Neutropenic Cancer Patients Research Articles

Cefoperazone-sulbactam plus amikacin empirical therapy for febrile neutropenia in children with cancer

Aim: To determine the efficacy and safety of cefoperazone-sulbactam combined with amikacin in the treatment of febrile neutropenia in children with cancer. Materials and Methods: The study included 20 cancer cases with 26 febrile neutropenia (FEN) episodes. Patient selection criteria were defined according to the guidelines issued by the Infectious Disease Society of America (IDSA). Results: Patients diagnosed with acute leukemia (58%) and solid tumors (42%) were recorded. Twelve (46.2%) of the primary disease cases were refractory. The number of infection episodes identified microbiologically and clinically was 10 (38.5%) and 12 (46.1%), respectively. Fever of unknown origin was observed in only 4 cases (15.4%). The success rate of the empirical treatment without additional modification was 42.3% (11 FEN episodes). Four episodes (15.4%) needed a replacement for sulbactam/cefoperazone because of persistent fever, adverse reactions, and/or clinical deterioration. Three patients died because of relapse or because they were refractory. As 15 (57.7%) of the patients deteriorated clinically and had fever, glycopeptide antibiotics were given after 48-72 h. The overall response rate at the end of the therapy was 80.8%, with/without modification. Conclusions: The combination of sulbactam/cefoperazone plus amikacin was effective and safe in the treatment of febrile episodes in neutropenic pediatric cancer patients.

Daptomycin Pharmacokinetics in Adult Oncology Patients with Neutropenic Fever

Daptomycin is the first antibacterial agent of the cyclic lipopeptides with in vitro bactericidal activity against gram-positive organisms, including vancomycin-resistant enterococci, methicillin-resistant staphylococci, and glycopeptide-resistant Staphylococcus aureus. The pharmacokinetics of daptomycin were determined in 29 adult oncology patients with neutropenic fever. Serial blood samples were drawn at 0, 0.5, 1, 2, 4, 8, 12, and 24 h after the initial intravenous infusion of 6 mg/kg of body weight daptomycin. Daptomycin total and free plasma concentrations were determined by high-pressure liquid chromatography. Concentration-time data were analyzed by noncompartmental methods. The results (presented as means +/- standard deviations and ranges, unless indicated otherwise) were as follows: the maximum concentration of drug in plasma (C(max)) was 49.04 +/- 12.42 microg/ml (range, 21.54 to 75.20 microg/ml), the 24-h plasma concentration was 6.48 +/- 5.31 microg/ml (range, 1.48 to 29.26 microg/ml), the area under the concentration-time curve (AUC) from time zero to infinity was 521.37 +/- 523.53 microg.h/ml (range, 164.64 to 3155.11 microg.h/ml), the volume of distribution at steady state was 0.18 +/- 0.05 liters/kg (range, 0.13 to 0.36 liters/kg), the clearance was 15.04 +/- 6.09 ml/h/kg (range, 1.90 to 34.76 ml/h/kg), the half-life was 11.34 +/- 14.15 h (range, 5.17 to 83.92 h), the mean residence time was 15.67 +/- 20.66 h (range, 7.00 to 121.73 h), and the median time to C(max) was 0.6 h (range, 0.5 to 2.5 h). The fraction unbound in the plasma was 0.06 +/- 0.02. All patients achieved C(max)/MIC and AUC from time zero to 24 h (AUC(0-24))/MIC ratios for a bacteriostatic effect against Streptococcus pneumoniae. Twenty-seven patients (93%) achieved a C(max)/MIC ratio for a bacteriostatic effect against S. aureus, and 28 patients (97%) achieved an AUC(0-24)/MIC ratio for a bacteriostatic effect against S. aureus. Free plasma daptomycin concentrations were above the MIC for 50 to 100% of the dosing interval in 100% of patients for S. pneumoniae and 90% of patients for S. aureus. The median time to defervescence was 3 days from the start of daptomycin therapy. In summary, a 6-mg/kg intravenous infusion of daptomycin every 24 h was effective and well tolerated in neutropenic cancer patients.

