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.     

Clinical efficacy of adjunctive G-CSF on solid tumor and lymphoma patients with established febrile neutropenia

Background

The use of granulocyte colony-stimulating factor (G-CSF) as a prophylaxis against febrile neutropenia (FN) is well documented in the literature; however, the therapeutic use of G-CSF in the treatment of FN remains controversial. This study assessed the efficacy of adjunctive G-CSF in the treatment of FN by evaluating clinical outcomes.

Methods

This was a single-center, prospective cohort study conducted at the National Cancer Center in Singapore. Adult patients who had received chemotherapy and developed FN between January 2009 and January 2012 were included in the analysis. The clinical efficacy of adjunctive G-CSF was evaluated by investigating the duration of hospitalization, duration to absolute neutrophil count (ANC) recovery, duration of grade IV neutropenia, duration to fever resolution, duration of antibiotic therapy, and incidence of documented infections. A multivariate analysis was performed to identify patients who could potentially benefit from adjunctive G-CSF.

Results

Four hundred and thirty patients were analyzed. Majority manifested low-risk FN (81.2 %) based on the Multinational Association of Supportive Care in Cancer (MASCC) scoring. Compared to patients who did not receive adjunctive G-CSF, patients receiving adjunctive G-CSF had a nonsignificant reduction in the duration of hospitalization (3.5 vs. 3.7 days, p?=?0.41) and in ANC recovery time (3.4 vs. 3.5 days, p?=?0.76). Neutropenia-related mortality was lower among those who have received adjunctive G-CSF (2.4 vs. 8.4 %, p?=?0.006). Patients of Indian ethnicity and those who underwent gemcitabine-containing chemotherapy were less likely to receive adjunctive G-CSF treatment.

Conclusions

This observational study suggested that adjunctive G-CSF may confer clinical benefits among solid tumor and lymphoma patients with established febrile neutropenia. Further research should be conducted to validate the findings.     

Meropenem versus ceftazidime as empirical monotherapy in febrile neutropenia of paediatric patients with cancer

This trial assessed the efficacy and safety of meropenem versus ceftazidime as empirical monotherapy for febrile neutropenia in paediatric cancer patients. In a prospective randomized study, 172 evaluable febrile episodes in the meropenem arm and 170 episodes in the ceftazidime arm were analysed for the clinical and microbiological response dependent on the kind of infection. About half the episodes were classified as fever of unknown origin (FUO) and the remainder as microbiologically or clinically documented infections. The most frequently documented infections in both arms were bacteraemias (22.1 versus 26.5%), predominantly caused by Gram-positive organisms (57.9 versus 71.1%). The success rate of the initial monotherapy differed significantly between the two arms and was 55.8% in the meropenem and 40.0% in the ceftazidime arm (P = 0.003). In addition, a significantly longer duration of fever and of antimicrobial therapy was observed in the ceftazidime arm than in the meropenem arm (median 5 versus 4 days, P = 0.022, and 7 versus 6 days, P = 0.009, respectively). With respect to the kind of infection, differences between the two arms were significant only in episodes classified as FUO but not in documented infections. In both arms, side effects were minimal. Despite the greater response rate for meropenem in FUO, the fact that ceftazidime has been proven to be as effective as meropenem in documented infections in the present study suggests that both drugs are useful as empirical monotherapy in febrile paediatric cancer patients.     

The outpatient management of low-risk febrile patients with neutropenia: risk assessment over the telephone

