piperacillin--tazobactam-drug-combination and Hematologic-Neoplasms

Pediatric patients with febrile neutropenia usually receive a combination of broad spectrum antimicrobials. Treatment without aminoglycoside seems to have advantages.. To compare the efficacy of piperacillin/tazobactam plus amikacin versus piperacillin/tazobactam.. Randomized, open label, controlled clinical trial. Sample size for an efficacy of 55%, and delta of 25%; 80 episodes were required for each group. Selection criteria were patients with febrile neutropenia, candidates to receive parenteral antimicrobial treatment; they were randomized to one of two groups, piperacillin/tazobactam plus amikacin (Group A), or piperacillin/tazobactam (Group B). The outcomes were failure, adverse events and death. Mantel-Haenszel chi squaretest and exact Fisher test were used. Reduction of relative and absolute risk (RRR and ARR), 95% confidence intervals (CI 95%) and number needed to treat (NNT) were calculated.. 88 Episodes were analyzed in group A and 76 in group B. There was no statistical difference in general characteristics of patients or type of infections. There was not significant statistical difference in: failure 31.8% group A, 30.2% group B (RR 1.05, CI 95% 0.66-1.66, p = 0.86), or adverse events (one in each group). The RRR was 1.5%, and ARR 2%, with a NNT of 67.. Piperacillin/tazobactam without amikacin was as effective as combination therapy in pediatric patients with febrile neutropenia.. los pacientes pediátricos con neutropenia febril habitualmente reciben una combinación de antimicrobianos de amplio espectro. La terapia sin aminoglucósido parece tener ventajas.. comparar la eficacia de piperacilina/tazobactam más amikacina frente a la de piperacilina/tazobactam.. ensayo clínico controlado aleatorizado. Tamaño de muestra para una eficacia de 55%, y delta de 25%; se calcularon 80 episodios por grupo. Fueron seleccionados pacientes con neutropenia febril, candidatos a recibir antimicrobiano parenteral; se aleatorizaron a recibir piperacilina/tazobactam más amikacina (grupo A) o piperacilina/tazobactam (grupo B). Los desenlaces fueron falla, eventos adversos y muerte. Se emplearon las pruebas Chi cuadrada de Mantel-Haenszel y exacta de Fisher. Se calculó la reducción de riesgo relativo y absoluto (RRR y RRA), intervalos de confianza 95% (IC 95%) y número necesario a tratar (NNT).. se analizaron 88 episodios en el grupo A y 76 en el grupo B. No hubo diferencias estadísticas en características generales ni en el tipo de infecciones. No se encontró diferencia significativa en: falla 31.8% grupo A, 30.2% grupo B (RR 1.05, IC 95% 0.66-1.66, p = 0.86), ni en los eventos adversos (uno en cada grupo). La RRR fue de 1.5%, RRA de 2%, con un NNT de 67.. la terapia con piperacilina/tazobactam sin amikacina fue tan efectiva como la terapia combinada para pacientes pediátricos con neutropenia febril.

Topics: Adolescent; Amikacin; Anti-Bacterial Agents; Child; Child, Preschool; Febrile Neutropenia; Female; Hematologic Neoplasms; Humans; Infant; Intention to Treat Analysis; Logistic Models; Male; Neoplasms; Piperacillin, Tazobactam Drug Combination

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

Febrile neutropenia may be a sign of severe infection and is associated with significant morbidity and mortality in high-risk patients with hematologic malignancies. Extended infusion of β-lactam antibiotics is associated with greater clinical response than is bolus infusion in nonneutropenic critically ill patients, but data are lacking for febrile neutropenic patients.. We designed a single-center, nonblinded, randomized trial to compare extended infusion (4 hours) and bolus infusion (30 minutes) of piperacillin-tazobactam or ceftazidime in high-risk patients with febrile neutropenia. The primary endpoint was overall response on day 4, defined as the combination of resolution of fever, sterile blood cultures, resolution of clinical signs and symptoms, and no need for a change in the antibiotic regimen. Outcome was adjudicated by investigators blinded to treatment allocation.. Of 123 enrolled patients, 105 had febrile neutropenia and were included in the intention-to-treat analysis: 47 in the extended infusion arm and 58 in the bolus infusion arm. Overall response occurred in 35 (74.4%) patients treated with extended infusion and 32 (55.1%) patients treated with bolus infusion (P = .044). The superiority of extended infusion was greatest for patients with clinically documented infections (overall response, 68.4% [13/19] vs 35.7% [10/28]; P = .039) and specifically for those with pneumonia (80% [4/5] vs 0% [0/8]; P = .007).. Extended infusion of β-lactams is associated with superior treatment outcomes compared with bolus infusion for high-risk patients with febrile neutropenia. The benefit of extended β-lactam infusion may be greatest for patients with pulmonary infections.. NCT02463747.

