacteria in intensive care units (ICUs) is linked with high morbidity and mortality in patients. In this study, we estimated the therapeutic coverage of various antibiotics, focusing on cefiderocol and comparators, administered empirically against an infection of unknown origin in the ICU. METHODS: In the ARTEMIS surveillance study, susceptibilities of 624 Italian Gram-negative isolates to amikacin, aztreonam-avibactam, cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, colistin, imipenem-relebactam, meropenem, and meropenem-vaborbactam were tested by broth microdilution, and results were interpreted by European Committee on Antimicrobial Susceptibility Testing breakpoints. The susceptibility rates from the ARTEMIS study were extrapolated to Gram-negative isolates obtained from 5,774 patients in Italian ICUs in 2021. The sum of the predicted susceptibilities of individual pathogens represented the overall likelihood of in vitro activity of each antibiotic as early targeted therapy for ICU patients. RESULTS: A total of 624 Italian Gram-negative isolates included 206 Pseudomonas aeruginosa, 138 Acinetobacter baumannii, 187 Klebsiella pneumoniae, and 93 Escherichia coli. Against A. baumannii, K. pneumoniae, P. aeruginosa, and E. coli, the overall susceptibility rates for cefiderocol were 87.7%, 96.8%, 99%, and 100%, respectively; and for comparator agents, 8.7-96.4%, 25.7-100%, 73.3-100%, and 89.2-100%, respectively. Among the subset of meropenem-resistant isolates, susceptibility rates of A. baumannii, K. pneumoniae, and P. aeruginosa to cefiderocol were 86.4%, 96.2% and 100%, respectively. Corresponding susceptibility rates to comparator agents were 0-96.8%, 0-100%, and 6.4-100%, respectively. There were no meropenem-resistant isolates of E. coli. The extrapolation of data to isolates from Italian ICUs showed that the highest likelihood of therapeutic coverage, both overall and among meropenem-resistant isolates, was reported for colistin (96.8% and 72.2%, respectively) and cefiderocol (95.7% and 71.4%, respectively). All other antibiotics were associated with a likelihood below 73% overall and between 0% and 41.4% for meropenem-resistant isolates. CONCLUSIONS: Based on confirmed susceptibility rates and reported ICU prevalence of multiple Gram-negative species, cefiderocol showed a higher predicted therapeutic coverage and utility in ICUs compared with comparator beta-lactam-beta-lactamase inhibitor antibiotics. Cefiderocol may be a promising early treatment option for patients at high risk of carbapenem-resistant Gram-negative bacterial infections in the ICU.
Asunto(s)
Antibacterianos , Carbapenémicos , Bacterias Gramnegativas , Infecciones por Bacterias Gramnegativas , Unidades de Cuidados Intensivos , Pruebas de Sensibilidad Microbiana , Humanos , Italia/epidemiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/epidemiología , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Bacterias Gramnegativas/efectos de los fármacos , Cefalosporinas/farmacología , Cefalosporinas/uso terapéutico , Klebsiella pneumoniae/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Acinetobacter baumannii/efectos de los fármacos , Meropenem/farmacología , Meropenem/uso terapéutico , Farmacorresistencia Bacteriana Múltiple , Cefiderocol , Colistina/farmacología , Colistina/uso terapéuticoRESUMEN
Proper use of antimicrobials in hospital and outpatient settings is critical for minimizing the occurrence of antimicrobial resistance. Some hospitals have intervened in the inappropriate use of third-generation oral cephalosporins. However, there have been no such studies in community pharmacy settings. This study aimed to investigate how the use of oral third-generation cephalosporins in community pharmacies affects the amount of antimicrobials used. Patients who visited Nakanomaru Pharmacy after being prescribed antimicrobials at target medical institutions between February 2021 and January 2023 were identified. The number of oral antimicrobials used, duration of use, number of prescriptions, patient age and sex, and infectious diseases in the target patients before and after the intervention for the proper use of oral third-generation cephalosporins were retrospectively investigated based on the patients' medication history and prescription receipts. Through efforts to ensure the proper use of oral third-generation cephalosporins, the amount of oral third-generation cephalosporins used has decreased, and the use of penicillins and oral first-generation cephalosporins has increased. There was no increase in the antimicrobial change or relapse rates associated with treatment failure before and after the initiation of appropriate antimicrobial use. By working toward the proper use of oral third-generation cephalosporins in community pharmacies, we were able to reduce the doses of oral third-generation cephalosporins without compromising their therapeutic efficacy. We believe that recommending the selection of narrow-spectrum antimicrobials based on these guidelines will contribute to their proper use.
