Development and validation of a method for quantitation of cefepime/avibactam in M-H broth: application to antibacterial activity using in vitro PK/PD Model / 中国临床药理学与治疗学

AIM: To establish a method for quantitation of cefepime and avibactam in M-H broth, and applicated in the in vitro dynamic PK/PD model. METHODS: The cefepime was also determined using the high-performance liquid chromatography method (HPLC), the avibactam was also determined using the liquid chromatography-mass spectrometry (LC-MS/MS), an in vitro dynamic PK/PD model was established to study the PK/PD relationship of cefepime/avibactam against carbapenem resistant Klebsiella pneumoniae (CRKP). RESULTS: The linear ranges of cefepime and avibactam were good at (0.5-20) and (0.1-25) μg/mL (r=0.999), and the lower limit concentrations were 0.5 and 0.1 μg/mL. The extraction recoveries of cefepime and avibactam in M-H broth were 88.0%-101.7% and 90.9%-95.2%, the relative standard deviation of intra-day precision and inter-day precision were less than 5.2%. The concentration-time curves were well simulated by the PK/PD model. All observed concentrations in each experiment were in the range of 20% of the targeted values. For the CRKP of MIC=8 μg/mL and MIC=16 μg/mL, the colony decreased to 2.783Log10 CFU/mL and 1.325Log10 CFU/mL at the cefepime/avibactam 2.5 g q8 h administration after 24 h. CONCLUSION: The determination method of cefepime and avibactam in broth established in this study has high sensitivity and good stability. For the CRKP with MIC≤8 μg/mL,cefepime/avibactam showed that good anti-CRKP activity under routine administration in vitro dynamic PK/PD model.

Cefepime/tazobactam as a new treatment option for multidrug resistant gram negative bacilli

Background: Every time an antibiotic is used, whether appropriately or not, the probability of the development and spread of antibiotic resistant bacteria is increased. Thus, multidrug resistant bacteria particularly ESBL (Extended spectrum β­lactamase), Amp C and carbapenemases producing gram negative bacilli have emerged as a major health problem all over the world. Considering new treatment options as a carbapenems sparing and resistance prevention modality, this study was aimed to know the in vitro susceptibility pattern of Cefepime/Tazobactam (CPM/TZ) in comparison to other β-Lactam/ β-Lactamase inhibitors (BL/BLI) and carbapenems against GNB.Methods: A prospective study was conducted on all clinical samples received for a period of about 1 year. Identification and susceptibility of all isolates was done by Vitek 2 Compact system. Susceptibility of CPM/ TZ was done by disc diffusion method on the basis of CLSI guidelines. Both fermenters (E. coli and Klebsiella pneumoniae) and non-fermenters (Acintobacter baumanii and Pseudomonas aeruginosa) were included in the study.Results: Out of 550 GNB isolates the most common was E. coli (61.8%), Acintobacter baumanii (16%), Klebsiella pneumoniae (14.9%) and Pseudomonas aeruginosa (7.3%). Cefepime/tazobactam had a much higher susceptibility of 68% compared to cefepime (28%). Among the BL/BLI combinations tested cefepime/tazobactam (68%) showed the maximum percentage of susceptibility followed by cefoperazone/sulbactam (61.5%) and piperacillin/tazobactam (57.6%). Amongst all GNB isolates cefepime/tazobactam (68%) sensitivity was very much comparable to imipenem (71.8%) and meropenem (69.6%).Conclusions: CPM/TZ exhibited the best in vitro activity in comparison to the other BL/BLI. This new combination of cefepime/tazobactam appears to be a promising alternative therapeutic option to carbapenems. Clinical studies are needed to confirm this in vitro study result.

Neutropenia asociada al uso de cefepime en pacientes pediátricos con fibrosis quística / Neutropenia associated with the use of cefepime in pediatric patients with cystic fibrosis

Resumen Las exacerbaciones pulmonares de causa infecciosa son una de las mayores complicaciones en los pacientes con fibrosis quística (FQ). Estas se asocian a un progresivo aumento en la morbilidad y mortalidad. El tratamiento antimicrobiano se realiza dependiendo del microorganismo aislado. Con frecuencia se utilizan antimicrobianos β-lactámicos, los cuales no están exentos de reacciones adversas. A continuación, se describen dos casos de neutropenia tras el uso prolongado de cefepime en pacientes con FQ.