Objective The purpose of this retrospective study is to evaluate the feasibility of the risk assessment over the telephone in the outpatient management of low-risk febrile patients with neutropenia. Materials and methods Febrile patients with neutropenia were eligible for outpatient management with oral ciprofloxacin if they demonstrated the following characteristics: resolution of neutropenia expected in <10 days, good performance status, controlled cancer, no symptoms or signs suggesting systemic infection other than fever, and no comorbidity requiring hospitalization. Eligible patients received oral ciprofloxacin (400 mg, three times daily) and were monitored as far as possible by telephone. Risk assessment concerning general condition was carried out over the telephone. Results Of the 60 consecutive patients who received neoadjuvant chemotherapy as a phase II trial of docetaxel (60 mg/m²) and doxorubicin (50 mg/m²) for primary breast cancer, 30 low-risk febrile patients received oral ciprofloxacin. Twenty-seven of these patients (90%) recovered uneventfully without hospitalization and the use of granulocyte colony-stimulating factor. Treatment was considered to have failed in the remaining three (10%) on the account of the need to modify or change their regimens. Conclusions For carefully selected low-risk febrile patients with neutropenia, risk assessment over the telephone may be convenient, and close daily medical scrutiny may be not routinely required in the outpatient.     

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.     

Treatment of febrile neutropenia with cefepime monotherapy

BACKGROUND AND OBJECTIVE: The empirical administration of a broad-spectrum beta-lactam antibiotic, either as monotherapy or in combination with an aminoglycoside, is an essential component of the initial management of patients with fever and severe neutropenia. Multiple antibiotics have been tested for this indication. Cefepime is a fourth-generation cephalosporin with in vitro activity against most gram-negative and many gram-positive bacteria. We have studied the use of this agent as monotherapy in this indication. METHODS: One hundred and twenty-six episodes of febrile neutropenia in 98 adults with hematological malignancies were treated with cefepime monotherapy. Cefepime was given at a dose of 2 g every 8 h i.v. Most episodes (49%) were fever of unexplained origin, while a microbiologically documented and clinically documented infection occurred in 25% episodes each. Seventy-six (61%) episodes occurred after conventional chemotherapy, while 51 (41%) after a hematopoietic stem cell transplantation. Results: Twelve episodes (10%) were not evaluable for response. Among the 114 evaluable episodes, 69 (55% of the initial sample and 61% of those evaluable) responded to cefepime monotherapy, while therapy failed in 45 cases (36% of the initial sample and 39% of those evaluable), including 14 cases who developed breakthrough bacteremia during therapy. There were no deaths due to bacterial infection. At the end of all antibiotic therapy (final outcome) 69 episodes were cured only with monotherapy, 47 were cured with modification of therapy and 10 patients died from an unrelated cause. The only variable that appeared to correlate with response to therapy was the duration of neutropenia, which was longer among patients who failed or developed breakthrough bacteremia than among those who responded to monotherapy. INTERPRETATION AND CONCLUSIONS: Initial empirical antibiotic therapy with cefepime as a single agent in patients with febrile neutropenia and a hematological malignancy is effective, but patients with prolonged neutropenia appear to be at higher risk for failure. However, with appropriate therapeutic changes the risk of dying from a bacterial infection is very low.     

Cefepime versus ceftazidime as empiric therapy for fever in neutropenic patients with cancer

OBJECTIVE: To compare the efficacies of cefepime and ceftazidime as empiric therapy during the management of fever in cancer patients with chemotherapy-induced neutropenia. METHODS: A prospective, double-blind, randomized study of cefepime 2 g every eight hours and ceftazidime 2 g every eight hours was performed in 276 adult neutropenic (absolute neutrophil count < 500/mm3) cancer patients with fever. RESULTS: Median duration of neutropenia was five days. Sixty-one percent (n = 188) of the patients were evaluable. Treatment was successful in 57% (58/101) of cefepime-treated patients and 60% (52/87) of ceftazidime-treated patients (95% CI -18 to 12; p = 0.77). Bacteremic clearance occurred in 71% (12/17) of cefepime-treated patients and 40% (6/15) of ceftazidime-treated patients (p = 0.3). Both drugs were well tolerated. CONCLUSIONS: Cefepime appears to be as effective as ceftazidime in the initial treatment of febrile episodes in adult cancer patients with chemotherapy-associated neutropenia of modest duration.     