Asunto(s)
Antibacterianos , Programas de Optimización del Uso de los Antimicrobianos , Cefalosporinas , Humanos , Cefalosporinas/uso terapéutico , Programas de Optimización del Uso de los Antimicrobianos/métodos , Femenino , Masculino , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Persona de Mediana Edad , Administración Oral , Anciano , Estudios Retrospectivos , Adulto , Anciano de 80 o más Años , Adulto Joven , Adolescente , Servicios Comunitarios de Farmacia , FarmaciasRESUMEN
Antibiotics may alter the gut microbiome, and this is one of the mechanisms by which antimicrobial resistance may be promoted. Suboptimal antimicrobial stewardship in Asia has been linked to antimicrobial resistance. We aim to examine the relationship between oral antibiotic use and composition and antimicrobial resistance in the gut microbiome in 1093 Bangladeshi infants. We leverage a trial of 8-month-old infants in rural Bangladesh: 61% of children were cumulatively exposed to antibiotics (most commonly cephalosporins and macrolides) over the 12-month study period, including 47% in the first 3 months of the study, usually for fever or respiratory infection. 16S rRNA amplicon sequencing in 11-month-old infants reveals that alpha diversity of the intestinal microbiome is reduced in children who received antibiotics within the previous 7 days; these samples also exhibit enrichment for Enterococcus and Escherichia/Shigella genera. No effect is seen in children who received antibiotics earlier. Using shotgun metagenomics, overall abundance of antimicrobial resistance genes declines over time. Enrichment for an Enterococcus-related antimicrobial resistance gene is observed in children receiving antibiotics within the previous 7 days, but not earlier. Presence of antimicrobial resistance genes is correlated to microbiome composition. In Bangladeshi children, community use of antibiotics transiently reprofiles the gut microbiome.
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Antibacterianos , Microbioma Gastrointestinal , ARN Ribosómico 16S , Humanos , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/genética , Bangladesh/epidemiología , Lactante , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , ARN Ribosómico 16S/genética , Masculino , Femenino , Administración Oral , Farmacorresistencia Bacteriana/genética , Heces/microbiología , Metagenómica/métodos , Bacterias/genética , Bacterias/efectos de los fármacos , Bacterias/clasificación , Bacterias/aislamiento & purificación , Cefalosporinas/administración & dosificación , Cefalosporinas/farmacología , Cefalosporinas/uso terapéutico , Enterococcus/efectos de los fármacos , Enterococcus/genética , Enterococcus/aislamiento & purificación , Programas de Optimización del Uso de los AntimicrobianosRESUMEN
BACKGROUND: Novel beta-lactams show activity against many multidrug-resistant Gram-negative bacteria that cause severe lung infections. Understanding pharmacokinetic/pharmacodynamic characteristics of these agents may help optimise outcomes in the treatment of pneumonia. OBJECTIVES: To describe and appraise studies that report pulmonary pharmacokinetic and pharmacodynamic data of cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/cilastatin/relebactam and meropenem/vaborbactam. METHODS: MEDLINE (PubMed), Embase, Web of Science and Scopus libraries were used for the literature search. Pulmonary population pharmacokinetic and pharmacokinetic/pharmacodynamic studies on adult patients receiving cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/cilastatin/relebactam, and meropenem/vaborbactam published in peer-reviewed journals were included. Two independent authors screened, reviewed and extracted data from included articles. A reporting guideline for clinical pharmacokinetic studies (ClinPK statement) was used for bias assessment. Relevant outcomes were included, such as population pharmacokinetic parameters and probability of target attainment of dosing regimens. RESULTS: Twenty-four articles were included. There was heterogeneity in study methods and reporting of results, with diversity across studies in adhering to the ClinPK statement checklist. Ceftolozane/tazobactam was the most studied agent. Only two studies collected epithelial lining fluid samples from patients with pneumonia. All the other phase I studies enrolled healthy subjects. Significant population heterogeneity was evident among available population pharmacokinetic models. Probabilities of target attainment rates above 90% using current licensed dosing regiments were reported in most studies. CONCLUSIONS: Although lung pharmacokinetics was rarely described, this review observed high target attainment using plasma pharmacokinetic data for all novel beta-lactams. Future studies should describe lung pharmacokinetics in patient populations at risk of carbapenem-resistant pathogen infections.
