piperacillin--tazobactam-drug-combination and Neoplasms

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

Bloodstream infections (BSIs) adversely affect clinical outcome in children with cancer. Over 1 decade, this retrospective cohort study describes pathogen distribution in BSIs and antimicrobial susceptibility against empirical antibiotics frequently prescribed in children with cancer. The antibiotic efficacy was evaluated through the determination of minimal inhibitory concentrations for piperacillin-tazobactam and meropenem and by disk diffusion for remaining antibiotics. From 2004 to 2013, 398 BSIs occurred in 196 children with cancer (median age: 5.4 y), resulting in 457 bacteria. Overall, 266 (58.2%) were Gram-positive, and 191 (41.8%) were Gram-negative with a significant Gram-positive increase over time (P=0.032). Coagulase-negative staphylococci (74, 16.2%), viridans group streptococci (67, 14.7%), Escherichia coli (52, 11.4%), and Staphylococcus aureus (39, 8.5%) were the most common pathogens. Susceptibility to piperacillin-tazobactam (95.9%, P=0.419) and meropenem (98.9%, P=0.752) was stable over time, and resistance was observed among viridans group streptococci against piperacillin-tazobactam (18%) and meropenem (7%) and among Enterobacterales against piperacillin-tazobactam (3%). Vancomycin showed 98% Gram-positive activity, gentamicin 82% Gram-negative activity and ampicillin, cefotaxime, and cefuroxime were active in 50%, 72%, and 69% of pathogens, respectively, and BSI-related mortality was 0%. In conclusion, over 1 decade, we report an increase in Gram-positive BSIs, and stable, low-resistance rates against currently recommended empirical antibiotics, piperacillin-tazobactam and meropenem.

Topics: Adolescent; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Meropenem; Microbial Sensitivity Tests; Neoplasms; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Sepsis

Although survival of children with hematological diseases and cancer has increased dramatically, febrile neutropenia (FN) is a frequently observed complication and is sometimes life-threatening in pediatric cancer patients. A prospective, randomized study was performed to clarify the usefulness of meropenem (MEPM) and piperacillin/tazobactam (PIPC/TAZ) for pediatric patients with FN. Ninety-nine patients with 394 episodes were randomly assigned to receive MEPM or PIPC/TAZ. MEPM was administered at 120 mg/kg/day as a 1-h drip infusion 3 times a day. On the other hand, PIPC/TAZ was administered at 360 mg/kg/day as a 1-h drip infusion 4 times a day. MEPM was effective in 69.5% of the 200 episodes, and PIPC/TAZ was effective in 77.2% of the 193 episodes. Compared with our previous study of MEPM 120 mg/kg/day as a 1-h drip infusion 3 times a day versus PIPC/TAZ 337.5 mg/kg/day as a 1-h drip infusion 3 times a day, the success rate of the MEPM group was not different. However, the success rate of the PIPC/TAZ group was higher than in the previous study (p = 0.001). In particular, the success rate in patients ≥ 15 years of age was improved in the PIPC/TAZ group of the present study compared with the previous study (p = 0.005).

Topics: Adolescent; Adult; Anti-Bacterial Agents; Bacteremia; Body Weight; Child; Child, Preschool; Drug Administration Schedule; Drug Therapy, Combination; Febrile Neutropenia; Historically Controlled Study; Humans; Immunologic Deficiency Syndromes; Infant; Infant, Newborn; Infusions, Intravenous; Maximum Tolerated Dose; Meropenem; Neoplasms; Piperacillin, Tazobactam Drug Combination; Stem Cell Transplantation; Young Adult

