Febrile Episodes In Patients Research Articles

Efficacy and Safety of Sitafloxacin in Treating Low-risk Febrile Neutropenia in Patients with Lung Cancer.

Introduction: Febrile episodes in patients with cancer and chemotherapy-induced neutropenia can be life-threatening and generally require prompt administration of broad-spectrum antimicrobials. However, little evidence exists for treating patients with solid tumors and febrile neutropenia (FN) with oral antimicrobials. Methods: In this prospective study, we aimed to determine the efficacy and safety of sitafloxacin (STFX) for treating FN in lung cancer patients. In this prospective study, low-risk FN patients with lung cancer received STFX. The primary endpoint was response rate, defined as 5 sequential days of absence of fever without adverse events. The study was registered as UMIN000010911. Results: As a result, STFX was administered to 26 patients, all of whom survived during its administration. Of the 26, 14 completed primary endpoint (53.85%). The low response rate was attributed to occurrence of fevers of unknown cause rather than failure of FN treatment. Only two patients received antibacterial agents other than STFX. If response rate omitted absence of fever and been defined only as recovery from FN without changing microbial agents or serious complications, the response rate would have been 91.67%. Adverse events occurred in eight patients, none of which were serious. Conclusions: In conclusion, STFX might be used to treat low-risk FN in patients with lung cancer; however, a more detailed study will be required in future.

Clinical presentation, causes and outcome of febrile episodes in a prospective cohort of HIV-infected patients

Background: Fever was frequently caused by opportunistic conditions in HIV-patients in the early years of the epidemic. Little is known about diagnostic spectrum and outcome of febrile episodes in patients with good access to antiretroviral therapy.Methods: We prospectively studied clinical presentation, diagnosis and outcome of febrile episodes in a contemporary cohort of HIV-patients with good access to antiretroviral therapy. Fever was defined as temperature 38.3 °C or higher, measured by a health care provider.Results: We found 220 febrile episodes in 146 patients. In 25.9% of episodes the patient had a CD4 less than 200/mm³ and in 78.6% the patient was on antiretroviral therapy. There were multiple episodes in 44 patients. A diagnosis was established in 91.8%. Infection accounted for 82.3%, mainly respiratory tract infections, viral syndromes and abdominal infections. Malignancy, drug reactions and inflammatory conditions accounted together for less than 12% of episodes. Fifteen percent were attributed to opportunistic conditions. Episodes in patients with CD4 less than 200 were less likely to be caused by infection, but more likely to be caused by malignancy, drug reactions and opportunistic conditions. In 6.4% the patient died within six months after the onset of fever. Risk factors for death at six months in multivariable analysis were higher age and lower CD4.Conclusions: HIV-patients with access to antiretroviral therapy present with fever mostly due to conditions common in the general population. HIV-patients with low CD4 remain at risk for fever due to opportunistic conditions and death.