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Antibacterianos , Cefalosporinas , Combinación de Medicamentos , Bacterias Gramnegativas , Inhibidores de beta-Lactamasas , beta-Lactamas , Humanos , Inhibidores de beta-Lactamasas/farmacocinética , Inhibidores de beta-Lactamasas/uso terapéutico , Inhibidores de beta-Lactamasas/farmacología , Antibacterianos/farmacocinética , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , beta-Lactamas/farmacocinética , beta-Lactamas/uso terapéutico , beta-Lactamas/farmacología , Cefalosporinas/farmacocinética , Cefalosporinas/uso terapéutico , Cefalosporinas/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Tazobactam/farmacocinética , Tazobactam/uso terapéutico , Tazobactam/farmacología , Neumonía Bacteriana/tratamiento farmacológico , Compuestos de Azabiciclo/farmacocinética , Compuestos de Azabiciclo/uso terapéutico , Compuestos de Azabiciclo/farmacología , Carbapenémicos/farmacocinética , Carbapenémicos/uso terapéutico , Carbapenémicos/farmacología , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Ceftazidima/farmacocinética , Ceftazidima/uso terapéutico , Cefiderocol , Meropenem/farmacocinética , Meropenem/uso terapéutico , Meropenem/farmacología , Imipenem/farmacocinética , Imipenem/uso terapéutico , Farmacorresistencia Bacteriana Múltiple , Pruebas de Sensibilidad Microbiana , Combinación Cilastatina e Imipenem/farmacocinética , Combinación Cilastatina e Imipenem/uso terapéutico , Ácidos Borónicos , Compuestos Heterocíclicos con 1 AnilloRESUMEN
In contrast to the epidemiology 10 years earlier at our hospital when the epidemic restriction endonuclease analysis (REA) group strain BI accounted for 72% of Clostridioides difficile isolates recovered from first-episode C. difficile infection (CDI) cases, BI represented 19% of first-episode CDI isolates in 2013-2015. Two additional REA group strains accounted for 31% of isolates (Y, 16%; DH, 12%). High-level resistance to fluoroquinolones and azithromycin was more common among BI isolates than among DH, Y, and non-BI/DH/Y isolates. Multivariable analysis revealed that BI cases were 2.47 times more likely to be associated with fluoroquinolone exposure compared to non-BI cases (95% confidence interval [CI]: 1.12-5.46). In addition, the odds of developing a CDI after third- or fourth-generation cephalosporin exposure was 2.83 times for DH cases than for non-DH cases (95% CI: 1.06-7.54). Fluoroquinolone use in the hospital decreased from 2005 to 2015 from a peak of 113 to a low of 56 antimicrobial days/1,000 patient days. In contrast, cephalosporin use increased from 42 to 81 antimicrobial days/1,000 patient days. These changes correlated with a decrease in geometric mean MIC for ciprofloxacin (61.03 to 42.65 mg/L, P = 0.02) and an increase in geometric mean MIC for ceftriaxone (40.87 to 86.14 mg/L, P < 0.01) among BI isolates. The BI strain remained resistant to fluoroquinolones, but an overall decrease in fluoroquinolone use and increase in cephalosporin use were associated with a decrease in the prevalence of BI, an increased diversity of C. difficile strain types, and the emergence of strains DH and Y.
