piperacillin--tazobactam-drug-combination and Neutropenia

Several beta-lactams are recommended as single agents for the treatment of febrile neutropenia.. To compare the effectiveness of different anti-pseudomonal beta-lactams as single agents in the treatment of febrile neutropenia. To compare the development of bacterial resistance, bacterial and fungal superinfections during or following treatment with the different beta-lactams.. We searched the Cochane Register of Controlled Trials (CENTRAL), Issue 3, 2010. MEDLINE, EMBASE, LILACS, FDA drug applications, conference proceedings and ongoing clinical trial databases up to August 2010. References of included studies were scanned.. Randomised controlled trials (RCTs) comparing an antipseudomonal beta-lactam to another antipseudomonal beta-lactam antibiotic, both given alone or with the addition of the same glycopeptide to both study arms, for the initial treatment of fever and neutropenia among cancer patients.. Two review authors applied inclusion criteria and extracted the data independently. Missing data were sought. Risk ratios (RR) were calculated with 95% confidence intervals (CI), and pooled using the fixed effect model. The primary outcome was all-cause mortality. Risk of bias was assessed using a domain-based evaluation and its effect of results was assessed through sensitivity analyses.. Forty-four trials were included. The antibiotics assessed were cefepime, ceftazidime, piperacillin-tazobactam, imipenem and meropenem. Adequate allocation concealment and generation were reported in about half of the trials and only two trials were double-blinded. The risk for all-cause mortality was significantly higher with cefepime compared to other beta-lactams (RR 1.39, 95% CI 1.04 to 1.86, 21 trials, 3471 participants), without heterogeneity and with higher RRs in trials at low risk for bias. There were no differences in secondary outcomes but for a non-significantly higher rate of bacterial superinfections with cefepime. Mortality was significantly lower with piperacillin-tazobactam compared to other antibiotics (RR 0.56, 95% CI 0.34 to 0.92, 8 trials, 1314 participants), without heterogeneity. Carbapenems resulted in similar all-cause mortality and a lower rate of clinical failure and antibiotic modifications as compared to other antibiotics, but a higher rate of diarrhea caused by Clostridium difficile.. Current evidence supports the use of piperacillin-tazobactam in locations where antibiotic resistance profiles do not mandate empirical use of carbapenems. Carbapenems result in a higher rate of antibiotic-associated and Clostridium difficile-associated diarrhea. There is a high level of evidence that all-cause mortality is higher with cefepime compared to other beta-lactams and it should not be used as monotherapy for patients with febrile neutropenia.

Topics: Anti-Bacterial Agents; beta-Lactams; Cefepime; Ceftazidime; Cephalosporins; Fever; Humans; Imipenem; Meropenem; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Randomized Controlled Trials as Topic; Thienamycins

Piperacillin-tazobactam is a beta-lactam/beta-lactamase inhibitor combination with a broad spectrum of antibacterial activity that includes Gram-positive and -negative aerobic and anaerobic bacteria. Piperacillin-tazobactam retains its in vitro activity against broad-spectrum beta-lactamase-producing and some extended-spectrum beta-lactamase-producing Enterobacteriaceae, but not against isolates of Gram-negative bacilli harboring AmpC beta-lactamases. Piperacillin-tazobactam has recently been reformulated to include ethylenediaminetetraacetic acid and sodium citrate; this new formulation has been shown to be compatible in vitro with the two aminoglycosides, gentamicin and amikacin, allowing for simultaneous Y-site infusion, but not with tobramycin. Multicenter, randomized, double-blinded clinical trials have demonstrated piperacillin-tazobactam to be as clinically effective as relevant comparator antibiotics. Clinical trials have demonstrated piperacillin-tazobactam to be effective for the treatment of patients with intra-abdominal infections, skin and soft tissue infections, lower respiratory tract infections, complicated urinary tract infections, gynecological infections and more recently, febrile neutropenia. Piperacillin-tazobactam has an excellent safety and tolerability profile and continues to be a reliable option for the empiric treatment of moderate-to-severe infections in hospitalized patients.

Topics: Anti-Bacterial Agents; beta-Lactamase Inhibitors; Clinical Trials as Topic; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Randomized Controlled Trials as Topic; Soft Tissue Infections

The authors had for aim to assess the effectiveness and toxicity of a piperacillin-tazobactam-netilmicin combination, and the possibility of avoiding using glycopeptide, in children with febrile neutropenic episodes induced by chemotherapy.. A retrospective study was made, including children treated for a febrile neutropenic episode (absolute neutrophile count < 0.5 x 10(9)/l) by a piperacillin-tazobactam-netilmicin combination. If fever persisted 48 hours after the beginning of antibiotic therapy, a glycopeptide could be added. The responses to the treatment were defined as follows: 1) total success (no fever or documented infection) at 48 hours and at 72 hours following the beginning of treatment; 2) partial success (apyrexia beyond 72 hours without any therapeutic change); 3) failure (persistent infectious signs 48 hours after the introduction of glycopeptide).. Sixty-nine episodes were assessable, corresponding to 41 patients, treated for a solid tumour (29), an acute leukaemia in remission (11), or a metabolic disease (1). The febrile episodes were divided into fever of unknown origin (71%), microbiologically documented fever (12%), and clinically documented fever (17%). No death occurred, no toxicity was reported. With this antibiotic therapy, total success at 72 hours was observed in 72% in case of fever of unknown origin and 45% in case of documented infections. The success rate reached 84% when a glycopeptide was added (30% of the cases).. The piperacillin-tazobactam-netilmicin combination is very effective and well tolerated in probabilistic treatment of febrile neutropenia induced by chemotherapy, but does not allow to decreasing the frequency of glycopeptide administration.

Topics: Adolescent; Anti-Bacterial Agents; Antineoplastic Agents; Bacterial Infections; Child; Child, Preschool; Clinical Trials as Topic; Drug Combinations; Drug Evaluation; Escherichia coli Infections; Female; Fever; Fever of Unknown Origin; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Infant; Male; Neoplasms; Netilmicin; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Postoperative Complications; Retrospective Studies; Treatment Outcome; Urinary Tract Infections