Treatment of adult hyper-IgD syndrome with canakinumab

Hyper-IgD and periodic fever syndrome (HIDS) is a rare, autosomal-recessive autoinflammatory disease characterized by lifelong recurrent episodes of systemic inflammation. HIDS frequently presents in infancy with intermittent fevers lasting from 4 to 7 days, recurring every 4 to 6 weeks. Febrile episodes may be unprovoked or precipitated by factors including infections, vaccinations, or stress. Associated symptoms may include abdominal pain, diarrhea, rashes, arthralgias, aphthous ulcers, and lymphadenopathy. During acute attacks, patients may exhibit leukocytosis, elevations in acute-phase reactants, and elevated levels of proinflammatory cytokines such as IL-1, IL-6, and TNF-a. At baseline, affected individuals may have elevated IgD levels; however, increases in IgD levels are not universal, particularly in very young patients. If clinical suspicion is high, HIDS should be considered despite normal serum IgD levels. Patients with HIDS may exhibit increased rates of infection, particularly with S pneumoniae; this may be secondary to infrequent IgG hypogammaglobulinemia or host conditions that may be permissive for persistence of this organism. HIDS is part of a clinical spectrum caused by decreased activity of mevalonate kinase, an enzyme involved in isoprenoid biosynthesis. Four mutations in MVK, the gene encoding mevalonate kinase (V377I, I268T, H20P/N, and P167L), account for more than 70% of the cases associated with HIDS. Lack of isoprenoid end products due to abnormal metabolism increases IL-1b secretion from mevalonate kinaseedeficient PBMCs, making IL-1 signaling a promising therapeutic target. Previous studies have shown inconsistent benefits of treatments including colchicine, cyclosporine, and statins. Many patients respond well to oral steroids, but the frequency of exacerbations makes a steroid-sparing therapy desirable. Biologic therapies have been successful in the treatment of other periodic fever syndromes. The cryopyrin-associated periodic syndromes are a group of fever disorders including familial cold autoinflammatory syndrome (FCAS) and Muckle-Wells syndrome (MWS). These conditions are also mediated through excessive IL-1b production. Canakinumab, a fully human antie IL-1b mAb, has been shown to induce rapid remission of symptoms in patients with cryopyrin-associated periodic syndromes and is approved by the Food and Drug Administration for the treatment of FCAS and MWS. Biologics including etanercept, adalimumab, and anakinra have all been shown to decrease the frequency and severity of febrile episodes in patients with HIDS. Small numbers of patients with HIDS treated with canakinumab have also shown clinical improvement. Here, we describe the case of a patient with HIDS who had significant clinical improvement with initiation of canakinumab therapy.

Aetiology of acute febrile episodes in children attending Korogwe District Hospital in north-eastern Tanzania.

IntroductionAlthough the burden of malaria in many parts of Tanzania has declined, the proportion of children with fever has not changed. This situation underscores the need to explore the possible causes of febrile episodes in patients presenting with symptoms at the Korogwe District Hospital (KDH).MethodsA hospital based cross-sectional study was conducted at KDH, north-eastern Tanzania. Patients aged 2 to 59 months presenting at the outpatient department with an acute medical condition and fever (measured axillary temperature ≥37.5°C) were enrolled. Blood samples were examined for malaria parasites, human immunodeficiency virus (HIV) and bacterial infections. A urine culture was performed in selected cases to test for bacterial infection and a chest radiograph was requested if pneumonia was suspected. Diagnosis was based on both clinical and laboratory investigations.ResultsA total of 867 patients with a median age of 15.1 months (Interquartile range 8.6–29.9) were enrolled from January 2013 to October 2013. Respiratory tract infections were the leading clinical diagnosis with 406/867 (46.8%) of patients diagnosed with upper respiratory tract infection and 130/867 (15.0%) with pneumonia. Gastroenteritis was diagnosed in 184/867 (21.2%) of patients. Malaria infection was confirmed in 72/867 (8.3%) of patients. Bacterial infection in blood and urine accounted for 26/808 (3.2%) infections in the former, and 66/373 (17.7%) infections in the latter. HIV infection was confirmed in 10/824 (1.2%) of patients. Respiratory tract infections and gastroenteritis were frequent in patients under 36 months of age (87.3% and 91.3% respectively). Co-infections were seen in 221/867 (25.5%) of patients. The cause of fever was not identified in 65/867 (7.5%) of these patients.ConclusionsThe different proportions of infections found among febrile children reflect the causes of fever in the study area. These findings indicate the need to optimise patient management by developing malaria and non-malaria febrile illnesses management protocols.

Differential diagnosis between bacterial infection and neoplastic fever in patients with advanced urological cancer: The role of procalcitonin

It is difficult to determine the cause of high fever in patients with advanced cancer, because they tend to have both neoplastic fever and concomitant bacterial infections with elevated white blood cells and C-reactive protein levels. Procalcitonin has been reported to be a valuable marker for bacterial infections in a wide range of clinical scenarios. However, there have been no studies regarding the usefulness of procalcitonin to differentiate between febrile episodes caused by bacterial infections and neoplastic fever in patients with advanced urological cancer. In the present study, 37 febrile episodes were retrospectively analyzed. Although there were no differences in white blood cell number, C-reactive protein level or body temperature between bacterial infections and non-bacterial infections, procalcitonin levels were significantly higher in the former than the latter. Our findings suggest that measurement of procalcitonin might be valuable to determine the cause of febrile episodes in patients with advanced urological cancer, and can help clinicians to make appropriate decisions for treatment.

