An analysis of interleukin-8, interleukin-6 and C-reactive protein serum concentrations to predict fever, gram-negative bacteremia and complicated infection in neutropenic cancer patients

A prospective study was performed to assess the potential value of interleukin (IL)-8, IL-6, and C-reactive protein (CRP) serum levels to predict fever, gram-negative bacteremia and complicated infection in neutropenic patients with cancer. Serum samples were obtained three times a week during 208 neutropenic episodes following cytotoxic chemotherapy. Fever of any cause developed during 104 out of 191 evaluable episodes. Serum levels of neither cytokine nor CRP were predictive of fever within more than 24 h before its onset. Unlike CRP, both IL-6 and IL-8 serum levels were significantly different between microbiologically documented infections and unexplained fevers. The highest values of IL-6 and IL-8 were observed in episodes of gram-negative bacteremia. Using receiver-operating-characteristic curves, the analysis of cytokine levels measured around the onset of fever indicated that IL-8 is potentially useful for predicting gram-negative bacteremia, with a high negative predictive value of > 90% and a moderate positive predictive value of 50% (sensitivity, 70%; specificity, 91%). In patients with persistent fever, predictions of further clinical complications, defined as prolonged fever of more than 7 days' duration, pneumonia, shock and/or death due to infection, were best predicted by IL-6. With an IL-6 cutoff value of 250 pg/ml in samples obtained 8 to 32 h after onset of fever, the positive predictive value was 92%, the negative predictive value 91% (sensitivity, 85%; specificity, 95%). The positive predictive value of IL-6 in samples obtained another 24 h later from patients still febrile remained > 90%, but the negative predictive value dropped to 47%. In any of the analyses, the predictive values of CRP levels were poor and inferior to either cytokine. These findings may have clinical value in identifying subgroups of patients requiring different therapeutic approaches.     

Clinical significance of serum cytokine patterns during start of fever in patients with neutropenia

Serum concentrations of tumour necrosis factor alpha (TNF-alpha), interleukin-1 receptor antagonist (IL-1ra), interferon gamma (IFN-gamma), interleukin-6 (IL-6) and interleukin-10 (IL-10) were studied in 31 patients with haematological malignancies during febrile neutropenia. Samples were obtained when blood cultures were performed (time 0) and, when possible, after 2, 4, 6, 12 and 24 h. Increased levels of all cytokines were detected after start of fever with peak values in gram-negative (Gr-) bacteraemias after 2 h (TNF-alpha, IL-1ra and IFN-gamma), 4 h (IL-6) and 6 h (IL-10), respectively. At time 0 the median TNF-alpha value was higher in the Gr- group (80 pg/ml; range 54-516 pg/ml) as compared to both gram-positive bacteraemias (Gr+, 14 pg/ml; range 7-60 pg/ml; P < 0.05) and blood culture negative episodes (BCN, 8 pg/ml; range 0-87 pg/ml; P < 0.05). Furthermore, the peak values of TNF-alpha, IL-1ra, IL-6 and IL-10 during the 24 h study period were significantly and/or numerically higher in the Gr- group in comparison to the Gr+ and BCN groups, respectively. It may be concluded that neutropenic patients have increased levels of both pro- and anti-inflammatory cytokines at start of fever, with the highest values recorded during the first hours in Gr- bacteraemias. Prospective studies will show whether monitoring of serum cytokines may be used as an early diagnostic tool before results of blood cultures are available, which may have important therapeutic implications.     