Piperacillin/tazobactam is a beta-lactam/beta-lactamase inhibitor combination with a broad spectrum of antibacterial activity against most Gram-positive and Gram-negative aerobic bacteria and anaerobic bacteria. Piperacillin/tazobactam is effective and well-tolerated in patients with lower respiratory tract infections (LRTI), intra-abdominal infections, skin and soft tissue infections, and febrile neutropenia. In comparative clinical trials against various other antibacterial regimens, piperacillin/tazobactam has shown higher clinical success rates, particularly in the treatment of patients with intra-abdominal infections and febrile neutropenia. Cost analyses of piperacillin/tazobactam have been variable, in part, because of differences in specific costs included. Three US cost analyses found that piperacillin/tazobactam had lower total medical costs than clindamycin plus gentamicin or imipenem/cilastatin in intra-abdominal infections, and ticarcillin/ clavulanic acid in community-acquired pneumonia. Piperacillin/tazobactam plus amikacin had lower total costs than ceftazidime plus amikacin in another cost analysis of patients with febrile neutropenic episodes modelled in nine European countries. However, piperacillin/tazobactam plus tobramycin was more costly than ceftazidime plus tobramycin in hospital-acquired pneumonia in a US cost analysis. In cost-effectiveness analyses, all studies of intra-abdominal infections, pneumonia and febrile neutropenic episodes consistently reported lower costs per unit of effectiveness versus comparators. Piperacillin/tazobactam was dominant (greater efficacy and lower costs) versus imipenem/cilastatin in intra-abdominal infections and ceftriaxone, ciprofloxacin or meropenem in pneumonia. Piperacillin/tazobactam plus amikacin was dominant over ceftazidime plus amikacin in the treatment of febrile neutropenic episodes. In a cost-effectiveness analysis of skin and soft tissue infection, piperacillin/tazobactam had lower costs per successfully treated patient than ceftriaxone or cefotaxime, but a slightly higher cost-effectiveness ratio than amoxicillin/clavulanic acid. All cost-effectiveness analyses were based on decision-analytical models.. Piperacillin/tazobactam is likely to reduce overall treatment costs of moderate to severe bacterial infections by increasing initial treatment success, thereby reducing the length of hospital stay and the use of additional antibacterials. Piperacillin/tazobactam has shown clinical and economic advantages over standard antibacterial regimens in the treatment of intra-abdominal infections, LRTIs, febrile episodes in patients with neutropenia, and skin and soft tissue infections, although more complete published data are needed to confirm these results. Present data regarding clinical efficacy, bacterial resistance and costs would support the use of piperacillin/tazobactam as an empirical first-line option in moderate to severe bacterial infections.

Topics: Bacterial Infections; Cost-Benefit Analysis; Cross Infection; Drug Therapy, Combination; Drug Tolerance; Economics, Pharmaceutical; Hospitalization; Humans; Microbial Sensitivity Tests; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

To describe the population pharmacokinetics of the piperacillin component of piperacillin/tazobactam.. This pharmacokinetic study included 21 pediatric (age 3-10 years) patients receiving piperacillin/tazobactam to treat fever with neutropenia. Each patient contributed 1-3 blood samples for piperacillin concentration determination. Population pharmacokinetic analyses were conducted using Pmetrics software. A 5,000 patient Monte Carlo simulation was performed to determine the probability of target attainment (PTA) for multiple dosing regimens, using 50% of free drug time above the minimum inhibitory concentration (MIC) as the primary pharmacodynamic threshold.. Mean ± SD body weight was 28.5 ± 9.7 kg. Piperacillin concentration data best fit a two-compartment model with linear clearance, using total body weight as a covariate for clearance (CLθ ) and volume of the central compartment (Vcθ ). Population estimates for CLθ , Vcθ , and intercompartment transfer constants were 0.204 ± 0.076 L/h/kg, 0.199 ± 0.107 L/kg, 0.897 ± 1.050 h(-1) , and 1.427 ± 1.609 h(-1) , respectively. R(2) , bias, and precision for the Bayesian fit were 0.998, -0.032, and 2.2 µg/ml, respectively. At the MIC breakpoint of 16 µg/ml for Pseudomonas aeruginosa, PTAs for 50 mg/kg q4h as a 0.5 hr infusion was 93.9%; for 100 mg/kg q8h as 0.5 and 4 hr infusion: 64.6% and 100%; for 100 mg/kg q6h as 0.5 and 3 hr infusion: 86.5% and 100%; and for 400 mg/kg continuous infusion: 100%, respectively.. In children with fever and neutropenia, piperacillin/tazobactam dosing regimens that are administered every 4 hr or that employ prolonged or continuous infusions should be considered to optimize pharmacodynamic exposure.

Topics: Anti-Bacterial Agents; Child; Child, Preschool; Female; Fever; Humans; Male; Models, Biological; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections

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

Determination of risk of severe bacterial infection complication in children with cancer is important to diminish the cost of hospitalization and therapy. In this study, children with cancer (leukemia excluded) were evaluated for risk of severe infection complication, success of therapy and the relation between clinical and inflammatory parameters during neutropenic fever attacks. Children who fulfilled the criteria of neutropenic fever with cancer were enrolled in the study. During admission, together with clinical and laboratory parameters; interleukin-6, interleukin-8, soluble tumor necrosis factor receptor II, and soluble interleukin 2 reseptor ve procalcitonin levels were detected. Empirical therapy was started with piperacillin/tazobactam and relation between the inflammatory cytokine levels and therapy response parameters were evaluated. The study population included 31 children and 50 neutropenic attacks were studied. In 48% of the attacks, absolute neutrophile count was >100/mm(3) and infectious agents were shown microbiologically in 12% of the attacks. In the study group with piperacillin/tazobactam monotherapy, the success rate without modification was 58%. In the therapy modified group mean duration of fever, antibiotherapy and hospitalization were significantly longer than the group without modification. Inflammatory cytokines' levels during admission (interleukin-6, interleukin-8, soluble tumor necrosis factor reseptor II) were higher in patients with fever >3 days and in multiple regression analysis, it has been shown that they have a determinative role on fever control time. Other cytokines did not show any significant relationship with risk of severe bacterial infection complication and success of therapy.

Topics: Adolescent; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Cytokines; Female; Fever; Humans; Infant; Inflammation Mediators; Male; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Predictive Value of Tests; Risk Factors

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

Monotherapy has tended to replace the combination therapy in emprical treatment of febrile neutropenia. There is no reported trial which compares the efficacy of cefoperazone-sulbactam (CS) and piperacillin-tazobactam (PIP/TAZO) monotherapies in the treatment of febrile neutropenia. In this prospective randomized study, we aimed to compare the safety and efficacy of CS versus PIP/TAZO as empirical monotherapies in febrile neutropenic children with cancer.. The study included febrile, neutropenic children hospitalized at our center for cancer. They were randomly selected to receive CS 100 mg/kg/day or PIP/TAZO 360 mg/kg/day. Duration of fever and neutropenia, absolute neutrophil count, modification, and success rate were compared between the two groups. Resolution of fever without antibiotic change was defined as success and resolution of fever with antibiotic change or death of a patient was defined as failure. Modification was defined as changing the empirical antimicrobial agent during a febrile episode.. One hundred and two febrile neutropenic episodes were documented in 55 patients with a median age of 4 years. In 50 episodes CS and in 52 episodes PIP/TAZO was used. Duration of fever and neutropenia, neutrophil count, age, sex, and primary disease were not different between two groups. Success rates in the CS and PIP/TAZO groups were respectively 56 and 62% (P > 0.05). Modification rate between two groups showed no significant difference (P > 0.05). No serious adverse effect occurred in either of the groups.. CS and PIP/TAZO monotherapy are both safe and effective in the initial treatment of febrile neutropenia in children with cancer.