Ciprofloxacin Reduces Occurrence of Fever in Children With Acute Leukemia who Develop Neutropenia During Chemotherapy

Fluoroquinolones reduce occurrence of fever in adult cancer patients who develop neutropenia, but there has been no randomized controlled trial in children, and there are only a few studies considering resistance in intestinal floral after ciprofloxacin has been used. Children younger than 18 years with acute lymphoblastic leukemia or lymphoma scheduled to undergo chemotherapy were randomized to receive oral ciprofloxacin 20mg/kg/day or placebo from the beginning of their chemotherapy. Rectal swab cultures were taken before and at 1 and/or 2 weeks after the intervention. Of the total of 95 patients, 45 and 50 patients received ciprofloxacin and placebo, respectively. Of the 71 patients who developed neutropenia, the proportion of children who developed fever was significantly lower in the ciprofloxacin group than in the placebo group (17/34 [50.0%] versus 27/37 [73.0%]; absolute difference in risk, -23.0%; 95% confidence interval: -45.0% to -0.9%; P = 0.046). Ciprofloxacin significantly reduced the occurrence of febrile episodes in patients with acute lymphoblastic leukemia in the induction phase of chemotherapy, but not in patients with lymphoma or in the consolidation phase of chemotherapy. Adverse effects were not different between the groups. After intervention, the percentages of Escherichia coli and Klebsiella pneumoniae susceptible to ciprofloxacin were significantly lower in the ciprofloxacin group. Ciprofloxacin can prevent fever in neutropenic patients with acute lymphoblastic leukemia during the induction phase of chemotherapy with good tolerance and no serious side effects. Due to the selective pressure of intestinal flora resistance to ciprofloxacin, the long-term effectiveness needs further investigation.

Efficacy and safety of moxifloxacin as antibacterial prophylaxis for patients receiving autologous haematopoietic stem cell transplantation: a randomised trial

Patients receiving high-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) are at high risk of infections, especially bacteraemia. A prospective, double-blind, randomised, placebo-controlled, single-centre, pilot study was performed on oral moxifloxacin 400mg versus placebo for preventing bacteraemia in PBSCT recipients. Patients received moxifloxacin or placebo for the duration of neutropenia or until emergence of fever or other infections necessitating intravenous antibiotic treatment. Of 68 patients included in the trial, 2 were excluded from the trial before taking their first dose. The remaining 66 patients were eligible for evaluation in the intention-to-treat analysis set. Neutropenia with an absolute neutrophil count of <500cells/μL developed in 30 moxifloxacin-treated patients (88.2%) and 21 patients in the placebo group (65.6%) (P<0.03). Nine patients (26.5%) and eight patients (25.0%), respectively, were prematurely discontinued from study treatment. Breakthrough bacteraemia occurred in 3 moxifloxacin-treated patients (8.8%) and 9 patients in the placebo group (28.1%) (P=0.042). The time period until fever was 9.5 days [95% confidence interval (CI) 8.06–10.94 days) and 7.69 days (95% CI 6.51–8.85 days), respectively (P=0.0499). There was no difference in adverse events or toxicities between the groups. Moxifloxacin prevented bacteraemia and shortened febrile episodes in patients receiving autologous PBSCT. No significant increase of adverse events in the moxifloxacin arm was observed, possibly due to the rather small sample size.