Topics: Aged; Anti-Bacterial Agents; beta-Lactams; Ceftazidime; Cephalosporins; Febrile Neutropenia; Female; Fever; Hematologic Neoplasms; Humans; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Prospective Studies; 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

This randomized, dual-center study compared the efficacy and safety of piperacillin-tazobactam (PTZ) and imipenem-cilastatin (IMP) in hematopoietic stem cell transplantation (HSCT) recipients with febrile neutropenia. HSCT recipients with febrile neutropenia were randomized into two groups receiving either PTZ or IMP as initial empiric antibiotic. Endpoints were defervescence rate after empiric antibiotic for 48 h, success at end of therapy, and side effects. Defervescence within 48 h after empiric antibiotic was observed in 46 patients with PTZ (75.4%) and 59 patients with IMP (95.2%) (p = 0.002). Ten patients (10/46) in the PTZ group and two patients (2/59) in the IMP group switched empiric antibiotics due to recurrent fever (p = 0.005). Success of initial antibiotic with modification was achieved in 34 patients with PTZ (55.7%) and 53 patients with IMP (85.5%) at the end of therapy (p = 0.001). To treat the bacteremia, seven of 10 patients in the PTZ group and one of eight patients in the IMP group needed to switch the empiric antibiotic (p = 0.025). Compared with PTZ, IMP had more gastrointestinal adverse events (p = 0.045). This study demonstrates that IMP had better efficacy than PTZ as an empiric antibiotic for febrile neutropenia in the HSCT setting, but with more gastrointestinal side reactions.

Topics: Adult; Anti-Bacterial Agents; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Febrile Neutropenia; Female; Follow-Up Studies; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Imipenem; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prognosis; Risk Factors

Empirical antibiotic therapy in neutropenic patients presenting with fever plays a significant role in reducing mortality related to infection. Empirical therapies with broad-spectrum intravenous bactericidal, anti-pseudomonal antibiotics are accepted treatments for febrile neutropenic patients. The aim of this study was to compare the efficacy of piperacillin-tazobactam (PIP-TAZO) and cefoperozone-sulbactam (CS) therapies in adult patients with haematological malignancies presenting with neutropenic fever in a prospective study design.. Patients with haematological malignancies (leukaemia, lymphoma, multiple myeloma, and myelodysplastic syndrome) were recruited from June 2010-May 2013. Participants were over 18 years old, with an absolute neutrophil count (ANC) of less than 500/mm³ following chemotherapy or expected to have an ANC less than 500/mm³ in the first 48 h post-chemotherapy, and with an oral body temperature ≥ 38.3°C at a single measurement or 38.0°C after 1-h monitoring. Patients were randomised to the two treatment groups. The initial empirical therapy comprised PIP-TAZO (4.5 g/6 h/day, IV) and CS (2 g/8 h/day, IV).. The overall success rate was 61% with CS and 49% with PIP-TAZO (p =0.247). Factors affecting the treatment success included a neutrophil count <100/mm3, being in the relapse/refractory stage of malignancy, and the presence of a microbiologically documented infection (p <0.05).. PIP-TAZO and CS monotherapies are equally effective and safe for the empirical treatment of febrile neutropenic patients.

Topics: Adult; Aged; Antineoplastic Agents; Cefoperazone; Drug Combinations; Drug Eruptions; Febrile Neutropenia; Female; Hematologic Neoplasms; Humans; Leukocyte Count; Male; Middle Aged; Neutrophils; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Sulbactam; Treatment Outcome; Young Adult

