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1.
Khirurgiia (Mosk) ; (12): 74-83, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31825346

RESUMO

AIM: To determine the place of new drugs with activity against multidrug resistant strains of microorganisms in the treatment of complicated intraabdominal infections. MATERIAL AND METHODS: The incidence and distribution of pathogens isolated from intra-abdominal specimens in patients with intra-abdominal infections are analyzed. RESULTS: The current situation on the growth of resistant strains among pathogens causing intra-abdominal infections is rewied. New combined drugs for the treatment of multidrug resistant infections - ceftolozane/tazobactam and ceftazidim/avibactam plus metronidazole, has been suggested. Their potential role in empiric and targeted antibacterial treatment of complicated intraabdominal infections is defined. CONCLUSION: Taking into consideration local monitoring data and risk factors of multi resistant strains Ceftolozane/tazobactam in combination with metronidazole can be used in empiric regime of treatment. Due to the high activity on carbapenem resistant strains of Klebsiella pneumonia and the lack of alternatives, it is advisable to use Ceftazidim/avibactam for the targeted therapy.


Assuntos
Antibacterianos/administração & dosagem , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções Intra-Abdominais/tratamento farmacológico , Infecções Intra-Abdominais/microbiologia , Compostos Azabicíclicos/administração & dosagem , Ceftazidima/administração & dosagem , Cefalosporinas/administração & dosagem , Combinação de Medicamentos , Humanos , Ácido Penicilânico/administração & dosagem
2.
Expert Opin Drug Metab Toxicol ; 15(11): 869-880, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31597049

RESUMO

Introduction: Cephalosporins are a major class of antibiotics, frequently used in children because of their remarkable antibacterial activity and excellent safety profile. Time above the minimal inhibitory concentration of the non-protein-bound fraction (fT>MIC) is the pharmacokinetic/pharmacodynamic parameter that correlates with the therapeutic efficacy. In the pediatric population, the inter-individual variability in cephalosporin pharmacokinetics is large because of maturational changes. However, the prescription of cephalosporins promotes emergence of Enterobacteriaceae producing broad-spectrum ß-lactamases.Areas covered: Here we describe in vitro activities and the main pharmacokinetic characteristics of cephalosporins in children. On the basis of these characteristics, we propose an estimation of the fT>MIC for each molecule as a tool to help optimize the use of cephalosporins. We also provide an inventory of the clinical use of cephalosporins and present prospects for the development of new molecules or associations to address the emergence of resistant strains.Expert opinion: Cephalosporins represent a heterogeneous group of antibiotics with various pharmacokinetics and in vitro antimicrobial activity that the clinician needs to master to optimize their use. However, their broad use plays a role in the emergence of broad-spectrum ß-lactamase-producing strains and must thus be restricted to probabilistic broad-spectrum therapy and situations without therapeutic alternatives.


Assuntos
Antibacterianos/administração & dosagem , Cefalosporinas/administração & dosagem , Animais , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Cefalosporinas/farmacocinética , Cefalosporinas/farmacologia , Criança , Desenvolvimento de Medicamentos , Farmacorresistência Bacteriana , Humanos , Testes de Sensibilidade Microbiana
3.
Med. clín (Ed. impr.) ; 153(8): 319-322, oct. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-185416

RESUMO

Antecedentes y objetivo: No hay datos relativos a los factores de riesgo asociados a la infección por Clostridium difficile (ICD) en los servicios de hospitalización domiciliaria (SHD) del sistema sanitario español. Pacientes y métodos: Estudio casos-controles. Los casos fueron pacientes ingresados en un SHD entre 1 de enero de 2011 y el 31 de diciembre de 2016, que desarrollaron ICD. Los controles procedían de la misma población, con sospecha clínica de ICD y toxina CD(-). Se analizaron 82 variables. Resultados: Fueron evaluados 17 casos y 95 controles, sin diferencias por sexo, edad o comorbilidad. Se registró diarrea en el 94% y 92%, y un porcentaje de exitus del 18% y 1%, respectivamente (p=0,001). La hemiplejia/paraplejia se asoció significativamente con la ICD (odds ratio [OR] ajustada=26,4; IC 95%: 2,9-235,6; p=0,003), mientras que la enfermedad respiratoria crónica y el uso de cefalosporinas presentaron una significación marginal (OR ajustadas de 2,9 [0,8-10,3] y 3,1 [0,8-11,3], ambas p=0,08). Conclusiones: Las acciones en el SHD frente a la ICD deberían incluir una reducción en el uso de antibióticos de riesgo -según lo observado, las cefalosporinas- especialmente ante ciertas comorbilidades, como una hemiplejia/tetraplejia o una enfermedad respiratoria crónica


