Expanding the Options for Risk-based Therapy in Febrile Neutropenia

Fever in neutropenic cancer patients is often due to the development of an infection. The standard management of febrile neutropenic patients involves the administration of empiric, hospital-based, parenteral antibiotic therapy. Although this treatment strategy has evolved from experience in high-risk patients with hematological malignancies, in whom bacterial infection can result in substantial morbidity and mortality, it has been adopted for all patients with febrile neutropenia, largely because of the inability of clinicians to reliably distinguish between patients who are at high risk for developing such morbidity/mortality and those who are not. The development of risk-assessment models has facilitated the recognition of high-, moderate-, and low-risk subgroups among febrile neutropenic patients and allows the administration of outpatient antibiotic therapy to the moderate- and low-risk groups, with the same degree of efficacy and safety as hospital-based therapy. Monotherapy with the carbapenems (imipenem/cilastatin and meropenem), with their broad spectrum of activity and established efficacy in high-risk patients, represents realistic options for risk-based treatment of febrile neutropenic patients within and outside the hospital setting.     

Outpatient antibiotic treatment in low-risk febrile neutropenic cancer patients

Traditionally febrile neutropenic patients have been treated with parenteral antibiotics in an inpatient setting; however, recent work by several investigators has demonstrated successful treatment with both parenteral and oral antibiotics in an ambulatory environment. This has been accomplished by identification of low-risk neutropenic patients, advances in broad-spectrum antibiotics with long half-lives and stabilities, the introduction of the oral quinolones, home health-care initiatives, improvements in vascular access devices, and development of technically enhanced antibiotic delivery systems. Outpatient antibiotic therapy for febrile episodes in low-risk neutropenic patients should now be considered an acceptable alternative to hospital-based treatment. This review focuses on the development and rationale of risk stratification and examines the results of various outpatient antibiotic trials recently completed.     

Febrile neutropenia: a prospective study to validate the Multinational Association of Supportive Care of Cancer (MASCC) risk-index score

Objective The objective of this study was to prospectively validate the Multinational Association of Supportive Care of Cancer (MASCC) risk-index score in an attempt to accurately predict on presentation with febrile neutropenia those cancer patients who are at low- or high-risk for development of serious medical complications during the episode.Patients and methods Patients who presented with febrile neutropenia during November 2000 and July 2002 were prospectively enrolled in the protocol. All patients were hospitalized until recovery or outcome of the event and were treated with broad-spectrum, empiric, intravenous antibiotic therapy. The MASCC risk-index score (based on seven independent factors present at onset of febrile neutropenia) was calculated in 64 patients with 80 febrile neutropenic episodes. Patients with a score of 21 were regarded as low risk; patients with a score of <21 were regarded as high risk.Results Of the 80 febrile neutropenic episodes, 58 were classified as low-risk and 22 as high-risk patients. Fifty-seven (98.3%) of the 58 low-risk patients recovered without complications, and three (13.6%) of the 22 high-risk patients did not develop medical complications. One low-risk patient developed a fungal infection but recovered completely in comparison to 11 high-risk patients (50%) who developed serious medical complications (p<0.001). None of the low-risk patients died. However, eight (36.4%) of the 22 high-risk patients died during the febrile neutropenic episode (p<0.001), six as a consequence of sepsis and two due to rapidly uncontrolled cancer.Conclusion We correctly predicted 98.3% of low-risk patients and 86.3% of high-risk patients. This study had a positive predictive value of 98.3% and a negative predictive value of 86.4% with both a sensitivity and specificity of 95%. The MASCC risk-index score correctly identifies low- and high-risk patients at presentation with febrile neutropenia.     