Deficiency of Mannose-Binding Lectin Is a Risk Factor for Invasive Pulmonary Aspergillosis in Patients with Multiple Myeloma: An Analysis of 482 Patients

Invasive pulmonary aspergillosis (IPA) is a major cause of morbidity and mortality in neutropenic cancer patients. Mannose-binding lectin (MBL) is a circulating pattern-recognition molecule that recognizes microbial carbohydrate motifs, leading to complement activation, opsonization, phagocytosis, and cell lysis and is considered an important component of innate immunity. Deficiency of MBL is common due to genetic polymorphisms and has been identified as a risk factor for severe infections among myeloma patients undergoing autologous stem cell transplantation (ASCT). MBL deficiency has also been reported as a predisposing factor for chronic necrotizing pulmonary aspergillosis, a locally invasive infection typically seen in patients with chronic lung disease. The association between MBL deficiency in cancer patients and susceptibility to IPA has never been evaluated.This study investigated whether MBL deficiency, as measured by serum MBL levels, is associated with the development of IPA in patients with multiple myeloma undergoing multiple cycles of antineoplastic chemotherapy including tandem ASCT and post-transplant consolidation chemotherapy. Baseline serum MBL level was measured using ELISA. The frequency of IPA was assessed retrospectively in 482 adult myeloma patients (2007–2008), 50 of whom developed IPA.Association between MBL levels and IPA was analyzed using logistic regression analysis (table 1). Patients with normal serum MBL levels (≥ 1000 ng/mL) had significantly fewer episodes of IPA [(21 in 303 patients; 6.9%); Odds ratio, 0.385; 95% CI (0.212–0.699); P = 0.0017] than patients with low (100–999 ng/mL; 18 episodes in 125 patients (14.4%)) and very low (<100 ng/mL) MBL levels (11 episodes in 54 patients; 20.4%) (Table 1). We conclude that MBL deficiency is associated with more frequent episodes of IPA among patients with myeloma undergoing intensive antineoplastic therapy including ASCT and should be added to the list of risk factors for chemotherapy-related IPA. Baseline MBL level may serve as a predictor for the risk of IPA among such patients. This novel finding may have important therapeutic implications because recombinant Human MBL replacement therapy is now available and could therefore be applied prophylactically to decrease the risk of IPA in MBL-deficient patients receiving chemotherapy.Table 1. Association between serum MBL level and risk of invasive pulmonary aspergillosis (482 pts)AspergillosisMBL (ng/mL)No (n=432)Yes (n=50)RateOdds ratio (95%C.I.)P-value<10043 (10%)11 (22%)11/54 (20% )ReferenceReference100–1000107 (25%)18 (36%)18/125 (14%)0.658 (0.287–1.507)0.32181000282 (65%)21 (42%)21/303 (7%)0.291 (0.131–0.646)0.0024MBL <1000150 (35%)29 (58%)29/179 (16%)Reference

Early diagnosis and preemptive therapy of pulmonary mold infections in high-risk patients

The management of pulmonary mold infections in at-risk patients is hampered by the difficulty in diagnosing these infections. Therefore, most practitioners rely on universal prophylaxis and on the early empirical use of antifungals, especially in neutropenic cancer patients and stem cell transplant recipients. However, a strategy of preemptive or diagnostic-driven antifungal therapy is being explored based on advances in imaging techniques and in fungal antigen detection methods. This article highlights the controversies surrounding the prevention and the early treatment of invasive mold infections in high-risk patients.

