piperacillin--tazobactam-drug-combination and Chemotherapy-Induced-Febrile-Neutropenia

Piperacillin-tazobactam is commonly used in neutropenic sepsis at standard doses that do not account for inter-individual differences in age, bodyweight and renal function. This study was designed to assess the rate of attainment of pharmacokinetic/pharmacodynamic (PK/PD) targets in patients receiving piperacillin/tazobactam therapy and to evaluate the effect on clinical outcomes.. Patients undergoing intensive chemotherapy for aggressive hematological malignancies were enrolled and treated with piperacillin/tazobactam 4 g/0.5 g every 6 h as initial antimicrobial therapy for first fever. Plasma drug concentrations were assayed at 50% and 100% of the dosing interval and compared with target MIC breakpoint of 16 mg/L to calculate the primary endpoints of 50% and 100% time above MIC (fT > MIC), respectively. Secondary endpoints included time to clinical cure, length of hospital stay, duration of antibiotics, and clinical treatment success.. Fifty-eight percent (14/24) of patients achieved 50% fT > MIC while only 4% (1/24) achieved 100% fT > MIC. Higher creatinine clearance was significantly associated with lower trough drug concentration and appeared to be the dominant reason for the poor PK/PD target attainment. Median time to clinical cure, duration of antibiotic therapy, and hospital length of stay was 3, 13 and 21 days, respectively. There were no statistically significant differences in these outcomes between patients who did and did not achieve 100% fT > MIC.. A significant majority of febrile neutropenic patients fail to achieve PK/PD targets with 6-hourly piperacillin dosing, although the clinical implications of this finding are unclear. Larger studies are needed to assess any impact on morbidity and mortality. This trial is registered on the ANZCTR (ACTRN12618000110280).

Topics: Adult; Aged; Anti-Bacterial Agents; Antineoplastic Agents; Chemotherapy-Induced Febrile Neutropenia; Female; Hematologic Neoplasms; Humans; Length of Stay; Male; Microbial Sensitivity Tests; Middle Aged; Piperacillin, Tazobactam Drug Combination; Sepsis; Time Factors; Treatment Outcome

This randomized prospective study was designed to assess whether piperacillin/tazobactam (PIPC/TAZ) is as effective as meropenem (MEPM) as a first-line antibiotic treatment for febrile neutropenia (FN).. FN episodes were randomly assigned to receive either PIPC/TAZ (337.5 mg/kg per day in three doses, 1-hr DIV, maximum 13.5 g per day) or MEPM (120 mg/kg per day in three doses, 1-hr DIV, maximum 3 g per day). Clinical responses were evaluated 120 hr after the DIV.. A total of 434 febrile episodes in 105 patients (42 females and 63 males) with a median age of 8 years (range 0-25) were included in this trial. Blood cultures were positive in 47 out of the 434 episodes (10.8%). Regarding responses to the treatment, success rates between the PIPC/TAZ and MEPM groups were similar (62.4 vs. 65.9%, P = 0.484), even if patients were restricted to those with bacteremia (26.1 vs 37.5%, P = 0.534). Mortality rates did not significantly differ between the two groups (0.8 vs. 0%, P = 0.500).. Both PIPC/TAZ and MEPM appeared to be equally efficacious and safe. Carbapenems are now broadly used to treat FN; however, this may increase the prevalence of drug-resistant bacteria. In this regard, the treatment using PIPC/TAZ for FN is more beneficial.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Chemotherapy-Induced Febrile Neutropenia; Child; Child, Preschool; Female; Hematologic Neoplasms; Humans; Infant; Infant, Newborn; Male; Meropenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Thienamycins