Performance of a modified MASCC index score for identifying low-risk febrile neutropenic cancer patients

GOALS OF WORK: This is a prospective and observational study comparing the efficacy of risk-assessment models in patients with neutropenic fever in a reference treatment center. The meaning of the complex infection was evaluated. MATERIALS AND METHODS: Patients were recruited throughout a 9-month period. Inclusion criteria were histologic diagnosis of malignancy, neutropenic febrile secondary to chemotherapy and/or radiotherapy (absolute neutrophil count of <500/microl and axillary temperature > or = 38 degrees C), and > or = 18 years of age. MAIN RESULTS: Fifty-three febrile neutropenic patients were included. Twenty one of them were classified as low risk by the Multinational Association of Supportive Care in Cancer (MASCC) risk-index score. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of the MASCC risk-index scores were, respectively 87.9, 85.0, 90.6, 80.9, and 86.8%. None of the low-risk patients died, but four patients classified as low risk by the MASCC model developed serious medical complications during febrile neutropenic episodes. When we subtracted patients with complex infections from the group of patients with the MASCC risk-index score of > or = 21, we got 15 patients that were classified as low risk by a proposed adjustment by complex infection (PACI) model. None of them developed serious medical complications. The sensitivity, specificity, PPV, NPV, and the accuracy of this new model were, respectively, 100, 75.0, 86.8, 100, and 90.6%. CONCLUSION: The MASCC risk-index score had high sensitivity and specificity to predict the absence of complications, but the PACI model was better than MASCC for predicting the absence of complications in this febrile neutropenic patients.     

Predicting febrile neutropenic patients at low risk using the MASCC score: does bacteremia matter?

Background  

Febrile neutropenic cancer patients represent a heterogeneous population with a limited proportion at risk of serious medical complications. The Multinational Association for Supportive Care in Cancer (MASCC) score has been developed and validated for identifying low-risk patients at the onset of febrile neutropenia. Since bacteremia, although not documented at baseline, is a predictor of pejorative outcome, the purpose of this study was to investigate the possible interaction between the MASCC score and bacteremic status and to assess whether, assuming that bacteremic status could be predicted at onset of febrile neutropenia, adding bacteremia as a covariate in a risk model would improve the accuracy of low-risk patients identification.     

Emergency Ambulatory Management of Low-Risk Febrile Neutropenia: Multinational Association for Supportive Care in Cancer Fits—Real-World Experience From a UK Cancer Center

BackgroundEmergency patient presentations with febrile neutropenia are a heterogeneous group. A small minority of these patients proceed to develop significant medical complications. Risk stratification using scores, such as the Multinational Association for Supportive Care in Cancer score, have been advocated to identify patients who are at low risk of adverse outcome suitable for treatment on an ambulatory care pathway.ObjectivesWe sought to report the experience of 100 patients presenting acutely with neutropenic fever managed in an emergency ambulatory fashion.MethodsPatients presenting as an emergency with low-risk febrile neutropenia managed in an ambulatory setting between January 2017 and February 2019 at a tertiary cancer hospital in England were prospectively studied. Patients with a fever >38.0°C and an absolute neutrophil count <1.0 × 10⁹/L were included. All patients with a Multinational Association for Supportive Care in Cancer score ≥21 and a National Early Warning Score ≤3 were potentially eligible for the pathway. Complications were classified as serious if the patient developed persistent hypotension, respiratory failure, intensive care unit admission, altered mental status, disseminated intravascular coagulation, renal failure requiring renal replacement therapy, electrocardiogram changes requiring antidysrhythmic treatment, and 30-day mortality.ResultsOne hundred patients with low-risk febrile neutropenia consecutively managed in an emergency ambulatory fashion were prospectively analyzed. Eighty-one patients were female and the median age was 51 y (range 17–79 y). No patients developed serious complications. Eight (8% [95% confidence interval 4.1–15.0%]) patients had a 7-day readmission.ConclusionOutpatient ambulatory care for emergency patients with low-risk febrile neutropenia can be delivered in a safe and effective fashion. Collaboration between acute care physicians and oncologists is required to develop local models based on national guidelines to facilitate individualised care for emergency oncology patients.     