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Antibacterianos , Clostridioides difficile , Infecciones por Clostridium , Fluoroquinolonas , Pruebas de Sensibilidad Microbiana , Clostridioides difficile/efectos de los fármacos , Clostridioides difficile/aislamiento & purificación , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones por Clostridium/epidemiología , Infecciones por Clostridium/microbiología , Infecciones por Clostridium/tratamiento farmacológico , Fluoroquinolonas/farmacología , Fluoroquinolonas/uso terapéutico , Masculino , Femenino , Anciano , Prevalencia , Persona de Mediana Edad , Prohibitinas , Hospitales , Brotes de Enfermedades , Azitromicina/uso terapéutico , Azitromicina/farmacología , Infección Hospitalaria/microbiología , Infección Hospitalaria/epidemiología , Infección Hospitalaria/tratamiento farmacológico , Anciano de 80 o más Años , Cefalosporinas/uso terapéutico , Cefalosporinas/farmacologíaAsunto(s)
Antibacterianos , Cefalosporinas , Streptococcus pneumoniae , Animales , Cefalosporinas/farmacocinética , Cefalosporinas/farmacología , Cefalosporinas/uso terapéutico , Cefalosporinas/administración & dosificación , Antibacterianos/farmacocinética , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Ratones , Streptococcus pneumoniae/efectos de los fármacos , Modelos Animales de Enfermedad , Pulmón/metabolismo , Pulmón/efectos de los fármacos , Pulmón/microbiología , Humanos , Neumonía Neumocócica/tratamiento farmacológico , Neumonía Neumocócica/microbiologíaRESUMEN
BACKGROUND: Universal surgical prophylaxis for pancreatoduodenectomy (PD) is practiced, with cephalosporins recommended in most guidelines. Recent studies suggest piperacillin-tazobactam (PTZ) prophylaxis in biliary-stented patients is superior in preventing surgical site infections (SSIs). This study aims to refine surgical prophylaxis recommendations based on the local microbial profile and evaluate the clinical outcomes of biliary-stented compared with non-stented patients. METHODS: This was a retrospective study of all consecutive PD patients at Singapore General Hospital between January 2013 to December 2019. The primary outcome was post-operative SSI rates. Secondary outcomes included rates of ceftriaxone-resistant Klebsiella pneumoniae, Escherichia coli, and Enterococcus species from intraoperative bile cultures and 30-day mortality. RESULTS: There were 130 biliary-stented and 211 non-stented patients included. Majority of biliary-stented patients received ceftriaxone ± metronidazole prophylaxis (83/130, 63.8 %) while 30/130 (23.8 %) received PTZ. Most non-stented patients received ceftriaxone ± metronidazole prophylaxis (163/211, 77.3 %). Between biliary-stented and non-stented patients, post-operative SSIs (40.8 % vs 38.4 %, p = 0.662), and 30-day mortality rates (1.5 % vs 1.4 %, p = 1.000) were comparable. The adjusted odds of post-operative SSIs was significantly lower in biliary-stented patients prescribed PTZ as compared to non-PTZ prophylaxis (0.29, 95 % CI (0.10-0.79), p = 0.015). Ceftriaxone-resistant Klebsiella spp. and/or Escherichia coli (27.6 % vs 3.8 %, p < 0.001) as well as Enterococcus species (46.1 % vs 11.5 %, p < 0.001), were more prevalent in intraoperative bile cultures of biliary-stented patients, while frequencies in non-stented patients were low. CONCLUSION: PTZ prophylaxis effectively reduced SSIs in stented patients post-pancreatoduodenectomy. Based on the local microbial profile, ceftriaxone prophylaxis may be used for prophylaxis in non-stented patients.
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Antibacterianos , Profilaxis Antibiótica , Pancreaticoduodenectomía , Stents , Infección de la Herida Quirúrgica , Humanos , Masculino , Femenino , Estudios Retrospectivos , Anciano , Infección de la Herida Quirúrgica/prevención & control , Antibacterianos/uso terapéutico , Persona de Mediana Edad , Profilaxis Antibiótica/métodos , Ceftriaxona/uso terapéutico , Cefalosporinas/uso terapéutico , Combinación Piperacilina y Tazobactam/uso terapéutico , Metronidazol/uso terapéutico , Anciano de 80 o más Años , Bilis , Escherichia coli/efectos de los fármacosRESUMEN
Carbapenem-resistant Pseudomonas aeruginosa (CRPa) infection is extremely challenging to manage. Cefepime-zidebactam is a novel combination that can be considered for salvage therapy when no other antimicrobials are susceptible. A 15-y-old boy presented with 56% thermal burns, followed by skin and soft tissue infection, secondary bacteraemia, complicated parapneumonic effusion and endophthalmitis due to CRPa, which was not susceptible to any of the routinely available antibiotics. He was treated with cefepime-zidebactam for 45 d, with which he recovered.
