RESUMEN
Cefepime is a fourth-generation cephalosporin with extended antimicrobial coverage. Concerns have been raised about the side effects of cefepime including myoclonus, encephalopathy, and seizures, especially when renal impairment is present. There have been reports of cases of adverse neurological consequences despite appropriate renal adjustment. Here, we present a case of a 69-year-old patient initially diagnosed with pneumonia and treated with cefepime. The patient later developed altered mental status, leading to differential diagnoses including stroke, drug overdose, or non-convulsive seizures. Following a comprehensive workup, it was determined that she had cefepime-induced encephalopathy, despite having normal kidney function, which resolved completely after discontinuing the medication. In addition, we include similar cases retrieved from PubMed up to the present date, to the best of our knowledge.
Asunto(s)
Antibacterianos , Encefalopatías , Cefepima , Unidades de Cuidados Intensivos , Síndromes de Neurotoxicidad , Humanos , Cefepima/efectos adversos , Anciano , Femenino , Antibacterianos/efectos adversos , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/diagnóstico , Encefalopatías/inducido químicamente , Cefalosporinas/efectos adversosRESUMEN
OBJECTIVES: The emergence of multidrug-resistant (MDR) Salmonella strains, especially resistant ones toward critically important antimicrobial classes such as fluoroquinolones and third- and fourth-generation cephalosporins, is a growing public health concern. The current study, therefore, aimed to determine the prevalence, and existence of virulence genes (invA, stn, and spvC genes), antimicrobial resistance profiles, and the presence of ß-lactamase resistance genes (blaOXA, blaCTX-M1, blaSHV, and blaTEM) in Salmonella strains isolated from native chicken carcasses in Egypt marketed in Mansoura, Egypt, as well as spotlight the risk of isolated MDR, colistin-, cefepime-, and levofloxacin-resistant Salmonella enterica serovars to public health. METHODS: One hundred fifty freshly dressed native chicken carcasses were collected from different poultry shops in Mansoura City, Egypt between July 2022 and November 2022. Salmonella isolation was performed using standard bacteriological techniques, including pre-enrichment in buffered peptone water (BPW), selective enrichment in Rappaport Vassiliadis broth (RVS), and cultivating on the surface of xylose-lysine-desoxycholate (XLD) agar. All suspected Salmonella colonies were subjected to biochemical tests, serological identification using slide agglutination test, and Polymerase Chain Reaction (PCR) targeting the invasion A gene (invA; Salmonella marker gene). Afterward, all molecularly verified isolates were screened for the presence of virulence genes (stn and spvC). The antimicrobial susceptibility testing for isolated Salmonella strains towards the 16 antimicrobial agents tested was analyzed by Kirby-Bauer disc diffusion method, except for colistin, in which the minimum inhibition concentration (MIC) was determined by broth microdilution technique. Furthermore, 82 cefotaxime-resistant Salmonella isolates were tested using multiplex PCR targeting the ß-lactamase resistance genes, including blaOXA, blaCTX-M1, blaSHV, and blaTEM genes. RESULTS: Salmonella enterica species were molecularly confirmed via the invA Salmonella marker gene in 18% (27/150) of the freshly dressed native chicken carcasses. Twelve Salmonella serotypes were identified among 129 confirmed Salmonella isolates with the most predominant serotypes were S. Kentucky, S. Enteritidis, S. Typhimurium, and S. Molade with an incidence of 19.4% (25/129), 17.1% (22/129), 17.1% (22/129), and 10.9% (14/129), respectively. All the identified Salmonella isolates (n = 129) were positive for both invA and stn genes, while only 31.8% (41/129) of isolates were positive for the spvC gene. One hundred twenty-one (93.8%) of the 129 Salmonella-verified isolates were resistant to at least three antibiotics. Interestingly, 3.9%, 14.7%, and 75.2% of isolates were categorized into pan-drug-resistant, extensively drug-resistant, and multidrug-resistant, respectively. The average MAR index for the 129 isolates tested was 0.505. Exactly, 82.2%, 82.2%, 63.6%, 51.9%, 50.4%, 48.8%, 11.6%, and 10.1% of isolated Salmonella strains were resistant to cefepime, colistin, cefotaxime, ceftazidime/clavulanic acid, levofloxacin, ciprofloxacin, azithromycin, and meropenem, respectively. Thirty-one out (37.8%) of the 82 cefotaxime-resistant Salmonella isolates were ß-lactamase producers with the blaTEM as the most predominant ß-lactamase resistance gene, followed by blaCTX-M1 and blaOXA genes, which were detected in 21, 16, and 14 isolates respectively). CONCLUSION: The high prevalence of MDR-, colistin-, cefepime-, and levofloxacin-resistant Salmonella serovars among Salmonella isolates from native chicken is alarming as these antimicrobials are critically important in treating severe salmonellosis cases and boost the urgent need for controlling antibiotic usage in veterinary and human medicine to protect public health.