Topics: Adolescent; Anti-Bacterial Agents; Cefoperazone; Child; Child, Preschool; Female; Fever; Humans; Infant; Male; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam; Time Factors

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 study was to evaluate the efficacy and safety of piperacillin/tazobactam (PIP/TAZO) and cefozopran (CZOP) monotherapy in pediatric cancer patients with febrile neutropenia (FN).. A total of 119 febrile episodes in 49 neutropenic pediatric cancer patients (20 females and 29 males) with a median age of 6.8 years (range, 0.3-18.4 years) received randomized treatment either with PIP/TAZO 125 mg/kg every 8 hr or CZOP 25 mg/kg every 6 hr. Clinical response was determined at completion of therapy. Durations of fever and neutropenia, the need for modification of the therapy, and mortality rates were compared between the two groups.. The frequency of success without modification of treatment was not significantly different between PIP/TAZO (59.6%) and CZOP (53.2%). Durations of fever and antibiotic therapy did not differ between the treatment groups, and no major side effects were observed in either group.. PIP/TAZO and CZOP monotherapy were both effective and safe for the initial empirical treatment of pediatric cancer patients with FN.

Topics: Adolescent; Anti-Bacterial Agents; Bacterial Infections; Cefozopran; Cephalosporins; Child; Child, Preschool; Female; Fever; Humans; Male; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

In view of the recent trend toward monotherapy in the treatment of febrile neutropenia, we evaluated the clinical efficacy and safety of imipenem-cilastatin versus piperacillin-tazobactam as an empiric therapy for febrile neutropenia in children with malignant diseases.. Febrile neutropenic patients received either imipenem-cilastatin or piperacillin-tazobactam randomly. Improvement without any changes in the initial antibiotic treatment was defined as "success" and improvement with modification of the initial treatment and death was defined as "failure".. Over 12 months, 99 febrile neutropenic episodes were treated with monotherapy in 63 patients with a median age of 5 years. At admission, median absolute neutrophil count was 50/mm(3) and in 67% of episodes, neutrophil count was under 100/mm(3). Median duration of neutropenia was 5 days. In 22% of episodes, neutropenia persisted for more than 10 days. Piperacillin-tazobactam was used in 52 episodes and imipenem-cilastatin was used in 47 episodes. There was no difference between groups in terms of age, sex, primary diseases, neutrophil count or duration of neutropenia. In the whole group, the success rate was 67% and the failure rate was 33%, whereas in the piperacillin-tazobactam group, the rates were 71% and 29%; and in the imipenem-cilastatin group they were 62% and 38%, respectively (P > 0.05). There were no deaths. No major adverse effects were seen in either group.. Although failure was slightly higher in the imipenem-cilastatin group, this was statistically insignificant. Both of these antibiotics can be used safely for initial empirical monotherapy of febrile neutropenia.

Topics: Adolescent; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Fever; Humans; Imipenem; Male; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies

Patients with fever and granulocytopenia are at risk of developing severe infection. We performed a prospective, randomized trial to evaluate the efficacy of low-dose cefepime plus amikacin (C-A) compared to low-dose piperacillin/tazobactam plus amikacin (PT-A). Patients received cefepime (2 g/12 h) plus amikacin (15 mg/kg/day) or piperacillin/tazobactam (4 g/500 mg/8 h) plus amikacin. A total of 317 episodes of febrile granulocytopenia in 190 patients were studied (152 in the C-A group, 165 in the PT-A group). A microbiologically documented infection was present in 53 (35%) episodes in the C-A group and 41 (25%) episodes in the PT-A group (p = ns); a clinically documented infection was observed in 39 (26%) and 47 (28%) episodes, respectively. Toxicity was observed in 6 (4%) episodes in the C-A group and in 5 (3%) episodes in the PT-A group. The antibiotic success rate (no change or addition of antibiotics) was recorded in 89 (59%) and 105 (64%) cases, respectively (p = ns). Mortality related to infection was similar in each arm (3.9% vs. 3.6%). Combination therapy of low-dose beta-lactam with an aminoglycoside achieves very good response rates and low rates of toxicity. It might be an attractive option in an environment of increasing resistance among gram-negative bacteria.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Cefepime; Cephalosporins; Female; Fever of Unknown Origin; Humans; Incidence; Male; Middle Aged; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Poisoning; Prospective Studies; Treatment Outcome; Young Adult

Empirical beta-lactam monotherapy has become the standard therapy in febrile neutropenia. The aim of this study was to compare the efficacy and safety of piperacillin-tazobactam versus carbapenem therapy with or without amikacin in adult patients with febrile neutropenia.. In this prospective, open, single-center study, 127 episodes were randomized to receive either piperacillin-tazobactam (4 x 4.5 g IV/day) or carbapenem [meropenem (3 x 1 g IV/day) or imipenem (4 x 500 mg IV/day)] with or without amikacin (1 g IV/day). Doses were adjusted according to renal function. Clinical response was determined during and at completion of therapy.. One hundred and twenty episodes were assessable for efficacy (59 piperacillin-tazobactam, 61 carbapenem). Mean duration of treatment was 14.8 +/- 9.6 days in the piperacillin-tazobactam group and 14.7 +/- 8.8 days in the carbapenem group (P > 0.05). Mean days of fever resolution were 5.97 and 4.48 days for piperacillin-tazobactam and carbapenem groups, respectively (P > 0.05). Similar rates of success without modification were found in the piperacillin-tazobactam (87.9%) and in the carbapenem groups (75.4%; P > 0.05). Fungal infection occurrence rates were 30.5 and 18% in piperacillin-tazobactam and carbapenem groups, respectively (P = 0.05). Antibiotic modification rates were 30.5 and 13.1% (P = 0.02) and the addition of glycopeptides to empirical antibiotic regimens rates were 15.3 and 44.3% for piperacillin-tazobactam and carbapenem groups, respectively (P = 0.001). The rude mortality rates were 14% (6/43) and 29.3% (12/41) in piperacillin-tazobactam and carbapenem groups, respectively (P = 0.08).. The effect of empirical regimen of piperacillin-tazobactam regimen is equivalent to carbapenem in adult febrile neutropenic patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Antineoplastic Agents; Bacterial Infections; Carbapenems; Drug Eruptions; Drug Therapy, Combination; Female; Fever; Humans; Male; Middle Aged; Multivariate Analysis; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Survival Rate; Young Adult

The efficacy and safety of piperacillin/tazobactam plus ceftazidime (PIPC/TAZ+CAZ) versus sulbactam/ampicillin plus aztreonam (SBT/ABPC+AZT) as empirical therapy for febrile neutropenia were assessed in children with hematologic disease and solid tumor.. A prospective randomized study was performed to evaluate the clinical response of 70 febrile episodes in the PIPC/TAZ+CAZ arm and 64 evaluable febrile episodes in the SBT/ABPC+AZT arm of the study. Clinical efficacy was evaluated at 120 hours, with treatment outcome criteria defined as follows. Success was defined as disappearance of fever, clinical improvement, eradication of the infecting organism, and maintenance of a response for at least 7 days after discontinuation of treatment.. An infection was documented microbiologically in 14 episodes (20%) in the PIPC/TAZ+CAZ arm and in 8 episodes (13%) in the SBT/ABPC+AZT arm. The success rate was 57.1% in the PIPC/TAZ+CAZ arm and 62.5% in the SBT/ABPC+AZT arm (P>0.05). No major adverse effects were observed in the study.. PIPC/TAZ+CAZ and SBT/ABPC+AZT are effective and safe for initial empirical treatment of febrile episodes in neutropenic pediatric patients. The clinical efficacy of SBT/ABPC+AZT is equivalent or superior to that of PIPC/TAZ+CAZ, the effect of which is already proven against febrile neutropenia. Therefore, SBT/ABPC+AZT may be a treatment of choice for febrile neutropenia in pediatric cancer patients.