Pulmonary exacerbations of infectious cause are one of the major complications in patients with cystic fibrosis (CF). These are associated with a progressive increase in morbidity and mortality. The treatment depending on the isolated microorganism. The β-lactam antibiotics are generally used which are not exempt from adverse reactions. Next, two report of neutropenia cases are described after prolonged use of cefepime in CF patients.

Cefepime Induced Encephalopathy Mimicking Acute Stroke

Cefepime is a fourth-generation cephalosporin, developed in 1994, and is well known for its adverse effects. In 2002, the Food and Drug Administration adjusted the labeling to account for increased risk of seizures, encephalopathy and myoclonus, especially in the setting of renal impairment. Here we present a case of an 86-year-old female, undergoing Cefepime treatment, with encephalopathy mimicking acute stroke.

Stability indicating RP-HPLC method development and validation of cefepime and amikacin in pure and pharmaceutical dosage forms

A simple, accurate, isocratic stability indicating RP-HPLC method was developed for the determination of cefepime and amikacin in Pure and its pharmaceutical formulations. The method consists of methanol: acetonitrile:acetate buffer 75:20:05 (v/v) mobile phase at pH 5.1 with C18 column as stationary phase. The flow rate and detection wave length were 1.0 mL/min and 212 nm respectively. The linearity range for the method was found to be 2.5-25 µg/mL for amikacin and 10-100 µg/mL cefepime respectively. The developed method was validated as per ICH guidelines and the results of all the validation parameters were well within their acceptance values. Also the forced degradation studies were conducted with standard drugs. Degradation products formed during the different stress conditions were separated from both drugs. This validated method was applied for the simultaneous estimation of cefepime and amikacin in commercially available formulation sample.

A meta-analysis of piperacillin/tazobactam versus cefepime treatment in cancer patients with febrile neutropenia / Uma meta análise de piperacilina/tazobactam versus tratamento com cefepima em pacientes oncológicos com neutropenia febril

Febrile neutropenia (FN) causes a major threat to cancer patients after chemotherapy. Broadspectrum antibiotic treatment is a well-established practice for febrile neutropenia. Piperacillin/Tazobactam (P/T) is the frequently used antibiotic in most of FN cases, whereas the use of cefepime remains unclear regarding its potential risk. However, little systematic analysis has been conducted about comparison between these two drugs. Thus, we undertook this meta-analysis to compare these two monotherapies for febrile neutropenia. Through searching Pubmed, Google scholar, Medline databases, EMBASE, OvidSP, ScienceDirect, Web of science, and China Journal Net (CJN) databases, we used the keywords "(Piperacillin/Tazobactam AND cefepime) AND (febrile neutropenia) AND (cancer or tumor)". Only studies with randomized controlled trials were included in the meta-analysis. We screened out a total number of seven clinical trials. This meta-analysis supported that P/T treatment was superior to cefepime treatment based on the average OR comparison, without statistical significance (OR = 1.27, 95% confidence interval = 0.98 to 1.64, p = 0.07). We further divided the seven studies into two subgroups based on age and treatment time. The young group (age <= 19) showed no significant difference (OR = 1.10, p = 0.65). While the old group (age > 19) showed that P/T treatment was better than cefepime with statistical difference (OR = 1.44, p = 0.05). The short-term group (time <= 3 ds) showed P/T treatment was better than cefepime with statistical difference (OR = 1.40, p = 0.05). While in the long-term group (time > 5 ds), there was no significant difference between P/T and cefepime therapy (OR = 1.06, p = 0.79) Asymmetry in Funnel plots indicated no publication bias (CHI2 = 1.47, I2=0%, and p-value = 0.96) in this meta-analysis. It would be a good clinical trial to use P/T treatment to cure FN in cancer patients compared with cefepime treatment, especially in adult patients or patients with a short-term treatment period. This meta-analysis is practically important during antibiotic treatment in FN management.