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

To evaluate the efficacy and safety of piperacillin/tazobactam (PIPC/TAZ) or cefepime (CFPM) monotherapy for febrile neutropenia (FN) in children, a total of 53 patients with 213 febrile episodes were randomly treated with either PIPC/TAZ 337.5 mg/kg/day, or CFPM 100 mg/kg/day. No significant differences were observed in the success rates of the PIPC/TAZ and CFPM treatments (62.1% vs. 59.1%, P = 0.650). Furthermore, no differences were noted in the rates of new infection and mortality, and no serious adverse effects occurred in either of groups. Both PIPC/TAZ and CFPM were effective and safe as an empirical therapy for FN in children. Pediatr Blood Cancer 2015;62:356-358. © 2014 Wiley Periodicals, Inc.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Bacterial Infections; Cefepime; Cephalosporins; Child; Child, Preschool; Febrile Neutropenia; Female; Hematologic Neoplasms; Humans; Infant; Infant, Newborn; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Young Adult

The objectives of this study were to describe piperacillin exposure in febrile neutropenia patients and determine whether therapeutic drug monitoring (TDM) can be used to increase the achievement of pharmacokinetic (PK)/pharmacodynamic (PD) targets.. In a prospective randomized controlled study (Australian New Zealand Registry, ACTRN12615000086561), patients were subjected to TDM for 3 consecutive days. Dose was adjusted in the intervention group to achieve a free drug concentration above the MIC for 100% of the dose interval (100% fT>MIC), which was also the primary outcome measure. The secondary PK/PD target was 50% fT>MIC. Duration of fever and days to recovery from neutropenia were recorded.. Thirty-two patients were enrolled. Initially, patients received 4.5 g of piperacillin/tazobactam every 8 h or every 6 h along with gentamicin co-therapy in 30/32 (94%) patients. At the first TDM, 7/32 (22%) patients achieved 100% fT>MIC and 12/32 (38%) patients achieved 50% fT>MIC. Following dose adjustment, 11/16 (69%) of intervention patients versus 3/16 (19%) of control patients (P = 0.012) attained 100% fT>MIC, and 15/16 (94%) of intervention patients versus 5/16 (31%) of control patients (P = 0.001) achieved 50% fT>MIC. After the third TDM, the proportion of patients attaining 100% fT>MIC improved from a baseline 3/16 (19%) to 11/15 (73%) in the intervention group, while it declined from 4/16 (25%) to 1/15 (7%) in the control group. No difference was noted in the duration of fever and days to recovery from neutropenia.. Conventional doses of piperacillin/tazobactam may not offer adequate piperacillin exposure in febrile neutropenic patients. TDM provides useful feedback of dosing adequacy to guide dose optimization.

Topics: Anti-Bacterial Agents; Drug Monitoring; Female; Fever of Unknown Origin; Hematologic Neoplasms; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Neutropenia; New Zealand; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Time Factors; Treatment Outcome

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

Our unit adopted the single administration of cefepime as the initial treatment for febrile episodes in neutropenic patients with hematological malignancies. However, recently, cefepime-resistant gram-negative bacteremia, including those with extended-spectrum β-lactamase (ESBL)-producers, was frequently observed in these patients. Therefore, we instituted a rotation of primary antibiotics for febrile neutropenic patients in an attempt to control antibiotic resistance.. This prospective trial was performed from August 2008 through March 2011 at our unit. After a pre-intervention period, in which cefepime was used as the initial agent for febrile neutropenia, 4 primary antibiotics, namely, piperacillin-tazobactam, ciprofloxacin, meropenem, and cefepime, were rotated at 1-month intervals over 20 months. Blood and surveillance cultures were conducted for febrile episodes, in order to assess the etiology, the resistance pattern (particularly to cefepime), and the prognosis.. In this trial, 219 patients were registered. A 65.9% reduction in the use of cefepime occurred after the antibiotic rotation. In the surveillance stool cultures, the detection rate of cefepime-resistant gram-negative isolates, of which ESBL-producers were predominant, declined significantly after the intervention (8.5 vs 0.9 episodes per 1000 patient days before and after intervention respectively, P<0.01). Interestingly, ESBL-related bacteremia was not detected after the initiation of the trial (1.7 vs 0.0 episodes per 1000 patient days before and after intervention respectively, P<0.01). Infection-related mortality was comparable between the 2 periods.. We implemented a monthly rotation of primary antibiotics for febrile neutropenic patients. An antibiotic heterogeneity strategy, mainly performed as a cycling regimen, would be useful for controlling antimicrobial resistance among patients treated for febrile neutropenia.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Cefepime; Cephalosporins; Ciprofloxacin; Drug Administration Schedule; Female; Fever; Gram-Negative Bacterial Infections; Hematologic Neoplasms; Humans; Male; Meropenem; Middle Aged; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Thienamycins