Topics: Adolescent; Ampicillin; Anti-Bacterial Agents; Aztreonam; beta-Lactams; Ceftazidime; Child; Child, Preschool; Drug Therapy, Combination; Female; Fever; Humans; Infant; Infant, Newborn; Male; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Severity of Illness Index; Sulbactam

This is a prospective, randomized, and open-label clinical trial that examines the efficiency and safety of PIP/TAZO monotherapy in comparison to cefepime (CEF), for the empirical treatment of pediatric cancer patients with neutropenia and fever.. One hundred thirty-one consecutive febrile episodes in 70 neutropenic pediatric cancer patients received randomized treatment either with piperacillin/tazobactam (PIP/TAZO) 80 mg/kg piperacillin/10 mg/kg tazobactam every 6 hr or CEF 50 mg/kg every 8 hr. Clinical response was determined at completion of therapy. Duration of fever, neutropenia, hospitalization, the need for modification of the therapy, and mortality rates were compared between the two groups.. One hundred twenty-seven episodes in 69 patients (35 females, 34 males) with a median age of 4.2 years were assessed for efficiency (65 PIP/TAZO, 62 CEF). The frequency of success without modification of treatment was nearly identical for both PIP/TAZO (60.0%) and CEF (61.3%) (P > 0.05). The overall response rate, with or without modification of assigned treatment, was 96.9% for PIP/TAZO and 98.4% for CEP (P > 0.05). Infection-related mortality at the end of the febrile episode was 2.4%. Duration of fever and hospitalization were not different between the treatment groups. No major side effects were observed in neither of the groups.. PIP/TAZO treatment was as effective and safe as CEF monotherapy as an initial empirical regimen in pediatric cancer patients with fever and neutropenia.

Topics: Adolescent; Anti-Bacterial Agents; Cefepime; Cephalosporins; Child; Child, Preschool; Female; Fever; Humans; Infant; Male; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies

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

We evaluated piperacillin-tazobactam in association with amikacin in the initial empirical therapy of febrile neutropenic children.. An open-labelled, non-randomised, prospective trial to assess the efficacy and safety of this association was conducted from June 1, 2001 to December 31, 2002. Children and adolescents were treated for a haematological malignancy or a primary, refractory or relapsed solid tumour, and presented with febrile neutropenia. Patients received intravenous piperacillin-tazobactam (90 mg/kg/dose every eight hours) plus a single daily dose of amikacin at 15 mg/kg/day, maximum 250 mg. If fever persisted, second-line therapy with carbapenem was administered. Teicoplanin was added for gram-positive isolates or for unremitting fever after 48 hours, if clinically indicated. Amphotericin B was added at 96 hours, if fever and neutropenia persisted.. 155 episodes of fever and neutropenia in 76 patients were evaluable. 40 (25.8 percent) episodes were a microbiologically-documented infection, 30 (19.4 percent) were clinically-documented, and 85 (54.8 percent) were unexplained fever. 77 (49.7 percent) episodes responded to piperacillin-tazobactam plus amikacin without a need for treatment modification. A higher success rate (63.5 percent) was observed in episodes with unexplained fever. The predominant pathogens isolated in our study were gram-negative organisms (70.7 percent). A mild gastrointestinal intolerance occurred in 35 out of 155 (22.6 percent) episodes.. This study suggests that piperacillin-tazobactam plus amikacin presents a satisfactory efficacy and a good tolerance as initial empirical therapy for febrile neutropenic children.

Topics: Adolescent; Adult; Amikacin; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Infant; Male; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

A prospective, randomized clinical trial was conducted to compare the efficacy of piperacillin/tazobactam and amikacin combination with carbapenem monotherapy for the empirical treatment of febrile neutropenic episodes of children with acute lymphoblastic leukemia or acute myeloblastic leukemia. Patients aged 2-16 years with hematological malignancies who had febrile neutropenia were randomly assigned to receive piperacillin/tazobactam (80 mg/kg piperacillin/10 mg/kg tazobactam, q6h) combined with amikacin (PTA) (7.5 mg/kg, q12h) or meropenem or imipenem (20 mg/kg, q8h) (C). Response to antimicrobial therapy, evaluated for etiological agents, was measured. Duration of fever, neutropenia, and hospitalization, mortality, and the need for additional antibiotics or antifungal drugs were compared for the treatment success between the two groups. Out of 87 febrile neutropenic episodes that were evaluable for comparison, 46 patients received PTA and 41 patients were treated with carbapenems (imipenem or meropenem). Overall, the microbiologically documented infection rate was 21.9%, with Staphylococcus epidermidis as the most common cause of bacteremia. The rate of treatment modification was 56.5% in the PTA group and 53.6% in the carbapenem group with no statistical difference (p > .05). There was no infection-related mortality during the study period. There was no difference between the two regimens for durations of fever, neutropenia, and hospitalization (p > .05 for all categories). PTA was as effective as carbapenem monotherapy as an initial empirical regimen in febrile neutropenic episodes of pediatric hematological malignancies.

Topics: Adolescent; Amikacin; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Carbapenems; Child; Child, Preschool; Drug Therapy, Combination; Enzyme Inhibitors; Female; Humans; Leukemia, Myeloid, Acute; Male; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Precursor Cell Lymphoblastic Leukemia-Lymphoma

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 safety and efficacy of early bacterial prophylaxis with piperacillin-tazobactam were prospectively evaluated in 51 autologous peripheral blood stem cell transplantation (PBSCT) recipients. The results were compared with those obtained in 51 control patients receiving oral fluoroquinolones in a retrospective matched-pair control study. Overall, 76% of the study group and 98% of the control group developed at least one febrile episode during neutropenia (P=0.002). Time from neutropenia to the first febrile episode (FFE) was significantly longer in the study group than in the control group (P=0.04). Once a febrile episode appeared, the duration of fever was significantly longer in cases than in controls (median of 5 and 2 days respectively, P<0.001), and led to a more frequent use of empirical amphotericin B (AmB), not statistically significant (P=0.13). However, the total time of antibiotic administration was significantly greater in the control than in the study group (P=0.05). The duration of AmB treatment shows a trend toward a longer duration in the control than in study group (P=0.2). Overall, 86% of the Gram-positive bacteremia and 85% of the Gram-negative bacteria were susceptible to the tested antibiotics. Our study suggests that a subgroup of patients could benefit from prophylaxis with piperacillin-tazobactam without increasing toxicity or bacterial resistance.