Background and objective: There are no data related to the risk factors associated with CDI in a Hospital-Based Home Care Service (HBHCS) of the Spanish health system. Patients and methods: Case-control study. The cases were patients admitted to the HBHCS between 01/01/2011 and 31/12/2016 who developed CDI. The controls came from the same population, with suspected CDI and CD(-) toxin. We analysed 82 variables. Results: We analysed 17 cases and 95 controls, without differences in sex, age or comorbidity. Diarrhoea was noted in 94% and 92%, and a percentage of deaths of 18% and 1%, respectively (P=.001). The presence of hemiplegia/paraplegia (adjusted odds ratio [OR]=26.4, 95% CI 2.9-235.6, P=.003) showed a significant relationship with CDI, while chronic respiratory disease and the use of cephalosporins did so with marginal significance (adjusted OR=2.9, 95% CI 0.8-10.3 and 3.1, 95% CI 0.8-11.3, respectively, both P=.08). Conclusions: Actions in the HBHCS directed towards CDI should include a reduction in the use of high-risk antibiotics -according to our results, cephalosporins- especially in patients with specific comorbidities, such as hemiplegia/tetraplegia or a chronic respiratory disease


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Infecções Bacterianas/epidemiologia , Infecções por Clostridium/tratamento farmacológico , Serviços de Assistência Domiciliar , Cefalosporinas/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Pacientes Ambulatoriais , Fatores de Risco , Sistemas de Saúde , Espanha , Estudos de Casos e Controles , Razão de Chances , Diarreia/complicações , Doenças Respiratórias/complicações , Modelos Logísticos
4.
Rev Esp Quimioter ; 32 Suppl 3: 11-16, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31364336

RESUMO

Ceftobiprole shows many similar pharmacokinetic properties to other cephalosporins, except for not being orally bioactive, and that it is administered by IV infusion as the prodrug ceftobiprole medocaril, which is subsequently hydrolyzed in the blood into the active molecule. Distribution focus in extracellular fluid and active antibiotic concentration has been proven in different corporal tissues using dosing regimen of 500 mg intravenous infusion over 2 h every 8 h. Ceftobiprole is eliminated exclusively into the urine, thus the reason why dose adjustment is required for patients with moderate or severe renal impairment, or increased creatinine clearance. However, there is no need for dose adjustments related with other comorbidities and patients' conditions such as age, body weight. Although considering distribution features, molecular weight and dose fraction, increase dosing regimen might be necessary in patients using renal replacement therapy. The half-life of ceftobiprole is more than 3 h, allowing to easily reach optimal PK/PD parameters with the infusion time of 2 h, using the usual dosing regimen.


Assuntos
Antibacterianos/farmacocinética , Cefalosporinas/farmacocinética , Fatores Etários , Antibacterianos/administração & dosagem , Antibacterianos/urina , Área Sob a Curva , Cefalosporinas/administração & dosagem , Cefalosporinas/metabolismo , Cefalosporinas/urina , Creatinina/metabolismo , Estado Terminal , Matriz Extracelular/metabolismo , Meia-Vida , Humanos , Infusões Intravenosas , Rim/metabolismo , Método de Monte Carlo , Obesidade/metabolismo , Pró-Fármacos/administração & dosagem , Pró-Fármacos/metabolismo , Insuficiência Renal/metabolismo , Terapia de Substituição Renal
5.
Rev Esp Quimioter ; 32 Suppl 3: 17-23, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31364337

RESUMO

Ceftobiprole is a fifth-generation cephalosporin with potent antimicrobial activity against Gram positive and Gram-negative bacteria. It has been approved in major European countries for the treatment of community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP), excluding ventilator-associated pneumonia (VAP). Ceftobiprole is currently in a phase 3 clinical program for registration in the U.S. In 2015, it was designated as an infectious disease product qualified for the treatment of lung and skin infections by the FDA. The efficacy of ceftobiprole in pneumonia has been demonstrated in two-phase III clinical trials conducted in patients with CAP and HAP. The recommended dose in the adult with pneumonia is 500 mg every 8 h infused in 2 h; in case of renal failure, the regimen of administration must be adjusted according to the patient's renal function. It is not necessary to adjust the dose according to gender, age, body weight or liver failure. In case of hyperfiltration, an extension to 4 h infusion of the 500mg TID is required.


Assuntos
Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Antibacterianos/administração & dosagem , Antibacterianos/metabolismo , Cefalosporinas/administração & dosagem , Cefalosporinas/metabolismo , Ensaios Clínicos como Assunto , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Estado Terminal , Infecção Hospitalar/microbiologia , Esquema de Medicação , Humanos , Pneumonia Bacteriana/microbiologia , Insuficiência Renal/metabolismo
6.
J Zoo Wildl Med ; 50(2): 466-469, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31260216

RESUMO

Pharmacokinetics study of ceftiofur crystalline free acid (CCFA) was conducted in 14 adult captive smooth dogfish (Mustelus canis). A single dose of CCFA at 6.6 mg/kg was administered intramuscularly. Blood samples were collected prior to treatment and at 1, 2, 6, 12, 24, 32, 48, 72, 96, 120, 144, and 168 hr posttreatment. Naïve pooling of data from four sharks was used to generate the average plasma drug concentration at each time point. After concluding the study, additional blood samples were opportunistically collected from five randomly selected sharks at 1,920 hr. Plasma ceftiofur and desfuroylceftiofur metabolite concentrations were determined using reversed-phase high performance liquid chromatography (HPLC). Pharmacokinetic analysis was performed using a noncompartmental technique. Peak plasma concentration (Cmax) was 3.75 µg/ml with a time to Cmax (Tmax) of 96 hr. Ceftiofur plasma concentrations were maintained above 2 µg/ml for at least 168 hr and were still quantifiable at 1,920 hr.


