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
Taniborbactam, a bicyclic boronate ß-lactamase inhibitor with activity against Klebsiella pneumoniae carbapenemase (KPC), Verona integron-encoded metallo-ß-lactamase (VIM), New Delhi metallo-ß-lactamase (NDM), extended-spectrum beta-lactamases (ESBLs), OXA-48, and AmpC ß-lactamases, is under clinical development in combination with cefepime. Susceptibility of 200 previously characterized carbapenem-resistant K. pneumoniae and 197 multidrug-resistant (MDR) Pseudomonas aeruginosa to cefepime-taniborbactam and comparators was determined by broth microdilution. For K. pneumoniae (192 KPC; 7 OXA-48-related), MIC90 values of ß-lactam components for cefepime-taniborbactam, ceftazidime-avibactam, and meropenem-vaborbactam were 2, 2, and 1 mg/L, respectively. For cefepime-taniborbactam, 100% and 99.5% of isolates of K. pneumoniae were inhibited at ≤16 mg/L and ≤8 mg/L, respectively, while 98.0% and 95.5% of isolates were susceptible to ceftazidime-avibactam and meropenem-vaborbactam, respectively. For P. aeruginosa, MIC90 values of ß-lactam components of cefepime-taniborbactam, ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam were 16, >8, >8, and >4 mg/L, respectively. Of 89 carbapenem-susceptible isolates, 100% were susceptible to ceftolozane-tazobactam, ceftazidime-avibactam, and cefepime-taniborbactam at ≤8 mg/L. Of 73 carbapenem-intermediate/resistant P. aeruginosa isolates without carbapenemases, 87.7% were susceptible to ceftolozane-tazobactam, 79.5% to ceftazidime-avibactam, and 95.9% and 83.6% to cefepime-taniborbactam at ≤16 mg/L and ≤8 mg/L, respectively. Cefepime-taniborbactam at ≤16 mg/L and ≤8 mg/L, respectively, was active against 73.3% and 46.7% of 15 VIM- and 60.0% and 35.0% of 20 KPC-producing P. aeruginosa isolates. Of all 108 carbapenem-intermediate/resistant P. aeruginosa isolates, cefepime-taniborbactam was active against 86.1% and 69.4% at ≤16 mg/L and ≤8 mg/L, respectively, compared to 59.3% for ceftolozane-tazobactam and 63.0% for ceftazidime-avibactam. Cefepime-taniborbactam had in vitro activity comparable to ceftazidime-avibactam and greater than meropenem-vaborbactam against carbapenem-resistant K. pneumoniae and carbapenem-intermediate/resistant MDR P. aeruginosa.
Asunto(s)
Antibacterianos , Cefepima , Farmacorresistencia Bacteriana Múltiple , Klebsiella pneumoniae , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa , Inhibidores de beta-Lactamasas , Cefepima/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Klebsiella pneumoniae/efectos de los fármacos , Antibacterianos/farmacología , Inhibidores de beta-Lactamasas/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Cefalosporinas/farmacología , Humanos , beta-Lactamasas/metabolismo , beta-Lactamasas/genética , Ácidos Borónicos/farmacología , Carbapenémicos/farmacología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Ceftazidima/farmacología , Ácidos Borínicos/farmacología , Combinación de Medicamentos , Compuestos de Azabiciclo/farmacología , Ácidos CarboxílicosRESUMEN
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
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.
Asunto(s)
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 , CiclooctanosAsunto(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
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 , HumanosRESUMEN
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 AsuntoAsunto(s)
Antibacterianos , Cefepima , Electroencefalografía , Síndromes de Neurotoxicidad , Humanos , Cefepima/efectos adversos , Electroencefalografía/efectos de los fármacos , Antibacterianos/efectos adversos , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/fisiopatología , Masculino , Cefalosporinas/efectos adversos , FemeninoRESUMEN
BACKGROUND: In the neonatal intensive care unit, infants are at risk for late-onset sepsis. When blood cultures are negative, antibiotic stewardship efforts encourage stopping antibiotics, yet the duration of therapeutic exposure after the last dose is unknown. METHODS: This retrospective cohort study of simulated antibiotic exposures used published population pharmacokinetic models within drug-specific neonatal intensive care unit cohorts of preterm and term infants, postnatal age 7-60 days and exposed to cefepime, piperacillin-tazobactam or tobramycin. Monte Carlo simulations (NONMEM 7.3) were used to predict steady-state exposures after a 72-hour antibiotic course per Neofax dosing. Exposure was assessed relative to drug-specific minimum inhibitory concentration (MIC) targets between 1 and 16 mcg/mL for Pseudomonas and Enterobacteriaceae species. Postdiscontinuation antibiotic exposure (PDAE) was defined as the time from the last dose to when antibiotic concentration decreased below a specific MIC. RESULTS: Piperacillin-tazobactam, cefepime and tobramycin cohorts included infants with median gestation age 29, 32 and 32 weeks and postnatal age 17, 19 and 15 days, respectively. The mean PDAE was 19-68 hours, depending on the specific antibiotic/MIC combination. PDAE was longer for infants <28 days old and preterm (vs. term) infants. Cefepime exhibited the longest mean PDAE of 68 hours for Enterobacteriaceae MIC 1. Piperacillin mean PDAE was 25 hours for Enterobacteriaceae MIC 8. Tobramycin had a short mean PDAE of 19 hours. CONCLUSIONS: Piperacillin and cefepime exposures remained therapeutic long after the expected 8- to 12-hour dosing interval. PDAE is an important consideration for antibiotic stewardship among hospitalized infants, particularly premature infants and those within 1 month postbirth.