Topics: Adolescent; Adult; Aged; Amphotericin B; Bacteremia; Bacterial Infections; Female; Fever; Fluoroquinolones; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Male; Matched-Pair Analysis; Middle Aged; Neutropenia; Penicillanic Acid; Peripheral Blood Stem Cell Transplantation; Piperacillin; Piperacillin, Tazobactam Drug Combination; Premedication; Transplantation, Autologous

This prospective, double-blind trial assessed whether the addition of a glycopeptide would be able to reduce the time to defervescence in neutropenic patients with cancer who had persistent fever 48-60 h after the initiation of empirical piperacillin-tazobactam monotherapy. Of 763 eligible patients, 165 with persistent fever were randomized to receive piperacillin-tazobactam therapy plus either vancomycin therapy or placebo. Defervescence was observed in 82 (95%) of 86 patients in the vancomycin group and in 73 (92%) of 79 patients in the placebo group (P=.52). The distributions of the time to defervescence were not statistically significant between the 2 groups (estimated hazard ratio, 1.03; 95% confidence interval, 0.75-1.43; P=.75). The number of additional episodes of gram-positive bacteremia and the percentage of patients for whom amphotericin B was empirically added to their therapy regimen were also similar in both groups. This study failed to demonstrate that the empirical addition of vancomycin therapy to the treatment regimen is of benefit to persistently febrile neutropenic patients with cancer.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Double-Blind Method; Fever; Humans; Middle Aged; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Treatment Outcome; Vancomycin

We aimed at comparing the effectiveness and safety of piperacillin/tazobactam(PIP-TAZ) versus imipenem/cilastin (IMI) administered as empiric monotherapy in patients with febrile neutropenia.. Patients with hematological diseases who were randomly assigned either PIP-TAZor IMI were enrolled in the study. A sequential strategy of antibiotic therapy addition was applied as long as fever persisted or microorganisms were isolated at 72 h. Moreover, if bacteriologically unconfirmed fever persisted after 5-7 days, an antifungal therapy was started. The treatment was considered successful if fever and clinical signs resolved and/or pathogens were cleared without adding further antibiotics at 72 h. Differences between percentages were analyzed using the *2test.. 137 patients were evaluated. The successful response rate of PIP-TAZ after 72 h was similar to IMI (32.2 and 35.2%). The defervescence time was shorter (3.6 and 4.2 days) and the bacterial response more favourable with PIP-TAZ than with IMI, but statistically significant differences were not reached. The overall response in both groups was 91%.18.2% of episodes were bacteriologically confirmed. The most frequent isolated microorganism was Staphylococcus coagulase-negative(48.8%). There was one only case of septic shock, within the IMI group, and the overall mortality of the group was 8.7%. The occurrence of vomiting in the IMI group was significantly higher than in the PIP-TAZ group (39.9 and 5.6%; p < 0.0001).. PIP-TAZ is as effective as IMI and it constitutes a good choice as an initial empiric monotherapy of febrile neutropenia.

Topics: Adolescent; Adult; Aged; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Fever; Humans; Imipenem; Male; Middle Aged; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

In a prospective, multicenter, double-blind, randomized clinical trial, we compared the efficacy of piperacillin-tazobactam (4.5 g 3 times daily intravenously) plus placebo versus piperacillin-tazobactam plus amikacin (7.5 mg/kg twice daily intravenously) for the treatment of 760 febrile, adult patients with cancer with chemotherapy-induced profound (<500 neutrophils/mm3) and prolonged (>10 days) neutropenia. A total of 733 patients were assessable for efficacy of the drug regimens, and an overall successful outcome was reported in 49% (179 of 364) of the patients who received monotherapy, compared with 53% (196 of 369) of patients who received combination therapy (P=.2). Response rates were similar with both regimens, as were incidences of bacteremia and clinically documented and possible infections. In our epidemiological setting, the initial empiric combination therapy was not associated with improved outcomes when compared with initial monotherapy.

Topics: Adolescent; Adult; Aged; Amikacin; Anti-Bacterial Agents; Bacterial Infections; Double-Blind Method; Drug Therapy, Combination; Female; Fever; Humans; Male; Middle Aged; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; 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 has a significant clinical and economic impact on cancer patients. This study evaluates the cost-effectiveness of different current empiric antibiotic treatments.. A decision analytic model was constructed to compare the use of cefepime, meropenem, imipenem/cilastatin, and piperacillin/tazobactam for treatment of high-risk patients. The analysis was performed from the perspective of U.S.-based hospitals. The time horizon was defined to be a single febrile neutropenia episode. Cost-effectiveness was determined by calculating costs and deaths averted. Cost-effectiveness acceptability curves for various willingness-to-pay thresholds (WTP), were used to address the uncertainty in cost-effectiveness.. The base-case analysis results showed that treatments were equally effective but differed mainly in their cost. In increasing order: treatment with imipenem/cilastatin cost $52,647, cefepime $57,270, piperacillin/tazobactam $57,277, and meropenem $63,778. In the probabilistic analysis, mean costs were $52,554 (CI: $52,242-$52,866) for imipenem/cilastatin, $57,272 (CI: $56,951-$57,593) for cefepime, $57,294 (CI: $56,978-$57,611) for piperacillin/tazobactam, and $63,690 (CI: $63,370-$64,009) for meropenem. Furthermore, with a WTP set at $0 to $50,000, imipenem/cilastatin was cost-effective in 66.2% to 66.3% of simulations compared to all other high-risk options.. Imipenem/cilastatin is a cost-effective strategy and results in considerable health care cost-savings at various WTP thresholds. Cost-effectiveness analyses can be used to differentiate the treatments of febrile neutropenia in high-risk patients.

Topics: Anti-Bacterial Agents; Cefepime; Cilastatin, Imipenem Drug Combination; Computer Simulation; Cost-Benefit Analysis; Decision Support Techniques; Fever; Health Care Costs; Humans; Meropenem; Neutropenia; Piperacillin, Tazobactam Drug Combination; Treatment Outcome