Assuntos
Antibacterianos/farmacocinética , Cefalosporinas/farmacocinética , Tubarões/sangue , Animais , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Área Sob a Curva , Cefalosporinas/administração & dosagem , Cefalosporinas/sangue , Injeções Intramusculares
7.
Am J Health Syst Pharm ; 76(8): 501-504, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-31361864

RESUMO

PURPOSE: The safe and effective use of ceftolozane-tazobactam delivered via continuous infusion in a cystic fibrosis (CF) patient with reduced body weight and presumed augmented renal clearance is reported. SUMMARY: A 30-year-old woman with CF was admitted for acute pulmonary exacerbations with positive respiratory cultures for Pseudomonas aeruginosa and extended-spectrum ß-lactamase-producing Escherichia coli. Susceptibility testing confirmed multidrug resistance, and the patient was transitioned to ceftolozane-tazobactam for definitive therapy. A novel strategy of administering ceftolozane-tazobactam 6 g by continuous i.v. infusion over 24 hours was initiated during hospitalization and continued at discharge for a total of 10 days. Therapeutic drug monitoring over the first 36 hours of the continuous infusion confirmed adequate exposure. The patient had clinical resolution with return to baseline of pulmonary function tests and no noted adverse drug events. CONCLUSION: A continuous infusion regimen of ceftolozane-tazobactam was successfully used in a CF patient with augmented renal clearance.


Assuntos
Antibacterianos/administração & dosagem , Cefalosporinas/administração & dosagem , Fibrose Cística/tratamento farmacológico , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Pseudomonas/tratamento farmacológico , Tazobactam/administração & dosagem , Adulto , Fibrose Cística/complicações , Fibrose Cística/microbiologia , Esquema de Medicação , Monitoramento de Medicamentos , Farmacorresistência Bacteriana Múltipla , Escherichia coli/isolamento & purificação , Escherichia coli/fisiologia , Infecções por Escherichia coli/microbiologia , Feminino , Humanos , Infusões Intravenosas/métodos , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Pseudomonas aeruginosa/fisiologia , Resultado do Tratamento
8.
PLoS One ; 14(7): e0220068, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31329639

RESUMO

A pair-matched longitudinal study conducted on three dairy farms in the U.S. High-Plains explored the temporal effects of two-dose ceftiofur crystalline-free acid (CCFA) treatment for metritis on third-generation cephalosporin (3GC) resistance among enteric E. coli in Holstein-Friesian cows. The current 13-day slaughter withholding period does not account for rising populations of third-generation cephalosporin (3GC) resistant bacteria in feces of animals following CCFA treatment. A total of 124 matched-pairs of cows were enrolled in the study. Cows diagnosed with postpartum metritis received the product twice at the labeled dose of 6.6 mg/kg subcutaneously at the base of alternating ears. Untreated cows-absent clinical metritis-were matched on lactation number and calving date. Feces were collected per rectum on days 0 (baseline), 6, 16, 28, and 56. Environmental samples, from watering troughs as well as surface manure from fresh-cow, hospital, maternity, and milking pens, and from the compost pile were collected prior to the animal sample collection period. Historical data on metritis rates and CCFA use were compiled from herd records. On day 0, cows exhibited an overall mean difference of over 4 log10 colony forming units (CFU) comparing 3GC resistant E. coli to the general E. coli population. At the first eligible slaughter date, the difference declined to 3.31 log10 CFU among cows in the CCFA group (P<0.01 compared to control cows). Such differences were no longer observed between the treated and control groups by day 28. Results suggest a 13-day withholding period following the final treatment is insufficient to allow levels of 3GC resistant E. coli to return to baseline. This effect varied by farm and was dependent upon the starting level of resistance. A farm-specific extended slaughter-withholding period could reduce the microbial risk to food products at slaughter.


Assuntos
Antibacterianos/administração & dosagem , Doenças dos Bovinos/tratamento farmacológico , Cefalosporinas/administração & dosagem , Farmacorresistência Bacteriana , Endometrite/tratamento farmacológico , Escherichia coli Extraintestinal Patogênica/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bovinos , Doenças dos Bovinos/microbiologia , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , Esquema de Medicação , Endometrite/microbiologia , Endometrite/veterinária , Escherichia coli Extraintestinal Patogênica/patogenicidade , Feminino
9.
Intern Med ; 58(19): 2891-2894, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31243204

RESUMO

Pivoxil-containing cephalosporins can result in symptomatic hypocarnitinemia in children. We herein report a case of an 85-year-old man at risk of carnitine deficiency who developed relapsing symptomatic hypoglycemia after treatment with cefcapene pivoxil for urinary tract infection. On admission, laboratory tests showed low blood carnitine concentrations with low normal blood ketone levels. The patient was successfully treated by the oral administration of levocarnitine and dietary modification, including aggressive consumption of meat and dairy products, and remained symptom-free for nine months after the correction of carnitine concentrations. Healthcare providers should be cautious when prescribing pivoxil-containing antimicrobials to patients at high risk of hypocarnitinemia.