Cefepime monotherapy for febrile neutropenia in patients with lung cancer

We assessed the efficacy and safety of cefepime monotherapy (1 g intravenously every 8 h) for febrile neutropenia in patients with lung cancer in a multi-institutional phase II study. Patients treated with chemotherapy with or without radiotherapy for lung cancer were eligible for this study. Other eligibility criteria included fever (temperature of ≥38.0 °C) and an absolute neutrophil count of <500/mm³ or <1000/mm³ with an expected decline to <500/mm³ within the next 48 h. Risk assessment was performed using the Multinational Association of Supportive Care in Cancer risk-index score. Cefepime 1 g was given intravenously every 8 h. The primary endpoint was the response rate at the end of cefepime therapy. Co-administration of granulocyte-colony-stimulating factor was permitted. Of 54 patients enrolled, 39 were classified in the low-risk group and 15 in the high-risk group. Overall response rate was 78% (95% CI: 64.4–88.0%). The response rates were 85% (95% CI: 69.5–94.1%) in the low-risk group and 60% (95% CI: 32.3–83.7%) in the high-risk group, respectively. One patient died from septic shock due to Enterobacter cloacae bacteremia. There was no significant adverse event. Cefepime 1 g intravenously every 8 h appears to be effective for febrile neutropenia in patients with lung cancer, especially in those with low-risk febrile neutropenia, and is well tolerated.Clinical trial registrationUMIN Clinical Trials Registry, UMIN000006157.     

Low-dose continuous-infusion ceftazidime monotherapy in low-risk febrile neutropenic patients

 One hundred and thirty-five cancer patients admitted with low-risk neutropenic fever received a low-dose schedule of ceftazidime as infusional monotherapy over a total of 180 episodes. Ceftazidime was administered as a 1-g bolus followed by a continuous infusion of 2 g per day. In this patient population the ceftazidime was both practical and well tolerated. Sixty-eight percent of patients responded with clinical improvement and complete resolution of fever within 48 h. Overall, 95% of patients responded, although 18% subsequently required antibiotic modification for persistent fever. Only 5% of episodes were considered failures due to clinical deterioration, and over the study period there was only 1 fatality due to respiratory failure. The median duration of hospitalisation was only 4 days (2–20). In conclusion, monotherapy with low-dose infusional ceftazidime appears safe and highly effective in this low-risk population of neutropenic patients and may reduce antibiotic costs appreciably. Published online: 7 March 2000     

Outpatient high-dose melphalan in multiple myeloma patients

BACKGROUND: The brief period of neutropenia and limited nonmarrow toxicity after high-dose melphalan (HDM) provide a rationale for outpatient treatment. STUDY DESIGN AND METHODS: Our experience with HDM (140-200 mg/m(2)) in 90 consecutive transplant episodes was retrospectively reviewed. Most patients were treated in an outpatient setting. Patients without a primary care provider (PCP) were electively admitted before the anticipated onset of neutropenia. Ceftriaxone was added to ciprofloxacin at the onset of neutropenia. All febrile patients were admitted. RESULTS: The median time from peripheral blood progenitor cell infusion to onset of neutropenia was 5 days (range, 4-6 days), and the mean duration of neutropenia was 5 days (range, 4-7 days). Thirty-eight transplants (42%) were performed entirely in the outpatient setting. The mean duration of hospitalization was 2.2 days in patients not electively admitted. The use of ceftriaxone was associated with a decreased risk for fever (39% vs. 79%) and reduced duration of hospitalization (1.6 days vs. 4.5 days) for nonelectively admitted patients. There was no treatment-related mortality. CONCLUSION: Ambulatory therapy with HDM is safe and can be achieved in a general outpatient setting. The predictable time to neutropenia allows even poor candidates for outpatient therapy to be admitted electively on Day +4. The apparent beneficial effect of ceftriaxone needs to be confirmed in randomized trials.     

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.     