Piperacillin-tazobactam is more effective than ceftriaxone plus gentamicin in febrile neutropenic patients with hematological malignancies: a randomized comparison

GOALS: Efficacy and costs of empirical antibacterial therapy in febrile neutropenic patients are important issues. Several strategies have been reported to be similarly effective: monotherapy with cefepime, ceftazidime or a carbapenem or duotherapy with an antipseudomonal beta-lactam antibiotic or ceftriaxone in combination with an aminoglycoside. Piperacillin-tazobactam monotherapy is promising, but its role in this setting still has to be defined. PATIENTS AND METHODS: Of 212 consecutive febrile episodes in 130 neutropenic patients with hematological malignancies randomized to receive either piperacillin-tazobactam (4.5 g every 8 h; group A) or ceftriaxone (2 g once daily plus gentamicin 5 mg/kg once daily; group B), 183 episodes (98 group A, 85 group B) were evaluable for response. RESULTS: Defervescence within 72 h without modification of the antibiotic therapy was achieved in 56/98 episodes (57.1%) in group A and in 30/85 (35.3%) in group B (P=0.0047). If fever persisted, teicoplanin plus gentamicin (group A) or teicoplanin plus ciprofloxacin (group B) were added. All patients still febrile then received meropenem, teicoplanin and amphotericin B. With these modifications of antibiotic therapy, 89.8% of patients in group A had responded at 21 days but only 71.8% in group B (P=0.005). The mean total antibiotic drug cost in group A was only 39.4% of that in group B (euro 445 versus euro 1129; P=0.010). CONCLUSION: Piperacillin-tazobactam monotherapy is significantly more effective and cost-efficient than ceftriaxone plus gentamicin as first-line therapy in febrile neutropenic patients with hematological malignancies.     

Monotherapy with piperacillin/tazobactam versus combination therapy with ceftazidime plus amikacin as an empiric therapy for fever in neutropenic cancer patients

Between July 1993 and September 1996, 107 consecutive febrile episodes in 83 neutropenic cancer patients with a median age of 41 years were randomized to treatment either with piperacillin/tazobactam 4.5 g every 8 h i.v. or ceftazidime 2 g every 8 h plus amikacin 15 mg/kg i.v. per day. In the case of fever >38° C 48 h after initiation of the antibiotic therapy, vancomycin 500 mg every 6 h i.v. was added. The study population was at serious risk of a poor outcome, since 67% of the patients had leukemia or lymphoma, 19% of the febrile events occurred after autologous bone marrow or blood stem cell transplantation, the median total duration of neutropenia was 16 days, and the median neutrophil count at study inclusion was 0.09 × 10⁹/l. The two patient groups were comparable in terms of risk factors. Bacteremia was found in 37%, other microscopically documented infections in 16%, and clinically documented infections in 26% of the febrile episodes. Most (96) febrile episodes were evaluable for response. No significant difference was found between piperacillin/ tazobactam and ceftazidime plus amikacin in terms of success rate (81% versus 83%), empirical addition of vancomycin (42% versus 38%), median time to fever defervescence (3.3 versus 2.9 days) or median duration of antibiotic therapy (7.2 versus 7.4 days). No patient died from the infection. Both antibiotic regimens were well tolerated, the study treatment being stopped only in 1 patient because of toxicity (cutaneous allergy to piperacillin/tazobactam). On the basis of the 107 febrile events encountered, we conclude that piperacillin/tazobactam is a safe and effective monotherapy. To define the definitive value of piperacillin/ tazobactam as a monotherapy for febrile neutropenic patients a large randomized trial is warranted.     

Domiciliary treatment of febrile episodes in cancer patients: a prospective randomized trial comparing oral versus parenteral empirical antibiotic treatment

Hospitalization and empirical broad-spectrum, intravenous antibiotics are the standard treatment for febrile cancer patients. Recent evidence supports the suggestion that febrile episodes in a low-risk population can be managed successfully in an outpatient setting, but the optimal drug regimen is unknown. In a prospective randomized clinical trial we compared ciprofloxacin 750 mg p.o. twice a day with ceftriaxone 2 g i.v. as a single daily dose for the empiric domiciliary treatment of febrile episodes in low-risk neutropenic and nonneutropenic cancer patients. A total of 173 patients, accounting for 183 febrile episodes, were enrolled in the study. Overall, successful outcomes were recorded for 76 of 93 (82%) febrile episodes in patients who were randomized to the oral regimen and for 68 of 90 (75%) febrile episodes in patients randomized to the i.v. regimen: this difference was not statistically significant. The success rate was similar in all subgroups of patients: neutropenic and nonneutropenic, with documented infection and with fever of unknown origin. There were 3 deaths in the group of patients treated with the parenteral regimen, and two of these were related to treatment failure. Both treatments were well tolerated, and the cost of the oral regimen was lower. This prospective study suggests that domiciliary antibiotic empiric monotherapy is feasible in febrile nonneutropenic or low-risk neutropenic outpatients in whom a bacterial infection is suspected, and that either an oral or a parenteral regimen can be used. A number of factors may influence the choice between an orally and an i.v.-administered antibiotic, but owing to the easier administration and lower cost, the oral regimen seems to be preferable. Published online: 5 March 1999     