The IDSA guideline for management of febrile neutropenic patients updated in 2010 recommends monotherapy with anti-pseudomonal-lactam agents, including piperacillin-tazobactam (PIPC/TAZ) for high-risk patients. However, clinical studies of PIPC/TAZ are limited in Japanese patients. In this study, we conducted an open-labeled non-randomized prospective trial to examine the efficacy and safety of PIPC/TAZ as an empirical treatment for Japanese patients with febrile neutropenia. Forty-nine febrile episodes in neutropenic patients excluding those undergoing allogeneic stem cell transplantation (high risk 36, low risk 13) were analyzed. The overall response rate was 71%, and no significant differences between the high-risk and the low-risk group were observed (high risk 72%, low risk 69%). Neither PS nor usage of G-CSF affected the response rate. No major side effects were observed in the study. The efficacy and the safety profile of PIPC/TAZ treatment were comparable to those in other previous Western studies. In conclusion, this study suggests PIPC/TAZ is effective and well tolerated as an initial empirical treatment for febrile neutropenic Japanese patients.

Topics: Anti-Bacterial Agents; Female; Fever; Hematologic Neoplasms; Humans; Japan; Male; Middle Aged; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Treatment Outcome

The aim of this randomized study was to evaluate the efficacy of cefozopran monotherapy and piperacillin-tazobactam plus ceftazidime (PIPC/TAZ + CAZ) combination therapy in pediatric neutropenic patients.. A total of 51 patients with 138 episodes of febrile neutropenia received antibiotic therapy. Of these episodes, 95 were considered eligible for the study. The episodes were treated randomly with either piperacillin-tazobactam (125 mg/kg/day) plus ceftazidime (100 mg/kg/day) or with cefozopran (100 mg/kg/day). Success was defined as resolution of fever and clinical signs of infection within 120 hr following initiation of antibiotic therapy. Duration of neutropenia did not differ statistically between the two groups, and resolution of fever in all cases without complication was seen before recovery from severe neutropenia.. The overall success rate was 61%. There was no statistically significant difference between the two groups: 53% for PIPC/TAZ + CAZ versus 69% for cefozopran (P = 0.122). Blood cultures were positive in eight episodes (8.4%), but there were not deaths as a result of infection.. Both cefozopran and PIPC/TAZ + CAZ combination therapy are safe and well tolerated in pediatric neutropenic patients. Our results show that cefozopran is a good candidate for monotherapy for neutropenic fever.

Topics: Adolescent; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Cefozopran; Ceftazidime; Cephalosporins; Child; Child, Preschool; Drug Therapy, Combination; Female; Hematologic Neoplasms; Humans; Infant; Infant, Newborn; Male; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prognosis; Prospective Studies; Survival Rate

The empirical treatment of febrile, neutropenic patients with cancer requires antibacterial regimens active against both gram-positive and gram-negative pathogens. This study was performed to demonstrate the noninferiority of monotherapy with piperacillin-tazobactam, compared with cefepime.. We conducted a randomized-controlled, open-label, multicenter clinical trial among high-risk patients from 34 university-affiliated tertiary care medical centers in the United States, Canada, and Australia who were undergoing treatment for leukemia or hematopoietic stem cell transplantation and were hospitalized for empirical treatment of febrile neutropenic episodes. Patients received piperacillin-tazobactam (4.5 g every 6 h) or cefepime (2 g every 8 h) intravenously. The primary outcome was success (defined by defervescence without treatment modification) at 72 h of treatment, end of treatment, and test of cure in the modified intent-to-treat analysis. Secondary outcomes included time to defervescence, microbiological efficacy, the additional use of glycopeptide antibiotics, emergence of resistant bacteria, and safety.. For 528 subjects (265 received piperacillin-tazobactam and 263 received cefepime), success rates were 57.7% and 48.3%, respectively (P = .04) at the 72-h time point, 39.6% and 31.6% (P = .06) at end of treatment, and 26.8% and 20.5% (P = .11) at the test-of-cure visit. The analyses demonstrated noninferiority for piperacillin-tazobactam at all time points (P< or = .0001). Treatment with piperacillin-tazobactam was independently associated with treatment success in multivariate analysis (odds ratio, 1.65; 95% confidence interval, 1.04-2.64; P = .035). Both regimens were well tolerated.. This study demonstrates the noninferiority and safety of piperacillin-tazobactam monotherapy, compared with cefepime, for the empirical treatment of high-risk febrile neutropenic patients with cancer.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefepime; Cephalosporins; Female; Fever; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Leukemia; Male; Middle Aged; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Treatment Outcome