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Antibacterianos , Compuestos de Azabiciclo , Cefalosporinas , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Terapia Recuperativa , Humanos , Masculino , Infecciones por Pseudomonas/tratamiento farmacológico , Antibacterianos/uso terapéutico , Compuestos de Azabiciclo/uso terapéutico , Pseudomonas aeruginosa/efectos de los fármacos , Cefalosporinas/uso terapéutico , Adolescente , Resultado del Tratamiento , Quemaduras/tratamiento farmacológico , Quemaduras/complicaciones , Cefepima/uso terapéutico , Combinación de Medicamentos , Piperidinas , CiclooctanosRESUMEN
BACKGROUND: In 2019, the shortage of cefazolin led to the demand for cefotiam and cefmetazole exceeding the supply. The Department of Nephro-urology at Nagoya City University Hospital used fosfomycin as a substitute for perioperative prophylaxis. This retrospective preliminary study evaluated the efficacy of fosfomycin and cefotiam for preventing infections following ureterorenoscopy. METHODS: The study included 182 patients who underwent ureterorenoscopy between January 2018 and March 2021). Perioperative antibacterial treatment with fosfomycin (n = 108) or cefotiam (n = 74) was administered. We performed propensity score matching in both groups for age, sex, preoperative urinary catheter use, and preoperative antibiotic treatment. RESULTS: The fosfomycin and cefotiam groups (n = 69 per group) exhibited no significant differences in terms of patients' median age, operative duration, preoperative urine white blood cell count, preoperative urine bacterial count, and the rate of preoperative antibiotic treatment. In the fosfomycin and cefotiam groups, the median duration of postoperative hospital stay was 3 and 4 days, respectively; the median maximum postoperative temperature was 37.3 °C and 37.2 °C, respectively. The fosfomycin group had lower postoperative C-reactive protein levels and white blood cell count than the cefotiam group. However, the frequency of fever > 38 °C requiring additional antibiotic administration was similar. CONCLUSIONS: During cefotiam shortage, fosfomycin administration enabled surgeons to continue performing ureterorenoscopies without increasing the complication rate.
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Antibacterianos , Cefalosporinas , Fosfomicina , Ureteroscopía , Humanos , Estudios Retrospectivos , Femenino , Masculino , Fosfomicina/uso terapéutico , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Anciano , Cefalosporinas/uso terapéutico , Profilaxis Antibiótica/métodos , Adulto , Infección de la Herida Quirúrgica/prevención & controlAsunto(s)
Antibacterianos , Cefepima , Cefalosporinas , Infecciones Urinarias , Humanos , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , Cefalosporinas/efectos adversos , Cefalosporinas/uso terapéutico , Cefepima/administración & dosificación , Cefepima/efectos adversos , Cefepima/uso terapéutico , Antibacterianos/efectos adversos , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Combinación de Medicamentos , Tiazoles/efectos adversos , Tiazoles/uso terapéutico , Tiazoles/administración & dosificaciónRESUMEN
BACKGROUND: Multidrug-resistant organisms are increasing and are a significant cause of mortality among lung transplant recipients (LTRs). To assist with this issue, novel pharmacotherapies are being developed. This study describes the utilization of a novel antibiotic, cefiderocol (FDC), in LTRs where limited data exists in the current literature. We primarily assessed the clinical indications, duration of therapy, resistance, and adverse effects. METHODS: Conducted as a single-center retrospective review, this study included adult LTRs who received FDC for at least 24 h. Data, extracted from electronic medical records, encompassed patient demographics, transplant history, antimicrobial dosing, adverse effects, bacterial cultures, and outcomes. The research protocol received institutional review board approval. RESULTS: FDC exhibited effectiveness against multidrug-resistant Pseudomonas aeruginosa, with 26% 30-day mortality and microbiological clearance observed in nine out of 13 cases. Notably, FDC was used in diverse clinical settings, including for prophylaxis, empiric, and targeted treatment. CONCLUSION: Further studies are needed to evaluate optimal clinical indications for FDC use in LTRs.
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Antibacterianos , Cefiderocol , Cefalosporinas , Farmacorresistencia Bacteriana Múltiple , Trasplante de Pulmón , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Receptores de Trasplantes , Humanos , Trasplante de Pulmón/efectos adversos , Estudios Retrospectivos , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Persona de Mediana Edad , Femenino , Masculino , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/efectos de los fármacos , Adulto , Cefalosporinas/uso terapéutico , Receptores de Trasplantes/estadística & datos numéricos , Anciano , Pruebas de Sensibilidad MicrobianaRESUMEN
OBJECTIVES: Acinetobacter baumannii is classified by the centre for Disease Control and Prevention (CDC) as an "urgent threat" due to its ability to acquire and develop resistance to multiple classes of antibiotics. As a result, it is one of the most concerning pathogens in healthcare settings, with increasing incidence of infections due to carbapenem-resistant Acinetobacter baumannii (CRAB) associated with high morbidity and mortality rates. Therefore, there are ongoing efforts to find novel treatment options, one of which is cefiderocol. We aim to review available evidence on cefiderocol use for severe nosocomial pneumonia due to carbapenem-resistant Acinetobacter baumannii. METHODS: A comprehensive review was conducted from 2017 to 2023, covering articles from databases such as Pubmed, Scopus, and Embase, along with conference proceedings from ECCMID 2023. The primary focus was on severe nosocomial pneumonia due A. baumannii and cefiderocol. DISCUSSION: Cefiderocol, targeting periplasmic space Penicillin-Binding Proteins (PBPs) via siderophore transport pathways, exhibits promise against multi-drug resistant Gram-negative bacilli. Its effectiveness in treating CRAB pneumonia remains debated. The CREDIBLE trial reported higher mortality with cefiderocol compared to the best available treatment, while other cohort studies showed contrasting outcomes. Patient variations and pharmacokinetic factors may underlie these discrepancies. The recommended cefiderocol dosage regimen may fall short of desired pharmacokinetic targets, especially in critically ill patients and lung infections. Pulmonary factors hindering cefiderocol's entry into bacteria through iron transporters are overlooked in clinical breakpoints. Optimized dosing or combination regimens may enhance infection site exposure and outcomes. CONCLUSIONS: Further research is needed to determine the optimal cefiderocol dosage and administration (mono vs. dual therapy, continuous vs. intermittent infusion), in severe Acinetobacter baumannii nosocomial pneumonia.