Gentamicin and low dose piperacillin in febrile neutropenic patients

One hundred and twenty-seven febrile neutropenic patients were randomized to receive empirical antibiotic therapy with intravenous gentamicin and 12 g/day or 8 g/day piperacillin. Despite a high incidence of Hickman catheter infections by antibiotic-resistant bacteria, there was an overall response in 56% of patients and no difference in the numbers responding to each antibiotic regimen. In addition, the duration of fever was not significantly different in the two groups of patients. The majority of the unresponsive patients responded to the addition of further antibiotics and there were only two infection related deaths. The results suggest that high dose antibiotics are not essential for the initial empirical therapy in febrile neutropenic patients.     

Fever without source in children. Recommendations for outpatient care in those up to 3

It is the author's goal to reduce risk to a minimum in children with fever without source at a reasonable cost with guidelines that are practical for office-based physicians. Recommendations are as follows: All febrile infants and children up to 36 months of age who have toxic manifestations are to be hospitalized for parenteral antibiotic therapy after an expeditious evaluation of their condition that includes cultures of blood, urine, and cerebrospinal fluid. All febrile infants 7 days of age or less should be hospitalized for empirical antibiotic therapy after a complete evaluation for sepsis and meningitis has been done. Some low-risk febrile infants 8 to 28 days of age who appear well may be observed closely, either in hospital (with or without empirical antibiotic therapy) or as outpatients if the physician believes that close follow-up is ensured. Febrile infants 28 to 90 days of age should have an evaluation to determine whether they are in a low-risk group. Those not meeting low-risk criteria should be hospitalized for a complete "sepsis workup" and close observation, with or without empirical antibiotic therapy. Those who are considered low-risk can be treated as outpatients, as described, if close follow-up is ensured. No laboratory tests or antibiotics are needed in a child over 90 days of age who has a temperature of less than 39 degrees C (102.2 degrees F) without identifiable source. A return visit is recommended if the child's fever persists for more than 2 to 3 days or if the condition deteriorates. A child with a fever of 39 degrees C or above can also be treated as an outpatient without antibiotics if close follow-up is ensured. Otherwise, a WBC count or ANC should be done. In those whose WBC count is 15,000/mm3 or more or whose ANC is 10,000 cells/mm3 or more, a blood culture should be done, and pending results, a single injection of ceftriaxone, 50 mg/kg, should be given.     

Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients: a systematic review and meta-analysis of randomized trials

CONTEXT: Neutropenia is one of the grave consequences of cancer chemotherapy, and the treatment of neutropenic febrile patients with intravenous (iv) antibiotics has been shown to reduce mortality. Oral therapy could be an alternative approach for selected patients. OBJECTIVES: To compare the efficacy of oral antibiotics versus iv antibiotic therapy in febrile neutropenic cancer patients. DATA SOURCES: The Cochrane Library, the Cochrane Cancer Network Register of trials, EMBASE, LILACS and MEDLINE, databases for ongoing trials and the conference proceedings of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). STUDY SELECTION: Randomized controlled trials comparing oral antibiotic/s and iv antibiotic/s for the treatment of neutropenic cancer patients with fever. DATA COLLECTION: Two reviewers independently assessed trial eligibility, methodological quality and extracted all data. Data concerning mortality, treatment failures and adverse events were drawn from included studies assuming an 'intention-to-treat' and 'per-protocol' basis for the outcome measures whenever possible. Relative risks (RR) with their 95% confidence intervals (CI) for dichotomous data were estimated. MAIN RESULTS: Fifteen trials (median mortality 0, range 0%-8.8%) were included in the analyses. The mortality rate was similar comparing oral and iv antibiotic treatment (RR 0.83, 95% CI 0.49-1.41, 2224 patients). Treatment failure rates were also similar (RR 0.94, 95% CI 0.84-1.05, 15 trials). No significant heterogeneity was shown for the primary outcomes. This effect was stable in a wide range of patients. Quinolones alone or combined with other antibiotics were used with comparable results. Adverse reactions, mostly gastrointestinal, were more common with oral antibiotics. CONCLUSIONS: Oral antibiotics may be safely offered to neutropenic patients with fever who are at low risk for mortality.     