We compared the efficacy of ceftriaxone (CA regimen) and piperacillin-tazobactam (PTA regimen) in association with amikacin in the treatment of febrile episodes in severely neutropenic hematological patients.. A total of 252 febrile episodes in 224 patients were randomized.. The CA regimen was effective in 62/122 evaluable episodes (50.8%), and the PTA regimen was effective in 64/121 (52.9%; P>0.2). Median time to failure was 4 and 5 days (P>0.1). Further infections developed in 21/122 episodes (17.2%) with the CA regimen and in 12/121 (9.9%) with the PTA regimen (P=0.06). The overall mortality at the end of the febrile episode was 11/243 (4.5%); seven deaths were considered to be related to infection.. Patients treated with piperacillin-tazobactam and amikacin tended to become afebrile sooner and to suffer a lower rate of further infections, even though our data did not show any statistically significant differences between the two groups.

Topics: Adult; Aged; Amikacin; Anti-Bacterial Agents; Ceftriaxone; Drug Therapy, Combination; Female; Fever; Hematologic Neoplasms; Humans; Male; Middle Aged; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Treatment Outcome

The efficacy of piperacillin-tazobactam as first line empiric therapy was assessed in 54 febrile neutropenic episodes in 42 patients (27 male, 15 female) with haematological malignancy. Nineteen (35%) episodes were bacteraemias (15 Gram-positive, 4 Gram-negative), 5 (9%) were clinically documented (Hickman line sites) and 30 (56%) were pyrexias of unknown origin. Study therapy was initiated after a median of 4 days of neutropenia (range 1-30). Eighteen (33%) episodes responded to piperacillin-tazobactam without a need for treatment modification. Four (7%) episodes initially responded to piperacillin-tazobactam but required treatment modification for fungal superinfection. Of the 19 bacteraemias, 6 (32%) were eradicated or presumed eradicated by piperacillin-tazobactam. Of the 32 (60%) episodes which failed to respond to piperacillin-tazobactam, 11 (34%) responded to anti-fungal therapy; 14 (44%) responded to a glycopeptide and 5 (16%) responded to a second-line broad spectrum antibacterial agent. Two (6%) patients died, both in the presence of progressive malignancy. There was no significant toxicity associated with piperacillin-tazobactam. We conclude that piperacillin-tazobactam is effective as empiric monotherapy in neutropenic fever and may reduce the requirement for glycopeptides.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; beta-Lactamase Inhibitors; Drug Combinations; Drug Therapy, Combination; Enzyme Inhibitors; Female; Fever; Gram-Negative Bacteria; Gram-Positive Bacteria; Hematologic Neoplasms; Humans; Male; Middle Aged; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Treatment Outcome

Febrile neutropenia (FN) is a life-threatening complication that predisposes cancer patients to serious infections. This study aims to describe the epidemiology and source of infection in cancer patients with FN in a tertiary care hospital.. A hospital-based retrospective study was conducted in a large tertiary care hospital from January 2020 to December 2021. Data on cancer patients with FN were collected from the hospital information system.. 150 cancer patients with FN were identified during the study period. Most patients were males (98; 65.3%), and the mean age of participants was 42.2 ± 16.0 years. Most patients (127; 84.7%) had hematologic malignancies, and acute myeloid leukemia was the most common diagnosis (42; 28%), followed by acute lymphocytic leukemia (28; 18.7%) and Hodgkin's lymphoma (20; 13.3%). Fifty-four (36%) patients had a median Multinational Association for Supportive Care in Cancer (MASCC) scores greater than 21. Regarding the outcome, nine (6%) died, and 141(94%) were discharged. The focus of fever was unknown in most patients (108; 72%). Among the known origins of fever were colitis (12; 8%), pneumonia (8; 5.3%), cellulitis (6; 4%), bloodstream infections (7; 4.6%), perianal abscess (2; 1.3%) and others. The median duration of fever was two days, and the median duration of neutropenia was seven days. Sixty-three (42%) patients had infections: 56 (73.3%) were bacterial, four (2.6%) were viral, two (1%) were fungal and 1 (0.7%) was parasitic. Among the bacterial causes, 50 cases (89.2%) were culture-positive. Among the culture-positive cases, 34 (68%) were gram-positive and 22 (44%) were gram-negative. The most frequent gram-positive bacteria were E. faecalis (9; 18% of culture-positive cases), and the most frequent gram-negative organisms were Klebsiella pneumoniae (5; 10%). Levofloxacin was the most commonly used prophylactic antibiotic (23; 15.33%), followed by acyclovir (1610.7%) and fluconazole in 15 patients (10%). Amikacin was the most popular empiric therapy, followed by piperacillin/tazobactam (74; 49.3%), ceftazidime (70; 46.7%), and vancomycin (63; 42%). One-third of E. faecalis isolates were resistant to ampicillin. Approximately two-thirds of Klebsiella pneumoniae isolates were resistant to piperacillin/tazobactam and ceftazidime. Amikacin resistance was proven in 20% of isolates.. The majority of patients suffered from hematologic malignancies. Less than half of the patients had infections, and the majority were bacterial. Gram-positive bacteria comprised two-thirds of cases. Therefore, empiric therapy was appropriate and in accordance with the antibiogram of the isolated bacteria.