Recently, due to inadequacies during immediate management of patients with febrile neutropenia, a new gold standard 'door-to-needle' time of 1 hour for the administration of intravenous antibiotics was introduced.. The aim of this audit was to identify whether that target was being met in our emergency department (ED). This is phase 1 of the study which will be followed by identification of barriers to the achievement of the target and recommendations for improvement.. Data were collected from January 2013 to April 2013 of consecutive patients (adult and pediatric age group) who presented to the ED with febrile neutropenia for various underlying causes. Fever was defined as single oral temperature of >38.3°C (101°F) or a temperature of >38.0°C (100.4°F) sustained for more than 1 hour. Neutropenia was defined as absolute neutrophil count <0.5 × 10(9)/l, or expected to fall below that number. Variables analyzed included age, gender, antibiotics administered, underlying diagnosis, day of presentation, and door-to-needle time.. During the study period, there were n = 81 patients who presented with febrile neutropenia. There were n = 49 were males and n = 32 were females. There were n = 37 patients in the pediatric age group while rest were adults. Patients most commonly had an underlying hematological malignancy (n = 49). A combination of piperacillin/tazobactam (4.5 g × Q8hrly) and amikacin (750 mg × once daily) was most frequently administered (n = 57) to these patients. The median door-to-needle time was 45 minutes (range ± SD: 10 minutes to 6 hours ± 1 hour 10 minutes). Long delays of over 4 hours occurred in n = 4 patients (all were adults). There were minimal delays observed in pediatric patients due to 'red alert' policy implementation. Long delays occurred on weekdays and weekends, equally.. The overall median door-to-needle time was 45 minutes, which was in the accepted range. However, delays that occurred demand improvements like introducing 'red alert' policy for adult patients, counseling of staff and residents, identifying potential barriers in achieving the target time along with solutions, and developing hospital-based guidelines on managing patients with neutropenic sepsis.

Topics: Adolescent; Adult; Aged; Amikacin; Anti-Bacterial Agents; Chemotherapy-Induced Febrile Neutropenia; Female; Hematologic Neoplasms; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Young Adult

Empiric antibiotic monotherapy is considered the standard of treatment for febrile neutropenic patients with cancer, but this approach may be inadequate because of the increasing prevalence of infections caused by multidrug resistant (MDR) bacteria.. In this multicenter, open-label, randomized, superiority trial, adult, febrile, high-risk neutropenic patients (FhrNPs) with hematologic malignancies were randomly assigned to receive piperacillin/tazobactam (4.5 g intravenously every 8 hours) with or without tigecycline (50 mg intravenously every 12 hours; loading dose 100 mg). The primary end point was resolution of febrile episode without modifications of the initial allocated treatment.. Three hundred ninety FhrNPs were enrolled (combination/monotherapy, 187/203) and were included in the intention-to-treat analysis (ITTA). The ITTA revealed a successful outcome in 67.9% v 44.3% of patients who had received combination therapy and monotherapy, respectively (127/187 v 90/203; absolute difference in risk (adr), 23.6%; 95% CI, 14% to 33%; P < .001). The combination regimen proved better than monotherapy in bacteremias (adr, 32.8%; 95% CI, 19% to 46%; P < .001) and in clinically documented infections (adr, 36%; 95% CI, 9% to 64%; P < .01). Mortality and number of adverse effects were limited and similar in the two groups.. The combination of piperacillin/tazobactam and tigecycline is safe, well tolerated, and more effective than piperacillin/tazobactam alone in febrile, high-risk, neutropenic hematologic patients with cancer. In epidemiologic settings characterized by a high prevalence of infections because of MDR microorganisms, this combination could be considered as one of the first-line empiric antibiotic therapies.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Antineoplastic Agents; Bacteremia; Chemotherapy-Induced Febrile Neutropenia; Drug Combinations; Female; Hematologic Neoplasms; Humans; Male; Middle Aged; Minocycline; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Risk Factors; Tigecycline; Young Adult

Topics: Acute Kidney Injury; Administration, Intravenous; Administration, Oral; Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy-Induced Febrile Neutropenia; Chemotherapy, Adjuvant; Cyclophosphamide; Doxorubicin; Female; Fluoroquinolones; Hospitalization; Humans; Medical Overuse; Neoplasm Staging; Piperacillin, Tazobactam Drug Combination; Risk Assessment; Vancomycin