Vancomycin is not an essential component of the initial empiric treatment regimen for febrile neutropenic patients receiving ceftazidime: a randomized prospective study.

The use of vancomycin as part of the initial antibiotic therapy of febrile neutropenic patients has become a controversial issue. Some studies support its incorporation in the initial regimen, and others suggest that vancomycin can be added later. We examined this issue in a prospective, randomized trial. We randomized 127 febrile neutropenic patients to receive either ceftazidime alone or ceftazidime plus vancomycin as the initial empiric antibiotic treatment. We added vancomycin to the ceftazidime arm of the study when fever persisted after 96 h of monotherapy, when new fever occurred after this time, or when a moderately ceftazidime-resistant gram-positive bacterium was isolated. Each of these regimens had similar initial response rates, similar durations of initial fever, similar frequencies of new fever during therapy, similar microbiological cure rates, similar superinfection rates, and similar survival rates. We observed more renal and cutaneous toxicities in patients receiving vancomycin and ceftazidime as initial therapy. We conclude that ceftazidime is appropriate as initial therapy for febrile neutropenic patients and that the addition of vancomycin is appropriate when fever persists after 4 days of monotherapy or when fever recurs following an initial response.     

Outcomes of treatment pathways in outpatient treatment of low risk febrile neutropenic cancer patients

Background We treated low-risk febrile neutropenic cancer patients utilizing two standard outpatient antibiotic pathways: oral ampicillin/clavulanate (500 mg) and ciprofloxacin (500 mg) or intravenous ceftazidime (2 g) and clindamycin (600 mg) every 8 h. The objectives were to determine the success of outpatient treatment of low-risk febrile neutropenia, to identify factors predicting outpatient failure, and to determine mortality related to the febrile episode.Methods Eligibility criteria included solid tumor diagnosis, stable vital signs, temperature 38.0°C, absolute neutrophil count (ANC) of <1000/ml, patient compliance, no significant organ dysfunction, ability to tolerate oral medication and fluids for oral pathway, residence within 30 miles of the institution, 24-h caregiver, and telephone and transportation access.Results There were 257 febrile episodes in 191 patients meeting the criteria. Patients were treated during March 1998 through February 2000. Median age was 48 (range, 17–77) years, and 60% (n=153) had an entry ANC of <100/ml; 205 (80%) febrile episodes successfully responded to outpatient treatment, and 52 (20%) were hospitalized. Logistic regression analysis showed the following were related to hospitalization: mucositis >grade 2 (p <0.002); Zubrod performance status 2 (p=0.029); ANC <100/ml (p=0.039), and age 70 years (p=0.048).Conclusions Outpatient treatment of low-risk febrile neutropenic cancer patients utilizing standard treatment pathways is associated with minimal morbidity and mortality and should be considered an acceptable standard of care with appropriate infrastructure available to provide strict and careful follow-up while on treatment. Certain factors are associated with higher risk of hospitalization and should be further examined in eligible patients with low-risk febrile neutropenia.Presented at the 2002 American Society of Clinical Oncology, Orlando, Florida, USA.     

Emergency Physicians' Risk Attitudes in Acute Decompensated Heart Failure Patients