Empirical antifungal therapy for patients with neutropenia and persistent fever: Systematic review and meta-analysis

Objectives To assess the evidence for the current standard of practice of using empirical antifungal treatment in febrile neutropenic cancer patients. Methods Systematic review and meta-analysis of randomised controlled trials comparing empirical or preemptive antifungal treatment with placebo, no intervention, or another antifungal. The primary outcomes were all-cause mortality and invasive fungal infections (IFI) (documented or probable). Relative risks (RR) with 95% confidence intervals (CI) were pooled. Results Six trials assessed the efficacy of empirical treatment compared to no treatment and one compared empirical to preemptive therapy. Empirical treatment did not decrease mortality significantly (RR 0.82, 95% CI 0.50–1.34), but significantly decreased IFIs (RR 0.25, 0.12–0.54). Twenty-three trials assessed the efficiency of different antifungals. All-cause mortality was lower with azoles compared to amphotericin B (AB) (RR 0.81, 0.65–1.01); IFI rates were not different while adverse events were less frequent with azoles (RR 0.40; 0.34–0.66). Liposomal AB was associated with lower mortality and IFIs than other AB formulations (RR 1.57, 1.10–2.23 and 1.48, 0.98–2.25, respectively). Caspofungin was associated with fewer adverse events, but otherwise comparable to liposomal AB. All trials included patients with haematological malignancies. Major limitations included per-protocol analysis, non-blinded design and inconsistent definitions of IFIs. Conclusions Empirical antifungal treatment is associated with a lower rate of IFIs but no significant difference in overall mortality. The assessment of IFIs in these trials may have been biased, offering only weak support to standard practice. Azoles, liposomal amphotericin B or caspofungin should be preferred. Pre-emptive antifungal therapy should be considered and further investigated.

Early diagnosis and treatment of lemierre syndrome in a neutropenic cancer patient

Lemierre syndrome (LS) is a rare but potentially life-threatening disease. It originates from an oropharyngeal infection of the internal jugular vein (IJV) leading to thrombophlebitis and metastatic infection. We report a 42-year-old woman with gastric adenocarcinoma presenting with febrile neutropenia, sore throat, and a tender induration in the left neck. Early LS was diagnosed by finding thrombophlebitis of the IJV following oropharyngeal infection but without bacteremia. Antibiotic treatment led to freedom from metastatic infection. Physicians should suspect LS after identifying the ”red-flag” signs, i.e., tender induration of the unilateral neck following an oropharyngeal infection. A prompt diagnosis can be made by finding thrombophlebitis of the IJV. Early antibiotic therapy may lead to favorable clinical outcomes.

Challenges in surgical management of abdominal pain in the neutropenic cancer patient.

Abdominal pain in neutropenic cancer patients presents a unique clinical challenge for surgeons. The purposes of this retrospective study were to characterize the clinicopathologic factors associated with the presentation of neutropenia and abdominal pain, examine the treatment strategies used, and define associated outcomes for these patients. We identified patients with concomitant neutropenia (absolute neutrophil count <1000 cells/microL) and abdominal pain who had been evaluated by surgical oncologists over a period of more than 6 years. A Cox proportional hazards regression model was used to analyze the association between clinicopathologic factors and overall survival time. Sixty patients were included in this analysis. After our clinical and radiographic evaluations, we determined that the most frequent causes of the abdominal pain were neutropenic enterocolitis (28%) and small bowel obstruction (12%); the cause remained uncertain in 35%. Surgical interventions had been performed in 9 patients. The 30- and 90-day mortality rates for all patients were 30% and 52%, respectively. Multivariate analysis revealed that severe sepsis, a relatively long duration of neutropenia, and the lack of surgical intervention were significant adverse prognostic factors for overall survival. Abdominal pain as a symptom in neutropenic patients continues to be a diagnostic and therapeutic challenge and is associated with a high mortality rate. Based on our results, we conclude that efforts should focus on improving neutrophil counts and on treating the frequent and serious comorbidities found in these patients. Surgery should be delayed, when possible, to allow for neutrophil recovery.

Conservative Management of Acute Appendicitis in Children With Hematologic Malignancies During Chemotherapy-induced Neutropenia

The management of acute appendicitis in the febrile neutropenic patient after intensive chemotherapy is controversial. We report our single-center-experience of 5 children diagnosed with appendicitis during febrile neutropenia after chemotherapy for acute leukemia or lymphoma. All patients presented with an isolated appendicitis without signs of overt mucositis or more diffuse enterocolitis. The clinical diagnosis was confirmed by ultrasonography. Perforation with retrocecal abscess was present in 1 patient. Administration of combination antimicrobial regimens including meropenem resulted in complete resolution in all patients. Our observations indicate that acute appendicitis in clinically stable neutropenic cancer patients can be managed conservatively without surgery.