Assuntos
Cardiomiopatias/induzido quimicamente , Carnitina/deficiência , Cefalosporinas/efeitos adversos , Hiperamonemia/induzido quimicamente , Hipoglicemia/induzido quimicamente , Doenças Musculares/induzido quimicamente , Administração Oral , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Cardiomiopatias/sangue , Cardiomiopatias/complicações , Carnitina/sangue , Cefalosporinas/administração & dosagem , Humanos , Hiperamonemia/sangue , Hiperamonemia/complicações , Hipoglicemia/sangue , Hipoglicemia/complicações , Masculino , Doenças Musculares/sangue , Doenças Musculares/complicações , Recidiva , Infecções Urinárias/tratamento farmacológico
10.
Aust Vet J ; 97(7): 233-234, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31236927

RESUMO

A clostridial 'syndrome' in suckling and weaner pigs, with risk factors of high injectable ceftiofur use and poor hygiene, presented an opportunity to engage in management change to improve pig health and reduce ceftiofur use on four farms. Management changes included all-in-all-out pig flow, batch disinfection with biofilm control, reduced protein starter diets, appropriate stocking density and the use of an anti-clostridial probiotic. Assessment of the program was obtained from a questionnaire. The health and production changes were positive across all farms and were associated with reduced use of antibiotics, together with cost and labour savings. Provided there is a good relationship between a committed, competent veterinarian, and a committed, competent manager, change management programs can be successfully implemented over 6-12 months.


Assuntos
Criação de Animais Domésticos/métodos , Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Doenças dos Suínos/prevenção & controle , Ração Animal/análise , Animais , Antibacterianos/administração & dosagem , Cefalosporinas/administração & dosagem , Clostridium/efeitos dos fármacos , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/prevenção & controle , Infecções por Clostridium/veterinária , Dieta/veterinária , Suínos , Doenças dos Suínos/diagnóstico , Doenças dos Suínos/microbiologia
11.
Cochrane Database Syst Rev ; 6: CD012902, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31163089

RESUMO

BACKGROUND: The main complication of cerebrospinal fluid (CSF) shunt surgery is shunt infection. Prevention of these shunt infections consists of the perioperative use of antibiotics that can be administered in five different ways: orally; intravenously; intrathecally; topically; and via the implantation of antibiotic-impregnated shunt catheters. OBJECTIVES: To determine the effect of different routes of antibiotic prophylaxis (i.e. oral, intravenous, intrathecal, topical and via antibiotic-impregnated shunt catheters) on CSF-shunt infections in persons treated for hydrocephalus using internalised CSF shunts. SEARCH METHODS: We conducted a systematic electronic search without restrictions on language, date or publication type. We performed the search on the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE and Embase, with the help of the Information Specialist of the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group. The search was performed in January 2018. SELECTION CRITERIA: All randomised and quasi-randomised controlled trials that studied the effect of antibiotic prophylaxis, in any dose or administration route, for the prevention of CSF-shunt infection in patients that were treated with an internal cerebrospinal fluid shunt. Patients with external shunts were not eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from included studies. We resolved disagreements by discussion or by referral to an independent researcher within our department when necessary. Analyses were also performed by at least two authors. MAIN RESULTS: We included a total of 11 small randomised controlled trials, containing 1109 participants, in this systematic review. Three of these studies included solely children, and the remaining eight included participants of all ages. Most studies were limited to the evaluation of ventriculoperitoneal shunts. However, five studies included participants with ventriculoatrial shunts, of which one study contained four participants with a subduroperitoneal shunt. We judged four out of 11 (36%) trials at unclear risk of bias, while the remaining seven trials (64%) scored high risk of bias in one or more of the components assessed.We analysed all included studies in order to estimate the effect of antibiotic prophylaxis on the proportion of shunt infections regardless of administration route. Although the quality of evidence in these studies was low, there may be a positive effect of antibiotic prophylaxis on the number of participants who had shunt infections (RR 0.55, 95% CI 0.36 to 0.84), meaning a 55% reduction in the number of participants who had shunt infection compared with standard care or placebo.Within the different administration routes, only within intravenous administration of antibiotic prophylaxis there may be evidence of an effect on the risk of shunt infections (RR 0.55, 95% CI 0.33 to 0.90). However, this was the only route that contained more than two studies (8 studies; 797 participants). Evidence was uncertain for both, intrathecal administration of antibiotics (RR 0.73, 95% CI 0.28 to 1.93, 2 studies; 797 participants; low quality evidence) and antibiotic impregnated catheters (RR 0.36, 95% CI 0.10 to 1.24, 1 study; 110 participants; very low quality evidence) AUTHORS' CONCLUSIONS: Antibiotic prophylaxis may have a positive effect on lowering the number of participants who had shunt infections. However, the quality of included studies was low and the effect is not consistent within the different routes of administration that have been analysed. It is therefore uncertain whether prevention of shunt infection varies by different antibiotic agents, different administration routes, timing and doses; or by characteristics of patients, e.g. children and adults. The results of the review should be seen as hypothesis-generating rather than definitive, and the results should be confirmed in adequately powered trials or large multicentre studies in order to obtain high-quality evidence in the field of ventricular shunt infection prevention.