Fever and neutropenia in children with malignant disease

Treatment of episodes of fever and neutropenia in pediatric hematology-oncology patients includes hospitalization and administration of intravenous antibiotics until the patient is afebrile and no longer neutropenic. The present analysis characterizes retrospectively febrile episodes in neutropenic pediatric hematology-oncology patients with regard to frequency of documented infections, organisms associated with these infections, efficacy of a standardized antibiotic regimen, and safety of early antibiotic discontinuation under defined conditions. A total of 149 pediatric febrile neutropenic episodes were identified during a 4-year period between 1990 and 1994. These occurred in 47 male and 19 female patients, of a mean age of 7.6 years (range 0.5-15). The most frequent diagnoses were leukemia (41% of patients), lymphoma (21%), rhabdomyosarcoma (7%), soft tissue sarcoma (5%), Ewing's sarcoma (5%), and osteosarcoma (4%). Infection was certain in 36% of febrile episodes, probable in 14%, and not determined in 50%. Patients with severe neutropenia (absolute neutrophil count < 100) had a slightly, although not significantly higher incidence of documented and probable infection (57%). Patients with solid tumor had documented infection in 40% of their febrile episodes, and the detection rate in the children with leukemia was 31% (P < .20) Blood cultures were positive in 21 (14%) of 149 episodes. Staphylococci (both coagulase-negative and coagulase-positive strains) and Pseudomonas were the organisms most frequently isolated (six episodes each). Mouth and throat (11), lungs (10), and skin (10) were the next most frequent sites of localized infection. Initial treatment consisted of piperacillin and amikacin or of vancomycin and amikacin when the source of fever was thought to be an infected central line catheter, with addition of amphotericin B by the seventh day of treatment when fever with neutropenia persisted or upon clinical suspicion of underlying fungal infection. There was a single fatality, of a patient with Burkitt's lymphoma. Antibiotics were discontinued when initial blood cultures had no growth after at least 48 hours and no source of infection was found, the blood count was improving, and if the patient became afebrile and clinically well. No patient needed readmission during the fortnight that followed discontinuation of antimicrobial therapy. Patients with negative blood cultures under defined conditions, as described above, could safely be discharged early, thus shortening the duration of intravenous antibiotic therapy and hospital stay.     

Possibilities and limits of ambulatory supportive measures in oncology exemplified by antibiotic therapy of febrile neutropenia

Neutropenia is common after intensive chemotherapy. Hospitalization and intravenous broad-spectrum antibiotics are the standard of care for febrile neutropenic patients because of the risk of serious complications and associated mortality. Short neutropenic periods (< 7 days) are considered to be at a low-risk in cases when fever occurs in clinically stable patients. Recent work suggests that such a low-risk population of febrile neutropenic patients might benefit from alternatives to inpatient care. The agents that best qualify for outpatient treatment include quinolones i.v./p.o., glycopeptides, ceftriaxone and aminoglycosides, particularly if the latter are given once daily. Response rates to antimicrobial therapy range from 80 to 95% in low-risk febrile neutropenia episodes. Treating these patients in an outpatient setting avoids hospitalization in 75 to 95%. There is no doubt that outpatient therapy may have several advantages, including lower costs and an improved quality of live. Outpatient antibiotic therapy for febrile low-risk neutropenia should be considered as an acceptable alternative to inpatient treatment.     

Ambulatory treatment with ceftriaxone in febrile neutropenic children

We conducted a prospective nonrandomized study of outpatient therapy with ceftriaxone as a single agent in 50 episodes of fever and neutropenia in children treated with various myelosuppressive regimens for different malignancies. All patients underwent clinical and radiological evaluation and blood/urine cultures taken before starting therapy. Patients with dehydration, hypotension, rigor and clinical exit-site infection of indwelling right-sided catheters were excluded. Forty-one patients completed an antibiotic course of 7 days: in 12 patients fever returned to normal on day 2, in 10 patients on day 3, and in 8 patients on day 4. The duration of neutropenia following the initial febrile episode was 3-10 days. In some patients fever returned to normal after 2 days, but neutropenia persisted up to 10 days. Two patients were bacteremic--Escherichia coli in one, and Acinetobacter/Staphylococcus coagulase negative in another; all isolates were sensitive to ceftriaxone. In nine episodes, antimicrobial therapy was modified because of persistent fever > 39 degrees C in five patients, bacteremia in two, enterocolitis in one, breakthrough fever in two, and bronchopneumonia in one. The low incidence of bacterial isolation is probably attributed to the selection of patients with low risk features. Patients and parents complied with and favored outpatient therapy to hospitalization.     