Both in hospitals and outpatient settings, fewer fluoroquinolones have been prescribed in Germany in recent years. The consumption of cephalosporins also decreased somewhat in favor of penicillin derivatives. The aminoglycosides, which have only rarely been prescribed, can now be used again as a suitable alternative - but only parenterally - due to their relatively favorable activity and low resistance rates among typical urinary tract infection pathogens. In acute severe infection such as sepsis, addition, e. g. of tobramycin, to a suitable betalactam of a single dose has been discussed as a useful option, but the evidence for such a recommendation is weak. There is little news about the rational use of antibiotics in hematology-oncology patients. In the case of fever and neutropenia, the initial empirical regimens of choice remain piperacillin-tazobactam or a pseudomonas-active carbapenem as monotherapy. These betalactams should be given with extended infusion times, e. g. over 4 hours. Linezolid should be considered as a reserve drug and not be used empirically, but only in targeted therapy. With regard to an alleged penicillin allergy, the risk of true allergic reactions can be differentiated by careful taking of the history; on that ground patient subgroups can be defined that may be re-exposed without further allergological examinations.. In Deutschland wurden in den letzten Jahren sowohl im Krankenhausbereich als auch im ambulanten Setting immer weniger Fluorchinolone verordnet. Auch der Verbrauch der Cephalosporine ging etwas zurück. RENAISSANCE VON AMINOGLYKOSIDEN?:  Die inzwischen relativ seltenen Substanzen können aufgrund einer recht guten Resistenzlage bei Harnwegsinfektionen als geeignete Alternative – allerdings nur parenteral – eingesetzt werden. Bei akuten schweren Infektionen ist eine einmalige Gabe, z. B. von Tobramycin, initial zusätzlich zu einem geeigneten Betalactam ebenfalls eine Option, aber keine klare Empfehlung. ANTIBIOTIKAEINSATZ IN DER HäMATOLOGIE/ONKOLOGIE:  Bei Fieber und Neutropenie gilt nach wie vor die initiale empirische Gabe von Piperacillin-Tazobactam oder einem pseudomonasaktiven Carbapenem als Standard. Diese Betalactame sollten mit verlängerter Infusionsdauer, z. B. über 4 h, verabreicht werden. Linezolid ist ein Reservemedikament und sollte auch bei hämatoonkologischen Patienten nicht empirisch, sondern nur in der gezielten Therapie verwendet werden.. Die anamnestische Angabe einer Penicillinallergie sollte durch genaues Hinterfragen differenziert werden. Patienten können so bezüglich ihres Risikos für allergische Reaktionen gruppiert werden – oft besteht kein oder ein sehr geringes Risiko bei einer (erneuten) Behandlung mit Penicillinderivaten. Niedrigrisikopatienten dürfen ohne weitergehende allergologische Untersuchungen reexponiert werden.

Topics: Aminoglycosides; Anti-Bacterial Agents; Antimicrobial Stewardship; beta-Lactams; Cephalosporins; Fluoroquinolones; Germany; Humans; Neutropenia; Piperacillin, Tazobactam Drug Combination; Urinary Tract Infections

We present the case of infected wet gangrene of right foot in the setting of poorly controlled type 2 diabetes in a 71-year-old woman. This patient presented with improved infection condition after intravenous piperacillin-tazobactam (PTZ) 2.25 gm every 6 hours treatment and below knee amputation surgery on day 3. However, neutropenia and thrombocytopenia developed on day 13. We consulted a haematologist and performed a series of examinations. However, no significant findings were noted thereafter. PTZ was suspected to be the most likely cause of neutropenia and thrombocytopenia and was hence terminated on day 14 (cumulative dose of PTZ: 126 g) following stabilisation of the infection condition. A transfusion was performed with two units of single donor platelets on day 14 and treated with intravenous dexamethasone 5 mg every 8 hours from day 14 to 16. Her white blood cell and platelet counts increased on day 15 and continued to recover thereafter.

Topics: Aged; Anti-Bacterial Agents; Diabetes Mellitus, Type 2; Diabetic Foot; Diagnosis, Differential; Female; Humans; Neutropenia; Piperacillin, Tazobactam Drug Combination; Thrombocytopenia

There are several empiric antibiotic treatment options for febrile neutropenia, yet there is no universally-accepted initial protocol. We aimed to assess the performance of a protocol (piperacillin, gentamicin and cefazolin) introduced over 40 years ago and compare its coverage against bacteria isolated from blood of neutropenic patients with that of various commonly used antibiotic treatment protocols.. Adults with neutropenia admitted between 2003 and 2012 to the hemato-oncologic departments and in whom blood cultures were taken on admission were included. Appropriateness of several common antibiotic protocols was assessed based on the susceptibility of the blood isolates. Crude mortality rates were computed by the susceptibility of bacteria isolated from patients' blood to the actual treatment given.. In total, 180 admissions of neutropenic patients (95 in patients who had fever above 38 °C) with positive blood cultures were analyzed. The actual antibiotic regimen prescribed was deemed appropriate in 82% of bacteremia episodes. The recommended institutional protocol was used in 62% of bacteremia episodes in neutropenic patients. This protocol would have been appropriate in 85% of all neutropenic bacteremia episodes and 89% of episodes in febrile neutropenia patients compared with piperacillin/tazobactam (79%, P = 0.13 and 76%, P = 0.002, respectively) and imipenem (93%, P = 0.004 and 92%, P = 0.74, respectively). Isolation of bacteria resistant to the actual antibiotic treatment given was associated with higher mortality at one week and at 30 days.. Common current antibiotic regimens provide similar coverage among febrile neutropenic patients, whereas broad spectrum antibiotic combinations maximize coverage among neutropenic patients.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Blood Culture; Carbapenem-Resistant Enterobacteriaceae; Cefazolin; Clinical Protocols; Enterobacteriaceae Infections; Gentamicins; Humans; Imipenem; Microbial Sensitivity Tests; Middle Aged; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus

We aimed to find the incidence and risk factors of hematologic adverse effects of piperacillin-tazobactam (TZP).. Adult patients who used TZP for more than 10 days were included in the study.. The incidence of leukopenia, neutropenia, and eosinophilia in 110 TZP therapy episodes was found to be 16.3%, 10%, and 10%, respectively. Lower Charlson Comorbidity Index score, lower initial leukocyte count, combination of TZP with another antibiotic, and total duration of TZP therapy were found to be independent risk factors for leukopenia, while initial higher eosinophil count (IHEC) and usage of TZP for >20 days were independent risk factors for neutropenia and IHEC and total duration of TZP therapy were independent risk factors for eosinophilia.. Longer duration of therapy, combination with other antibiotics, younger age with fewer comorbidities, and IHEC could result in hematologic adverse effects in patients treated with TZP. Patients with IHEC may be more prone to allergic reactions, so immunological mechanisms may facilitate the development of hematological adverse effects of TZP.. Piperasilin-tazobaktamın (TZP) hematolojik istenmeyen etki insidansını ve risk faktörlerini bulmayı amaçladık.. On günden uzun süre TZP kullanan erişkin hastalar çalışmaya dahil edildi.. Yüz on tedavi epizodunda lökopeni, nötropeni ve eozinofili insidansları sırasıyla %16,3, %10 ve %10 olarak bulundu. Charlson’ın Komorbidite İndeksi’nin düşük olması, başlangıç lökosit sayısının düşük olması, TZP ile başka antibiyotiğin kombine kullanılması ve TZP’nin toplam tedavi süresi; başlangıç eozinofil sayısının yüksek olması (BESYO) ve 20 günden uzun süreli TZP kullanımı; BESYO ve TZP’nin toplam tedavi süresi sırasıyla lökopeni, nötropeni ve eozinofili için bağımsız risk faktörleri olarak bulundu.. TZP ile tedavi edilen hastaların tedavi süresinin uzun olması, kombine antibiyotik tedavisi almaları, daha genç yaşta daha az komorbiditelerinin olması ve BESYO hematolojik istenmeyen etkilerin gelişmesine neden olabilir. BESYO olması hastaların alerjik reaksiyonlara daha yatkın olmasına neden olabilir, bu nedenle immünolojik mekanizmalar TZP kullanımıyla hematolojik istenmeyen etkilerin gelişmesini kolaylaştırabilir.