Topics: Adult; Amikacin; Anti-Bacterial Agents; Ceftazidime; Developing Countries; Febrile Neutropenia; Female; Fever; Hematologic Neoplasms; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Therapy, Combination; Febrile Neutropenia; Female; Hematologic Neoplasms; Humans; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Changes in fecal microbiota affect the incidence and extent of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Most patients with hematological malignancies receive antibiotics for the treatment of febrile neutropenia prior to allogeneic HSCT, and pre-transplant use of antibiotics may influence the fecal microbiota and GVHD.. We retrospectively analysed consecutive adult patients with hematological malignancies who received allogeneic HSCT at Chungnam National University Hospital between 2007 and 2018. Pre-transplant use of antibiotics was defined as the use of antibiotics before conditioning chemotherapy.. Pre-transplant use of glycopeptide tends to increase the incidence of extensive cGVHD.

Topics: Adult; Aged; Anti-Bacterial Agents; Carbapenems; Cefepime; Disease-Free Survival; Female; Glycopeptides; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Transplantation, Homologous; Treatment Outcome; Young Adult

Infection is a major complication for patients with haematological malignancies. It is important to better understand the use of antimicrobial agents and antibiotic resistance for appropriate treatment and prevention of drug resistance. However, very few multi-centre analyses have focused on the use of antimicrobial agents and antibiotic resistance have been carried out in Japan. This study aimed to describe the characteristics of the use of antimicrobial agents and antibiotic resistance in patients with haematological malignancies.. We conducted a cross-sectional study using administrative claims data and antimicrobial susceptibility data in Japan. We included patients diagnosed with haematological malignancies, who were hospitalized in a haematology ward between 1 April 2015 and 30 September 2017 in 37 hospitals. Descriptive statistics were used to summarize patient characteristics, antimicrobial utilization, bacterial infections, and antibiotic resistance.. In total, 8064 patients were included. Non-Hodgkin lymphoma (50.0%) was the most common malignancy. The broad-spectrum antibiotics displayed a following antimicrobial use density (AUD): cefepime (156.7), carbapenems (104.8), and piperacillin/tazobactam (28.4). In particular, patients with lymphoid leukaemia, myeloid leukaemia, or myelodysplastic syndromes presented a higher AUD than those with Hodgkin lymphoma, non-Hodgkin lymphoma, or multiple myeloma. The most frequent bacterial species in our study cohort was Escherichia coli (9.4%), and this trend was also observed in blood specimens. Fluoroquinolone-resistant E. coli (3.6%) was the most frequently observed antibiotic-resistant strain, while other antibiotic-resistant strains were rare.. Broad-spectrum antibiotics were common in patients with haematological malignancies in Japan; however, antibiotic-resistant bacteria including carbapenem-resistant or multidrug-resistant bacteria were infrequent. Our results provide nationwide, cross-sectional insight into the use of antimicrobial agents, prevalence of bacteria, and antibiotic resistance, demonstrating differences in antimicrobial utilization among different haematological diseases.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Cefepime; Cross-Sectional Studies; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Escherichia coli; Female; Hematologic Neoplasms; Humans; Japan; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Young Adult