头孢吡肟或头孢他啶联合阿米卡星治疗白血病化疗后粒细胞缺乏合并感染的疗效比较

目的:比较头孢吡肟或头孢他啶联合阿米卡星在治疗白血病化疗后粒细胞缺乏合并感染中的疗效。方法:回顾分析我科近年收治的白血病患者化疗后粒细胞缺乏合并重症感染者共117例,比较临床经验抗感染治疗方案头孢他啶+阿米卡星与头孢吡肟+阿米卡星的疗效。结果:头孢吡肟+阿米卡星组痊愈率为51.61%,有效率为64.52%;头孢他啶+阿米卡星组痊愈率为49.02%,有效率为62.75%。经统计学分析,两组患者的临床疗效差异无显著性。结论:头孢吡肟+阿米卡星与头孢他啶+阿米卡星在治疗白血病化疗后粒细胞缺乏合并重症感染时疗效相似。     

A comparative study of cefepime versus ceftazidime as empiric therapy of febrile episodes in neutropenic patients.

An open-label, randomized comparative study was conducted to evaluate the efficacy and safety of cefepime (2.0 g q. 8 h) and ceftazidime (2.0 g q. 8 h) in the empiric therapy of febrile neutropenic patients. A total of 45 eligible febrile episodes were randomized (1:1) to be treated with the study regimen. Nineteen febrile episodes treated with cefepime and 22 febrile episodes treated with ceftazidime were evaluable for efficacy. The two groups were comparable in terms of age, sex, height, weight, underlying neoplasm, number of pretherapy neutrophil, duration of neutropenia and types of infections. The overall therapeutic success rate of the cefepime group (53%) was comparable to the ceftazidime group (50%). It did not differ significantly (95% confidence interval: -0.28 to 0. 34, p = 0.85). Eighty-eight percent of pathogens in each group were bacteriologically eradicated. The safety profile was similar in both groups. No patients in either group discontinued the therapy because of adverse events. None (0%) of the cefepime patients and 2 (9%) of the ceftazidime patients died of infection. The results of this study suggest that cefepime is an effective and safe agent in the empiric therapy of febrile episodes in neutropenic patients.     

Ceftriaxone plus once daily aminoglycoside with filgrastim for treatment of febrile neutropenia: early hospital discharge vs. Standard In-patient care

BACKGROUND: In febrile neutropenic patients, ceftriaxone plus an aminoglycoside is effective for the treatment of infection, while filgrastim reduces the extent and duration of neutropenia. Because the once daily dosing regimen of this combination permits ambulatory treatment, there is a need to test criteria for early hospital discharge. METHODS: Hospitalized adult patients with febrile neutropenia (following chemotherapy) considered to be potentially treatable on a follow-up out-patient basis were entered into this open-label, multinational study. Patients received a once daily combination of ceftriaxone for > or =5 days, aminoglycoside for > or =2 days, and filgrastim until the absolute neutrophil count was > or =1.0x10(9)/l for 2 days. Those initially responding to therapy (reduction of fever by > or =1 degrees C within 72 h, and clinical improvement) were randomized into standard in-patient or follow-up out-patient treatment groups, the latter patients being discharged from hospital early, after meeting defined criteria. RESULTS: 105 patients were enrolled, of whom 21 initial non-responders were not randomized. Efficacy was evaluable in 80 patients. Success (resolution of fever and symptoms, maintained for 7 days after cessation of therapy, and eradication of infecting pathogens) was similar among in-patients (40/42, 95%) and out-patients (34/38, 89%). The duration of hospitalization was shorter for out-patients than in-patients (median of 4 vs. 6 days, respectively). No hospital readmissions were necessary in out-patients. All other efficacy parameters assessed were comparable in both groups, as was tolerability/safety. One potentially drug-related death was reported. CONCLUSIONS: Patients who satisfy prospectively defined criteria for early discharge can be treated safely on an out-patient basis with a regimen of once daily ceftriaxone plus an aminoglycoside with filgrastim. In addition to reducing healthcare costs, it may improve patients' quality of life. Copyright Copyright 1999 S. Karger AG, Basel.     