Assuntos
Antibacterianos/administração & dosagem , Antibioticoprofilaxia/métodos , Derivações do Líquido Cefalorraquidiano/efeitos adversos , Infecções Relacionadas à Prótese/prevenção & controle , Cefalosporinas/administração & dosagem , Vias de Administração de Medicamentos , Gentamicinas/administração & dosagem , Humanos , Penicilinas/administração & dosagem , Infecções Relacionadas à Prótese/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Vancomicina/administração & dosagem
12.
Am J Vet Res ; 80(6): 539-546, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31140842

RESUMO

OBJECTIVE: To assess whether IV regional limb perfusion (IVRLP) and intraosseous regional limb perfusion (IORLP) of ceftiofur sodium resulted in clinically relevant drug concentrations in the synovial fluid of the tibiotarsal-tarsometatarsal joint of chickens (ie, an avian model) and to determine whether one of those techniques was superior to the other. ANIMALS: 12 healthy adult hens. PROCEDURES: Birds were randomly assigned to receive ceftiofur sodium (2 mg/kg) by the IVRLP (n = 4), IORLP (4), or IM (control; 4) route once daily for 6 consecutive days. Blood and tibiotarsal-tarsometatarsal synovial fluid samples were collected 15 minutes after ceftiofur administration on predetermined days for quantification of ceftiofur concentration. Plasma and synovial fluid ceftiofur concentrations were compared among the 3 groups. RESULTS: All 4 birds in the IVRLP group developed mild to moderate bruising around the injection site, but this bruising did not prohibit completion of the prescribed treatment regimen. No adverse effects were observed in any of the other birds. The mean plasma and synovial fluid ceftiofur concentrations exceeded the therapeutic threshold for most common bacterial pathogens (> 1.0 µg/mL) at all sample acquisition times for all 3 groups. The mean synovial fluid ceftiofur concentration for the IVRLP group was significantly greater than that for the IORLP and control groups at all sample acquisition times. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that IVRLP may be a safe and effective technique for antimicrobial administration to birds with joint infections, contaminated wounds, pododermatitis, and other musculoskeletal infections of the distal aspect of a limb.


Assuntos
Antibacterianos/administração & dosagem , Cefalosporinas/administração & dosagem , Galinhas/metabolismo , Administração Intravenosa/veterinária , Animais , Antibacterianos/farmacocinética , Cefalosporinas/farmacocinética , Feminino , Membro Anterior , Perfusão/veterinária , Distribuição Aleatória , Líquido Sinovial/metabolismo
13.
J Infect Chemother ; 25(9): 702-707, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30982729

RESUMO

Oral antibiotic therapy for patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) usually involves an aminopenicillin with clavulanic acid, a macrolide, or a quinolone. To date, however, the clinical efficacy and safety of the oral cephalosporin cefditoren pivoxil has not been evaluated in Japanese patients with acute exacerbations of COPD. We conducted a prospective, multicenter, single arm, interventional study from January 2013 to March 2017 to determine the efficacy and safety of oral administration of 200 mg cefditoren pivoxil three times daily for 7 days in a cohort of 29 eligible patients from 15 hospitals. The mean age (SD) of participants was 73.1 (8.1) years and 28 had a smoking history (the mean [SD] of smoking index, 1426.7 [931.7]). The primary efficacy endpoint was clinical response (cure rate) at test of cure, which was set at 5-10 days after treatment ceased. Of the 23 patients finally analyzed, cure was achieved in 15 (65.2%), while 8 (34.8%) remained uncured. Previous experience of acute exacerbations significantly affected the cure rate: none of the three patients who had at least two prior exacerbations were cured, while 15 of the 20 patients with one or fewer prior exacerbations were cured (p = 0.032). The microbiological eradication rate was 88.9% at test of cure. During treatment, mild pneumonia was reported as an adverse event in one patient (3.4%) but resolved within 10 days of onset. We conclude that cefditoren pivoxil represents a viable alternative for antibiotic therapy in patients with few prior exacerbations.