Objectives:  Despite the existence of various clinical prediction rules, no data exist defining what frequency of death or serious nonfatal outcomes comprises a realistic "low-risk" group for clinicians. This exploratory study sought to identify emergency physicians' (EPs) definition of low-risk acute decompensated heart failure (ADHF) emergency department (ED) patients.
Methods:  Surveys were mailed to full-time physicians ( n =  88) in a multihospital EP group in southwestern Pennsylvania between December 2004 and February 2005. Participation was voluntary, and each EP was asked to define low risk (low risk of all-cause 30-day death and low risk of either hospital death or other serious medical complications) and choose a risk threshold at which they might consider outpatient management for those with ADHF. A range of choices was offered (<0.5, <1, <2, <3, <4, and <5%), and demographic data were collected.
Results:  The response rate was 80%. Physicians defined low risk both for all-cause 30-day death and for hospital death or other serious complications, at <1% (38.8 and 40.3%, respectively). The decision threshold to consider outpatient therapy was <0.5% risk both for all-cause 30-day death (44.6%) and for hospital death or serious medical complications (44.4%).
Conclusions:  Emergency physicians in this exploratory study define low-risk ADHF patients as having less than a 1% risk of 30-day death or inpatient death or complications. They state a desire to have and use an ADHF clinical prediction rule that can identify low-risk ADHF patients who have less than a 0.5% risk of 30-day death or inpatient death or complications.
ACADEMIC EMERGENCY MEDICINE 2010; 17:108–110 © 2010 by the Society for Academic Emergency Medicine     

Procalcitonin – a sensitive inflammation marker of febrile episodes in neutropenic children with cancer

Objective Sensitive parameters of inflammations, are rare or of limited validity in neutropenic patients. Procalcitonin (PCT) proven to be a sensitive inflammatory marker in nonneutropenic patients was evaluated for its diagnostic relevance in febrile episodes of neutropenic patients with cancer Methods Plasma levels of PCT were determined by an immunoluminometric assay in children with febrile neutropenic episodes (n=376) starting at the date of admission until the resolution of fever and were correlated with serum levels of the C-reactive protein (CrP). Febrile episodes were classified as fever of unknown origin (FUO), microbiologically or clinically documented infections and were also differentiated according to the site of the infection (unknown, bacteremia, respiratory, soft tissue, gastrointestinal and urinary tract infection). Results Independently from the aetiology and the site of infection the PCT peak value occurred mostly on the second hospital day and decreased rapidly in cases of successful antibiotic therapy and with the resolution of fever to the normal range (0.1–0.5 μg/l). The highest PCT peak levels at the onset of fever and during the febrile course were observed in patients with gramnegative bacteremia (n=22, median 12.1 μg/l, range 0.4–568.2 μg/l). There was a positive correlation between PCT peak levels and CrP peak levels (r=0.48, p=0.001) which mostly were observed 24 h later than for PCT. Conclusions PCT is a sensitive and specific parameter in the diagnostic and in the sequential assessment of febrile neutropenic episodes, especially in gramnegative infections. Its diagnostic accuracy in neutropenic patients is clearly higher than that of CrP.     

Procalcitonin - a sensitive inflammation marker of febrile episodes in neutropenic children with cancer

Objective: Sensitive parameters of inflammations are rare or of limited validity in neutropenic patients. Procalcitonin (PCT) proven to be a sensitive inflammatory marker in nonneutropenic patients was evaluated for its diagnostic relevance in febrile episodes of neutropenic patients with cancer.¶Methods: Plasma levels of PCT were determined by an immunoluminometric assay in children with febrile neutropenic episodes (n = 376) starting at the date of admission until the resolution of fever and were correlated with serum levels of the C-reactive protein (CrP). Febrile episodes were classified as fever of unknown origin (FUO), microbiologically or clinically documented infections and were also differentiated according to the site of the infection (unknown, bacteremia, respiratory, soft tissue, gastrointestinal and urinary tract infection).¶Results: Independently from the aetiology and the site of infection the PCT peak value occurred mostly on the second hospital day and decreased rapidly in cases of successful antibiotic therapy and with the resolution of fever to the normal range (0.1-0.5 wg/l). The highest PCT peak levels at the onset of fever and during the febrile course were observed in patients with gramnegative bacteremia (n = 22, median 12.1 wg/l, range 0.4-568.2 wg/l). There was a positive correlation between PCT peak levels and CrP peak levels (r = 0.48, p = 0.001) which mostly were observed 24 h later than for PCT.¶Conclusions: PCT is a sensitive and specific parameter in the diagnostic and in the sequential assessment of febrile neutropenic episodes, especially in gramnegative infections. Its diagnostic accuracy in neutropenic patients is clearly higher than that of CrP.     