Topics: Eosinophilia; Female; Humans; Leukopenia; Male; Middle Aged; Neutropenia; Piperacillin, Tazobactam Drug Combination; Risk Factors

Implementing a mouse model of Acinetobacter baumannii (AB) digestive colonization and studying the propensity of an intestinal reservoir of AB to be at the origin of pneumonia.. After a disruption of the digestive flora by piperacillin-tazobactam, two multidrug-resistant AB strains were intranasally inoculated to two cohorts of ten mice daily. For each strain, five mice were rendered transiently neutropenic.. One strain persisted several weeks in the digestive tract, even after stopping piperacillin-tazobactam injections, leading to the hypothesis that some AB strains can authentically colonize the gut. Most of the immunocompromised mice experienced clinical signs and positive lung cultures, which were associated with positive spleen cultures, an argument in favor of bacterial translocation.

Topics: Acinetobacter; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Translocation; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Gastrointestinal Tract; Immunosuppression Therapy; Lung; Mice; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial

Although the proportion of Pseudomonas aeruginosa infections has reduced after the introduction of antibiotics with anti-pseudomonal effects, P. aeruginosa bacteremia still causes high mortality in immunocompromised patients. This study determined the clinical characteristics and outcomes of P. aeruginosa bacteremia and the antibiotic susceptibilities of strains isolated from febrile neutropenic patients.. Thirty-one febrile neutropenic children and adolescents with underlying hematologic/oncologic disorders diagnosed with P. aeruginosa bacteremia between 2011 and 2016 were enrolled in the study. Their medical records were retrospectively reviewed to evaluate the demographic and clinical characteristics. Antibiotic susceptibility rates of the isolated P. aeruginosa to eight antibiotic categories (anti-pseudomonal penicillin, anti-pseudomonal penicillin and β-lactamase inhibitor combination, anti-pseudomonal cephalosporin, monobactam, carbapenem, aminoglycoside, fluoroquinolone, and colistin) were also determined. Among the investigated factors, risk factors for mortality and infections by a multidrug-resistance (MDR) strain were determined.. Thirty-six episodes of P. aeruginosa bacteremia were identified. The mean age of the enrolled patients was 9.5 ± 5.4 years, and 26 (72.2%) episodes occurred in boys. Acute myeloid leukemia (41.7%) and acute lymphoblastic leukemia (33.3%) were the most common underlying disorders. The 30-day mortality was 38.9%, and 36.1% of the episodes were caused by MDR strains. The deceased patients were more likely to experience breakthrough infection (P = 0.036) and bacteremia (P = 0.005) due to MDR strains when compared with the patients who survived. The survived patients more likely received appropriate empirical antibiotic therapy (P = 0.024) and anti-pseudomonal β-lactam and aminoglycoside combination therapy (P = 0.039) compared with the deceased patients. The antibiotic susceptibility rates of the isolated P. aeruginosa strains were as follows: piperacillin/tazobactam, 67.6%; meropenem, 72.2%; and amikacin, 100%.. Mortality due to P. aeruginosa bacteremia remained at 38.9% in this study, and more than one-third of the isolated strains were MDR. In this context, empirical antibiotic combination therapy to expand the antibiotic spectrum may be a strategy to reduce mortality due to P. aeruginosa bacteremia in febrile neutropenic patients.

Topics: Adolescent; Amikacin; Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Carbapenems; Cephalosporins; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Female; Fever; Fluoroquinolones; Humans; Male; Meropenem; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Thienamycins

Recent findings have identified Escherichia coli strains that are pan-β-lactam susceptible (PBL-S) but piperacillin-tazobactam resistant (TZP-R) in vitro We assessed the in vivo significance of this resistance profile in a neutropenic murine pneumonia model using humanized exposures of TZP with 18 clinical E. coli isolates, 8 TZP-S/PBL-S and 10 genotypically confirmed TZP-R/PBL-S. Despite phenotypically and genotypically defined resistance, TZP displayed efficacy against these isolates. Additional studies are required to define the clinical implications of these TZP-R/PBL-S strains.

Topics: Animals; Anti-Bacterial Agents; Cephalosporins; Colistin; Culture Media; Disease Models, Animal; Drug Administration Schedule; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Tobramycin; Treatment Outcome

A series of cases of piperacillin-tazobactam (P/T)-associated neutropenia has been observed recently in children in our center. Because neutropenia was seldom observed in children treated with ticarcillin-clavulanic acid (T/C), we conducted a study to determine if there is an increased risk of neutropenia in children exposed to P/T in comparison with T/C.. Medical records of subjects aged <18 years who received at least 1 dose of P/T or T/C between 1 January 2008 and 30 June 2011 were reviewed.. Two hundred ninety-nine episodes of treatment (65 P/T, 234 T/C) met inclusion criteria. Among those episodes, 213 had data allowing complete white blood cell count analysis and were included in the final analysis. Thirteen cases of neutropenia were observed during the study period. The average time to onset was 17.6 days and all patients were aged <13 years. Seven cases (10.8%) occurred in the P/T group and 6 (2.6%) in the T/C group (unadjusted odds ratio, 4.59; 95% confidence interval, 1.48-14.17). Although a statistically significant correlation was observed between age, treatment duration, and total dose and the development of neutropenia (r = -0.121, P = .037; r = 0.267, P < .001; r = 0.260, P < .001, respectively), this was not the case for sex, indications, neutrophil count at initiation, and concomitant drug treatments.. Although our results need to be confirmed, they suggest that children receiving long courses of therapy (>2 weeks) with P/T may be at increased risk of neutropenia, compared with T/C.

Topics: Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Clavulanic Acids; Cohort Studies; Female; Humans; Infant; Male; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Assessment; Ticarcillin

Neutropenic fever is a common complication of myelosuppressive therapy in pediatric oncology patients. Piperacillin-tazobactam (PIP/TAZO) is a broad spectrum antibiotic used for empiric treatment of neutropenic fever. We describe four cases of suspected PIP/TAZO induced nephrotoxicity occurring in children with pediatric malignancies admitted to the hospital and treated for fever ± neutropenia. All patients exhibited acute renal injury shortly after PIP/TAZO administration with one of these cases having biopsy evidence of acute interstitial nephritis. These findings are suggestive of PIP/TAZO induced nephrotoxicity in pediatric oncology patients with fever ± neutropenia and that PIP/TAZO should be used judiciously in this population.

Topics: Adolescent; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Kidney Diseases; Male; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prognosis

The study through Monte Carlo simulation of β-lactam pharmacokinetic/pharmacodynamic target attainment and determination of subsequent serum concentrations of piperacillin-tazobactam administered through continuous infusion to children treated for fever and neutropenia shows that 400 mg/kg/day has the highest probability of target attainment against Pseudomonas aeurginosa in our oncology ward compared with the standard regimen of 300 mg/kg/day.