Pharmacokinetics of meropenem in febrile neutropenic patients. Swedish study group

To determine the impact of neutropenia on the pharmacokinetics of meropenem, 14 patients with fever and neutropenia were given 1 g of meropenem i.v. every 8 h as an infusion over 30 min. The volume of distribution (16.2 l/1.73 m2) and the nonrenal clearance [75 ml/(min x 1.73 m2)] in this group were significantly increased compared to healthy subjects studied previously with identical techniques. The kinetic study was repeated when the patients had a normal temperature and a raised neutrophil count; most kinetic variables did not differ from the findings on the first day of treatment. The pharmacokinetic profile of meropenem in febrile neutropenic patients differs from earlier findings in healthy subjects. Considering these data and known minimum inhibitory concentration values for common pathogens, meropenem administered every 6 to 8 h seems an appropriate regimen in patients with febrile neutropenia. The shorter time interval may be used for treatment of Pseudomonas infection.     

Randomised comparison of ceftazidime and imipenem as initial monotherapy for febrile episodes in neutropenic cancer patients

With the availability of new, broad-spectrum antibiotics, initial therapy with a single agent has become an alternative to classic combinations in the management of febrile, neutropenic cancer patients. The aims of this study were to compare the efficacy of ceftazidime and imipenem as empirical monotherapy of febrile episodes in neutropenic patients, and to examine the frequency with which second-line antibiotics (amikacin, vancomycin, or both) were required. A prospective clinical trial was carried out in a single centre. Eligible patients with solid tumours or lymphoma were randomised to receive monotherapy with ceftazidime or imipenem. In the event of no response, amikacin and/or vancomycin were added in 48-72 h intervals (sequentially, or according to clinical or microbiological data). Efficacy was evaluable for 111 assessable episodes. Median neutrophil count at entry was 100 cells/microliters and median duration of neutropenia was 4 days. Febrile episodes were classified as microbiologically (34%) or clinically documented (42%), and fever of unknown origin (24%). Gram-negative infections (57%) predominated over gram-positive isolates (30%). The overall success rate with monotherapy (69% versus 70%), or with modification (20% versus 23%) were equivalent for ceftazidime and imipenem (P = 0.75). The mortality in this series was 5%. Single-agent therapy with either ceftazidime or imipenem is effective for the empirical treatment of febrile episodes in neutropenic patients with solid tumours. Early addition of amikacin and/or vancomycin resolves most failures of the first step.     

Influences of nutrition and stress on people at risk for neutropenia: nursing implications

Neutropenia may be influenced by malignancy type, treatment, age extremes, inadequate nutrition, or psychological stress. Of these five factors, only nutrition and stress are amenable to nursing intervention and management. The increasing trend of providing treatment in the outpatient setting and managing the patient with neutropenia in the home challenges nurses to develop innovative methods of care. This article offers suggestions to assist nurses in the creative management of individuals at risk for neutropenia by maximizing nutrition and minimizing psychological stress. This discussion addresses the physiology of the inflammatory immune response; pathophysiology of neutropenia; factors that may influence the risk of infection, such as sustained stress, dietary fiber, antioxidant vitamins, and food-borne bacteria; and interventions that reduce the potential for neutropenic sepsis. Nursing implications that reduce the risk of neutropenic infection include patient education related to nutrition, stress management, and self-care.     