Daptomycin Use in Cancer Patients with Neutropenia.

Infections occurring during neutropenia in cancer patients (pts) frequently involve Gram-positive pathogens and are complicated by antibiotic resistance. Outcomes for infections due to either methicillin-resistant or -susceptible Staphylococcus aureus (MRSA, MSSA) treated with vancomycin are considered suboptimal by many clinicians (Sakoulas G. J Clin Microbiol 2004; 42:2398–402). New effective agents are needed for treatment. Data were collected retrospectively as part of an ongoing registry (Cubicin Outcomes Registry and Experience; CORE, 2005 and 2006 program years). Data were collected on demographic and microbiologic characteristics; prior, concomitant and follow-up antibiotics; DAP regimen; and clinical data. Outcomes were assessed at the end of DAP therapy by the investigator who, in most cases, was the infectious disease physician involved in the treatment of the patient. The definitions for clinical outcome were: Cure - clinical signs and symptoms resolved (and/or) no additional antibiotic therapy necessary (or) negative culture reported at the end of therapy; Improved - partial resolution of clinical signs and symptoms (and/or) additional antibiotic therapy warranted at the end of therapy; Failure - inadequate response to therapy: worsening or new/recurrent signs and symptoms (or) need for a change in antibiotic therapy (or) positive culture reported at the end of therapy. Pts reported with neutropenia during DAP, a history of cancer, and evaluable for outcome (cure, improved, failure) were analyzed. Eighty-four pts had a history of cancer and had neutropenia during DAP treatment, of these, 72 (86%) were evaluable for DAP outcome. Sixty-five of 72 (90%) pts had either cure (n=40, 56%) or improved (n=25, 35%) as an outcome. Success rates (cure plus improved) stratified by the lowest WBC during DAP were; 29/34 (85%) for < 100 cells/m3, 26/28 (93%) for 100–499 cells/m3, and 10/10 (100%) for 500–1000 cells/m3, P=0.32. The median (range) time to clinical response in those successfully treated (data reported in 47 pts) was 4 days (1–21). Fifty-nine of 72 (82%) had a hematological malignancy. Fifty-eight percent were male, 22% were ≥66 yrs old, 7% had an initial CrCl <30 mL/min, 18% received DAP in an ICU. Eighty-eight percent of pts received antibiotics before DAP, most frequently with vancomycin (83%), cefepime (17%), and linezolid (16%). The most frequent reason for switching to DAP was prior clinical failure / resistance (54%). The major infections being treated with DAP were bacteremia (76%), UTI / pyelonephritis (10%), and uncomplicated skin and skin structure (6%). Seventy-four percent of pts with a WBC < 100 cells/m3 had a bacteremia. The most common Gram-positive pathogens reported were vancomycin-resistant enterococci (52%), coagulase-negative staphylococci (21%), and S. aureus (14%; 7/11, 64% were MRSA). The median (range) initial DAP dose was 6.0 mg/kg (3–7). The median (range) DAP duration of therapy was 13 days (1–86). Nineteen percent of the pts received DAP as an outpatient at some time during their therapy. There were 37 adverse events (AE) reported in 20 (28%) pts; however, only three AEs in 3 pts (4%) were assessed as possibly related to DAP. The data from the registry provide useful information about the clinical characteristics of neutropenic cancer patients treated with DAP for primarily bacteremia. Most of the pts were bacteremic and there was no difference in outcome regardless of the degree of neutropenia. These data require confirmation via prospective 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.