Monotherapy with intravenous followed by oral high-dose ciprofloxacin versus combination therapy with ceftazidime plus amikacin as initial empiric therapy for granulocytopenic patients with fever

The aim of the present study was to obtain clinical experience with the use of high-dose ciprofloxacin as monotherapy for the treatment of febrile neutropenia episodes (granulocyte count, <500/mm(3)) compared to a standard regimen and to clarify whether ciprofloxacin administration may be switched to the oral route. In a prospective randomized study ciprofloxacin was given at 400 mg three times a day (t.i.d.) for at least 72 h followed by oral administration at 750 mg twice a day (b.i.d). That regimen was compared with ceftazidime given intravenously at 2 g t.i.d. plus amikacin given intravenously at 500 mg b.i.d. The frequency of successful clinical response without modification at the end of therapy was almost identical for ciprofloxacin (50% [62 of 124 patients]) compared with that for ceftazidime plus amikacin (50.8% [62 of 122 patients]) in an intent-to-treat analysis; the frequencies were 48.3% (57 of 118 patients) versus 49.6% (56 of 113 patients), respectively, in a per-protocol analysis (P values for one-sided equivalence, 0.0485 and 0.0516, respectively; delta = 10%), with no significant differences among patients with bacteremia and other microbiologically or clinically documented infections and fever of unknown origin. For 82 (66.1%) patients, it was possible to switch from parenteral ciprofloxacin to the oral ciprofloxacin, and the response was successful for 61 (74.4%) patients. The efficacies of the regimens against streptococcal bacteremias were 16.6% (one of six patients) for the ciprofloxacin group and 33.3% (one of three patients) for the combination group (it was not statistically significant), with one breakthrough streptococcal bacteremia observed among the ciprofloxacin-treated patients. Adverse events were mostly self-limited and were observed in 27 (20.6%) ciprofloxacin-treated patients and 26 (19.7%) patients who were receiving the combination. This study demonstrates that high-dose ciprofloxacin given intravenously for at least 3 days and then by the oral route is therapeutically equivalent to the routine regimen of intraveneous ceftazidime plus amikacin even in febrile patients with severe neutropenia (polymorphonuclear leukocyte count, <100 mm(3)). However, it is very important that before an empirical therapy is chosen each hospital determine bacteriologic predominance and perform resistance surveillance.     

Ceftazidime versus imipenem-cilastatin as initial monotherapy for febrile neutropenic patients.

One hundred febrile episodes in 89 neutropenic patients after cytotoxic chemotherapy were randomized to be treated with either ceftazidime or imipenem as initial monotherapy. The clinical characteristics of the two groups of patients were comparable. The response of the fever in patients who received imipenem was significantly better than that in those who received ceftazidime (77 versus 56%, respectively; P = 0.04), especially in those with microbiologically documented infection (81 versus 33%, respectively; P = 0.02). The in vitro susceptibilities and the clinical responses suggested that, with the possible exception of Pseudomonas spp., imipenem was more effective than ceftazidime in treating neutropenic infections caused by both gram-positive and -negative organisms. An additional 23 and 21% of the patients in the ceftazidime and imipenem groups, respectively, responded to the addition of cloxacillin and amikacin following failure of monotherapy. The majority of the treatment failures, relapses, and superinfections were related to resistant infective organisms such as methicillin-resistant Staphylococcus spp. and Pseudomonas spp. or disseminated fungal infections.     

Randomized prospective study of ceftazidime versus ceftazidime plus cephalothin in empiric treatment of febrile episodes in severely neutropenic patients.