Temperature, age, and recurrence of febrile seizure

OBJECTIVE: Prediction of a recurrent febrile seizure during subsequent episodes of fever. DESIGN: Study of the data of the temperatures, seizure recurrences, and baseline patient characteristics that were collected at a randomized placebo controlled trial of ibuprofen syrup to prevent febrile seizure recurrences. SETTING: Two pediatric hospitals in the Netherlands. PATIENTS: A total of 230 children with an increased risk of febrile seizure recurrence. MAIN OUTCOME MEASURE: Seizure recurrence during a subsequent fever episode. RESULTS: A total of 509 episodes of fever were registered with 67 recurrences; 35 (52%) recurrences within the first 2 hours after fever of onset had a lower median temperature (39.3 degrees C) than 32 (48%) after more than 2 hours of fever (40.0 degrees C, P<.001). Poisson regression analysis resulted in 3 univariably significant (P<.05) predictors of a recurrence of seizure during a subsequent episode of fever. In a multivariable model, they were corrected for their correlation: interval between the last previous seizure and fever of onset less than 6 months (relative risk= 1.3 [95% confidence interval: 0.8-2.4]), age at fever of onset (relative risk=0.7 [95% confidence interval: 0.5-1.0] per year increase) and temperature at fever of onset (relative risk = 1.7 [95% confidence interval: 1.1-2.8] per degree Celsius increase). CONCLUSIONS: Half of the recurrent seizures occur in the first 2 hours after fever of onset of a subsequent fever episode. If seizure recurs at a later time, the temperature at seizure is higher compared with recurrences occurring in the first 2 hours of fever. Young age at fever of onset, high temperature at fever of onset, and high temperature during the episode of fever are associated with an increased risk of a recurrent febrile seizure at the moment that a child with a history of febrile seizures has fever again.     

Frequency and risk factors of infectious complications in neutropenic patients infected with HIV

OBJECTIVE: To determine causes, incidence and factors associated with infections in neutropenic [polymorphonuclear neutrophil (PMN), 1000 x 10(6)/l] HIV-infected patients. DESIGN: Prospective study. SETTING: Infectious disease service of a 1000-bed university teaching hospital in Paris, France. PATIENTS: HIV-infected patients with a PMN count of < 1000 x 10(6)/l confirmed on two occasions were included in the study. Baseline characteristics, cause of neutropenia and occurrence of infectious episodes were analysed. RESULTS: The cause of neutropenia was lymphoma in four cases (6.5%), antineoplastic chemotherapy in seven (11.3%), zidovudine in 32 (51%), trimethoprim-sulphamethoxazole (TMP-SMX) in 28 (45%) and ganciclovir in 11 (18%). Fifteen patients (24%) developed infectious complications. Neutropenia induced by chemotherapy or lymphoma was more frequently complicate by infectious episodes (P = 0.02). Neutropenia in the previous 3 months (P = 0.05), presence of a central venous catheter (P = 0.05) and a trough PMN count (P = 0.02) were the three risk factors of infection retained in a logistic model. CONCLUSION: Neutropenia induced by zidovudine, gangiclovir or TMP-SMX, are less complicated by infectious episodes than neutropenia induced by antineoplastic chemotherapy. Overall, infectious episodes in neutropenic HIV-infected patients appear lower than in patients with haemobiologic malignancies.     

Respiratory virus infections during anticancer treatment in children

To evaluate the occurrence and clinical significance of respiratory virus infections in children during anticancer treatment, we studied 75 consecutive episodes of febrile infection in 32 children during 17 months. Viral antigen detection for 7 respiratory viruses, viral culture for rhinoviruses and enzyme immunoassay serology were used. Evidence for respiratory virus infection was found in 28 (37%) cases. Rhinovirus was the most common virus detected in 13 (17%) episodes. The other etiologic agents were respiratory syncytial virus (6 episodes), parainfluenza virus type 3 (5 episodes), adenovirus (4 episodes), influenza A virus (3 episodes), and influenza B virus (1 episode). Respiratory virus infections were diagnosed as often in leukopenic as in non-leukopenic patients (37% vs. 38%). In 4 cases bacteremic infection was diagnosed. We found no difference in serum C-reactive protein values when episodes positive for respiratory viruses were compared with virus-negative episodes. Our observations show that respiratory virus infections are common in febrile children receiving anticancer treatment. Diagnostic tests for respiratory viruses should be used more often in evaluation of fever in these patients.     