A Neutropenia Febril (NF) apresenta-se como uma grande ameaça aos pacientes oncológicos após a quimioterapia. O tratamento antibiótico de amplo espectro é uma prática bem estabelecida para a neutropenia febril. Piperacilina/tazobactam (P/T) é o antibiótico frequentemente na maioria dos casos de NF, enquanto que o uso de cefepima permanece pouco claro em relação ao seu potencial risco. No entanto, pouca análise sistemática foi feita sobre a comparação entre esses dois fármacos. Assim, nós realizamos esta meta-análise para comparar estas duas monoterapias para a neutropenia febril. Através da pesquisa na Pubmed, Google Scholar, nas bases de dados da Medline, EMBASE, OvidSP, ScienceDirect, Web of science e nas bases de dados do China Journal Net (CJN), nós usamos as palavras-chave "(Piperacillin/Tazobactam AND cefepime) AND (febrile neutropenia) AND (cancer or tumor)". Apenas estudos com ensaios clínicos randomizados foram incluídos na meta-análise. Nós selecionamos um número total de sete ensaios clínicos. Esta meta-análise suportou que o tratamento com P/T foi superior ao tratamento com cefepima baseado na média da comparação OU (average OR comparision, em inglês), sem significância estatística (OR = 1.27, 95% confidence interval = 0.98 to 1.64, p = 0.07). Posteriormente, nós dividimos os sete estudos em dois subgrupos baseados na idade e no tempo de tratamento. O grupo jovem (idade <= 19) não mostrou uma diferença significativa (OR = 1.10, p = 0.65). Enquanto que o grupo mais velho (idade > 19) mostrou que o tratamento com P/T foi melhor do que o com cefepima com diferença estatística (OR = 1.44, p = 0.05). O grupo de curto prazo (tempo <= 3 ds*) mostrou que o tratamento com P/T foi melhor do que o com cefepima com diferença estatística (OR = 1.40, p = 0.05). Enquanto isso, no grupo de longo termo (tempo > 5 ds) não houve diferença significativa entre as terapias com P/T e Cefepima (OR = 1.06, p = 0.79). A assimetria nos gráficos de funil (funnel plots, em inglês) não indicaram viés de publicação (CHI2 = 1.47, I2=0%, and pvalue = 0.96) nesta meta-análise. Seria um bom ensaio clínico utilizar o tratamento P/T para curar NF em pacientes oncológicos comparados com o tratamento com cefepima, especialmente em pacientes adultos ou pacientes submetidos a um tratamento de curto prazo. Esta meta-análise é importante na prática durante o tratamento com antibióticos na administração de NF.

Clinical efficacy of cefepime in treating acute infection after chemotherapy / 中国基层医药

Objective To study the efficacy and adverse reactions of different kinds of antibiotics in the treatment of patients with acute leukemia after chemotherapy.Methods 112 cases with acute leukemia after chemo-therapy and infected were selected as the research subjects,and were randomly divided into the study group and the control group,56 cases in each group,Two groups of patients were intravenously injected amikacin sulfate,control group was intravenously injected ceftazidime and study group was given cefepime,two groups of patients were treated for 7 days.The clinical efficacy,the defervescence time,C -reactive protein (CRP)level,peripheral blood neutro-philic granulocyte (ANA)distribution levels and adverse reactions were observed.Results In the control group,the total effective rate was 83.9%,which of the study group was 94.6%,the difference between the two groups was statis-tically significant (χ2 =4.92,P =0.02).The normal rate of ANC in the study group was significantly higher than the control group (χ2 =6.62,P =0.01).The average defervescence time of the control group was (3.9 ±0.8)d,which of the study group was (2.6 ±0.8)d,there was significant difference between the two groups (t =8.44,P =0.00);CRP level of the study group after treatment was (21.18 ±4.07)mg/L,which was significantly lower than (37.27 ± 5.32)mg/L of the control group,with significant difference between the two groups (t =7.71,P =0.00).The incidence rate of adverse reaction of study group was 5.3%,which was significantly lower than 19.6% in the controlgroup,with significant difference between the two groups (χ2 =5.22,P =0.02).Conclusion Cefepime in the treat-ment of acute leukemia chemotherapy after infection has significant curative effect,can improve patients'neutral granu-locyte number and adverse reactions are mild,it is worthy of popularization in clinical.