Asunto(s)
Antibacterianos , Cefepima , Pollos , Colistina , Farmacorresistencia Bacteriana Múltiple , Levofloxacino , Pruebas de Sensibilidad Microbiana , Salmonella enterica , Serogrupo , Animales , Egipto , Salmonella enterica/efectos de los fármacos , Salmonella enterica/genética , Salmonella enterica/aislamiento & purificación , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Colistina/farmacología , Levofloxacino/farmacología , Cefepima/farmacología , beta-Lactamasas/genética , Factores de Virulencia/genética , Proteínas Bacterianas/genética , Salmonelosis Animal/microbiología , HumanosAsunto(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
The impact of chromosomally encoded wild-type or extended-spectrum (ESAC) AmpC ß-lactamases of Escherichia coli on susceptibility to ceftazidime, cefepime, and cefiderocol was evaluated in different genetic backgrounds, including wild-type, PBP3-modified, and porin-deficient E. coli strains. Recombinant E. coli strains possessing the different backgrounds and producing variable ESACs were evaluated. Although ESAC enzymes conferred resistance to ceftazidime and decreased susceptibility to cefepime as expected, we showed here that cefiderocol was also a substrate of ESAC enzymes. IMPORTANCE: We showed here that chromosomally encoded intrinsic extended-spectrum cephalosporinases of Escherichia coli may impact susceptibility not only to ceftazidime and cefepime but also to cefiderocol.
Asunto(s)
Antibacterianos , Proteínas Bacterianas , Cefiderocol , Cefalosporinas , Escherichia coli , Pruebas de Sensibilidad Microbiana , beta-Lactamasas , Escherichia coli/genética , Escherichia coli/efectos de los fármacos , Escherichia coli/enzimología , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Cefalosporinas/farmacología , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Ceftazidima/farmacología , Cromosomas Bacterianos/genética , Cefepima/farmacologíaRESUMEN
Cefepime and piperacillin/tazobactam are antimicrobials recommended by IDSA/ATS guidelines for the empirical management of patients admitted to the intensive care unit (ICU) with community-acquired pneumonia (CAP). Concerns have been raised about which should be used in clinical practice. This study aims to compare the effect of cefepime and piperacillin/tazobactam in critically ill CAP patients through a targeted maximum likelihood estimation (TMLE). A total of 2026 ICU-admitted patients with CAP were included. Among them, (47%) presented respiratory failure, and (27%) developed septic shock. A total of (68%) received cefepime and (32%) piperacillin/tazobactam-based treatment. After running the TMLE, we found that cefepime and piperacillin/tazobactam-based treatments have comparable 28-day, hospital, and ICU mortality. Additionally, age, PTT, serum potassium and temperature were associated with preferring cefepime over piperacillin/tazobactam (OR 1.14 95% CI [1.01-1.27], p = 0.03), (OR 1.14 95% CI [1.03-1.26], p = 0.009), (OR 1.1 95% CI [1.01-1.22], p = 0.039) and (OR 1.13 95% CI [1.03-1.24], p = 0.014)]. Our study found a similar mortality rate among ICU-admitted CAP patients treated with cefepime and piperacillin/tazobactam. Clinicians may consider factors such as availability and safety profiles when making treatment decisions.