Ambulatory therapy in low-risk patients with cancer, fever, and neutropenia seems to be a secure and effective alternative. This study aimed to compare the effectiveness and safety of the antimicrobial treatment in early discharge vs. in-hospital treatment in children with cancer and febrile neutropenia (FN) with low risk of invasive bacterial infection (IBI).. Quasi-experimental design with a historical cohort control group. Children with cancer during an episode of FN and low risk of IBI were included. The control group were inpatient children that received intravenous piperacillin/tazobactam. The experimental group was early discharge patients, who received 48 h of IV treatment and were switched to oral treatment. Outcomes: fever resolution, readmissions, and mortality.. Eighty low-risk FN episodes were included; the median age was 6 years old (2.6-11 years), and 43 (54%) were female. Main diagnoses were solid tumors (52 patients) and leukemia or lymphoma (28 patients). Forty-three patients received in-hospital treatment, and 37 were selected for early discharge (31 patients received ciprofloxacin and six received amoxicillin/clavulanate). Two patients were readmitted, one due to a relapse of fever with tumor progression and the other due to epistaxis. Adverse effects occurred in 21.6% of the early discharge group and 12% of the inpatient treatment group (p = 0.04).. Early discharge in pediatric patients with cancer, fever, and neutropenia is an acceptable and safe alternative for low-risk patients.. El tratamiento ambulatorio en pacientes con cáncer, fiebre y neutropenia de bajo riesgo parece ser una alternativa segura y efectiva. El objetivo de este trabajo fue comparar la efectividad y la seguridad del tratamiento antimicrobiano en la modalidad de egreso temprano vs. el tratamiento intrahospitalario en niños con cáncer y neutropenia febril (NF), con bajo riesgo de infección bacteriana invasiva (IBI).. Diseño cuasi-experimental con un grupo control histórico. Se incluyeron niños con cáncer durante un episodio de NF con bajo riesgo de IBI. El grupo control fue constituido por pacientes que recibieron tratamiento hospitalario con piperacilina-tazobactam intravenosa. Los pacientes en el grupo de egreso temprano recibieron 48 horas de tratamiento intravenoso y egresaron con antimicrobianos por vía oral. Desenlaces: resolución de la fiebre, reingreso al hospital y muerte.. Se incluyeron 80 pacientes con NF de bajo riesgo; la mediana de edad fue de 6 años; 43 pacientes (54%) eran de sexo femenino. Los diagnósticos principales fueron tumores sólidos (52) y leucemia o linfoma (28). Cuarenta y tres pacientes recibieron tratamiento hospitalario y 37 fueron seleccionados para egreso temprano. En el grupo de egreso temprano, 31 pacientes recibieron ciprofloxacino y 6 recibieron amoxicilina-clavulanato. Dos pacientes reingresaron, uno por fiebre secundaria a progresión tumoral y otro por epistaxis. Los efectos adversos se presentaron en el 21.6% de los pacientes en el grupo de egreso temprano y en el 12% del grupo de tratamiento hospitalario (p = 0.04).. El egreso temprano para niños con cáncer y NF de bajo riesgo es una alternativa aceptable y segura.

Topics: Ambulatory Care; Anti-Bacterial Agents; Bacterial Infections; Case-Control Studies; Chemotherapy-Induced Febrile Neutropenia; Child; Child, Preschool; Female; Hospitalization; Hospitals, Pediatric; Humans; Male; Mexico; Neoplasms; Patient Discharge; Piperacillin, Tazobactam Drug Combination; Risk; Tertiary Care Centers

Patients with febrile neutropenia (FN) exhibit changes in extracellular fluid that may alter the plasma concentrations of beta-lactams and result in therapeutic failure or toxicity. We evaluated the pharmacokinetics of piperacillin/tazobactam in patients with hematological malignancies and FN after receiving chemotherapy at a primary public cancer center.. This was an open, nonrandomized, observational, descriptive, and prospective study. Samples from 15 patients with hematological malignancies and FN were evaluated after the administration of chemotherapy. Five blood samples were taken from each patient when the antibiotic level was at steady-state 10, 60, 120, 180, and 350 min after each dose. Antibiotic concentrations were measured using gel diffusion with Bacillus subtilis. All study participants provided written informed consent.. We investigated the pharmacokinetics of piperacillin in 14 patients between the ages of 18 years and 59 years and with a mean absolute neutrophil count of 208 cells per mm³ (standard deviation (SD) ± 603.2). The following pharmacokinetic measurements were obtained: maximum concentration, 94.1-1133 mg/L; minimum concentration, 0.47-37.65 mg/L; volume of distribution, 0.08-0.65 L/kg (mean, 0.34 L/kg); drug clearance (CL), 4.42-27.25 L/h (mean, 9.93 L/h); half-life (t(1/2)), 0.55-2.65 h (mean, 1.38 h); and area under the curve, 115.12-827.16 mg · h/L.. Patients with FN after receiving chemotherapy exhibited significant variations in the pharmacokinetic parameters of piperacillin compared with healthy individuals; specifically, FN patients demonstrated an increase in t1(/2) and decreased CL.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Chemotherapy-Induced Febrile Neutropenia; Female; Hematologic Neoplasms; Humans; Leukocyte Count; Male; Middle Aged; Neutrophils; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Young Adult