Analysis of One Case of Nervous System Damage Caused by Cefepime / 中国药师

Objective:To find out the general regularity of antibiotic encephalopathy caused by cefepime through the case analy -sis, and give reasonable suggestions according to the clinical features .Methods: According to the patient's conditions , the clinical pharmacist consulted a large number of literatures and excluded the other factors such as the clinical manifestation of the patient and the used drugs.The clinical pharmacist analyzed the possibility of drug-induced nervous system damage in the aspects of the administration time, dose, drug interactions and changes of symptoms and signs after the drug withdrawal .Results:The clinical pharmacist performed the rational analysis and judgment , provided suggestions for the doctors , and terminated the nervous system damage caused by cefepime in time.Conclusion:In clinical practice , clinical pharmacists analyze drug therapy events and provide pharmaceutical care , which is beneficial to safe and rational drug use .

Comparison of effects of cefepime, ceftazidime and cefathiamidine on bacterial infection in gynecology / 中国基层医药

Objective To evaluate the efficacy and safety of domestic cefepime ,ceftazidime and cefathiami-dine on bacterial infection in gynecology .Methods 460 patients were randomly divided into Group A (155 patients) for 2.0g.bid of cefepime,Group B (155 patients) for 2.0g.bid of ceftazidime and Group C (150 patient) for 2.0g. bid of cefathiamidine ( intramuscular injection:once every 12 hours ) , and the periods of treatment were all 7 to 10 days.Control observation and study was carried out following Guiding Principle of Clinical Application of Antibacterial Agents.Results The clinical efficacies in Groups A ,B and C were 94.84%,82.58% and 67.33%respectively(χ2 =11.63,37.96,all Pthat of Group B>that of Group C;the adverse effectives were 9.68%,10.32% and 9.33% respectively (χ2 =0.09,P>0.05).Conclusion Cefepime may still be used as the first line drugs ,and drug resistance of various degrees has occurred to ceftazidime and cefathi -amidine,and especially cefathiamidine ,which should be used with caution .

Cefepime-resistance in Clinical Isolates of Pseudomonas aeruginosa and Klebsiella spp in Ogbomoso.

Aims: Our goal was to identify resistance rate of Cefepime-resistant Pseudomonas aeruginosa and Klebsiella spp infections in the hospital setting within Ogbomoso. Study Design: The study includes clinical isolates of Klebsiella spp and Pseudomonas aeruginosa obtained by screening samples of blood (for blood culture), urine, aspirate, wound, throat, sputum etc. Place and Duration of Study: Clinical isolates were obtained from Medical Microbiology and Parasitology Laboratory of the Ladoke Akintola University of Technology Teaching Hospital, Ogbomoso, between March and August 2013. Methodology: Sixty-six clinical isolates of Pseudomonas aeruginosa and Klebsiella spp obtained from different clinical sites were analyzed using standard bacteriological methods. The sensitivity of clinical isolates of Pseudomonas aeruginosa and Klebsiella spp to Cefepime (30μg) was determined using disk diffusion method. The isolates were divided into three groups sensitive, intermediate and resistance. Results: The results shows that Pseudomonas aeruginosa had 34.38% sensitivity, 6.25% intermediate and 59.37% resistance while Klebsiella spp had 41.18% sensitivity, 5.88% intermediate and 52.94% resistance. Overall susceptibility pattern of the clinical isolates to Cefepime is 37.87% sensitivity, 6.06% intermediate and 56.06% resistance. Conclusion: There was a great Cefepime–resistance among the clinical isolates analyzed. The resistance pattern of Pseudomonas aeruginosa and Klebsiella spp calls for continuous surveillance for Cefepime resistance control.

Quantification and stress degradation studies of cefepime/tazobactam in dry injection form by an RP-HPLC method

A simple, specific, precise, accurate, linear, rapid, economic and validated stability indicating an RP-HPLC method for the simultaneous quantification of cefepime and tazobactam in a dry injection dosage form has been developed. Separation was performed on a 5 µm ACE C18 column with phosphate buffer, pH adjusted to 4.5 with phosphoric acid: methanol (70:30) at a flow rate of 1 mL/min and at a temperature of 25 °C. Regression analysis showed linearity at a detector wavelength of 290 nm in the range of 200-600 μg/mL for cefepime and 25-75 μg/mL for tazobactam. All of the analytes were adequately resolved with acceptable tailing. The percentage content found for cefepime was 99.98% and of tazobactam was 99.49% in the parenteral formulation. The method was validated in terms of linearity, precision, accuracy, specificity, robustness and system suitability according to ICH guidelines. Stress degradation studies were performed on the placebo and drug products, drugs of interest were well resolved from the degradation products. The developed method was effectively applied for the simultaneous quantification of cefepime and tazobactam in a dry injection formulation.