Asunto(s)
Antibacterianos , Cefepima , Infecciones Comunitarias Adquiridas , Enfermedad Crítica , Unidades de Cuidados Intensivos , Combinación Piperacilina y Tazobactam , Humanos , Cefepima/uso terapéutico , Cefepima/administración & dosificación , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/mortalidad , Combinación Piperacilina y Tazobactam/uso terapéutico , Masculino , Femenino , Anciano , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Funciones de Verosimilitud , Neumonía/tratamiento farmacológico , Neumonía/mortalidad , Piperacilina/uso terapéuticoRESUMEN
SOURCE CITATION: Wagenlehner FM, Gasink LB, McGovern PC, et al; CERTAIN-1 Study Team. Cefepime-taniborbactam in complicated urinary tract infection. N Engl J Med. 2024;390:611-622. 38354140.
Asunto(s)
Antibacterianos , Cefepima , Meropenem , Infecciones Urinarias , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Antibacterianos/efectos adversos , Cefepima/uso terapéutico , Combinación de Medicamentos , Meropenem/uso terapéutico , Resultado del Tratamiento , Infecciones Urinarias/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Wagenlehner and colleagues1 demonstrated non-inferiority and superiority with respect to a primary endpoint of composite success (microbiological plus clinical) of cefepime/taniborbactam vs. meropenem in treating complicated urinary tract infections and acute pyelonephritis caused by carbapenem-susceptible gram-negative bacteria in adults. A major area of interest in real-world application of cefepime/taniborbactam is its potential role in treating carbapenem-resistant infections, which deserves further investigation.
Asunto(s)
Antibacterianos , Carbapenémicos , Cefepima , Infecciones Urinarias , Cefepima/uso terapéutico , Cefepima/farmacología , Humanos , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Carbapenémicos/uso terapéutico , Carbapenémicos/farmacología , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , Cefalosporinas/uso terapéutico , Cefalosporinas/farmacología , Pielonefritis/tratamiento farmacológico , Pielonefritis/microbiología , Combinación de Medicamentos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Meropenem/uso terapéutico , Meropenem/farmacología , Ácidos Borínicos , Ácidos CarboxílicosRESUMEN
There are increasing reports of carbapenem-resistant Enterobacterales (CRE) that test as cefepime-susceptible (S) or susceptible-dose dependent (SDD). However, there are no data to compare the cefepime testing performance of BD Phoenix automated susceptibility system (BD Phoenix) and disk diffusion (DD) relative to reference broth microdilution (BMD) against carbapenemase-producing (CPblaKPC-CRE) and non-producing (non-CP CRE) isolates. Cefepime susceptibility results were interpreted according to CLSI M100Ed32. Essential agreement (EA), categorical agreement (CA), minor errors (miEs), major errors (MEs), and very major errors (VMEs) were calculated for BD Phoenix (NMIC-306 Gram-negative panel) and DD relative to BMD. Correlates were also analyzed by the error rate-bounded method. EA and CA for CPblaKPC-CRE isolates (n = 64) were <90% with BD Phoenix while among non-CP CRE isolates (n = 58), EA and CA were 96.6%, and 79.3%, respectively. CA was <90% with DD for both cohorts. No ME or VME was observed for either isolate cohort; however, miEs were >10% for CPblaKPC-CRE and non-CP CRE with BD Phoenix and DD tests. For error rate-bounded method, miEs were <40% for IHigh + 1 to ILow - 1 ranges for CPblaKPC-CRE and non-CP CRE with BD Phoenix. Regarding disk diffusion, miEs were unacceptable for all MIC ranges among CPblaKPC-CRE. For non-CP CRE isolates, only IHigh + 1 to ILow - 1 range was acceptable at 37.2%. Using this challenge set of genotypic-phenotypic discordant CRE, the BD Phoenix MICs and DD susceptibility results trended higher (toward SDD and resistant phenotypes) relative to reference BMD results yielding lower CA. These results were more prominent among CPblaKPC-CRE than non-CP CRE.