Febrile neutropenia (FN) is a common complication in children who receive chemotherapy for cancer.. The objective of this study was to evaluate the clinical efficacy of the continuous versus intermittent infusion of piperacillin/tazobactam (TZP) in febrile neutropenic pediatric patients.. This is a non-blinded randomized controlled clinical trial. Eligible group consisted of hemato-oncological patients with FN who were candidates to receive TZP. Patients were randomized to one of two groups: Group 1 received antibiotic treatment through intravenous intermittent infusion of TZP 300 mg/kg/day based on piperacillin, divided into four doses, not exceeding 16 g/day; Group 2 received an initial TZP loading dose of 75 mg/kg infusion over 30 min, and then a continuous infusion of TZP 300 mg/kg/day through central line with pump over 24 h.. There were 176 episodes that could be assessed, 100 in Group 1 and 76 in Group 2. There was no statistically significant difference in treatment failure in the experimental group (continuous infusion) compared with the intermittent group, 21% versus 13% (p = 0.15). The increase in the absolute risk reduction was 0.08% (95% confidence interval 0.12-0.30), and the number needed to treat was 12.4. One patient in each group died.. There were no differences in fever resolution, clinical cure rate, or mortality when comparing the continuous with the intermittent TZP infusion.

Topics: Adolescent; Anti-Bacterial Agents; Antineoplastic Agents; Child; Child, Preschool; Drug Administration Schedule; Febrile Neutropenia; Female; Humans; Infant; Infusions, Intravenous; Male; Neoplasms; Piperacillin, Tazobactam Drug Combination

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

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

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

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 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

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

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

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

Gram-positive bacteria have become the predominant infecting organisms in granulocytopenic cancer patients. Empiric antibiotic regimens used in febrile neutropenic patients often include an extended-spectrum cephalosporin, but the response to therapy in gram-positive coccal bacteremia has been unsatisfactory. Thus, new antibiotics with better activity against gram-positive bacteria should be tested. The objective of this prospective randomized controlled study was to evaluate and compare the efficacy and tolerance of piperacillintazobactam plus amikacin with that of ceftazidime plus amikacin, the standard regimen of the International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer, in the empiric treatment of febrile granulocytopenic cancer patients. A total of 858 episodes were eligible for this study, and 706 episodes were assessable for efficacy. The antibiotic treatment was successful in 210 (61%) of 342 episodes in the piperacillin-tazobactam-amikacin group compared with 196 (54%) of 364 episodes treated with ceftazidime plus amikacin (P = 0.05). The time to defervescence was significantly shorter (P = 0.01) and the time to failure was significantly longer (P = 0.02) in the piperacillin-tazobactam-amikacin group. A significant difference in response to bacteremic infections between the two patient groups was found: piperacillin-tazobactam plus amikacin was successful in 40 of 80 episodes (50%), and ceftazidime plus amikacin was successful in 35 of 101 episodes (35%) (P = 0.05). A multivariate analysis showed that the probability of failure was significantly greater with ceftazidime plus amikacin than with piperacillin-tazobactam plus amikacin (P = 0.02). This trial suggests that piperacillin-tazobactam plus amikacin is more effective than ceftazidime plus amikacin for the empiric treatment of fever and bacteremia in granulocytopenic cancer patients. Although cutaneous reaction was more frequently associated with piperacillin-tazobactam plus amikacin than with ceftazidime-amikacin, this unwanted effect was relatively mild and its incidence was comparable to that of other penicillin compounds.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Amikacin; Ceftazidime; Child; Child, Preschool; Drug Therapy, Combination; Female; Fever; Humans; Infant; Male; Middle Aged; Neoplasms; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies

Children with febrile neutropenia commonly exhibit alterations of pharmacokinetic (PK) parameters, leading to decreased β-lactam concentrations.. This study evaluated piperacillin PK and probability of target attainment (PTA) with continuous infusion of piperacillin-tazobactam, in order to optimize the dosing regimen.. This prospective PK study included children with cancer, aged 1-17 years, who were treated with piperacillin-tazobactam for suspected or verified infection. A piperacillin-tazobactam loading dose (100 mg/kg) was administered followed by continuous infusion (300 mg/kg/day). The unbound fraction of piperacillin was quantified by high-performance liquid chromatography and PK were described using population PK modeling. PK data was used to update and extend a previous PK model built on data following intermittent administration. Monte Carlo simulations were performed to assess PTA for targets of 100% time above the minimum inhibitory concentration (100% fT > MIC) and 50% fT > 4xMIC.. We included 68 fever episodes among 38 children with a median (IQR) age of 6.5 years and body weight of 27.4 kg (15.1-54.0). A three-compartment model adequately described the concentration-time data. Median (95% confidence interval) estimates for clearance and piperacillin concentration at steady state were 14.2 L/h/70 kg (13.0; 15.3) and 47.6 mg/L (17.2; 129.5), respectively. Body weight or lean body weight was significantly associated with the PK parameters, and body weight was integrated in the final PK model. Based on piperacillin exposure, continuous infusion was the only dosing regimen to achieve optimal PTA for the P. aeruginosa breakpoint (16 mg/L) with the target of 100% fT > MIC, and a daily dose of 300 mg/kg reached optimal PTA. The strict target of 50% fT > 4xMIC (64 mg/L) was not feasibly attained by any dosing regimen at recommended doses.. Unlike conventional piperacillin intermittent administration and extended infusion regimens, continuous infusion allows the target of 100% fT > MIC to be reached for children with febrile neutropenia.

Topics: Anti-Bacterial Agents; Body Weight; Child; Febrile Neutropenia; Fever; Humans; Neoplasms; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies

Among patients with febrile neutropenia that developed after chemotherapy, high-risk patients, such as those having clinical instability or Multinational Association of Supportive Care in Cancer score of < 21, require hospitalization for intravenous empiric antibiotic therapy. Monotherapy with an anti-pseudomonal ß-lactam agent is recommended. Although many studies reported the microbial etiology of infections and resistant patterns of febrile neutropenia, the patients were not well characterized as having neutropenic septic shock. Therefore, this study aimed to determine the microbial spectrum of infections and resistance patterns of their isolates in patients with chemotherapy-induced neutropenic septic shock.. Data of adult patients diagnosed with neutropenic septic shock in the emergency department between June 2012 and December 2016 were extracted from a prospectively compiled septic shock registry at a single academic medical center. Thereafter, microbiological studies and antimicrobial susceptibility tests were conducted.. In total, 109 bacteria were found in patients with neutropenic septic shock. Gram-negative bacteria were the predominant causative organisms (84, 77.1%). Moreover, 33 microorganisms (30.3%) were multidrug-resistant (MDR) bacteria with extended-spectrum ß-lactamase-producing Escherichia coli (17, 50%) being the commonest. The most commonly affected sites in patients with MDR bacterial infections were the gastrointestinal tract (45%) and unknown (43.5%). Approximately 48.5% of MDR bacteria were resistant to cefepime but not to piperacillin-tazobactam or carbapenem.. MDR bacteria were prevalent in patients with chemotherapy-induced neutropenic septic shock. Therefore, piperacillin-tazobactam or carbapenem may be considered as empiric antibiotics if MDR bacteria are suspected to be causative agents.

Topics: Adult; Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Neoplasms; Piperacillin, Tazobactam Drug Combination; Shock, Septic

Nephrotoxic medication exposure and associated acute kidney injury (AKI) occur commonly in hospitalized children. At Cincinnati Children's Hospital Medical Center, there is an initiative to increase awareness of nephrotoxic medication exposure and decrease rates of associated AKI. The oncology service utilized these data in a quality improvement project to drive reductions in AKI rates.. Three interventions were implemented targeted at decreasing the incidence of nephrotoxic exposure, as well as protecting against the conversion of exposures to AKI episodes. Cefepime replaced piperacillin-tazobactam for febrile neutropenia, vancomycin stewardship limited empiric courses to 72 hours, and nephroprotection for intravenous contrast administration was standardized for defined high-risk patients.. The study cohort comprised 42 520 noncritically ill patient days admitted to the oncology service at Cincinnati Children's Hospital Medical Center. A total of 273 unique patients were exposed to combination nephrotoxic medications, leading to 111 AKI episodes. The rate of nephrotoxic medication exposure within the oncology service decreased by 49% from 16.08 to 8.17 per 1000 patient days. Episodes of AKI associated with nephrotoxic medication exposure decreased by 45% from 3.48 to 1.92 per 1000 patient days.. Interventions to decrease AKI took a three-pronged approach. Collectively, this approach was proven successful with significant reductions in both rates of nephrotoxic medication exposure and associated AKI among hospitalized oncology patients.