Assuntos
Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração Oral , Adulto , Idoso , Antibacterianos/administração & dosagem , Gestão de Antimicrobianos , Cefalosporinas/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
15.
Surg Today ; 49(10): 859-869, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31030266

RESUMO

PURPOSES: This study compared the effectiveness of 1-day vs 3-days antibiotic regimen to prevent surgical site infection (SSI) in open liver resection. METHOD: We performed a randomized controlled non-inferiority trial in 480 patients at 39 hospitals across Japan (registered as UMIN000002852). Patients with hepatocellular carcinoma scheduled to undergo resection were randomly assigned to receive either a 1-day regimen for antimicrobial prophylaxis, or a 3-day regimen. The primary endpoint was the incidence of SSI. RESULTS: Among 480 randomized patients, 232 assigned to the 1-day regimen and 235 to the 3-day regimen were included in the full analysis set. Baseline characteristics of the two groups were well balanced. SSI was diagnosed in 22 patients (9.5%) in the 1-day group vs 23 patients (9.8%) in the 3-day group (difference, - 0.30; 90% CI - 4.80 to 4.19% [95% CI - 5.66% to 5.05%]; one-sided P = 0.001 for non-inferiority), meeting the non-inferiority hypothesis. In both groups, remote site infection (16 [6.9%] vs 22 [9.4%], P ˂ 0.001 for non-inferiority) and drain-related infection (5 [2.2%] vs 4 [1.7%], P ˂ 0.001 for non-inferiority) were comparable. CONCLUSION: To prevent SSI in liver cancer surgery, a 1-day regimen of flomoxef sodium is recommended for antimicrobial prophylaxis because of confirming the non-inferiority to longer usage.


Assuntos
Antibacterianos/administração & dosagem , Antibioticoprofilaxia , Carcinoma Hepatocelular/cirurgia , Cefalosporinas/administração & dosagem , Neoplasias Hepáticas/cirurgia , Infecção da Ferida Cirúrgica/prevenção & controle , Idoso , Feminino , Hepatectomia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Infecção da Ferida Cirúrgica/epidemiologia , Fatores de Tempo
16.
J Dairy Sci ; 102(6): 5438-5457, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30981475

RESUMO

The objective of this negatively controlled, randomized clinical trial was to examine clinical outcomes of 2-d or 8-d treatment using an approved intramammary (IMM) product containing ceftiofur hydrochloride compared with no antimicrobial treatment of nonsevere, gram-negative cases of clinical mastitis (CM). Additionally, we contrasted clinical outcomes of cases caused by Escherichia coli (n = 56) or Klebsiella pneumoniae (n = 54). Cases (n = 168) of nonsevere (abnormal milk or abnormal milk and udder) CM were randomly assigned to receive 2 d (n = 56) or 8 d (n = 56) of IMM ceftiofur or assigned to a negative control group (n = 56). At enrollment, quarter milk samples were collected and used for on-farm culture, somatic cell count (SCC), and confirmatory microbiological analysis. Quarter milk samples were collected weekly from 7 to 28 d after enrollment for microbiological and SCC analysis. Clinical outcomes were followed for 90 d or until the end of lactation (follow-up period, FUP). Overall, no significant differences in quarter-level recurrence of CM (32% for negative control, 34% for the 2-d treatment, and 32% for the 8-d treatment), culling (18% for negative control, 12% for 2-d treatment, and 11% for 8-d treatment), voluntary dry-off of affected quarters (20% for negative control, 30% for 2-d treatment, and 27% for 8-d treatment), days until return to normal milk (4.2 days for negative control, 4.8 days for 2-d treatment, 4.5 days for 8-d treatment), weekly quarter-SCC during the FUP (6.1, 6.3, and 6.0 log10SCC for the negative control, 2-d, and 8-d treatments, respectively), or daily milk yield during the FUP (37.1, 36.3, and 37.6 kg/cow per day for the negative control, 2-d, and 8-d treatments, respectively) were observed among experimental groups. Days of discarded milk were greater for cows assigned to 8-d IMM ceftiofur (11.1 d) than for cows assigned to 2-d (6.9 d) or cows assigned to negative control (5.6 d). Bacteriological cure (BC) at 14 and 21 d after enrollment was greater in cows assigned to 8-d (89%) and 2-d (84%) treatment than in cows assigned to negative control (67%), but this outcome was confounded by pathogen. For CM caused by Kleb. pneumoniae, BC was greater for quarters assigned to receive treatment (combined 2-d and 8-d groups; 74% BC) than for quarters assigned to negative control (18%). In contrast, no differences in BC were observed for CM caused by E. coli (97-98%). Culling and voluntary dry-off of affected quarters were significantly greater for cows with quarters affected by Kleb. pneumoniae (22% culled, 39% voluntary dry-off of quarters) than for cows with quarters affected with E. coli (7% culled, 11% voluntary dry-off of quarters). Overall, use of IMM ceftiofur did not result in improvement of most clinical outcomes, but differences between E. coli and Kleb. pneumoniae were evident. In contrast to E. coli, Kleb. pneumoniae caused chronic intramammary infection and induced worse clinical outcomes. Intramammary antibiotic treatment of most mild and moderate cases of CM caused by E. coli is not necessary, but more research is needed to identify which quarters affected by Kleb. pneumoniae may benefit from antimicrobial therapy.