Asunto(s)
Antibacterianos , Enterobacteriaceae Resistentes a los Carbapenémicos , Cefepima , Pruebas de Sensibilidad Microbiana , Cefepima/farmacología , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana/métodos , Humanos , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Pruebas Antimicrobianas de Difusión por Disco/métodos , Infecciones por Enterobacteriaceae/microbiología , Cefalosporinas/farmacologíaRESUMEN
Background: ß-Lactam antibiotics are widely used with increased utilization in hospitalized patients. Of this population, as high as 10-20% report an allergy to ß-lactam antibiotics but <5% are at risk of developing clinically significant immunoglobulin E- or T-lymphocyte-mediated reactions. Most of the time, these reported allergies are present during an illness with no previous inquiry of their validity, which makes investigation and possible removal of this allergy label a challenge. Methods: We report a 16-year-old boy who presented with 1 week of night sweats, chills, headaches, and fatigue, followed by 1 day of fever and right knee swelling and who was diagnosed with septic bursitis. Due to concern of a penicillin allergy label, the patient was started on a cefepime infusion. Five minutes into the infusion, the patient reported puffy eyes and itchy throat, followed by a witnessed cascading flat nonpruritic erythematous rash from head to shoulders. This rash went away in 3 minutes after stopping the infusion and the patient being given 50 mg of intravenous diphenhydramine and 10 mg of oral dexamethasone. He was subsequently diagnosed with a cefepime allergy. Results: Allergy/immunology was the speciality consulted, and, by using a screening questionnaire, the patient's reported penicillin allergy was determined to be low risk. Subsequent 1-step oral challenge was the key to providing the patient with the necessary antibiotic course to resolve his infection. Conclusion: Multiple reported antibiotic allergies lead to poor antibiotic stewardship that causes impactful health and financial burden on the patient and health-care system. It is thus important to have an evidence-based systematic approach to de-label penicillin antibiotic allergy labels to reduce these potential harms.
Asunto(s)
Antibacterianos , Cefalosporinas , Hipersensibilidad a las Drogas , Penicilinas , Humanos , Masculino , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/etiología , Adolescente , Penicilinas/efectos adversos , Antibacterianos/efectos adversos , Cefalosporinas/efectos adversos , Etiquetado de Medicamentos , Alérgenos/inmunología , Hospitalización , Cefepima/efectos adversosRESUMEN
Importance: Experimental and observational studies have suggested that empirical treatment for bacterial sepsis with antianaerobic antibiotics (eg, piperacillin-tazobactam) is associated with adverse outcomes compared with anaerobe-sparing antibiotics (eg, cefepime). However, a recent pragmatic clinical trial of piperacillin-tazobactam and cefepime showed no difference in short-term outcomes at 14 days. Further studies are needed to help clarify the empirical use of these agents. Objective: To examine the use of piperacillin-tazobactam compared with cefepime in 90-day mortality in patients treated empirically for sepsis, using instrumental variable analysis of a 15-month piperacillin-tazobactam shortage. Design, Setting, and Participants: In a retrospective cohort study, hospital admissions at the University of Michigan from July 1, 2014, to December 31, 2018, including a piperacillin-tazobactam shortage period from June 12, 2015, to September 18, 2016, were examined. Adult patients with suspected sepsis treated with vancomycin and either piperacillin-tazobactam or cefepime for conditions with presumed equipoise between piperacillin-tazobactam and cefepime were included in the study. Data analysis was conducted from December 17, 2022, to April 11, 2023. Main Outcomes and Measures: The primary outcome was 90-day mortality. Secondary outcomes included organ failure-free, ventilator-free, and vasopressor-free days. The 15-month piperacillin-tazobactam shortage period was used as an instrumental variable for unmeasured confounding in antibiotic selection. Results: Among 7569 patients (4174 men [55%]; median age, 63 [IQR 52-73] years) with sepsis meeting study eligibility, 4523 were treated with vancomycin and piperacillin-tazobactam and 3046 were treated with vancomycin and cefepime. Of patients who received piperacillin-tazobactam, only 152 (3%) received it during the shortage. Treatment groups did not differ significantly in age, Charlson Comorbidity Index score, Sequential Organ Failure Assessment score, or time to antibiotic administration. In an instrumental variable analysis, piperacillin-tazobactam was associated with an absolute mortality increase of 5.0% at 90 days (95% CI, 1.9%-8.1%) and 2.1 (95% CI, 1.4-2.7) fewer organ failure-free days, 1.1 (95% CI, 0.57-1.62) fewer ventilator-free days, and 1.5 (95% CI, 1.01-2.01) fewer vasopressor-free days. Conclusions and Relevance: Among patients with suspected sepsis and no clear indication for antianaerobic coverage, administration of piperacillin-tazobactam was associated with higher mortality and increased duration of organ dysfunction compared with cefepime. These findings suggest that the widespread use of empirical antianaerobic antibiotics in sepsis may be harmful.