Molecular Insights into Quorum Sensing in the Human Pathogen Pseudomonas aeruginosa from the Structure of the Virulence Regulator LasR Bound to Its Autoinducer

Many Gram-negative bacteria communicate via molecules called autoinducers to coordinate the activities of their populations. Such communication is termed quorum sensing and can regulate pathogenic virulence factor production and antimicrobial resistance. The quorum sensing system of Pseudomonas aeruginosa is currently the most intensively researched, because this bacterium is an opportunistic human pathogen annually responsible for the death of thousands of cystic fibrosis sufferers and many other immunocompromised individuals. Quorum sensing inhibitors can attenuate the pathogenicity of P. aeruginosa. Here we present the crystal structure of the P. aeruginosa LasR ligand-binding domain bound to its autoinducer 3-oxo-C(12)-acylhomoserine lactone. The structure is a symmetrical dimer, with each monomer exhibiting an alpha-beta-alpha fold similar to the TraR and SdiA quorum sensing proteins of Agrobacterium tumefaciens and Escherichia coli. The structure was determined up to 1.8-A resolution and reveals the atomic interactions between LasR and its autoinducer. The monomer structures of LasR, TraR, and SdiA are comparable but display differences in their quaternary organization. Inspection of their binding sites shows some unexpected variations resulting in quite different conformations of their bound autoinducers. We modeled interactions between LasR and various quorum sensing inhibitors, yielding insight into their possible mechanisms of action. The structure also provides a platform for the optimization, or de novo design, of quorum sensing inhibitors.

Safety and Efficacy of Itraconazole Compared to Amphotericin B as Empirical Antifungal Therapy for Neutropenic Fever in Patients with Haematological Malignancy*

Safety, tolerability and efficacy of itraconazole and amphotericinB (AMB) were compared for empirical antifungal treatmentof febrile neutropenic cancer patients. Patients and Methods:In an open, randomised study, 162 patients with at least 72 h ofantimicrobial treatment received either intravenous followed byoral itraconazole suspension or intravenous AMB for a maximum of28 days. Permanent discontinuation of study medication due to anyadverse event was the primary safety parameter. Efficacy parametersincluded response and success rate for both treatment groups.Results: Significantly fewer itraconazole patients discontinued treatmentdue to any adverse event (22.2 vs. 56.8% AMB; p < 0.0001).The main reason for discontinuation was a rise in serum creatinine(1.2% itraconazole vs. 23.5% AMB). Renal toxicity was significantlyhigher and more drug-related adverse events occurred in the AMBgroup. Intention-to-treat (ITT) analysis showed favourable efficacyfor itraconazole: response and success rate were both significantlyhigher than for AMB (61.7 vs. 42% and 70.4 vs. 49.3%, bothp < 0.0001). Treatment failure was markedly reduced in itraconazolepatients (25.9 vs. 43.2%), largely due to the better tolerability.Conclusions: Itraconazole was tolerated significantly better thanconventional AMB and also showed advantages regarding efficacy.This study confirms the role of itraconazole as a useful andsafe agent in empirical antifungal therapy of febrile neutropeniccancer patients.

P725 European survey on the use of antibacterial prophylaxis in neutropenic cancer patients: a joint project of the EORTC and the EBMT

P725 European survey on the use of antibacterial prophylaxis in neutropenic cancer patients: a joint project of the EORTC and the EBMT

Tobramycin once versus three times daily, given with penicillin G, to febrile neutropenic cancer patients in Norway: a prospective, randomized, multicentre trial

Penicillin G with an aminoglycoside is the standard initial empirical treatment in febrile neutropenia in Norway. It has been argued that giving the aminoglycoside once daily to neutropenic patients with Gram-negative bacteraemia may be hazardous when penicillin G is the beta-lactam antibiotic. We questioned this argument and hypothesized that tobramycin once daily was as efficacious as three times daily. We conducted a randomized prospective multicentre study, comparing the efficacy of tobramycin 6 mg/kg once (arm A) versus three times (arm B) daily, plus penicillin G 5 million IU x 4, in febrile neutropenic cancer patients. modification of the antibiotic regimen. One hundred and seventy-four patients were evaluable for intention-to-treat analyses. One hundred and fifty-five patients had lymphoma or leukaemia as the underlying cancer diagnosis. In arm A, 35 of 88 patients and in arm B, 34 of 86 patients, that is 40% in both arms had no modification of the antibiotic regimen. No patients died while participating in the study. Upon modification of the antibiotic regimen, all patients were successfully treated. The increase in serum creatinine was modest and similar in the two treatment groups. When administered with penicillin G, tobramycin given once daily was as efficacious and safe as tobramycin given three times daily in cancer patients with febrile neutropenia in Norway, provided the regimen was modified according to the clinical response.