Desenvolveu-se método específico, preciso, exato, linear, rápido e econômico, de validação de estabilidade, indicando o método de CLAE-FR para a quantificação simultânea de cefepima e tazobactam na forma de dosagem injetável seca. A separação foi realizada em coluna C18 de ACE 5 mM com tampão fosfato, pH ajustado para 4,5 com ácido fosfórico:metanol (70:30), em fluxo de 1 mL/min e temperatura de 25 °C. A análise de regressão mostrou linearidade no detector de comprimento de onda de 290 nm, na faixa de 200-600 μg/mL, para cefepima, e 25-75 μg/mL, para tazobactam. Todos os analitos foram, adequadamente, resolvidos com cauda aceitável. O teor percentual encontrado na formulação parenteral foi de 99,98%, para cefepima, e de 99,49%, para o tazobactam. O método foi validado em termos de linearidade, precisão, exatidão, especificidade, robustez e adequação do sistema de acordo com as diretrizes ICH. Estudos de degradação por estresse foram realizados no grupo placebo e nos medicamentos e os fármacos de interesse foram bem resolvidos a partir dos produtos de degradação. O método desenvolvido foi efetivamente aplicado para quantificação simultânea de cefepima e tazobactam na formulação injetável seca.

Cefepime-induced encephalopathy without renal impairment

Cefepime is an extended-spectrum, fourth-generation cephalosporin that has been widely used for approved indications such as febrile neutropenia. Common adverse events of cefepime include headache, skin rash, gastrointestinal problems, and fever. However, encephalopathathy caused by cefepime has been sporadically reported worldwide over the last decade. We experienced a rare case of cefepime-induced encephalopathy. A 75-year-old man with a 30-year history of chronic obstructive pulmonary disease was admitted to the medical intensive care unit under a diagnosis of pneumonia. Initial antibiotic therapy was started with piperacillin/sulbactam and ciprofloxacin. His condition was improved with this treatment. About 2 months later, his condition was aggravated again, with mild fever and purulent sputum. Intravenous cefepime was selected on the basis of antibiotic susceptibility to Pseudomonas aeruginosa isolated from his sputum. However, his mentality became drowsy 48 hours after cefepime adminstration. He showed tremors and right facial paralysis. Neurologic examination for motor power and sensory function revealed normal findings. Laboratory tests, including serum electrolytes, glucose, osmolality, and ammonia, gave normal results. Brain magnetic resonance imaging showed chronic ischemic and atropic changes, and an electroencephalography revealed triphasic waves. The administration of cefepime was stopped, and his symptoms started to improve within 48 hours. Electroencephalography results became normalized, and he completely recovered within 48 hours after discontinuation of cefepime.

Susceptibility of Escherichia coli from Community-Acquired Urinary Tract Infection to Fosfomycin, Nitrofurantoin, and Temocillin in Korea

With increase of multi-drug resistant Escherichia coli in community-acquired urinary tract infections (CA-UTI), other treatment option with a therapeutic efficacy and a low antibiotic selective pressure is necessary. In this study, we evaluated in vitro susceptibility of E. coli isolates from CA-UTI to fosfomycin (FM), nitrofurantoin (NI), temocillin (TMO) as well as trimethoprim-sulfamethoxazole (SMX), ciprofloxacin (CIP) and cefepime (FEP). The minimal inhibitory concentrations were determined by E-test or agar dilution method according to the Clinical and Laboratory Standards Institute guidelines, using 346 E. coli collected in 12 Korean hospitals from March 2010 to February 2011. FM, NI and TMO showed an excellent susceptibility profile; FM 100% (346/346), TMO 96.8% (335/346), and NI 99.4% (344/346). Conversely, resistance rates of CIP and SMX were 22% (76/346) and 29.2% (101/349), respectively. FEP still retained an activity of 98.5%. In Korea, NI and TMO in addition to FM are a good therapeutic option for uncomplicated CA-UTI, especially for lower UTI.