Asunto(s)
Antibacterianos , Unidades de Cuidado Intensivo Neonatal , Pruebas de Sensibilidad Microbiana , Sepsis , Humanos , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Recién Nacido , Estudios Retrospectivos , Masculino , Femenino , Sepsis/tratamiento farmacológico , Sepsis/microbiología , Tobramicina/administración & dosificación , Tobramicina/farmacocinética , Tobramicina/uso terapéutico , Tobramicina/farmacología , Cefepima/farmacocinética , Cefepima/uso terapéutico , Cefepima/farmacología , Cefepima/administración & dosificación , Lactante , Método de Montecarlo , Combinación Piperacilina y Tazobactam/uso terapéutico , Combinación Piperacilina y Tazobactam/farmacocinética , Combinación Piperacilina y Tazobactam/administración & dosificación , Programas de Optimización del Uso de los Antimicrobianos , Recien Nacido PrematuroRESUMEN
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
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/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
OBJECTIVES: This study was performed to investigate the activity of the novel ß-lactam/ß-lactamase inhibitor combination cefepime/enmetazobactam, against recently circulating Enterobacterales isolates from Europe from 2019 to 2021. METHODS: A total of 2627 isolates were collected, and antimicrobial susceptibility was determined according to the European Committee on Antimicrobial Susceptibility Testing guidelines. Isolates with phenotypic resistance to ceftriaxone and ceftazidime (but susceptible to meropenem) and isolates nonsusceptible to meropenem were screened for the presence of ß-lactamases. RESULTS: Overall, susceptibility to third-generation cephalosporins was 77%, and 97.3% were susceptible to meropenem. Cefepime/enmetazobactam susceptibility was 97.9% (72% of these isolates were Klebsiella pneumoniae from Italy), compared with 80.0% susceptibility to piperacillin/tazobactam and 99.4% to ceftazidime/avibactam. A total of 320 isolates (12.2%) were resistant to third-generation cephalosporins but susceptible to meropenem, and virtually all (96.3%) carried an extended-spectrum ß-lactamase with or without an AmpC and these were all susceptible to cefepime/enmetazobactam. Most meropenem-nonsusceptible isolates carried a KPC (68%), which were not inhibited by cefepime/enmetazobactam but were inhibited by ceftazidime/avibactam. Additionally, most meropenem-nonsusceptible isolates carrying OXA-48 (9/12 isolates) were susceptible to cefepime/enmetazobactam. CONCLUSIONS: Cefepime/enmetazobactam was highly active against Enterobacterales isolates, especially those resistant to third-generation cephalosporins. These data suggest that cefepime/enmetazobactam could be used as a carbapenem-sparing agent to replace piperacillin/tazobactam.
Asunto(s)
Antibacterianos , Cefepima , Infecciones por Enterobacteriaceae , Enterobacteriaceae , Pruebas de Sensibilidad Microbiana , Cefepima/farmacología , Humanos , Antibacterianos/farmacología , Europa (Continente) , Enterobacteriaceae/efectos de los fármacos , Enterobacteriaceae/aislamiento & purificación , Infecciones por Enterobacteriaceae/microbiología , beta-Lactamasas/metabolismo , Compuestos de Azabiciclo/farmacología , Inhibidores de beta-Lactamasas/farmacología , Ceftazidima/farmacología , Combinación Piperacilina y Tazobactam/farmacología , Cefalosporinas/farmacología , Meropenem/farmacología , Combinación de Medicamentos , TriazolesRESUMEN
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
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
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
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 EdadRESUMEN
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.