Assuntos
Antibacterianos/administração & dosagem , Cefalosporinas/administração & dosagem , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Klebsiella/tratamento farmacológico , Mastite Bovina/tratamento farmacológico , Leite/microbiologia , Animais , Bovinos , Indústria de Laticínios , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/microbiologia , Fazendas , Feminino , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Lactação , Glândulas Mamárias Animais/microbiologia , Mastite Bovina/microbiologia , Distribuição Aleatória
17.
Pharm Res ; 36(5): 74, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30923922

RESUMO

PURPOSE: This study aimed to compare in vivo activity between cefquinome (CEQ)-loaded poly lactic-co-glycolic acid (PLGA) microspheres (CEQ-PLGA-MS) and CEQ injection (CEQ-INJ) against Klebsiella pneumonia in a rat lung infection model. METHODS: Forty-eight rats were divided into control group (sham operated without infection and drug treatment), Klebsiella pneumonia model group (KPD + Saline), CEQ-PLGA-MS and CEQ-INJ therapy groups (KPD + CEQ-PLGA-MS and KPD + INJ, respectively). In the KPD + Saline group, rats were infected with Klebsiella pneumonia ATCC 10031. In the KPD + CEQ-PLGA-MS and KPD + INJ groups, infected rats were intravenously injected with 12.5 mg/kg body weight CEQ-PLGA-MS and CEQ-INJ, respectively. RESULTS: Compared to CEQ-INJ treatment group, CEQ-PLGA-MS treatment further decreased the number of bacteria colonies (decreased to 1.94 lg CFU/g) in lung tissues and the levels of inflammatory cytokine including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-4 (p < 0.05 or p < 0.01) in bronchoalveolar lavage fluid at 48 h. Consistently, a significant decreases of scores of inflammation severity were showed at 48 h in the KPD + CEQ-PLGA-MS treatment group, compared to the KPD + CEQ-INJ treatment group. CONCLUSION: Our results reveal that CEQ-PLGA-MS has the better therapeutic effect than CEQ-INJ for Klebsiella pneumonia lung infections in rats. The vehicle of CEQ-PLGA-MS as the promising alternatives to control the lung infections with the important pathogens.


Assuntos
Antibacterianos/administração & dosagem , Cefalosporinas/administração & dosagem , Sistemas de Liberação de Medicamentos , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Pneumonia Bacteriana/tratamento farmacológico , Animais , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Cefalosporinas/farmacocinética , Cefalosporinas/uso terapêutico , Citocinas/análise , Modelos Animais de Doenças , Portadores de Fármacos/química , Composição de Medicamentos , Inflamação , Injeções Intravenosas , Infecções por Klebsiella/imunologia , Infecções por Klebsiella/microbiologia , Masculino , Microesferas , Pneumonia Bacteriana/imunologia , Pneumonia Bacteriana/microbiologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ratos Wistar
18.
Int J Antimicrob Agents ; 53(6): 830-837, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30716446

RESUMO

This post-hoc analysis compared the pharmacokinetics and clinical outcomes of ceftaroline fosamil 600 mg every 12 (q12h) versus every 8 hours (q8h) in patients with acute bacterial skin and skin-structure infection (ABSSSI) and signs of sepsis. Clinical outcomes at test-of-cure in patients with ABSSSI and systemic inflammatory signs/systemic inflammatory response syndrome (SIRS) as well as ceftaroline minimum inhibitory concentrations (MICs) against baseline pathogens were compared between the COVERS trial (ceftaroline fosamil 600 mg q8h, 2-h infusion) and the CANVAS 1 and 2 trials (ceftaroline fosamil 600 mg q12h, 1-h infusion). Ceftaroline exposure among patients in COVERS with or without markers of sepsis was compared using population pharmacokinetic modelling. In COVERS, 62% (312/506) and 41% (208/506) of ceftaroline fosamil-treated patients had ≥1 systemic inflammatory sign or SIRS, respectively, compared with 55% (378/693) and 22% (155/693), respectively, in the CANVAS trials. Clinical cure rates for the modified intent-to-treat population in COVERS and CANVAS were similar for ceftaroline fosamil-treated patients with ≥1 sign of sepsis [82% (255/312) and 85% (335/394)] and for those with SIRS [84% (168/199) and 85% (131/155)]. Ceftaroline MIC distributions were similar across trials. Sepsis did not affect predicted individual steady-state ceftaroline exposure. Clinical cure rates in patients with ≥1 systemic inflammatory sign or SIRS were comparable for both ceftaroline fosamil dosage regimens. Pathogen susceptibilities to ceftaroline were similar across trials. Ceftaroline exposure was not affected by disease severity. Ceftaroline fosamil 600 mg q12h is a robust dosage regimen for most ABSSSI patients with sepsis [ClinicalTrials.gov ID: NCT01499277, NCT00424190, NCT00423657].