Susceptibility of Escherichia coli from Community-Acquired Urinary Tract Infection to Fosfomycin, Nitrofurantoin, and Temocillin in Korea

With increase of multi-drug resistant Escherichia coli in community-acquired urinary tract infections (CA-UTI), other treatment option with a therapeutic efficacy and a low antibiotic selective pressure is necessary. In this study, we evaluated in vitro susceptibility of E. coli isolates from CA-UTI to fosfomycin (FM), nitrofurantoin (NI), temocillin (TMO) as well as trimethoprim-sulfamethoxazole (SMX), ciprofloxacin (CIP) and cefepime (FEP). The minimal inhibitory concentrations were determined by E-test or agar dilution method according to the Clinical and Laboratory Standards Institute guidelines, using 346 E. coli collected in 12 Korean hospitals from March 2010 to February 2011. FM, NI and TMO showed an excellent susceptibility profile; FM 100% (346/346), TMO 96.8% (335/346), and NI 99.4% (344/346). Conversely, resistance rates of CIP and SMX were 22% (76/346) and 29.2% (101/349), respectively. FEP still retained an activity of 98.5%. In Korea, NI and TMO in addition to FM are a good therapeutic option for uncomplicated CA-UTI, especially for lower UTI.

Efficacy evaluation of aztreonam in combination with cefepime for the treatment of urinary tract infectious / 中国基层医药

Objective To explore the clinical efficacy of aztreonam in combination with cefepime for the treatment of urinary tract infections.Methods A randomized block grouping,123 cases of urinary tract infections were divided into observation group,aztreonam group and cefepime group,41 cases in each group.The observation group was treated with aztreonam (2.0g) and cefepime (2.0g),control group were given aztreonam and cefepime,respectively.The treatment time lasted 7 days.Results The total effective rate of observation group was 95.1％,compared with cefepime(85.4％)or aztreonam(82.9％) group,the difference was statistically significant(x2 =12.89、13.56,all P ＜ 0.05).After the end of treatment,the observation group bacterial clearance rate (94.3％) was slightly higher than that of cefepime group or aztreonam group.Each group had only minor adverse reaction,which did't affect the continued medication.And the difference in the incidence was not statistically significant(P ＞0.05).Conclusion Cefepime joint aztreonam in the treatment of urinary tract infection can improve the therapeutic efficacy,and adverse events doesn't increase.

Cefepime encephalopathy and normal renal function / Encefalopatia induzida por cefepime em um paciente com função renal normal

BACKGROUND: Several cases of cefepime neurotoxicity have been reported. Herein reported is a case of cephalosporin-associated neurotoxicity in apatient with normal renal function. CASE REPORT: A 64-year-old woman with a history of post-transplantation chronic myeloid leukemia was admittedto hospital due to hyporexia, fever, productive cough and mild dyspnea. Initial blood screen revealed pancytopenia and a normal renal function.Intravenous cefepime was empirically started and after 40 hours the patient developed sudden mental confusion. Neurological examination was normal. Cranial computed tomography and brain magnetic resonance scans were normal. Electroencephalography showed triphasic waves of diffuse slowness without ongoing epileptic activity. Lumbar puncture was normal. Cefepime neurotoxicity was promptly considered and antibiotics were switched to piperacillin and tazobactam. After five days, the patient recovered completely with remission of myoclonus. CONCLUSIONS: Awareness should be given to possible central nervous system complications induced by cefepime, especially in the elderly, even without renal failure