Topics: Adolescent; Anti-Bacterial Agents; Child; Female; Fever of Unknown Origin; Humans; Infusions, Intravenous; Male; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas Infections; Treatment Outcome

Australian guidelines for neutropenic fever recommend piperacillin/tazobactam (PIP-TAZ) or cefepime for first-line empiric treatment of neutropenic fever. We compared outcomes among haematology patients before and after changing our first-line neutropenic fever treatment from imipenem to PIP-TAZ. Forty-five patients received imipenem and 60 PIP-TAZ. Despite a higher rate of antibiotic modification in the PIP-TAZ cohort, treatment success and time to defervescence were similar, with a trend towards fewer Clostridium difficile infections in the PIP-TAZ cohort.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cohort Studies; Drug Substitution; Female; Fever; Humans; Imipenem; Male; Middle Aged; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Treatment Outcome; Young Adult

Piperacillin/tazobactam (PTZ) is frequently used in patients with diabetic foot infections. Herein, we report a patient who developed severe neutropenia, thrombocytopenia, and fever while receiving PTZ for a diabetic foot infection. We recommend vigilance when long-term PTZ use is planned in patients with diabetic foot infections.

Topics: Aged; Anti-Bacterial Agents; Diabetes Mellitus, Type 2; Diabetic Foot; Fever; Humans; Male; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Thrombocytopenia

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

The incidence of Gram-negative bacteremia has increased in hematopoietic stem cell transplant (HSCT) recipients. We prospectively collected data from 13 Brazilian HSCT centers to characterize the epidemiology of bacteremia occurring early post transplant, and to identify factors associated with infection due to multi-drug-resistant (MDR) Gram-negative isolates. MDR was defined as an isolate with resistance to at least two of the following: third- or fourth-generation cephalosporins, carbapenems or piperacillin-tazobactam. Among 411 HSCT, fever occurred in 333, and 91 developed bacteremia (118 isolates): 47% owing to Gram-positive, 37% owing to Gram-negative, and 16% caused by Gram-positive and Gram-negative bacteria. Pseudomonas aeruginosa (22%), Klebsiella pneumoniae (19%) and Escherichia coli (17%) accounted for the majority of Gram-negative isolates, and 37% were MDR. These isolates were recovered from 20 patients, representing 5% of all 411 HSCT and 22% of the episodes with bacteremia. By multivariate analysis, treatment with third-generation cephalosporins (odds ratio (OR) 10.65, 95% confidence interval (CI) 3.75-30.27) and being at one of the hospitals (OR 9.47, 95% CI 2.60-34.40) were associated with infection due to MDR Gram-negative isolates. These findings may have important clinical implications in the decision of giving prophylaxis and selecting the empiric antibiotic regimen.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteremia; Brazil; Carbapenems; Cephalosporins; Child; Child, Preschool; Drug Resistance, Multiple; Female; Gram-Negative Bacterial Infections; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Infant; Male; Middle Aged; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Predictive Value of Tests; Prospective Studies; Risk Factors

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

Piperacillin-Tazobactam (Pip-Taz) is an evidence-based empirical treatment of febrile neutropenia in adolescents and adults. No data are available in pediatric cancer patients <25 months of age. In this retrospective, multicenter data survey, the analysis focuses on safety, tolerance, and efficacy. The daily dose administered was 240 mg/kg given in three equally divided doses. Data on 156 Pip-Taz treatment courses in 69 children <25 months from five pediatric cancer treatment centers (2001-2005) were analyzed. The median duration of treatment with Pip-Taz was 5 days (range, 1-23 days; 1-12 Pip-Taz courses per patient). Pip-Taz was started on the first day of fever in 90% of all courses, in 6% in the first 72 h, and in 4% as second- or third-line agent. Forty-five percent of all patients were neutropenic. In all patients, the outcome was favorable independent whether Pip-Taz was given as monotherapy (42 courses; 27%) or in combination. Overall, Pip-Taz was well tolerated and discontinued due to adverse events in only two patients who experienced non-life-threatening allergic reactions (skin rash and wheezing). The results of this study are preliminary due to the methodological limitations of a retrospective survey. Taking this bias into consideration, Pip-Taz appears to be a safe, and feasible alternative in pediatric cancer patients with febrile neutropenia <25 months of age suggesting that the inclusion of children of all age groups in future prospective controlled studies evaluating Pip-Taz is justified.

Topics: Bacterial Infections; Fever of Unknown Origin; Humans; Hypersensitivity; Infant; Infant, Newborn; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Treatment Outcome; Withholding Treatment

A case of central venous catheter-related bacteraemia due to Roseomonas mucosa in a neutropenic patient with acute myelogenous leukaemia is reported. The patient was successfully treated with amikacin and piperacillin-tazobactam. The clinical isolate was identified as R. mucosa by 16S rRNA gene sequencing.

Topics: Acute Disease; Adult; Amikacin; Anti-Bacterial Agents; Antimetabolites, Antineoplastic; Antineoplastic Agents; Bacteremia; Base Sequence; Catheterization, Central Venous; Cytarabine; Humans; Leukemia, Myeloid; Male; Methylobacteriaceae; Molecular Sequence Data; Neutropenia; Penicillanic Acid; Phylogeny; Piperacillin; Piperacillin, Tazobactam Drug Combination; RNA, Bacterial; RNA, Ribosomal, 16S; Vidarabine

Until now, studies confirming the safety of glycopeptide restriction in the empirical treatment of prolonged fever and neutropenia included only nine children. In an open-label observational study, the use of teicoplanin in paediatric oncology patients was investigated. A period of unrestricted use (2001-2003) was compared with a second period (2004) following implementation of a restrictive treatment guideline. Empirical first-line treatment consisted of piperacillin/tazobactam; in 2004, fosfomycin was added after 72 h as the second-line combination instead of teicoplanin. In total, 213 episodes (n=163 in 2001-2003; n=50 in 2004) managed with teicoplanin or fosfomycin (only 2004) were eligible. Empirical treatment of fever of unknown origin with teicoplanin was reduced by 97%. In 2004, the mean length of stay was 0.4 days shorter, no infection-related death occurred and no vancomycin-resistant enterococci were detected. Restriction of empirical glycopeptides is safe in paediatric cancer patients after first-line treatment with piperacillin/tazobactam. Fosfomycin appears to offer a feasible and cost-saving alternative in second-line combination therapy.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Drug Therapy, Combination; Female; Fever; Fever of Unknown Origin; Fosfomycin; Glycopeptides; Humans; Infant; Length of Stay; Male; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Teicoplanin; Treatment Outcome

Of 41 patients with bone-related infections who were treated for > or =10 days with piperacillin-tazobactam, 14 (34%) developed neutropenia. Cumulative doses of piperacillin administered to neutropenic patients were higher than those administered to nonneutropenic ones (330 vs. 237 g; P=.008), and an inverse correlation was detected between the absolute neutrophil count at the end of treatment and the cumulative dose of piperacillin (r=-0.47, P=.002). Moreover, the incidence of piperacillin-tazobactam-induced neutropenia increased with an increase in the cumulative dose of piperacillin: 0% of patients in the first quartile of cumulative piperacillin doses, 33.3% in the second quartile, 40% in the third quartile, and 66.7% in the fourth quartile.

Topics: Age Factors; Aged; Drug Therapy, Combination; Female; Fever; Humans; Incidence; Male; Middle Aged; Neutropenia; Osteomyelitis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination