Low-risk Febrile Neutropenic Patients Research Articles

Can Risk Stratification Tools Be Utilized to Safely Discharge Low-Risk Febrile Neutropenic Patients from the Emergency Department?

BackgroundChemotherapy-induced febrile neutropenia (FN) is one of the more common oncological emergencies. Despite evidence in the oncology literature suggesting that low-risk cases of FN can be managed safely at home, most patients with FN who present to the emergency department (ED) are admitted. FN risk stratification methods, such as Multinational Association for Supportive Care in Cancer (MASCC) and Clinical Index of Stable Febrile Neutropenia (CISNE) scores, may be useful when considering patient disposition. We sought to address whether the existing body of literature is adequate to support the use of these methods when treating patients with FN in the ED. MethodsA PubMed search from January 1, 2016 to March 19, 2021 was performed using the following search strategy: “febrile neutropenia” OR (fever AND neutropenia)) AND (emerg* OR outpatient) AND (admit OR admission OR hospitalization). General review articles and case reports were omitted. Each of the articles selected underwent a structured review. ResultsThe search yielded 371 articles, which were independently screened for relevance by two authors, and 23 articles were selected for inclusion. MASCC score was used in 10 of the identified studies and each of these studies concluded that the score was useful in the ED. Most of the identified studies found that CISNE score had a higher sensitivity than MASCC score (96.7% vs. 32.9%, respectively), but a lower specificity (22.2% vs. 89.5%). ConclusionsFN risk stratifications tools, such as MASCC and CISNE scores, are supported by the existing literature and may be included as part of the decision-making process when considering patient disposition.

Is current initial empirical antibiotherapy appropriate to treat bloodstream infections in short-duration chemo-induced febrile neutropenia?

Fever of unknown origin is by far the most common diagnosis in low-risk febrile neutropenic patients undergoing chemotherapy. The current empirical regimen combines amoxicillin-clavulanic acid and fluoroquinolones in low-risk neutropenic patients. The aim of this study was to assess the appropriateness of antibiotherapy and the outcome of bloodstream infections (BSI) in patients with expected neutropenia of short duration. This 2-year monocentric retrospective study included all consecutive neutropenic febrile adult patients with expected duration of neutropenia ≤ 7days. They were classified into low- and high-risk groups for complications using the MASCC index. Appropriateness of initial empirical antibiotic regimen was assessed for each BSI. Multivariate analysis was performed to identify factors associated with mortality. Over the study period, 189 febrile episodes with positive blood cultures in neutropenic patients were reported, of which 44 occurred during expected duration of neutropenia ≤ 7days. Patients were classified as high-risk (n = 27) and low-risk (n = 17). Gram-negative bacteria BSI represented 57% of cases, including only two multidrug-resistant bacteria in high-risk patients. Initial empirical antibiotherapy was appropriate in 86% of cases, and inappropriate in the event of coagulase-negative Staphylococcus BSI (14%), although the outcome was always favorable. In low-risk patients, no deaths and only 12% of severe complications were reported, contrasting with mortality and complication rates of 48% (p < 0.001) and 63% in high-risk patients (p < 0.001), respectively. Outcome of BSI is favorable in low-risk febrile neutropenic patients, even with inappropriate empirical initial antibiotic regimen for coagulase-negative Staphylococcus BSI. Initial in-hospital assessment and close monitoring of these patients are however mandatory.

Comparison of the MASCC and CISNE scores for identifying low-risk neutropenic fever patients: analysis of data from three emergency departments of cancer centers in three continents.

Patients with febrile neutropenia are a heterogeneous group with a minority developing serious medical complications. Outpatient management of low-risk febrile neutropenia has been shown to be safe and cost-effective. Scoring systems, such as the Multinational Association for Supportive Care in Cancer (MASCC) score and Clinical Index of Stable Febrile Neutropenia (CISNE), have been developed and validated to identify low-risk patients. We aimed to compare the performance of these two scores in identifying low-risk febrile neutropenic patients. We performed a pooled analysis of patients presenting with febrile neutropenia to three tertiary cancer emergency centers in the USA, UK, and South Korea in 2015. The primary outcome measures were the occurrence of serious complications. Admission to an intensive care unit (ICU) and 30-day mortality were secondary outcomes. The predictive performance of each score was analyzed. Five hundred seventy-one patients presented with febrile neutropenia. With MASCC risk index, 508 (89.1%) were classified as low-risk febrile neutropenia, compared to 60 (10.5%) with CISNE classification. Overall, the MASCC score had a greater discriminatory power in the detection of low-risk patients than the CISNE score (AUC 0.772, 95% CI 0.726-0.819 vs. 0.681, 95% CI 0.626-0.737, p = 0.0024). Both MASCC and CISNE scores have reasonable discriminatory value in predicting patients with low-risk febrile neutropenia. Risk scores should be used in conjunction with clinical judgment for the identification of patients suitable for outpatient management of neutropenic fever. Developing more accurate scores, validated in prospective settings, will be useful in facilitating more patients being managed in an outpatient setting.

Application of the MASCC and CISNE Risk-Stratification Scores to Identify Low-Risk Febrile Neutropenic Patients in the Emergency Department

Although validated risk-stratification tools have been used to send low-risk febrile neutropenic patients home from clinic and inpatient settings, there is a dearth of research evaluating these scores in the emergency department (ED). We compare the predictive accuracy of the Multinational Association for Supportive Care in Cancer (MASCC) and Clinical Index of Stable Febrile Neutropenia (CISNE) scores for patients with chemotherapy-induced febrile neutropenia and presenting to the ED. We conducted a retrospective cohort study to evaluate all patients with febrile neutropenia (temperature ≥38°C [100.4°F], absolute neutrophil count <1,000 cells/μL) who presented to 2 academic EDs from June 2012 through January 2015. MASCC and CISNE scores were calculated for all subjects, and each visit was evaluated for several outcome variables, including inpatient length of stay, upgrade in level of care, clinical deterioration, positive blood culture results, and death. Descriptive statistics are reported and continuous variables were analyzed with Wilcoxon rank sum. During our study period, 230 patients presented with chemotherapy-induced febrile neutropenia. The CISNE score identified 53 (23%) of these patients as low risk and was highly specific in the identification of a low-risk cohort for all outcome variables (98.3% specific, 95% confidence interval [CI] 89.7% to 99.9%; positive predictive value 98.1%, 95% CI 88.6% to 99.9%). Median length of stay was shorter for low-risk versus high-risk CISNE patients (3-day difference; P<.001). The MASCC score was much less specific (54.2%; 95% CI 40.8% to 67.1%) in the identification of a low-risk cohort. Our results suggest that the CISNE score may be the most appropriate febrile neutropenia risk-stratification tool for use in the ED.

Fluoroquinolone resistance in bacteremic and low risk febrile neutropenic patients with cancer

BackgroundThe low risk febrile neutropenic patients with Multinational Association for Supportive Care in Cancer (MASCC) score of more than 20 are recommended to be treated with fluoroquinolone-based oral treatment by the National Comprehensive Cancer Network (NCCN) guideline. This recommendation relies, at least partially, on the high sensitivity of the blood culture isolates to fluoroquinolone in clinical trials conducted in Western countries. Whether this also applies in middle or low income countries like China where antibiotic resistance is becoming prevalent recently has not been evaluated.MethodsAll the positive blood culture results from January 2010 to December 2013 in the 2 large Chinese cancer centers were reviewed. The patients were included into the study with the following criteria: febrile neutropenia, solid tumor or lymphoma, MASCC score >20, positive blood cultures within two days of the onset of fever, and detailed treatment history.ResultsA total of 38 patients were included in this analysis. Two patients had polymicrobial bacteremia (Enterococcus faecalis and Flavimonas oryzihabitans). Other isolates included coagulase-negative staphylococcus, micrococcal species, viridans streptococci, Klebsiella pneumoniae, and Escherichia coli. The majority of the monomicrobial isolates from these 36 patients was Escherichia coli (28 patients, 74%). Notably, in contrast to the high sensitivity to fluoroquinolone from blood culture of the low risk patients in previous reports in Westen countries, a very high drug resistance was observed: 13 out of 28 Escherichia coli isolates (46%) or 14 out of all 38 positive cultures (37%).ConclusionThe results warrant further validations in prospective clinical trials in countries where antibiotic resistance is prevalent to ensure appropriate antibiotic administration.

The Multinational Association for Supportive Care in Cancer (MASCC) risk index score: 10 years of use for identifying low-risk febrile neutropenic cancer patients

The Multinational Association for Supportive Care in Cancer risk index score developed, through a multinational collaboration, was published in 2000 with the aim to identify patients with chemotherapy-induced febrile neutropenia at low risk of serious medical complication development. It has been endorsed as a reliable tool since 2002 by Infectious Diseases Society of America. Ten years after, we thought worth to review its use, its characteristics in the external validations that occurred after the initial publication and also to review how the recognition of a group of patients at low risk has changed the management of febrile neutropenia. We also raise the issue of identification of high-risk patients that remains a challenge today.

Oral Antibiotics for Fever in Low-Risk Neutropenic Patients With Cancer: A Double-Blind, Randomized, Multicenter Trial Comparing Single Daily Moxifloxacin With Twice Daily Ciprofloxacin Plus Amoxicillin/Clavulanic Acid Combination Therapy—EORTC Infectious Diseases Group Trial XV

This double-blind, multicenter trial compared the efficacy and safety of a single daily oral dose of moxifloxacin with oral combination therapy in low-risk febrile neutropenic patients with cancer. Inclusion criteria were cancer, febrile neutropenia, low risk of complications as predicted by a Multinational Association for Supportive Care in Cancer (MASCC) score > 20, ability to swallow, and ≤ one single intravenous dose of empiric antibiotic therapy before study drug treatment initiation. Early discharge was encouraged when a set of predefined criteria was met. Patients received either moxifloxacin (400 mg once daily) monotherapy or oral ciprofloxacin (750 mg twice daily) plus amoxicillin/clavulanic acid (1,000 mg twice daily). The trial was designed to show equivalence of the two drug regimens in terms of therapy success, defined as defervescence and improvement in clinical status during study drug treatment (< 10% difference). Among the 333 patients evaluated in an intention-to-treat analysis, therapy success was observed in 80% of the patients administered moxifloxacin and in 82% of the patients administered combination therapy (95% CI for the difference, -10% to 8%, consistent with equivalence). Minor differences in tolerability, safety, and reasons for failure were observed. More than 50% of the patients in the two arms were discharged on protocol therapy, with 5% readmissions among those in either arm. Survival was similar (99%) in both arms. Monotherapy with once daily oral moxifloxacin is efficacious and safe in low-risk febrile neutropenic patients identified with the help of the MASCC scoring system, discharged early, and observed as outpatients.

Oral moxifloxacin for outpatient treatment of low-risk, febrile neutropenic patients

Low-risk febrile neutropenic patients can be treated without hospitalization with oral antibiotic regimens. Combination regimens are recommended. Our objective was to evaluate the feasibility of quinolone monotherapy (moxifloxacin) in this setting. In this open-label pilot study, eligible low-risk febrile neutropenic patients identified using pre-defined criteria (MASCC Risk Index) received oral moxifloxacin (400 mg) in our emergency center and were discharged after a 4-8 h observation period to ensure clinical stability. They subsequently received moxifloxacin 400 mg daily as outpatients. Success of monotherapy, outpatient management, the development of adverse events, and major medical complications were recorded. The trial was closed without reaching the target sample size of 40 patients due to slow accrual. Twenty-one evaluable patients were enrolled, with sarcoma and breast cancer being the predominant underlying neoplasms. Most patients (76%) were severely neutropenic (</=100 cells/mm(3)) on enrollment. There were 13 episodes (62%) of unexplained fever and eight documented infections including five episodes (24%) of bacteremia. The overall success rate of monotherapy was 95%. One patient with unexplained fever and persistent neutropenia required hospitalization and responded to alternative therapy. No significant toxicity or severe medical complications occurred. Oral outpatient quinolone monotherapy for low-risk febrile neutropenic patients appears feasible and needs to be formally evaluated in large randomized clinical trials.

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

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. 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. 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%. 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.

Identifying low-risk febrile neutropenic cancer patients in the West of Scotland

18592 Background: Febrile neutropenia (FN) is a potentially life threatening complication of chemotherapy. In-patient treatment using intravenous antibiotics reduces FN related mortality. However, most patients with FN are at low risk of complication. Identifying them could result in new strategies such as out-patient, oral antibiotic, based treatment resulting in improved quality of life and cost savings. The Multinational Association for Supportive Care in Cancer (MASCC) and the Talcott model were developed to identify such patients. Two randomised controlled trials have shown that oral antibiotics in low risk patients are safe and effective. However are such models appropriate in populations with a high incidence of co-morbidity such as the West of Scotland? This study reviews FN admissions to our cancer centre to determine the proportion of patients that would fall into a low risk group according to the MASCC and/or Talcott models and to identify other factors that might predict for low risk. Methods: Review of FN admissions between June–December 2002. Data included: patient demographics, MASCC score, Talcott group, co-morbidity, haematological and biochemical values, prior use of antibiotics and growth factors (GFs) and whether the fever resolved without serious medical complication (FRWMC). Results: 77 episodes of FN involving 68 patients. Mean age = 51 (range 16–79). 94% involved patients with solid malignancies. Commonest tumour type was breast (29%). Patients were classified as MASCC and Talcott low risk in 52% and 31% of episodes respectively. There was a significant association between low risk MASCC score and low risk Talcott score (χ2 28.665, d.f.3, p &lt; 0.001). Low risk MASCC was associated with FRWMC (χ2 4.193, d.f.1, p &lt; 0.05). Multiple logistic regression of risk factors showed that high bilirubin and low albumin were associated with a worse outcome. FN mortality rate was 7.8%. Conclusions: The use of clinical risk models to identify low risk patients can predict for an uncomplicated recovery in our patients. Bilirubin and albumin values at presentation added predicted value for low risk over and above the MASCC model. Future trials may validate this observation. No significant financial relationships to disclose.

Once daily, oral, outpatient quinolone monotherapy for low‐risk cancer patients with fever and neutropenia

The objective of this study was to assess the feasibility of empiric, oral, outpatient quinolone monotherapy in 40 adult patients with fever and neutropenia who were at low risk for serious medical complications. Patients with breast cancer or sarcoma who presented with fever and neutropenia and were identified as low risk received empiric, oral, quinolone monotherapy (gatifloxacin at a dose of 400 mg once daily). Patients who had a significant source/focus of infection on presentation were excluded. After an initial observation period of 4 to 8 hours in the emergency center, the remainder of their management was ambulatory. Patients were evaluated for response to therapy, development of complications and/or the need for hospital admission, and drug-related adverse events. Three of 43 patients studied were ineligible medically because of the presence of Common Toxicity Criteria (version 3.0) Grade>2 mucositis. Of the 40 eligible patients, 38 patients (95%) responded to gatifloxacin monotherapy, although 1 patient requested hospital admission (92% response for ambulatory management). The mean duration of therapy was 7 days, and the median number of days from enrollment to defervescence was 4 days. There were no serious medical complications, no drug-related adverse events, and no deaths on study or during 30 days of follow-up. The results from this study indicated that outpatient quinolone monotherapy in low-risk febrile neutropenic patients is safe, effective, and well received. These conclusions need to be validated in a randomized trial.

Clinical guidelines for the management of neutropenic patients with unexplained fever in Japan: validation by the Japan Febrile Neutropenia Study Group

The Japan Febrile Neutropenia Study Group (JFNSG) Trial was a multicenter, open, randomized study designed to validate the first Japanese guidelines for the management of neutropenic cancer patients with unexplained fever issued in 1998. The trial compared cefepime monotherapy with cefepime plus amikacin combination therapy in febrile neutropenic patients with hematological disorders. The JFNSG found that monotherapy with cefepime was, in general, as effective as combination therapy. In terms of subset analyses, defervescence appeared to occur more frequently in leukemic patients and in those with profound neutropenia treated with the dual combination. The conclusion of the trial was that the 1998 guidelines were applicable to the Japanese febrile neutropenic patient population. The JFNSG met again in 2003 to revise these guidelines. An important addition to the guidelines was a distinction between low- and high-risk patients. Low-risk febrile neutropenic patients can receive oral ciprofloxacin or levofloxacin, with or without amoxicillin/clavulanic acid, on an outpatient basis, or intravenous (i.v.) monotherapy with cefepime, ceftazidime or a carbapenem. High-risk patients can receive i.v. cefepime, ceftazidime or a carbapenem, or an i.v. dual combination with cefepime, ceftazidime or a carbapenem plus an aminoglycoside. Those patients with a documented infection with methicillin-resistant Staphylococcus aureus should also receive a glycopeptide. It remains to be determined whether existing assessment scoring systems apply to Japanese patients; whether a broad-spectrum cephalosporin plus an aminoglycoside combination is required as the initial management of patients with acute leukemia and/or profound neutropenia; which antibacterial drugs should be used when first- and second-line agents fail; what are the appropriate oral agents and dosing regimens for low-risk patients; whether serology or the polymerase chain reaction should be the preferred marker for initiating pre-emptive antifungal therapy; and whether the azoles or the candins should be the preferred antifungal agents.