INTRODUÇÃO: Existem vários relatos de casos de toxicidade do sistema nervoso central induzida pelo cefepime. Relata-se um caso de toxicidade do sistema nervoso central associada ao uso de uma cefalosporina em um paciente com função renal normal. RELATO DE CASO: Uma mulher de 64 anos com história de transplante de medula óssea devido a leucemia mielóide crônica foi admitida ao hospital devido a hiporexia, febre, tosse produtiva e dispnéia leve. Os exames laboratoriais de rotina demonstraram pancitopenia e função renal normal. O cefepime intravenoso foi empiricamente iniciado e, após 40 horas da administração, o paciente apresentou quadro súbito de confusão mental. Exame neurológico foi normal, assim como a tomografia computadorizada craniana e a ressonância magnética encefálica. O eletroencefalograma demonstrou ondas trifásicas de lentificação difusa sem evidência de atividade epileptiforme. O líquor estava normal. A toxicidade do sistema nervoso central pelo cefepime foi rapidamente considerada e o antibiótico foi trocado para piperacilina e tazobactan. Após cinco dias, o paciente apresentou recuperação completa com remissão da mioclonia. CONCLUSÃO: Deve-se dar atenção às possíveis complicações do sistema nervoso central induzidas pelo cefepime, especialmente em idosos, mesmo sem insuficiência renal.

Características demográficas, morbilidad y mortalidad de los pacientes adultos con neutropenia febril tratados con cefepima / Demographics, morbidity, and mortality febrile neutropenic adult patients treated with cefepime

Introduction: Cefepime efficacy for treatment of febrile neutropenia (FN) in cancer adult patients is a controversial issue. Objective: To describe the demographic characteristics and general mortality of patients suffering from febrile neutropenia treated with cefepime in a fourth-level Latin American hospital. Patients and Methods: A cross-sectional observational study was performed. Study settled at San Ignacio of Bogotá, Colombia. University Hospital from January 2004 to December 2008. Results: A total of 333 patients were treated with cefepime, of whom 125 had suffered FN and met pre established inclusion and exclusion criteria. The general mortality was 14.4%, which was similar to the overall mortality in FN in other reports. Conclusions: Although there is still no clarity regarding the efficacy of cefepime in FN, its use has not been restricted. This study did not identify an excess risk of mortality in patients treated with cefepime.

Introducción: La eficacia de cefepima en pacientes adultos con cáncer y neutropenia febril (NF) es objeto de controversia en las publicaciones científicas. Objetivo: Describir las características demográficas y la mortalidad general de los pacientes adultos con NF tratados con cefepima en un hospital latinoamericano de cuarto nivel. Pacientes y Métodos. Estudio observacional descriptivo, de corte transversal en el que se incluyeron todos los pacientes tratados con cefepima en el Hospital Universitario San Ignacio de Bogotá, Colombia entre enero de 2004 y diciembre de 2008. Resultados: Recibieron cefepime un total 333 pacientes, de los cuales 125 tenían diagnóstico de NF y cumplían criterios pre-establecidos de inclusión y exclusión. Como desenlace final se encontró una mortalidad de 14,4%, un porcentaje similar a la mortalidad general en NF reportada en la literatura médica. Conclusiones: Aún no hay claridad sobre la eficacia del uso de cefepima en NF; sin embargo, tampoco se ha proscrito su uso y los datos del presente estudio no encontraron un riesgo adicional de mortalidad.

Pharmacokinetcs of single dose cefepime injection in Chinese Han, Mongolia, Korean, Uigur, and Hui healthy volunteers / 中国药学杂志