Assuntos
Antibacterianos/administração & dosagem , Cefalosporinas/administração & dosagem , Dermatopatias Bacterianas/complicações , Dermatopatias Bacterianas/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacocinética , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Cefalosporinas/farmacocinética , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Dermatopatias Bacterianas/patologia , Síndrome de Resposta Inflamatória Sistêmica/patologia , Resultado do Tratamento
19.
J Dairy Sci ; 102(4): 3321-3338, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30738678

RESUMO

The objective of this negatively controlled randomized clinical trial was to compare clinical outcomes of 5-d intramammary treatment using ceftiofur hydrochloride and no antimicrobial treatment of nonsevere culture-negative cases of clinical mastitis (CM). A total of 121 cases of nonsevere (abnormal milk or abnormal milk and udder) culture-negative CM were randomly assigned to either treatment (n = 62) or negative control (n = 59) groups. Quarters assigned to treatment received 1 daily intramammary infusion with an approved commercially available product containing ceftiofur hydrochloride for 5 d. Quarters assigned to the negative control group did not receive any interventions. Enrolled cows were followed for 90 d or until the end of lactation. At enrollment, milk samples from the affected quarter were used for on-farm culture, somatic cell count (SCC) analysis, and further microbiological analysis. During the follow-up period, milk samples were collected for microbiological analysis and SCC analysis. No significant differences between treatment and negative control groups were identified for treatment failure (5% for treatment vs. 10% for negative control, n = 121), quarter-level CM recurrence (8 vs. 5%, n = 91), intramammary infection at 14 or 28 d after enrollment (13 vs. 26%, n = 86), days until clinical cure (4.2 vs. 4.0 d), days to culling (48.3 vs. 36.8 d), daily milk production (43.3 vs. 43.6 kg/cow per day), or weekly quarter SCC (5.5 vs. 5.4 log10 SCC). Days of milk discard were greater for cows assigned to the treatment group (8.5 d) compared with cows assigned to the negative control group (5.6 d). During the follow-up period, cases in the treatment group had a 50% risk reduction in IMI compared with cases in the negative control group. Irrespective of group, negative outcomes such as quarter-level CM recurrence (12%), treatment failure (12%), and culling (5%) occurred infrequently in nonsevere culture-negative cases of CM. Use of intramammary ceftiofur for treatment of nonsevere culture-negative cases of CM did not improve any economically relevant clinical outcome such as culling, milk production, or SCC.


Assuntos
Antibacterianos/administração & dosagem , Cefalosporinas/administração & dosagem , Glândulas Mamárias Animais/efeitos dos fármacos , Mastite Bovina/tratamento farmacológico , Animais , Bovinos , Contagem de Células , Feminino , Lactação/efeitos dos fármacos , Glândulas Mamárias Animais/metabolismo , Mastite Bovina/fisiopatologia , Leite/metabolismo , Distribuição Aleatória
20.
Aust Vet J ; 97(3): 75-80, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30809814

RESUMO

BACKGROUND: Cefovecin has a long duration of antibiotic activity in cats and dogs, somewhat attributable to its high plasma protein binding. AIMS: To determine the cefovecin binding to plasma proteins in vitro in selected Australian marsupials and to quantify the change in cetovecin concentration over time following subcutaneous injection in koalas. METHODS AND RESULTS: Various cefovecin concentrations were incubated with plasma and quantified using HPLC. The median (range) bound percentages when 10 µg/mL of cefovecin was incubated with plasma were 11.1 (4.1-20.4) in the plasma of the Tasmanian devil, 12.7 (5.8-17.3) in the koala, 18.9 (14.6-38.0) in the eastern grey kangaroo, 16.9 (15.7-30.2) in the common brush-tailed possum, 37.6 (25.3-42.3) in the eastern ring-tailed possum and 36.4 (35.0-38.3) in the red kangaroo, suggesting that cefovecin may have a shorter duration of action in these species than in cats and dogs. Cefovecin binding to plasma proteins in thawed, frozen equine plasma was also undertaken for assay quality control and the median (range) plasma protein binding (at 10 µg/mL) was 95.6% (94.9-96.6%). Cefovecin was also administered to six koalas at 8 mg/kg subcutaneously and serial blood samples were collected at 3, 6, 24, 48, 72, 96 h thereafter. Cefovecin plasma concentrations were not quantifiable in four koalas and in the other two, the mean plasma concentration at t = 3 h was 1.04 ± 0.01 µg/mL. CONCLUSION: Because of the limited pharmacokinetic data generated, no further pharmacokinetic analysis was performed; however, a single injected bolus of cefovecin is likely to have a short duration of action in koalas (hours, rather than days).


Assuntos
Antibacterianos/metabolismo , Proteínas Sanguíneas/metabolismo , Cefalosporinas/metabolismo , Marsupiais/sangue , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Austrália , Cefalosporinas/administração & dosagem , Cefalosporinas/farmacocinética , Cromatografia Líquida de Alta Pressão/veterinária , Feminino , Técnicas In Vitro , Injeções Subcutâneas/veterinária , Masculino , Marsupiais/metabolismo , Phascolarctidae/sangue , Phascolarctidae/metabolismo
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