205: An evaluation of infections and resistance patterns after implementation of antibiotic prophylaxis in neutropenic cancer patients

205: An evaluation of infections and resistance patterns after implementation of antibiotic prophylaxis in neutropenic cancer patients

A prospective study of febrile neutropenia in lung cancer patients

BACKGROUND There are few data on microbiology of febrile neutropenia (FN) in lung cancer patients. The primary objective of this study was to evaluate the epidemiology of FN in this population. PATIENTS AND METHODS All patients with lung cancer treated with chemotherapy in the Institut Jules Bordet (a cancer hospital) and who developed FN (PMN <500/mm3) were included in the present prospective study. Febrile neutropenia was defined as any febrile episode (38.5°C once or 38.0°C twice) occurring during neutropenia (neutrophil count <500/mm3). RESULTS Ninety five patients, 62 with non-small cell and 33 with small cell lung carcinoma developed FN. A total of 102 FN episodes were observed. Of these, 46 were microbiologically and 14 clinically documented. The most frequent site of infection was the lung (31%). Gram-negative bacteria, mainly Escherichia coli and Haemophilus influenzae, were most commonly observed. In bacteremic patients, Gram-positive bacteria, essentially Streptococcus sp, Enterococcus sp and Staphylococcus aureus, accounted for 39% of the micro-organisms. CONCLUSION Lung constitutes the predominant site of infection in febrile neutropenic lung cancer patients. In these patients, E. coli and H. influenzae are the most commonly documented pathogens, except in case of bacteremia where Streptococcus sp and S. aureus as well as E. coli are the principal pathogens. I N T R O D U C T I O N Infection is one of the commonest complications associated with cancer. Different factors are contributing: immunosuppression related to cancer or its treatment, visceral neoplastic obstruction, use of implantable devices and invasive procedures, disruption of physiological barriers or blood product transfusion [1]. In lung cancer patients neutropenia, chronic obstructive bronchopulmonary disease (COPD) and bronchial obstruction are probably the main causes favouring infection. Epidemiological data on infections in lung cancer patients are scarce. We have previously reported a prospective epidemiological study demonstrating that the majority of lung infections were predominantly due to Gram negative bacteria [2]. Few other studies have assessed the respective frequency of the infection types and microbiology in these patients, also demonstrating that infections occur essentially in the lung. Chemotherapy is now generally accepted as part of the treatment of patients with lung cancer, whatever stage or histology are considered [3-5]. Chemotherapy is ORIGINAL ARTICLE HOSPITAL CHRONICLES 2007, 2(1): 38–43 Address for correspondence: Dr T. Berghmans Institut Jules Bordet Rue Hιger-Bordet, 1 1000 Bruxelles Belgium Tιl: +322.5413191 Fax: +322.5343756 e-mail: thierry.berghmans@bordet.be KEy-wORDS: febrile neutropenia, microbiology, non-small cell lung cancer, small cell lung cancer, epidemiology, risk

Significance of Laminar Air Flow Room for the Reverse Isolation in Neutropenic Cancer Patients.