Topics: Acute Kidney Injury; Adolescent; Cefepime; Child; Child, Preschool; Databases, Factual; Febrile Neutropenia; Female; Humans; Infant; Male; Neoplasms; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Pseudomonas aeruginosa bacteraemia is associated with a very high mortality, conditioned by comorbidity, source, severity of the episode and lack of adequate treatment. The aim of the study is to know the mortality and prognostic factors of bacteraemia by P.aeruginosa in our hospital.. We conducted a retrospective study of P.aeruginosa bacteraemia detected between 2009 and 2014. Epidemiological, clinical and microbiological characteristics were described. A risk factor analysis for mortality was performed.. We analysed 110 episodes of bacteraemia, which was more frequent in men of advanced age and with a history of hospitalisation, comorbidity and immunosuppression. Most of the bacteraemias were secondary (mainly of respiratory or urinary source) and led to a significant clinical deterioration. The presence of antibiotic resistance was very high, with 27.3% of multiresistant strains. Empirical treatment was adequate in 60.0% and 92.3% for definite treatment. Overall mortality was 37.3% and attributable mortality was 29.1%. The most important prognostic factors were Charlson index ≥3, history of haematologic malignancy, neutropenia and previous use of corticosteroids, source of bacteraemia, Pitt index ≥4, renal insufficiency, adequate definite treatment, empiric treatment with piperacillin/tazobactam in severe episodes and focus control.. P.aeruginosa bacteraemia is associated with a very high mortality, possibly more related to previous comorbidity and severity of the episode than to the treatment chosen. However, the main goal in management remains to optimise treatment, including focus control.

Topics: Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Community-Acquired Infections; Comorbidity; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Hospitalization; Humans; Immunocompromised Host; Male; Middle Aged; Neoplasms; Piperacillin, Tazobactam Drug Combination; Prognosis; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Spain; Tertiary Care Centers

Topics: Child; Fever; Humans; Neoplasms; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

The β-lactam antibiotic piperacillin (in combination with tazobactam) is commonly chosen for empirical treatment of suspected bacterial infections. However, pharmacokinetic variability among patient populations and across ages leads to uncertainty when selecting a dosing regimen to achieve an appropriate pharmacodynamic target.. To guide dosing by establishing a population pharmacokinetic model for unbound piperacillin in febrile children receiving cancer chemotherapy, and to assess pharmacokinetic/pharmacodynamic target attainment (100% fT > 1×MIC and 50% fT > 4×MIC) and resultant exposure, across body weights.. Forty-three children admitted for 89 febrile episodes contributed 482 samples to the pharmacokinetic analysis. The typical doses required for target attainment were compared for various dosing regimens, in particular prolonged infusions, across MICs and body weights.. A two-compartment model with inter-fever-episode variability in CL, and body weight included through allometry, described the data. A high CL of 15.4 L/h (70 kg) combined with high glomerular filtration rate (GFR) values indicated rapid elimination and hyperfiltration. The target of 50% fT > 4×MIC was achieved for an MIC of 4.0 mg/L in a typical patient with extended infusions of 2-3 (q6h) or 3-4 (q8h) h, at or below the standard adult dose (75 and 100 mg/kg/dose for q6h and q8h, respectively). Higher doses or continuous infusion were needed to achieve 100% fT > 1×MIC due to the rapid piperacillin elimination.. The licensed dose for children with febrile neutropenia (80 mg/kg q6h as a 30 min infusion) performs poorly for attainment of fT>MIC pharmacokinetic/pharmacodynamic targets. Given the population pharmacokinetic profile, feasible dosing regimens with reasonable exposure are continuous infusion (100% fT > 1×MIC) or prolonged infusions (50% fT > 4×MIC).