In a prospective randomized study, ceftazidime monotherapy was compared with a combination of ceftazidime plus cephalothin in 102 febrile neutropenic patients. Thirty bacteriologically documented infections, of which 23 were bacteremias, in 48 clinically assessable patients were treated with ceftazidime alone. Twenty-four bacteriologically proven infections, of which 18 were bacteremias, in 42 clinically assessable patients were treated with a combination of ceftazidime and cephalothin. The clinical response rates in assessable patients were 77% for ceftazidime monotherapy and 88% for the combination. The bacteriological clearance rate was 70% for ceftazidime monotherapy and 79% for the combination. Efficacy against gram-negative pathogens appeared to be excellent, with 93% clearance for ceftazidime monotherapy and 100% clearance for the combination. The bacteriological clearance of gram-positive infections was only 60% for both regimens, with failures mainly due to Streptococcus faecalis and Streptococcus sanguis, which are primarily resistant to both ceftazidime and cephalothin. After addition of vancomycin to those infections which did not respond to empiric therapy, bacteriological clearance rates of 94% (ceftazidime plus vancomycin) and 90% (ceftazidime and cephalothin plus vancomycin) were achieved. Three superinfections were registered in the ceftazidime group and two were seen in the combination group. Other adverse effects of ceftazidime were minimal and were not enhanced by combination with cephalothin. It is concluded that ceftazidime is an effective drug for the empiric treatment of febrile neutropenic patients, especially if one is prepared to modify therapy if resistant gram-positive strains or mycotic infections are encountered. Neither the clinical nor bacteriological cure rates could be substantially improved by adding cephalothin to ceftazidime in initial empiric treatment of febrile neutropenic patients.     

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.     

Piperacillin/tazobactam plus tobramycin versus ceftazidime plus tobramycin as empiric therapy for fever in severely neutropenic patients

The objective of this trial was to evaluate the potential advantages of the combination of piperacillin and tazobactam in the control of fever in neutropenic patients. In this single-center study, patients who experienced a total of 247 febrile episodes were prospectively randomized to receive either our standard regimen, ceftazidime 3 g/day (1 g t.i.d.) plus tobramycin 3 mg/kg per day (1.5 mg/kg b.i.d.), or piperacillin 12 g/day plus tazobactam 1.5 g/day (4 g+0.5 g t.i.d.) plus tobramycin 3 mg/kg per day (1.5 mg/kg b.i.d.). Vancomycin was added in all cases of persistent fever in the ceftazidime arm, but only when there was microbiologically documented resistance in the piperacillin/tazobactam arm. All 247 episodes were evaluable by "intent-to-treat" analysis. The two populations were well matched in terms of age, gender, underlying disease, chemotherapy received, oral decontamination, clinical and bacterial documentation, and severity and duration of neutropenia. Initial antibacterial therapy was successful (apyrexia at 72 h, without antibiotic change) more frequently (P=0.008) with the regimen containing piperacillin/tazobactam (54.4%) than with the one including ceftazidime (37.6%). Fewer (P=0.02) major infectious events (infectious death or delay in treatment of underlying disease due to infection) were observed during piperacillin/ tazobactam treatment (2.6%) than with the ceftazidime regimen (11.3%), despite a lower frequency of glycopeptide addition when piperacillin/tazobactam was used (54.4% versus 77.4%) according to the rules adopted. This trial confirmed the efficacy of the piperacillin/tazobactam combination for empirical treatment of febrile neutropenic patients. This antibiotic combination permitted a dramatic decrease in empiric glycopeptide antibiotic administration in such patients. Electronic publication: 12 January 1999     

Risk-adapted strategy for the management of febrile neutropenia in cancer patients

Background Among patients who develop fever and neutropenia after having received cancer chemotherapy, we have to distinguish at least three categories of risk levels for complications and death: patients at low risk and eligible for oral treatment and possibly outpatient management, patients at low risk who require intravenous therapy, and patients at higher risk. Results and discussion The Multinational Association for Supportive Care in Cancer scoring system identifies patients at low risk (<5%) of severe complications with very low mortality (<1%) during an episode of febrile neutropenia; this group represents roughly 70% of an unselected population of patients with febrile neutropenia. A significant percentage (≈50%) of these patients are eligible for treatment with orally administered antibiotics and can be discharged early and safely from the hospital after a short (24–48 h) observation period.