Cefepime plus amikacin versus piperacillin-tazobactam plus amikacin for initial antibiotic therapy in haematology patients with febrile neutropenia: results of an open,randomized, multicentre trial

BACKGROUND: Standard therapy for suspected infections in patients with profound neutropenia is the combination of a beta-lactam antibiotic plus an aminoglycoside. Cefepime's broad-spectrum activity makes it an option for initial empirical therapy in neutropenic patients. The aim of this study is to evaluate the efficacy and safety of cefepime plus amikacin compared with piperacillin-tazobactam plus amikacin for initial empirical treatment of fever in adult haematology patients with severe neutropenia. METHODS: In this prospective multicentre trial, 969 patients with 984 febrile neutropenic episodes were randomized to receive iv amikacin (20 mg/kg every 24 h) combined with either cefepime (2 g every 8 h) or piperacillin-tazobactam (4 g/500 mg every 6 h). Clinical response was determined at 72 h and at completion of therapy. RESULTS: Eight hundred and sixty-seven episodes were assessable for efficacy (432 cefepime, 435 piperacillin-tazobactam). The frequency of success without modification of the empirical therapy was nearly identical for cefepime plus amikacin (49%) compared with piperacillin-tazobactam plus amikacin (51%). Similar rates of success were found for microbiologically documented infection: 40% versus 39%, respectively. Antibiotic modification was necessary in 49% of cefepime and 44% of piperacillin-tazobactam patients. The overall response rate, with or without modification of the assigned treatment, was 94% in both groups. Drug-related adverse events were reported in 10% of cefepime plus amikacin versus 11% of piperacillin-tazobactam plus amikacin patients. Mortality due to infection occurred in a total of 10 patients (two cefepime, eight piperacillin-tazobactam). CONCLUSION: The empirical regimen of cefepime plus amikacin is equivalent to piperacillin-tazobactam plus amikacin in febrile adult haematology patients with severe neutropenia. Keywords: cefepime, piperacillin-tazobactam, amikacin, empirical antibiotic therapy, febrile neutropenia, haematological malignancy     

Evaluation and management of infants and young children with fever

A practice guideline for the management of febrile infants and children younger than three years of age sparked controversy when it was published in 1993. Surveys indicate that many office-based physicians do not agree with recommendations for venipuncture and bladder catheterization in nontoxic febrile children, and that many employ watchful waiting rather than empiric antibiotic therapy. Surveys of parents note a preference for less testing and treatment. More aggressive management may be appropriate in febrile infants younger than three months old; however, criteria have been proposed to identify infants older than one month who are at low risk for serious bacterial infection. Because of widespread vaccination against Haemophilus influenzae infection, Streptococcus pneumoniae has become the cause of most cases of bacteremia. The risk of serious bacterial infection is greater in younger children and in those with higher temperatures and white blood cell counts. Controversy persists regarding the age, temperature and white blood cell count values that serve as indications for further evaluation or empiric antibiotic therapy.     

Comparison of cefepime versus ceftriaxone-amikacin as empirical regimens for the treatment of febrile neutropenia in acute leukemia patients

BACKGROUND: High-intensity regimes of chemotherapy have led to longer and more severe episodes of neutropenia with a resulting increase in morbidity and mortality due to infections. Which empiric antibiotic regimen to use in these cases is still under debate. METHODS: We performed a randomized comparative study to evaluate the efficacy of cefepime versus ceftriaxone plus amikacin as the initial treatment in an escalating, empirical, antibiotic therapy regimen in febrile neutropenic patients. Both adults and children were included. All patients had less than 500 neutrophils/microl at the time of infection. Patients were randomized to receive either cefepime or ceftriaxone plus amikacin. If infection continued 72 h later, patients in both groups received vancomycin, and if infection had not disappeared 7 days after starting antibiotics, amphotericin B was started. RESULTS: Twenty patients were included in each group. Both treatment and control groups were comparable for age and sex, among other factors. There were 18 cures in the cefepime group and 17 in the ceftriaxone plus amikacin group (p = 0.9). No patient discontinued therapy because of toxicity. CONCLUSIONS: Cefepime is a safe and very effective therapy for patients with acute leukemia and febrile neutropenia; in addition, it is a cheaper regimen in our country, and lacks the potential toxicity of the aminoglycosides.