To assess population pharmacokinetics (PK) and pharmacodynamics (PD) of both piperacillin and tazobactam in neutropenia patients and examine dosage requirements related to the MIC distribution for Gram-negative bacteria involved in bloodstream infections (BSIs).. We conducted a prospective study including adult haematological malignancy patients with febrile neutropenia receiving piperacillin/tazobactam as short (30 min) or prolonged (4 h) intravenous infusions. Concentration data were analysed using a population approach. Dosing simulations with the final model investigated factors influencing the PK/PD of piperacillin/tazobactam quantified by fT>MIC or PTA for piperacillin and tazobactam, respectively. In parallel, the local MIC distribution of β-lactams was documented for Gram-negative bacteria involved in BSIs.. Over 10 months, 31 patients were enrolled, with 11 (35.5%) short and 20 (64.5%) prolonged infusion regimens. A one-compartment model adequately described the data for both drugs. Prolonged infusion, increased serum alkaline phosphatase (ALP) values and renal function impairment were associated with increased piperacillin fT>MIC. For patients with normal or augmented renal CL, dosing regimens q8h or q6h with 30 min of infusion were insufficient to achieve acceptable PTA for piperacillin/tazobactam at the median MIC value of 8 mg/L. Prolonged infusion of large doses was associated with the best PTA for both piperacillin and tazobactam.. In a population of haematological malignancy patients with neutropenia, renal function and ALP influenced the PK of piperacillin/tazobactam. Prolonged intravenous infusion would optimize the PK of piperacillin/tazobactam, especially in the case of augmented renal CL and/or low-range bacterial susceptibility.

Topics: Adult; Aged; Anti-Bacterial Agents; Biomarkers; Dose-Response Relationship, Drug; Drug Monitoring; Febrile Neutropenia; Female; Hematologic Neoplasms; Humans; Infusions, Intravenous; Male; Microbial Sensitivity Tests; Middle Aged; Piperacillin, Tazobactam Drug Combination; Treatment Outcome; Young Adult

Febrile neutropenia (FN) is a life-threatening complication of cancer therapy, and initial ineffective therapy is associated with poor outcomes. Piperacillin/tazobactam (PTZ) is a commonly used empiric antibiotic for the treatment of FN, but resistance among Gram-negative pathogens is well described. We conducted a retrospective case-control study to identify risk factors for PTZ-resistant (PTZ-R) Gram-negative isolates.. Hematology/oncology patients with FN from November 2007 to November 2013 with a positive culture for Gram-negative bacilli were divided into two groups: PTZ-sensitive (PTZ-S) and PTZ-R. A multivariable model using logistic regression was constructed to identify risk factors for PTZ-R.. A total of 171 patients were included (25 PTZ-R, 146 PTZ-S), yielding a 14.6 % resistance rate. Thirty-day all-cause mortality was significantly higher in the PTZ-R group (29 vs 11 %, P = 0.024). Multivariable analysis yielded intensive care unit (ICU) status (odds ratio (OR) 20.18; 95 % confidence interval (CI) 1.03-397.35; P = 0.048), antibiotics for > 14 days in the previous 90 days (OR 6.02; CI 1.17-30.93; P = 0.032), and respiratory source (OR 13.65; CI 1.14-163.57; P = 0.039) as significant risk factors for PTZ-R, and the receiver operating characteristic area under the curve of the model was 0.894. Among PTZ-R isolates, 88 % were sensitive to meropenem and 100 % were sensitive to amikacin.. Given the high mortality rates in the PTZ-R group, a risk-factor-guided approach driven by this multivariable model may help identify patients that could benefit from amikacin combination therapy to help optimize empiric therapy in this setting.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Case-Control Studies; Drug Resistance, Multiple, Bacterial; Febrile Neutropenia; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hematologic Neoplasms; Humans; Male; Middle Aged; Neoplasms; Penicillanic Acid; Penicillin Resistance; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Factors; Young Adult

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

Invasive aspergillosis (IA) remains one of the most significant causes of morbidity and mortality in patients with hematological malignancies undergoing chemotherapy and hematopoietic stem cell transplantation (HSCT), mainly due to the difficulty in its early diagnosis. Monitoring of galactomannan (GM) antigen, an exoantigen of Aspergillus, in the blood by sandwich ELISA is a useful and noninvasive method for early diagnosis of IA. The GM test has a sensitivity of 67-100% with a specificity of 81-99% in neutropenic patients and allogeneic transplant recipients [1-3]. Although it has been widely used as a diagnostic criterion for IA [4,5], one of the major limitations of this assay is false-positivity, particularly in pediatric patients [1], patients with graft-versus-host disease (GVHD) [6,7], and those taking dietary GM [8,9] or fungus-derived antibiotics, such as piperacillin-tazobactam (PIPC/TAZ) [10-12].