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Infecciones por Acinetobacter , Acinetobacter baumannii , Antibacterianos , Carbapenémicos , Cefiderocol , Cefalosporinas , Neumonía Asociada a la Atención Médica , Humanos , Acinetobacter baumannii/efectos de los fármacos , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Neumonía Asociada a la Atención Médica/tratamiento farmacológico , Neumonía Asociada a la Atención Médica/microbiología , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/microbiología , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Cefalosporinas/uso terapéutico , Cefalosporinas/administración & dosificación , Cefalosporinas/farmacología , Farmacorresistencia Bacteriana Múltiple , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/microbiologíaRESUMEN
Background: To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund antimicrobials based on an evaluation of their value as opposed to the volumes used. The aim of this project was to evaluate the population-level health benefit of cefiderocol in the NHS in England, for the treatment of severe aerobic Gram-negative bacterial infections when used within its licensed indications. The results were used to inform the National Institute for Health and Care Excellence guidance in support of commercial discussions regarding contract value between the manufacturer and NHS England. Methods: The health benefit of cefiderocol was first derived for a series of high-value clinical scenarios. These represented uses that were expected to have a significant impact on patients' mortality risks and health-related quality of life. The clinical effectiveness of cefiderocol relative to its comparators was estimated by synthesising evidence on susceptibility of the pathogens of interest to the antimicrobials in a network meta-analysis. Patient-level costs and health outcomes of cefiderocol under various usage scenarios compared with alternative management strategies were quantified using decision modelling. Results were reported as incremental net health effects expressed in quality-adjusted life-years, which were scaled to 20-year population values using infection number forecasts based on data from Public Health England. The outcomes estimated for the high-value clinical scenarios were extrapolated to other expected uses for cefiderocol. Results: Among Enterobacterales isolates with the metallo-beta-lactamase resistance mechanism, the base-case network meta-analysis found that cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.32, 95% credible intervals 0.04 to 2.47), but the result was not statistically significant. The other treatments were also associated with lower susceptibility than colistin, but the results were not statistically significant. In the metallo-beta-lactamase Pseudomonas aeruginosa base-case network meta-analysis, cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.44, 95% credible intervals 0.03 to 3.94), but the result was not statistically significant. The other treatments were associated with no susceptibility. In the base case, patient-level benefit of cefiderocol was between 0.02 and 0.15 quality-adjusted life-years, depending on the site of infection, the pathogen and the usage scenario. There was a high degree of uncertainty surrounding the benefits of cefiderocol across all subgroups. There was substantial uncertainty in the number of infections that are suitable for treatment with cefiderocol, so population-level results are presented for a range of scenarios for the current infection numbers, the expected increases in infections over time and rates of emergence of resistance. The population-level benefits varied substantially across the base-case scenarios, from 896 to 3559 quality-adjusted life-years over 20 years. Conclusion: This work has provided quantitative estimates of the value of cefiderocol within its areas of expected usage within the NHS. Limitations: Given existing evidence, the estimates of the value of cefiderocol are highly uncertain. Future work: Future evaluations of antimicrobials would benefit from improvements to NHS data linkages; research to support appropriate synthesis of susceptibility studies; and application of routine data and decision modelling to assess enablement value. Study registration: No registration of this study was undertaken. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment Policy Research Programme (NIHR award ref: NIHR135591), conducted through the Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions, PR-PRU-1217-20401, and is published in full in Health Technology Assessment; Vol. 28, No. 28. See the NIHR Funding and Awards website for further award information.