Topics: Adolescent; Anti-Bacterial Agents; Bacterial Infections; Body Weight; Child; Child, Preschool; Female; Fever; Glomerular Filtration Rate; Humans; Infant; Male; Microbial Sensitivity Tests; Neoplasms; Piperacillin; Piperacillin, Tazobactam Drug Combination; Tazobactam

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

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

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

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

The clinical characteristics and treatment results of febrile neutropenia attacks that occurred in patients with lymphoma and solid tumors were analyzed.. A total of 50 patients with 94 high-risk attacks were evaluated for malignant diseases in this study.. The fever etiology was determined as clinical (50%), microbiological (5.31%), clinical-microbiological (5.31%), or unknown (39.3%). A few of the attacks (21.3%) were observed in lymphoma cases and 77.7% were observed in patients with solid tumors. Patients who were in remission had 59.6% of the attacks, and 39.4% occurred in patients not in remission. Among the groups tested, 73% (the imipenem/amikacin group) and 47.9% (the piperacillin-tazobactam/amikacin group) of patients were in remission. Glycopeptide addition rates in these groups were 22.2% and 40.8% and antifungal addition rates were 8.8% and 18.3%, respectively.. Clinical progress was more problematic in patients who were not in remission during the attacks. This was due to the fact that some patients had other factors that placed them in the high-risk group, as well as increased C reactive protein and procalcitonin values on the first day. Therefore, it may not be accurate to associate the success achieved in the different treatment regimens with antibiotics alone.

Topics: Amikacin; Anti-Bacterial Agents; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Febrile Neutropenia; Female; Humans; Imipenem; Lymphoma; Male; Neoplasms; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Protein Precursors

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

Extensively drug resistant (XDR) Acinetobacter baumannii infections are increasing. Knowledge of risk factors can help to prevent these infections.. We designed a 1∶1∶1 case-case-control study to identify risk factors for XDR A. baumannii bacteremia in Singapore and Thailand. Case group 1 was defined as having infection due to XDR A. baumannii, and case group 2 was defined as having infection due to non-XDR A. baumannii. The control group comprised patients with blood cultures obtained to determine possible infection.. There were 93 patients in each group. Pitt bacteremia score (adjusted odds ratio [aOR], 2.570 [95% confidence interval (CI), 1.528-4.322]), central venous catheters (CVCs; aOR, 12.644 [95% CI, 2.143-74.620]), use of carbapenems (aOR, 54.391 [95% CI, 3.869-764.674]), and piperacillin-tazobactam (aOR, 55.035 [95% CI, 4.803-630.613]) were independently associated with XDR A. baumannii bacteremia. In case group 2, Pitt bacteremia score (aOR, 1.667 [95% CI, 1.265-2.196]) and third-generation cephalosporins (aOR, 2.965 [95% CI, 1.224-7.182]) were independently associated with non-XDR A. baumannii bacteremia. Concurrent infections (aOR, 3.527 [95% CI, 1.479-8.411]), cancer (aOR, 3.172 [95% CI, 1.135-8.865]), and respiratory source (aOR, 2.690 [95% CI, 1.160-6.239]) were associated with an increased risk of 30-day mortality. Survivors received more active empirical therapy (16.7% vs 9.6%; P = .157), had fewer cases of XDR bacteremia (45.8% vs 52.6%; P = .452), and received higher median definitive polymyxin B doses (840,000 units vs 700,000 units; P = .339) CONCLUSIONS: Use of CVC and broad spectrum antibiotics were unique risk factors of XDR A. baumannii bacteremia. Effective antimicrobial stewardship together with use of a CVC bundle may reduce the incidence of these infections. Risk factors of acquisition and mortality may help identify patients for early initiation of polymyxin B therapy.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Carbapenems; Case-Control Studies; Central Venous Catheters; Cephalosporins; Coinfection; Drug Resistance, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Neoplasms; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Polymyxin B; Respiratory Tract Infections; Risk Factors; Severity of Illness Index; Treatment Outcome