Bacterial infections in low‐risk, febrile neutropenic patients

Accurate identification of low-risk, febrile neutropenic patients has become possible only recently. Many such patients are treated with oral antibiotics without hospitalization. To the authors' knowledge, data concerning the spectrum of bacterial infections in these patients are scarce, and collecting such data may have an impact on the choice of empiric oral regimen(s). Using the same risk-prediction and eligibility criteria, four studies of empiric therapy in low-risk, febrile neutropenic patients were conducted at the authors' institution. Based on that experience, patients also were entered on clinical pathways for outpatient therapy. For the current study, microbiologic data were pooled from those trials and clinical pathways (757 episodes) to describe the nature and spectrum of infections seen in this setting. Unexplained fever occurred most often (58% of episodes), and both clinically documented and microbiologically documented infections were seen with equal frequency (21% of episodes, respectively). The most common clinical sites of infection were the upper respiratory tract, skin, and skin structure. Among microbiologically documented infections, monomicrobial, gram-positive infections accounted for 49% (with coagulase-negative staphylococci the most frequent); monomicrobial, gram-negative infections accounted for 36% (with Escherichia coli the most frequent); and 15% of infections were polymicrobial. In this description of the spectrum of infections in the largest cohort of low-risk febrile neutropenic patients to date, episodes of unexplained fever were predominant, but gram-positive, gram-negative, and polymicrobial infections also were documented. Although these patients were at low risk for complications, they required broad-spectrum antibiotic therapy when they developed neutropenic fever.

Low-risk patients with fever and neutropenia during chemotherapy: Current clinical practice patterns

8089 Background: Fever during neutropenia is a common complication of cytotoxic chemotherapy. There is increasing evidence that oral antibiotics, outpatient treatment, or both may be appropriate for a select group of low-risk febrile neutropenic (F&N) patients. The objective of this study is to describe the role of oral and/or outpatient therapies in clinical practice patterns of physicians treating cancer patients. Methods: A national survey of 3600 randomly selected oncologists and hematologists (ASCO members) in the U.S. was used to determine current clinical practice patterns for low-risk F&N patients. Questions included therapy choices and 4 case scenarios designed to assess factors associated with physicians' willingness to use outpatient antibiotics. Probability of willingness to use outpatient antibiotics was modeled as a function of 8 key criteria: tumor type, presenting ANC, expected neutropenia duration, comorbidities, age, renal and hepatic function, pulmonary status, and distance from the hospital. Results: Completed surveys were received from 34% of actively practicing physicians: 69% private practice, 27% academic, 3% managed care; 16 yrs (mean) in practice. 82% of respondents use outpatient antibiotics for selected low risk F&N patients - 28% of them indicated use of such treatment in ≥ 65% of their patients . For respondents indicating outpatient treatment for ≥ 5% of their F&N patients, factors predicting for outpatient antibiotic therapy were disease (breast cancer vs. leukemia/non-Hodgkin = s lymphoma), serious infection (catheter, prior invasive fungal, prior resistant bacterial vs. other) and x-ray evidence of infiltrate (present vs. absent). When outpatient monotherapy is used, oral levofloxacin is most commonly prescribed (50%), followed by ciprofloxacin alone (36%), and ciprofloxacin + amoxicillin/clavulanate (35%). 4% of physicians routinely add vancomycin to empiric regimens, 48% add G- or GM-CSF to treatment. Fluoroquinolone prophylaxis for low-risk patients is used by 45%. Conclusions: Physicians are willing to accept outpatient treatment for low-risk F&N patients, although treatment algorithms vary. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ortho-McNeil