Asunto(s)
Antibacterianos , Cefepima , Combinación Piperacilina y Tazobactam , Sepsis , Humanos , Cefepima/administración & dosificación , Cefepima/uso terapéutico , Combinación Piperacilina y Tazobactam/administración & dosificación , Combinación Piperacilina y Tazobactam/uso terapéutico , Masculino , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Femenino , Sepsis/tratamiento farmacológico , Sepsis/mortalidad , Estudios Retrospectivos , Anciano , Persona de Mediana EdadAsunto(s)
Antibacterianos , Cefepima , Infecciones por Enterobacteriaceae , Infecciones Urinarias , Anciano , Femenino , Humanos , Masculino , Antibacterianos/uso terapéutico , Antibacterianos/efectos adversos , Cefepima/uso terapéutico , Cefalosporinas/uso terapéutico , Cefalosporinas/efectos adversos , Infecciones Urinarias/complicaciones , Infecciones Urinarias/tratamiento farmacológico , Ensayos Clínicos Fase III como Asunto , Meropenem/uso terapéutico , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Enterobacteriaceae , Farmacorresistencia BacterianaAsunto(s)
Antibacterianos , Cefepima , Infecciones Urinarias , Anciano , Femenino , Humanos , Masculino , Antibacterianos/uso terapéutico , Antibacterianos/efectos adversos , Cefepima/uso terapéutico , Cefalosporinas/uso terapéutico , Cefalosporinas/efectos adversos , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , Ensayos Clínicos Fase III como Asunto , Farmacorresistencia Bacteriana , Meropenem/efectos adversos , Meropenem/uso terapéutico , Pruebas de Sensibilidad MicrobianaAsunto(s)
Antibacterianos , Cefepima , Infecciones por Enterobacteriaceae , Infecciones Urinarias , Anciano , Femenino , Humanos , Masculino , Antibacterianos/uso terapéutico , Antibacterianos/efectos adversos , Cefepima/uso terapéutico , Cefalosporinas/uso terapéutico , Cefalosporinas/efectos adversos , Ensayos Clínicos Fase III como Asunto , Farmacorresistencia Bacteriana , Enterobacteriaceae , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Meropenem/uso terapéutico , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiologíaAsunto(s)
Antibacterianos , Cefepima , Infecciones Urinarias , Humanos , Antibacterianos/uso terapéutico , Antibacterianos/efectos adversos , Cefepima/efectos adversos , Cefepima/uso terapéutico , Cefalosporinas/uso terapéutico , Cefalosporinas/efectos adversos , Infecciones Urinarias/complicaciones , Infecciones Urinarias/tratamiento farmacológico , Ensayos Clínicos Fase III como Asunto , Farmacorresistencia BacterianaRESUMEN
CERTAIN-1 was a Phase 3, double-blind, randomized, parallel group study of the efficacy and safety of cefepime-taniborbactam versus meropenem in the treatment of adults with complicated urinary tract infection (cUTI), including acute pyelonephritis. We determined susceptibility of Enterobacterales and Pseudomonas aeruginosa baseline pathogens to cefepime-taniborbactam and comparators and characterized ß-lactam resistance mechanisms. Microbiologic response and clinical response were assessed in patient subsets defined by baseline pathogens that were of cefepime-, multidrug-, or carbapenem-resistant phenotype or that carried ß-lactamase genes. Among Enterobacterales baseline pathogens, 26.8%, 4.1%, and 3.0% carried genes for extended-spectrum ß-lactamases (ESBLs), AmpC, and carbapenemases, respectively. Within each treatment group, while composite success rates at Test of Cure in resistant