The aim of this study was to compare the efficacy of piperacillin/tazobactam (P/T) and cefoperazone/sulbactam (C/S) in the empirical treatment of adult neutropenic fever.. Data and outcomes of low-risk adult cases with neutropenic fever and treated with P/T (4.5 g q6h) or C/S (2 g q8h) between 2005 and 2011 June were extracted from our database. Risk evaluation was made according to criteria of Multinational Association for Supportive Care in Cancer (MASCC) and a score of ≥ 21 was considered as low risk. Data were collected prospectively by daily visits and evaluated retrospectively. Primary outcome was - fever defervescence at 72 h in combination with success without modification (referring to episodes where the patient recovered from fever with disappearance of signs of infection without modification to initial empirical treatment). All-cause mortality referred to death resulting from a documented or presumed infection or unidentified reason during the treatment and 30-day follow-up period.. A total of 172 patients (113 cases P/T and 59 cases C/S) fulfilled the study inclusion criteria. Persistent response in P/T arm was 73.5%, whereas it was 64.5% in C/S arm (p > 0.05). Rates of any modification were also similar in both treatment arms. All-cause mortality during the treatment and 30-day follow-up period was not significantly different (P/T: 4/113 vs. C/S: 2/59, p > 0.05). There was no severe adverse effect requiring antibiotic cessation in both cohorts.. In conclusion, our data suggest that C/S may be a safe alternative to P/T in the empirical treatment of adult low-risk febrile neutropenia cases.

Topics: Anti-Bacterial Agents; Cefoperazone; Drug Combinations; Febrile Neutropenia; Female; Humans; Male; Middle Aged; Neoplasms; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Retrospective Studies; Sulbactam; Treatment Outcome

Infection is a serious cause of mortality in febrile neutropenia of pediatric cancer patients. Recently, monotherapy has replaced the combination therapy in empirical treatment of febrile neutropenia. Since there has been no reported trial comparing the efficacy of meropenem and piperacillin-tazobactam (PIP/ TAZ) monotherapies, the present retrospective study was conducted to compare safety and efficacy in febrile neutropenic children with cancer.. Charts of febrile, neutropenic children hospitalized at our center between March 2008 and April 2011 for hemato-oncological malignancies were reviewed. Patients received PIP/TAZ 360 mg/kg/day or meropenem 60 mg/kg/day intravenously in three divided doses. 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.. Two hundred eighty four febrile neutropenic episodes were documented in 136 patients with a median age of 5 years. In 198 episodes meropenem and in 86 episodes PIP/ TAZ were used. Duration of fever and neutropenia, neutrophil count, sex, and primary disease were not different between two groups. Success rates and modification rate between two groups showed no significant differences (p>0.05). Overall success rate in the meropenem and PIP/TAZ groups were 92.4% and 91.9% respectively. No serious adverse effects occurred in either of the groups.. Meropenem and PIP/TAZ monotherapy are equally safe and effective in the initial treatment of febrile neutropenia in children with cancer.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Child; Child, Preschool; Drug Therapy, Combination; Febrile Neutropenia; Female; Humans; Infant; Male; Meropenem; Neoplasms; Neutrophils; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Thienamycins; Young Adult

Raoultella planticola (formerly Klebsiella planticola) is a Gram-negative bacterium that has been rarely reported in association with human infection. Here we describe a case of cholangitis complicated with septic shock caused by R. planticola in an immunocompromised patient with advanced cancer who underwent endoscopic retrograde cholangiopancreatography to extract common bile duct stones. The infection was cleared by piperacillin-tazobactam treatment.

Topics: Aged; Anti-Bacterial Agents; Cholangitis; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Immunocompromised Host; Male; Neoplasms; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Shock, Septic; Treatment Outcome

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

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

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