This project tested new methods for estimating the value to the NHS of an antimicrobial, cefiderocol, so its manufacturer could be paid fairly even if very little drug is used in order to reduce the risk of bacteria becoming resistant to the product. Clinicians said that the greatest benefit of cefiderocol is when used for complicated urinary tract infections and pneumonia acquired within hospitals caused by two types of bacteria (called Enterobacterales and Pseudomonas aeruginosa), with a resistance mechanism called metallo-beta-lactamase. Because there were no relevant clinical trial data, we estimated how effective cefiderocol and alternative treatments were by doing a systematic literature review of studies that grew bacteria from infections in the laboratory and tested the drugs on them. We linked this to data estimating the long-term health and survival of patients. Some evidence was obtained by asking clinicians detailed questions about what they thought the effects would be based on their experience and the available evidence. We included the side effects of the alternative treatments, some of which can cause kidney damage. We estimated how many infections there would be in the UK, whether they would increase over time and how resistance to treatments may change over time. Clinicians told us that they would also use cefiderocol to treat intra-abdominal and bloodstream infections, and some infections caused by another bacteria called Stenotrophomonas. We estimated how many of these infections there would be, and assumed the same health benefits as for other types of infections. The total value to the NHS was calculated using these estimates. We also considered whether we had missed any additional elements of value. We estimated that the value to the NHS was £1871 million over 20 years. This reflects the maximum the NHS could pay for use of cefiderocol if the health lost as a result of making these payments rather than funding other NHS services is not to exceed the health benefits of using this antimicrobial. However, these estimates are uncertain due to limitations with the evidence used to produce them and assumptions that had to be made.
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Antibacterianos , Cefiderocol , Cefalosporinas , Análisis Costo-Beneficio , Infecciones por Bacterias Gramnegativas , Años de Vida Ajustados por Calidad de Vida , Evaluación de la Tecnología Biomédica , Humanos , Cefalosporinas/uso terapéutico , Antibacterianos/uso terapéutico , Antibacterianos/economía , Inglaterra , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Medicina Estatal , Calidad de VidaRESUMEN
Skin and soft tissue infections (SSTIs), and particularly diabetic-related foot infections (DFI), present diagnostic and therapeutic complexities, often leading to severe complications. This study aims to evaluate the in vitro efficacy of cefditoren and amoxicillin/clavulanic acid against typical DFI pathogens. Clinical samples from 40 patients with mild SSTIs were analyzed, revealing a predominance of Staphylococcus spp. and Streptococcus spp. species. Cefditoren exhibited activity against 90% of isolates, with superior potency over amoxicillin/clavulanic acid. These findings underscore the utility of cefditoren in empirical treatment of DFI, although a larger sample size would be desirable for further validation.
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Combinación Amoxicilina-Clavulanato de Potasio , Antibacterianos , Cefalosporinas , Pie Diabético , Pruebas de Sensibilidad Microbiana , Humanos , Pie Diabético/tratamiento farmacológico , Pie Diabético/microbiología , Antibacterianos/uso terapéutico , Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Cefalosporinas/uso terapéutico , Streptococcus/efectos de los fármacos , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Infecciones de los Tejidos Blandos/microbiología , Masculino , Femenino , Staphylococcus/efectos de los fármacos , Persona de Mediana EdadRESUMEN
Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a serious clinical challenge with high mortality rates. Antibiotic combination therapy is currently used in cases of persistent infection; however, the limited development of new antibiotics will likely increase the need for combination therapy, and better methods are needed for identifying effective combinations for treating persistent bacteremia. To identify pairwise combinations with the most consistent potential for benefit compared to monotherapy with a primary anti-MRSA agent, we conducted a systematic study with an in vitro high-throughput methodology. We tested daptomycin and vancomycin each in combination with gentamicin, rifampicin, cefazolin, and oxacillin, and ceftaroline with daptomycin, gentamicin, and rifampicin. Combining cefazolin with daptomycin lowered the daptomycin concentration required to reach 95% growth inhibition (IC95) for all isolates tested and lowered daptomycin IC95 below the sensitivity breakpoint for five out of six isolates that had daptomycin minimum inhibitory concentrations at or above the sensitivity breakpoint. Similarly, vancomycin