subsets by pathogen species were similar to those by pathogen overall, composite success rates in meropenem patients were numerically lower for cefepime-resistant Escherichia coli (9/19; 47.4%) and ESBL E. coli (13/25; 52.0%) compared with E. coli overall (62/100; 62.0%). Cefepime-taniborbactam achieved composite success in 7/8 (87.5%) patients with carbapenem-resistant Enterobacterales and 8/9 (88.9%) patients with Enterobacterales with a carbapenemase gene (5 OXA-48-group; 2 KPC-3; 2 NDM-1). Cefepime-taniborbactam also achieved composite success in 8/16 (50.0%) patients and clinical success in 13/16 (81.3%) patients with P. aeruginosa; corresponding rates were 4/7 (57.1%) and 6/7 (85.7%) for meropenem. Cefepime-taniborbactam demonstrated efficacy in adult cUTI patients with cefepime-, multidrug-, and carbapenem-resistant pathogens including pathogens with ESBL, AmpC, and carbapenemase genes. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT03840148.
Asunto(s)
Antibacterianos , Cefepima , Cefalosporinas , Meropenem , Pruebas de Sensibilidad Microbiana , Infecciones Urinarias , beta-Lactamasas , Humanos , Meropenem/uso terapéutico , Meropenem/farmacología , Cefepima/uso terapéutico , Cefepima/farmacología , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , Cefalosporinas/uso terapéutico , Cefalosporinas/farmacología , beta-Lactamasas/genética , Adulto , Femenino , Masculino , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/genética , Persona de Mediana Edad , Método Doble Ciego , Proteínas Bacterianas/genética , Genotipo , Fenotipo , Anciano , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Resultado del Tratamiento , Ácidos Borínicos , Ácidos CarboxílicosRESUMEN
OBJECTIVES: This research aimed to overcome challenges posed by cefepime excessive elimination rate and poor patient compliance by developing transdermal delivery system using nano-transfersomes based chitosan gel. METHODS: Rotary evaporation-sonication method and the Box-Behnken model were used to prepare cefepime loaded nano-transfersomes (CPE-NTFs). The physiochemical characterization of CPE-NTFs were analyzed including DLS, deformability index, DSC and antimicrobial study. Optimized CPE-NTFs loaded into chitosan gel and appropriately characterized. In vitro release, ex vivo and in vivo studies were performed. RESULTS: The CPE-NTFs were physically stable with particle size 222.6 ± 1.8 nm, polydispersity index 0.163 ± 0.02, zeta potential -20.8 ± 0.1 mv, entrapment efficiency 81.4 ± 1.1% and deformability index 71 ± 0.2. DSC analysis confirmed successful drug loading and thermal stability. FTIR analysis showed no chemical interaction among the excipients of CPE-NTFs gel. The antibacterial activity demonstrated a remarkable reduction in the minimum inhibitory concentration of cefepime when incorporated into nano-transfersomes. CPE-NTFs based chitosan gel (CPE-NTFs gel) showed significant physicochemical properties. In vitro release studies exhibited sustained release behavior over 24 h, and ex vivo studies indicated enhanced permeation and retention compared to conventional cefepime gel. In vivo skin irritation studies confirmed CPE-NTFs gel was nonirritating and biocompatible for transdermal delivery. CONCLUSION: This research showed nano-transfersomes based chitosan gel is a promising approach for cefepime transdermal delivery and provides sustained release of cefepime.