Topics: Amoxicillin; Antibiotic Prophylaxis; Antigens, Fungal; Artifacts; Aspergillosis; Aspergillus; False Positive Reactions; Galactose; Hematologic Diseases; Hematologic Neoplasms; Humans; Immunoglobulin G; Mannans; Multiple Myeloma; Myeloma Proteins; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sensitivity and Specificity

The efficacy of conventional doses of piperacillin/ tazobactam (PTZ) plus amikacin (AMK) were compared retrospectively to low doses of cefepime (CEF) plus amikacin in high risk febrile neutropenic patients with an underlying hematologic malignancy, and CEF versus PTZ (without AMK) in low risk individuals with febrile neutropenia and underlying solid tumor malignancies.. Fifty-six high risk hematologic malignancy patients received a combination of PTZ 4.5 grams administered every 8 hours plus AMK 15 mg/kg/day, while 46 received CEF 1 gram administered every 12 hours plus AMK 15 mg/kg/day. In addition, 19 febrile neutropenic individuals with underlying solid malignancies received PTZ 4.5 grams every 8 hours and 25 received CEF 1 gram every 12 hours. All patients were treated in an isolation unit section of a general internal medicine ward.. There was no significant difference between the groups in terms of age, depth of neutropenia, microbiologic result, morbidity, length of hospital stay or mortality.. PTZ and CEF in combination with AMK were equally efficacious in neutropenic patients with hematologic malignancies. In addition, monotherapy with CEF or PTZ proved to be equally efficacious in neutropenic patients with solid tumors. Low dose CEF is safe and allows a reduction of cost and less antibiotic exposure.

Topics: Adult; Aged; Amikacin; Anti-Bacterial Agents; Cefepime; Cephalosporins; Drug Therapy, Combination; Female; Fever; Hematologic Neoplasms; Humans; Male; Middle Aged; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Factors; Treatment Outcome

In this prospective study including 78 adult patients with haematological malignancy (90 episodes) we performed galactomannan (GM) (Platelia Aspergillus) screening twice weekly for the diagnosis of invasive aspergillosis. There were five proven and four probable invasive aspergillosis cases. The sensitivity, specificity and positive and negative predictive values were 100, 88, 47 and 100%, respectively. There were eight patients with false positive GM (10.2%). In six patients the false GM reactivity was due to the administration of piperacillin-tazobactam (P-T). A significant association was found between false positive GM (= or > 0.5) and the administration of P-T (p < 0.01). Two other patients with no invasive aspergillosis (2.5%) and false GM reactivity had graft versus host disease (GVHD) and one of them had also mucositis grade IV. The kinetic patterns of false positive GM due to P-T is discussed.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Artifacts; Aspergillosis; Biomarkers; Combined Modality Therapy; Enzyme-Linked Immunosorbent Assay; False Positive Reactions; Female; Fungemia; Galactose; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Mannans; Middle Aged; Mucositis; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Predictive Value of Tests; Prospective Studies; Sensitivity and Specificity

We report the occurrence of a high rate of false-positive test results during the surveillance of hematology patients for galactomannan (GM) antigenemia. Among 218 patients surveyed from June 2002 through June 2003, 42 (19.3%) had > or =1 serum sample positive for GM (optical density index, >1.5). Of these patients, 38 had no additional evidence of invasive aspergillosis, and, therefore, their test results were considered to be false-positives. Case-control analysis showed that treatment with piperacillin-tazobactam was the only risk factor significantly associated with receiving false-positive test results. When tested for GM antigen, 3 of 4 piperacillin-tazobactam batches had positive results. Physicians should be aware of the possible interference of treatment with piperacillin-tazobactam when interpreting the results of the GM assay.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Antigens, Fungal; Aspergillus; Case-Control Studies; False Positive Reactions; Female; Galactose; Hematologic Neoplasms; Humans; Male; Mannans; Microbiological Techniques; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sensitivity and Specificity