Infection is one of the most important causes of death in cancer patients. So many physicians make every effort to control the infection, especially in neutropenic cancer patients. The aim of this study is to find out the role of HEPA filter equipped laminar air flow room reverse isolation for the management of chemotherapy induced febrile neutropenic children with cancer. We evaluated febrile neutropenic patients following chemotherapy from January 2003 to April 2006 at the Department of Pediatrics, Kyungpook National University Hospital, Daegu, Korea. They were promptly managed by antibiotics and antifungal agents and if possible, they were isolated in the aseptic room. They were allocated to three groups of standard ward care, isolation after onset of fever and isolation before onset of fever. Profiles of infection, clinical courses and survival rate were compared among three groups. One hundred and nine episodes of febrile neutropenia from thirty eight cancer patients were observed. Twenty nine were boys and nine were girls with their median age were 5.5 years. The diagnoses included acute leukemia (36.8%), malignant lymphoma (15.8%), and other solid tumor (47.4%). Fifty five episodes were included to standard ward care, forty four episodes to isolation after onset of fever and thirteen episodes to isolation before onset of fever. We found out that one in thirteen episodes of isolation before onset of fever (8%) and twenty six in ninety six episodes in other groups (27%) were microbiologically or clinically defined infections. Fifty six episodes recovered and only one died of infectious cause both isolation after and before onset of fever group, especially all recovered in isolation before onset of fever group. Forty eight episodes recovered and four died in general ward care group, but there was no statistical difference among three groups (p=0.93). Age, sexual difference, underlying disease, absolute neutrophil count (ANC), duration of ANC recovery and incidence of disseminated intravascular coagulation were no difference among three groups. In early isolated group, duration of fever and antibiotics medication were significantly shorter (p=0.002, 0.009) and CRP level was lower than other two groups (p=0.04). Reverse isolation in laminar air flow room for neutropenic cancer children before onset of fever affect the durations of fever and antibiotics treatment with beneficial effect.

Venous Thromboembolic Disease

Venous thromboembolic disease is a common and life-threatening condition in cancer patients. Results from a recent retrospective study of 66,106 hospitalized adult neutropenic cancer patients showed that 2.74% to 12.10% of these patients, depending on the type of malignancy, experienced a venous thromboembolism (VTE) during first hospitalization. These guidelines specifically outline strategies to prevent and treat VTE in adult inpatients with either a diagnosis of cancer or for whom cancer is clinically suspected. These guidelines evaluate the therapeutic advantages of implementing pharmacologic anticoagulation measures based on both the perceived risk for bleeding (i.e., contraindications to anticoagulation) and the status of the cancer. For the most recent version of the guidelines, please visit NCCN.org

In vitro antimicrobial activity of moxifloxacin against bacterial strains isolated from blood of neutropenic cancer patients

In vitro antimicrobial activity of moxifloxacin against bacterial strains isolated from blood of neutropenic cancer patients

Amphotericin B Is Still the Drug of Choice for Invasive Aspergillosis

We read with interest the recent article by Drs. Segal andWalsh, wherein the authors review the epidemiology, diagnosis, and management of invasive aspergillosis (1). The authors recommend voriconazole as the drug of choice in the treatment of invasive aspergillosis. However, we do not agree with the recommendations of the authors that voriconazole be considered the new standard of care for invasive aspergillosis. We believe that it is too early to accept voriconazole as the drug of choice for invasive aspergillosis. Amphotericin B is a highly effective antifungal agent, and is used as the gold standard against which newer agents are compared in trials of antifungal drugs. The conclusion that amphotericin B is inferior to voriconazole is based on two published trials (2, 3); however, both the trials are limited by their study design (4). The first trial was flawed by its design in using the deoxycholate preparation without requirements for premedication (used for minimizing infusion-related toxicity), or substitutionwith fluid and electrolytes (to reduce nephrotoxicity) (2). Moreover, voriconazole was given on an average of 77 d, but amphotericin B was given only for 10 d, precluding any meaningful comparison of the two study drugs. The second trial was a noninferiority trial that compared voriconazole with liposomal amphotericin B as an empirical treatment of fever of unknown origin in neutropenic cancer patients (3). Despite misleading definitions, voriconazole was significantly inferior to amphotericin B (4, 5). In fact, there was less survival in the voriconazole group, and a claimed significant reduction in the so-called breakthrough fungal infections (defined as those confirmed more than 24 h postenrollment) in favor of voriconazole disappeared when baseline infections that persisted despite treatment (infections arbitrarily excluded from analysis) were included (4). Thus, the available evidence does not support a recommendation to use voriconazole instead of amphotericin B for the treatment of invasive aspergillosis. To the contrary, amphotericin B is significantly more effective than voriconazole and is currently the drug of choice (6).