Asunto(s)
Administración Cutánea , Antibacterianos , Cefepima , Quitosano , Geles , Tamaño de la Partícula , Absorción Cutánea , Piel , Quitosano/química , Cefepima/administración & dosificación , Cefepima/farmacocinética , Cefepima/química , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Antibacterianos/química , Antibacterianos/farmacología , Geles/química , Animales , Absorción Cutánea/efectos de los fármacos , Piel/metabolismo , Ratas , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Pruebas de Sensibilidad Microbiana , Masculino , Portadores de Fármacos/química , Nanopartículas/química , Ratas WistarRESUMEN
The world population is rapidly aging. Societal aging poses many challenges for individuals, families, nations, and the global healthcare system. Therefore, geriatric care is a crucial issue that demands our attention. In this case report, we describe a woman in her early 70s with multiple comorbidities, polypharmacy, and renal insufficiency who developed cefepime-induced encephalopathy with moderate to severe cerebral dysfunction during treatment of a urinary tract infection. The patient's consciousness level gradually improved, and no further seizures were observed following the discontinuation of cefepime for several days. This case report underscores the fact that polypharmacy and medication safety are significant concerns that are often overlooked when caring for older patients. The report also highlights the increased susceptibility of older individuals to antibiotic-associated adverse reactions during the management of infectious diseases. Therefore, optimization of antibiotic therapy for older patients is a critical issue that requires thorough investigation and consideration in geriatric care.
Asunto(s)
Antibacterianos , Encefalopatías , Cefepima , Polifarmacia , Insuficiencia Renal , Infecciones Urinarias , Humanos , Cefepima/efectos adversos , Cefepima/uso terapéutico , Femenino , Anciano , Encefalopatías/inducido químicamente , Infecciones Urinarias/tratamiento farmacológico , Insuficiencia Renal/inducido químicamente , Antibacterianos/efectos adversos , Antibacterianos/uso terapéuticoRESUMEN
Cefepime/enmetazobactam (EXBLIFEP®), an intravenous (IV) antibacterial fixed-dose combination of a 4th generation cephalosporin and an extended-spectrum ß-lactamase (ESBL) inhibitor, is being developed by Allecra Therapeutics and ADVANZ PHARMA for the treatment of infections caused by multi-drug-resistant (MDR) Gram-negative bacteria. In February 2024, cefepime/enmetazobactam was approved in the USA for use in adults with complicated urinary tract infections (cUTI) including pyelonephritis, caused by susceptible strains of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, and Enterobacter cloacae complex. In March 2024, cefepime/enmetazobactam was approved in the EU for use in adults for the treatment of cUTI, including pyelonephritis, and hospital-acquired pneumonia, including ventilator associated pneumonia, and the treatment of patients with bacteraemia occurring in association with or suspected to be associated with any of these infections. This article summarizes the milestones in the development of cefepime/enmetazobactam leading to this first approval for the treatment of adults with infections caused by MDR Gram-negative bacteria.