Piperacillin/tazobactam versus cefepime as initial empirical antimicrobial therapy in febrile neutropenic patients: a prospective randomized pilot study

The objective of the presented prospective, randomized study was to compare the efficacy of empirical antimicrobial monotherapy with piperacillin/tazobactam (PIP/TAZ) to cefepime (CEFP) for treatment of infections in neutropenic patients. From a total of 102 febrile episodes 100 were evaluable. The most frequent microorganisms were gram-negative, documented in 22% vs. 24% of the febrile episodes (gram-positives 18% vs. 16%, fungi 2% vs. 4%). The response rate was similar with 22/51 (43%) of episodes treated with PIP/TAZ vs. 19/49 (39%) with CEFP. Of the different infection types classified at the end of the febrile episodes, patients with fever of unknown origin (FUO) and primary bacteremias showed the best initial responses with 25/44 (57%) and 11/22 (50%). Lower initial response rates were found in pneumonias with totally 3/13 (23%) and other clinically documented infections with 2/21 (10%), without any difference between both groups. Gram positive infections showed a higher response with PIP/TAZ than with CEFP (4/9 vs. 0/8), gram negative responded less frequently (3/11 vs. 7/13). The median time until persistent defervescence was equal in both groups (2.5 vs. 2 days), likewise the response rates after the different steps of therapy modifications (change to imipenem or ceftazidim, or addition of gentamycin, vancomycin or amphotericin B). Totally, 96% of febrile episodes responded in both therapy arms. Overall, we found no significant differences in efficacy between the two therapeutic regimens. In conclusion, PIP/TAZ as well as CEFP might be a sufficient initial therapy for febrile neutropenia, but further randomized trials with larger patient numbers are necessary.     

The role of pulmonary epithelial cells in lung cellular reaction to asbestos exposure

BACKGROUND: Standard therapy for febrile neutropenia after chemotherapy has consisted of intravenous antibiotic until resolution of both fever and neutropenia. We attempted to shorten the hospital stay by discontinuing intravenous antibiotics in blood culture negative patients who remained clinically stable and afebrile for 48 hours. PATIENTS AND METHODS: Febrile neutropenic admissions of non-leukemic patients were reviewed. They were divided by three consecutive six month intervals into Group 1 (prior to initiation of the policy), Group 2 (after the policy was instituted), and Group 3 (to monitor the implementation of the policy after the initial six months). RESULTS: There were 134 admissions for neutropenic fever. Median duration of intravenous antibiotic for Group 1 was 7 days (95% Confidence Interval 6-9). It was significantly decreased to 5 days (4-6) and 4 days (3-5) for Groups 2 and 3 respectively (p = 0.004 and p < 0.001). Median duration of hospital stay for Group 1 was 10 days (7-13). It was also significantly decreased to 7 (5-8) and 6 days (5-7) for Groups 2 and 3 respectively (p = 0.04 and p = 0.002). CONCLUSION: Early discontinuation of intravenous antibiotics in patients with negative blood culture who remain afebrile and clinically stable for 48 hours results in shorter duration of hospital stay with potential for reduction in hospital costs.     

Ketamine inhibits the proinflammatory cytokine-induced reduction of cardiac intracellular cAMP accumulation

The proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), are increased in heart failure and sepsis, clinical conditions for which the IV anesthetic ketamine is useful. The proinflammatory cytokines cause beta-adrenergic receptor (betaAR) hypofunction secondary to reduced function of the enzyme adenylylcyclase (AC). In this study, we evaluated the effect of ketamine alone, TNF-alpha and IFN-gamma, and ketamine plus TNF-alpha and IFN-gamma, on isoproterenol (ISO, a betaAR agonist) and forskolin (FSK, an activator of AC)-induced intracellular accumulation of cAMP. An in vitro culture of a rat heart cell line (H9c2) was labeled with [3H]adenine to produce [3H]ATP, and we measured the intracellular accumulation of [3H]cAMP after stimulation with ISO or FSK to convert the [3H]ATP to [3H]cAMP. Pretreatment with either cytokine alone did not significantly affect ISO or FSK-induced intracellular cAMP accumulation, whereas the combination of TNF-alpha and IFN-gamma caused a significant (P < 0.05 compared with untreated cells) reduction. Pretreatment with ketamine caused a significant (P < 0.05 compared with untreated cells) increase in ISO or FSK-induced cAMP accumulation. Pretreatment of the H9c2 cells with ketamine, plus the combination of TNF-alpha and IFN-gamma, inhibited the reduction of ISO or FSK-induced intracellular cAMP accumulation caused by the proinflammatory cytokines alone. These results demonstrate that the combination of the proinflammatory cytokines TNF-alpha and IFN-gamma reduce poststimulation (ISO or FSK) intracellular cAMP accumulation. This action of the proinflammatory cytokines is consistent with the observation of betaAR hyporesponsiveness to betaAR agonist therapy in sepsis and heart failure. Ketamine augments the poststimulation cAMP accumulation in H9c2 cells while inhibiting the cytokine-induced reduction of cAMP accumulation. This may partly explain the improvement in cardiac function after ketamine use in clinical conditions known to have increased systemic levels of proinflammatory cytokines, such as sepsis and heart failure. IMPLICATIONS: Tumor necrosis factor-alpha and interferon-gamma reduced poststimulation intracellular cAMP levels, whereas ketamine inhibits this action of the proinflammatory cytokines. Because cAMP is the second messenger for the beta-adrenergic receptor, this may be a mechanism for improved blood pressure and cardiac output in sepsis and heart failure after ketamine use.     

Contrast media reactions and extravasation: relationship to intravenous injection rates

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.     

A retrospective study of infections in neutropenic patients

This is a retrospective non-randomised study of 37 episodes of infections in neutropenic patients (grades III and IV myelosuppression). The commonest presentation of infection in these patients was fever which was followed by diarrhoea. Infection was documented bacteriologically in 22.6% of episodes and blood culture was positive in 5.5% of episodes only. More than half episodes (56.8%) received quinolone and aminoglycoside combination, 24.3% 3rd generation cephalosporin and aminoglycoside combination and 18.9% combination of quinolone and cephalosporin in cross over. These combinations of antibiotics were successful in 90.5% with quinolone arm, 44.4% with cephalosporin arm and 71.4% in cross over arm. This difference in success was statistically significant and is independent of grade of neutropenia.     

Ceftazidime plus amikacin plus teicoplanin or vancomycin in the empirical antibiotic therapy in febrile neutropenic cancer patients

A prospective randomized trial was performed to compare teicoplanin to vancomycin as part of the empirical antibiotic therapy of febrile neutropenic cancer patients. Fifty-three patients were randomized to receive ceftazidime (100 mg/kg daily every 8 h), amikacin (15 mg/kg daily every 8 h) and teicoplanin (6 mg/kg once a day) and 53 other patients received ceftazidime, amikacin (same dosages) and vancomycin (30 mg/kg/day every 6 h). In 99 evaluable episodes, the success rates were 54% for patients receiving teicoplanin and 52% for patients receiving vancomycin (p=0.76, 95% CI-18-23). The response rates were similar for patients with unexplained fever and for patients with documented infections. There were no differences in renal toxicity or cutaneous side effects between the two groups. The overall death rate was 18.9%, with 10 deaths in each group. The most important factor associated with death was the diagnosis of a fungal infection (p=0.001). Teicoplanin seems to be well tolerated and as effective as vancomycin in the empirical antibiotic therapy of fever in neutropenic cancer patients.     