Envolving treatment of fever and neutropenia in cancer patients

Management of febrile neutropenia is evolving as we learn to prospectively identify risk factors influencing outcome. High risk patients should still be promptly hospitalized and treated with parenteral antibiotics and colony-stimulating factors until resolution of the febrile neutropenia episode. A number of broad spectrum antibiotics can be safely used in monotherapy, although initial combination antibiotic treatment is recommended in patients presenting clinical signs predictive of gram-negative sepsis. The incorporation of glycopeptides to initial therapeutic regimens shall be used only in clinical situations associated with increased risk of fulminant gram-positive bacterial infections. Validated risk-assessment models are now available and have enabled clinicians to identify patients at low risk of complications who may benefit from therapeutic approaches associated with reduced toxicity and cost, such as oral antibiotic therapy, early hospital discharge and outpatient care. Hospital-based oral antibiotic therapy has proven to be safe and effective in low-risk populations. Early hospital discharge and outpatient care may be also appropriate in low-risk febrile neutropenic patients in selected settings. However, the safety of these treatment strategies in the general medical community remains to be proven. A risk-based approach should also be applied to the use of colony-stimulating factors in this setting. While the routine use of growth factors in neutropenic patients with uncomplicated febrile episodes is not warranted, recent data support their use in populations with high risk neutropenic fever.

The Multinational Association for Supportive Care in Cancer Risk Index: A Multinational Scoring System for Identifying Low-Risk Febrile Neutropenic Cancer Patients

Febrile neutropenia remains a potentially life-threatening complication of anticancer chemotherapy, but some patients are at low risk for serious medical complications. The purpose of this study was to develop an internationally validated scoring system to identify these patients. Febrile neutropenic cancer patients were observed in a prospective multinational study. Independent factors assessable at fever onset, predicting low risk of complications, on a randomly selected derivation set, were assigned integer weights to develop a risk-index score, which was subsequently tested on a validation set. On the derivation set (756 patients), predictive factors were a burden of illness indicating absence of symptoms or mild symptoms (weight, 5; odds ratio [OR], 8.21; 95% confidence interval [CI], 4.15 to 16.38) or moderate symptoms (weight, 3; OR, 3.70; 95% CI, 2.18 to 6.29); absence of hypotension (weight, 5; OR, 7.62; 95% CI, 2.91 to 19.89); absence of chronic obstructive pulmonary disease (weight, 4; OR, 5. 35; 95% CI, 1.86 to 15.46); presence of solid tumor or absence of previous fungal infection in patients with hematologic malignancies (weight, 4; OR, 5.07; 95% CI, 1.97 to 12.95); outpatient status (weight, 3; OR, 3.51; 95% CI, 2.02 to 6.04); absence of dehydration (weight, 3; OR, 3.81; 95% CI, 1.89 to 7.73); and age less than 60 years (weight, 2; OR, 2.45; 95% CI, 1.51 to 4.01). On the validation set, a Multinational Association for Supportive Care in Cancer risk-index score >/= 21 identified low-risk patients with a positive predictive value of 91%, specificity of 68%, and sensitivity of 71%. The risk index accurately identifies patients at low risk for complications and may be used to select patients for testing therapeutic strategies that may be more convenient or cost-effective.

Use of fluoroquinolones for empirical management of febrile neutropenia in pediatric cancer patients.

Empiric antibiotic therapy has become a standard of care for the febrile neutropenic patient. Many clinical trials over the previous three decades have demonstrated that a variety of antibiotic combinations and more recently potent antibiotic monotherapies may preserve the patient through the critical time of fever and neutropenia. Recently attempts have been made to identify "low risk" patients who may not require traditional, intensive, hospitalized intravenous antimicrobial therapy. Therefore the need for new treatment alternatives for the febrile neutropenic pediatric cancer patient in particular revolves around the desire for less complex regimens, agents with minimal toxicity and expense and the option of an oral formulation for outpatient management. Fluoroquinolones, especially ciprofloxacin and ofloxacin, are examined in this paper as potential oral alternatives for managing the low risk neutropenic pediatric cancer patient population. Attention must be paid to their antibacterial spectra, however, and in some cases fluoroquinolones should be combined with a second agent for additional Gram-positive coverage. Several studies, including one ongoing trial at the National Cancer Institute, have shown the potential benefits of oral fluoroquinolone therapy among low risk febrile neutropenic patients. Joint complaints in children after ciprofloxacin therapy in the National Cancer Institute trial thus far have been minimal, reversible and felt to be unrelated to ciprofloxacin treatment. The use of outpatient therapy, such as the fluoroquinolones, to manage febrile neutropenic episodes must be approached with caution and should be undertaken only in selected low risk patients.

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.