Asunto(s)
Antibacterianos , Cefepima , Aprobación de Drogas , Infecciones Urinarias , Humanos , Cefepima/farmacología , Cefepima/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Cefalosporinas/uso terapéutico , Cefalosporinas/farmacología , Inhibidores de beta-Lactamasas/farmacología , Inhibidores de beta-Lactamasas/uso terapéutico , Inhibidores de beta-Lactamasas/administración & dosificación , Estados Unidos , Combinación de Medicamentos , Pielonefritis/tratamiento farmacológico , Pielonefritis/microbiologíaRESUMEN
Piperacillin-tazobactam (TZP), cefepime (FEP), or meropenem (MEM) and vancomycin (VAN) are commonly used in combination for sepsis. Studies have shown an increased risk of acute kidney injury (AKI) with TZP and VAN compared to FEP or MEM. VAN guidelines recommend area under the curve (AUC) monitoring over trough (Tr) to minimize the risk of AKI. We investigated the association of AKI and MAKE-30 with the two VAN monitoring strategies when used in combination with TZP or FEP/MEM. Adult patients between 2015 and 2019 with VAN > 72 hours were included. Patients with AKI prior to or within 48 hours of VAN or baseline CrCl of ≤30 mL/min were excluded. Four cohorts were defined: FEP/MEM/Tr, FEP/MEM/AUC, TZP/Tr, and TZP/AUC. A Cox Proportional Hazard Model was used to model AKI as a function of the incidence rate of at-risk days, testing monitoring strategy as a treatment effect modification. Multivariable logistic regression was used to model MAKE-30. Overall incidence of AKI was 18.6%; FEP/MEM/Tr = 115 (14.6%), FEP/MEM/AUC = 52 (14.9%), TZP/Tr = 189 (26%), and TZP/AUC = 96 (17.1%) (P < 0.001). Both drug group [(TZP; P = 0.0085)] and monitoring strategy [(Tr; P = 0.0007)] were highly associated with the development of AKI; however, the effect was not modified with interaction term [(TZP*Tr); 0.085)]. The odds of developing MAKE-30 were not different between any group and FEP/MEM/AUC. The effect of VAN/TZP on the development of AKI was not modified by the VAN monitoring strategy (AUC vs trough). MAKE-30 outcomes were not different among the four cohorts.
Asunto(s)
Lesión Renal Aguda , Antibacterianos , Cefepima , Meropenem , Combinación Piperacilina y Tazobactam , Vancomicina , Humanos , Vancomicina/efectos adversos , Vancomicina/administración & dosificación , Vancomicina/uso terapéutico , Meropenem/administración & dosificación , Meropenem/uso terapéutico , Meropenem/efectos adversos , Lesión Renal Aguda/inducido químicamente , Cefepima/administración & dosificación , Cefepima/uso terapéutico , Cefepima/efectos adversos , Combinación Piperacilina y Tazobactam/efectos adversos , Combinación Piperacilina y Tazobactam/administración & dosificación , Combinación Piperacilina y Tazobactam/uso terapéutico , Masculino , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Femenino , Persona de Mediana Edad , Anciano , Área Bajo la Curva , Quimioterapia Combinada , Estudios Retrospectivos , Sepsis/tratamiento farmacológicoRESUMEN
BACKGROUND: The problem of resistance to beta-lactam antibiotics, which is caused by ESBL and AmpC ß-lactamases, is getting worse globally. Infections caused by bacterial isolates harboring these enzymes are difficult to treat with carbapenems being the sole effective treatment option for such infections. The objective of this study was to determine the frequency of ESBLs and AmpC-producing Gram-negative bacilli isolated from clinical specimens and to evaluate the sensitivity of cefepime-tazobactam combination against them. METHODS: This is an observational cross-sectional study carried out on 100 Gram-negative bacilli at Theodor Bilharz Research Institute Hospital during the period from February 2015 to January 2016. ESBL production was screened by using the disc diffusion test followed by confirmation by the combined disc confirmatory test, the screening for AmpC production was conducted using the cefoxitin disc test, which was subsequently confirmed by the AmpC disc test. Isolates confirmed positive for ESBL and/ or AmpC production were investigated for their susceptibility to antibiotics. RESULTS: Among 100 Gram-negative bacilli, 44 isolates were confirmed as ESBL producers by the combined disc confirmatory test out of 56 isolates that tested positive for ESBL production through the disc diffusion test. The presence of AmpC production was assessed using the cefoxitin disc test, 32 isolates were screened to be AmpC producers, and the AmpC disc test confirmed AmpC production in 9 isolates of them. Using the Mast® D68C set, 32 isolates were ESBL producers, 3 were AmpC producers, and 4 isolates were ESBL/AmpC co-producers. The highest sensitivity was to cefepime-tazobactam (91.48%) followed by the carbapenems. CONCLUSION: Cefepime-tazobactam showed remarkable activity against ESBL and/or AmpC-producing Gram-negative bacilli and may be considered as a therapeutic alternative to carbapenems.