Treatment of febrile neutropenia in patients with solid tumors

BACKGROUND: Febrile neutropenia (FN) is one of the most serious complications of anti-tumourous treatment calling for early diagnosis and intensive treatment. The objective of the trial was to recommend a standard procedure for the treatment of febrile neutropenia at their Oncological Clinic, based on analyses of attacks of febrile neutropenia and the current microbial situation. METHODS AND RESULTS: In 1995-1997 in 30 patients (24 women, 6 men) 39 attacks of febrile neutropenia were treated. The age distribution of patients was within the range of 20-68 years, the mean age being 50 years. In the group patients with breast cancer predominated (14), soft tissue sarcomas (4), colorectal carcinoma (3), other diagnoses participated with 9 episodes. The analysis of the microbial situation was based on cultivation findings made in patients with attacks of FN. For empirical treatment of FN the authors use at combined treatment piperacillin-gentamicin or sultamicillin-cefpodoxim/or ciprofloxacin. If empirical treatment fails, therapy is based on the results of cultivation and the patient's clinical condition. Growth factors are indicated for treatment only in FN complicated by mycotic infection, inflammatory pulmonary infiltrates or cardiopulmonary failure. CONCLUSIONS: The standard procedure in the treatment of FN should be broad spectrum bactericidial antibiotics. The use of growth factors is reserved for complicated episodes of FN.     

Efficacy of fluconazole in the treatment of upper gastrointestinal candidiasis in neutropenic patients with cancer: factors influencing the outcome

Fluconazole has proved to be effective in treating oropharyngeal and esophageal candidiasis in immunocompromised patients. However, sufficient data are lacking regarding the efficacy of this agent in neutropenic hosts. The aim of the present study was to determine the clinical and mycological efficacy of fluconazole and to define the factor(s) affecting the outcome of fluconazole therapy in severely neutropenic patients (peripheral neutrophil count, < 500/microL) with cancer who have oropharyngeal and/or esophageal candidiasis. One hundred eleven patients with 129 episodes of candidal infections were treated with intravenous and consequently oral fluconazole (200 mg/d and 100 mg/d, respectively). Overall clinical cure and mycological eradication rates were 82% and 56%, respectively. Persistent neutropenia (P < .01), infection with a non-albicans strain of Candida (P = .012), and administration of antifungal therapy during the second or a later neutropenic episode (P < .002) were independently associated with a worse outcome. We conclude that fluconazole is effective in the treatment of upper gastrointestinal candidiasis in neutropenic patients with cancer. Effective treatment of the underlying malignancy, with the resultant recovery from neutropenia, and the determination of the species of infecting Candida isolates are required for the prediction of the outcome of antifungal therapy.     

Standards, Options, and Recommendations for the management of brief neutropenias. Fedération Nationale des Centres de Lutte Contre le Cancer

CONTEXT: The "Standards, Options and Recommendations" (SOR), initiated in 1993, is a collaborative project between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcomes for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary experts group, with feedback from specialists in cancer care delivery. OBJECTIVE: To develop a clinical practice guideline for the management of neutropenic cancer patients (excluding prolonged neutropenia). METHODS: Data have been identified by literature search using Medline and Current Contents (up to February 1997) and personal reference lists. The main end points considered were mortality, morbidity, risk factors, fever, source of infection, microbiological documentation, incidence and length of hospital stays, quality of life, efficacy of treatment, safety and costs. Once the guideline was defined, the document was submitted to 48 reviewers for peer review and to the medical committees of the 20 French Cancer Centres for review and agreement. RESULTS: The key recommendations are: 1) before receiving cytotoxic chemotherapy, patients must be informed of potential risks and precautions to observe; 2) non-febrile neutropenic patients can be followed at home (except specific context); antibiotic prophylaxis is not recommended; 3) initial empirical antibiotic therapy for febrile patients is mandatory, whether associated beta-lactam and aminoglycoside, or monotherapy with a broad-spectrum beta-lactam (except in case of septic shock or pneumopathy). A glycopeptide can be added in case of overt catheter-related or cutaneous infection, in case of microbiologically documented infection with a oxacillin-resistant Gram positive bacteria, or in case of persistent fever in a clinically deteriorating patient; 4) at the present time, there is insufficient evidence to recommend the management of febrile neutropenic patients at home. We recommend participation in studies to identify predicting factors of low-risk patients and to assess the feasibility and safety of early discharge and home therapy.