IC95s were decreased when vancomycin was combined with cefazolin for 86.7% of the isolates tested. This was a higher percentage than was achieved by adding any other secondary antibiotic to vancomycin. Adding rifampicin to daptomycin or vancomycin did not always reduce IC95s and failed to produce synergistic interaction in any of the isolates tested; the addition of rifampicin to ceftaroline was frequently synergistic and always lowered the amount of ceftaroline required to reach the IC95. These analyses rationalize further in vivo evaluation of three drug pairs for MRSA bacteremia: daptomycin+cefazolin, vancomycin+cefazolin, and ceftaroline+rifampicin.IMPORTANCEBloodstream infections caused by methicillin-resistant Staphylococcus aureus (MRSA) have a high mortality rate despite the availability of vancomycin, daptomycin, and newer antibiotics including ceftaroline. With the slow output of the antibiotic pipeline and the serious clinical challenge posed by persistent MRSA infections, better strategies for utilizing combination therapy are becoming increasingly necessary. We demonstrated the value of a systematic high-throughput approach, adapted from prior work testing antibiotic combinations against tuberculosis and other mycobacteria, by using this approach to test antibiotic pairs against a panel of MRSA isolates with diverse patterns of antibiotic susceptibility. We identified three antibiotic pairs-daptomycin+cefazolin, vancomycin+cefazolin, and ceftaroline+rifampicin-where the addition of the second antibiotic improved the potency of the first antibiotic across all or most isolates tested. Our results indicate that these pairs warrant further evaluation in the clinical setting.
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Antibacterianos , Bacteriemia , Daptomicina , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Rifampin , Infecciones Estafilocócicas , Vancomicina , beta-Lactamas , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Humanos , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Daptomicina/farmacología , Daptomicina/uso terapéutico , Vancomicina/farmacología , beta-Lactamas/farmacología , beta-Lactamas/uso terapéutico , Rifampin/farmacología , Rifampin/uso terapéutico , Ceftarolina , Cefalosporinas/farmacología , Cefalosporinas/uso terapéutico , Cefazolina/farmacología , Cefazolina/uso terapéutico , Quimioterapia Combinada , Sinergismo Farmacológico , Oxacilina/farmacología , Gentamicinas/farmacología , Gentamicinas/uso terapéuticoRESUMEN
We described the emergence of ceftazidime/avibactam and cefiderocol cross-resistance in patients with KPC-producing Klebsiella pneumoniae infections. All strains with ceftazidime/avibactam and cefiderocol cross-resistance showed point mutations on KPC Ω-loop. Taken together, our results indicate that prolonged exposure to ceftazidime/avibactam can confer cross-resistance to ceftazidime/avibactam and cefiderocol.
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Antibacterianos , Compuestos de Azabiciclo , Cefiderocol , Ceftazidima , Cefalosporinas , Combinación de Medicamentos , Farmacorresistencia Bacteriana Múltiple , Infecciones por Klebsiella , Klebsiella pneumoniae , Pruebas de Sensibilidad Microbiana , beta-Lactamasas , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/genética , Ceftazidima/farmacología , Ceftazidima/uso terapéutico , Compuestos de Azabiciclo/farmacología , Compuestos de Azabiciclo/uso terapéutico , Humanos , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Cefalosporinas/uso terapéutico , Cefalosporinas/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Masculino , Femenino , Anciano , Persona de Mediana Edad , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Mutación PuntualRESUMEN
INTRODUCTION: Nosocomial meningitis may occur after procedures affecting the central nervous system or following traumatic injury. The causative infectious organism is commonly Staphylococcus aureus, a Gram-positive bacterium. The aim of the present study was to compare the effectiveness of two antibacterial agents, ceftobiprole and vancomycin, in an animal model of methicillin-resistant S. aureus (MRSA) meningitis. METHOD: The strain of MRSA used was ATCC 43300. The animals were divided into three groups and infected intracisternally with MRSA. Controls received no antibiotherapy while the ceftobiprole group received 25 mg/kg and the vancomycin group received 20 mg/kg intravenously. Blood and cerebrospinal fluid (CSF) samples were collected at three time points. All animals were euthanized at 73 h after start of treatment. RESULTS: There was a significant difference (p < 0.05) between both treatment groups and the control animals at 24 h (drug trough) and 73 h (1 h after third dose) after start of treatment in terms of CSF bacterial levels. At 73 h, there was a significant difference in survival between the control group and the two treatment groups but no difference between the treated animal survival rates. CONCLUSION: Intravenous treatment with ceftobiprole and vancomycin appears to be equally effective in a rabbit model of MRSA meningitis.