OBJECTIVE: To investigate and compare the pharmacokinetics of cefepime in healthy volunteers of different Chinese nationalities (Han, Mongolia, Uigur, Korea, and Hui) and different genders, thus to provide instruction and help for using cefepime safely, rationaly and effectively in both ordinary clinic and remedy of battle wound. METHODS: A single dose of 1.0 g cefepime was given by intravenous infusion under fasting condition to ten healthy volunteers (five males and five females) of each Chinese nationality. Plasma samples were obtained before dosing and at various predetermined time points after the dosing, and the plasma concentrations were determined by a validated HPLC-UV method. The pharmacokinetic parameters were calculated by DAS2.0 software and were compared by SPSS11.5 software. RESULTS: The PK parameters of cefepime in Han, Mongolia, Uigur, Korea and Hui nationalities after a single intravenous administration of 1.0 g were as follows: t1/2β (1.97 ± 0.20), (2.10 ± 0.33), (2.06 ± 0.33), (2.40 ± 0.65), and (1.94 ± 0.24) h; AUC0-β (139.69 ± 23.78), (153.92 ± 22.79), (165.58 ± 24.49), (142.11 ± 29.77), and (132.78 ± 23.79) mg · h · L-1;ρmax(68.75 ± 10.41), (78.22 ± 13.87), (83.19 ± 10.31), (73.82 ± 9.59), and (62.91 ± 10.09) mg · L-1 , respectively. The PK parameters of cefepime in 25 male volunteers and 25 female volunteers after a single intravenous administration of 1.0 g were as follows: t1/2β (2.06 ± 0.54) and (2.13 ± 0.44)h; AUC0-β (134.06 ± 22.33) and (158.68 ± 24.85)mg · h · L-1;ρmax (66.94 ± 9.14) and (78.95 ± 12.71)mg · L-1, respectively. Results of ANOVA and Kruskal-Wallis rank test showed that there were no significant differences in the PK parameters Vd, CL, InAUC, and t1/2β of different nationalities and in Vd and t1/2β of different genders, but there were significant differences in lnρmax of different nationalities and CL, InAUC, and lnρmax of different genders. Then, it was found there was high linear correlation( P < 0.01) between body weight and CL, InAUC and lnρmax. The differences of the above PK parameters became insignificant after normalization by body weight. CONCLUSION: When cefepime is given in doses based on body weight, its pharmacokinetics has no significant differences among five nationalities and between genders. Copyright 2012 by the Chinese Pharmaceutical Association.

Cefepime Neurotoxicity in Patients with Renal Insufficiency

Cefepime is a fourth-generation cephalosporin that is active against both gram-positive and gram-negative organisms. It is administered parenterally for the treatment of severe infections. Approximately 85% of the drug is excreted unchanged by the kidneys. Neurotoxicity in patients with renal failure who are treated with cefepime has been reported sporadically. We report on two senile patients with renal impairment who developed neurotoxicity including lethal outcome after treatment with cefepime.

Pitfalls of the Clinical and Laboratory Standards Institute's Revised Breakpoints on Interpretation of the Cephalosporin Susceptibility of an Extended-Spectrum beta-lactamase Producing Klebsiella pneumoniae: Analysis of a 2010 Nationwide Proficiency Surve / 임상검사와정도관리

BACKGROUND: In 2010, the Clinical and Laboratory Standards Institute (CLSI) revised the minimum inhibitory concentration (MIC) breakpoints of cephalosporins and aztreonam to exempt extended-spectrum beta-lactamase (ESBL) confirmatory tests for Enterobacteriaceae. However, the CLSI did not change the MIC breakpoint of cefepime. Here, a proficiency survey of a strain of ESBL-producing Klebsiella pneumoniae was analyzed for MIC distribution and interpretation of cephalosporins and aztreonam. METHODS: The survey strain, K. pneumoniae, which produced SHV-18, was distributed to 170 clinical laboratories as 1 of 5 presumptive clinical specimens through the proficiency survey of the clinical microbiology division of the Korean Association of Quality Assurance for Clinical Laboratories (KAQACL). MIC, zone diameter of inhibition (ZDI), and interpretation of tested antimicrobials, methods of antimicrobial susceptibility testing (AST), and ESBL confirmatory results were collected. RESULTS: According to the revised breakpoints of the 2010 CLSI guidelines, MIC results indicated resistance to aztreonam in 100%, cefepime in 5.5%, cefotaxime in 20%, ceftazidime in 100%, and ceftriaxone in 100% of samples by broth microdilution methods. ZDI results also indicated resistance to aztreonam in 75%, cefepime in 0%, cefotaxime in 66.7%, ceftazidime in 100%, and ceftriaxone in 80% of samples by disk diffusion method. Ninety (75.6%) participants performed an ESBL confirmatory test, and 89 (98.9%) reported ESBL-positive tests. Of the 55 laboratories that tested the susceptibility of cefepime, 50 (90.9%) self-reported to be "resistant" because of ESBL-positive results. CONCLUSIONS: In conclusion, susceptibility testing of ESBL producers against certain cephalosporins is not reliable enough to apply the revised breakpoints presented in the 2010 CLSI guidelines. It is therefore necessary to reach a consensus for interpretation of ASTs of ESBL producers in Korea. Ideally, clinicians should be provided two interpretations based on both the revised breakpoints and ESBL confirmatory testing.