Low Circulating Mannan-Binding Leptin Levels Correlate with Increased Number of Febrile Episodes in Myeloma Patients Who Undergo High Dose Melphalan with Autologous Hematopoietic Stem Cell Transplantation and Do Not Receive Antibiotic Prophylaxis

Abstract 4457Patients with multiple myeloma (MM) are at a higher risk of infections compared to general population. High dose melphalan (HDM) with autologous stem cell support (ASCT) is the recommended treatment for MM patients ≤65 years of age. Up to 80% of patients who undergo an ASCT develop neutropenic fever and up to one third of them have culture positive infections. The mannan binding leptin (MBL) pathway of the complement system is part of the innate immune system and seems to influence the risk of infections in cancer patients during treatment. In contrast to the classical complement pathway, MBL pathway is not antibody-dependent. MBL is a protein that belongs to the collectin family and is produced by hepatocytes. MBL acts via binding to the surface of bacteria, thus facilitating complement activation with formation of the membrane attack complex, leading to microbial lysis. In general population, 15–20% of people have MBL levels <500 mg/L, while even lower levels (<100 mg/L) are associated with increased frequency of infections. The impact of the MBL on the occurrence of infections during chemotherapy in malignant diseases has been explored in different studies with conflicting results. The aim of this study was to evaluate the impact of MBL levels on the risk of infections and on the risk of development of febrile episodes in patients with MM who receive HDM and ASCT.We studied 100 MM patients who underwent an ASCT between 1996–2011 in a single center (Department of Clinical Therapeutics, University of Athens, Greece). All patients received prophylactic therapy with 200 mg fluconazole daily and 500 mg valacyclovir daily. Sixty-seven patients participated in a randomized study, where in the first arm patients received prophylactic antibiotics, including vancomycin at a dosage of 1 g once daily and ciprofloxacin at a dosage of 400 mg twice daily, while in the arm B there was no antibiotic prophylaxis. All patients received G-CSF 300 μ g twice daily from day of stem cell reinfusion to neutrophil counts >1500/mm3. In case of neutropenic fever, prophylactic antibiotics were interrupted and first line regimen was administered, including vancomycin 1g twice daily, amikacin 500 mg twice daily and ceftazidime 2 g TID. In case of failure of first line treatment, a second line antibiotic combination was administered, usually including a carbapenem and linezolide. Antibiotic regimens were also modified according to results of blood or urine cultures. MBL serum levels were measured in all patients on the day of mobilization, before the administration of cyclophosphamide, using an ELISA methodology (R&D Systems, Minneapolis, MN, USA).Seventeen (17%) patients had MBL levels <500 mg/L. Of those, 11 received antibiotics prophylaxis and 6 did not. In general, there was no statistical difference regarding the development of fever or neutropenic fever between patients with MBL serum levels of <500 mg/L or ≥500 mg/L. However, among 17 patients with MBL levels of <500 mg/L, 6 /11 patients who received antibiotics prophylaxis developed a febrile episode compared to 6/6 patients who did not receive antibiotics prophylaxis and developed a febrile episode (p=0.049). There was no difference in the incidence of septicemia, the severity of infection, the number of days of hospitalization or the number of days with fever between patients with MBL serum levels of <500 mg/L or ≥500 mg/L. Nevertheless, patients with MBL levels <500 mg/L attained a lower response rate to first line therapy with antibiotics, i.e. lower percentage of fever resolution and higher incidence of necessitated administration of a second line antibiotic regimens, compared to patients with MBL levels of ≥500 mg/L (66.7% versus 88.9%, respectively; p=0.05).The results of our study suggests that myeloma patients who underwent ASCT and had low levels of MBL had a lower response rate in first line antibiotic regimens, requiring more often administration of a second more advanced line of antibiotics. Furthermore, the administration of prophylactic antibiotics to these patients seems to reduce the number of febrile episodes. These observations underscores the importance of innate immune system in permitting antibiotics to exercise their protective effect in severely immunocompromised patients and raise the question about the necessity of administering prophylactic antibiotics in this subgroup of patients. Disclosures:No relevant conflicts of interest to declare.

Clinical and Demographic Factors Associated with Antipyretic Use in Gram-Negative Severe Sepsis and Septic Shock

Antipyretic therapy is commonly prescribed for patients with infection, but studies of its impact on clinical outcomes have yielded mixed results. No data exist to characterize the use of antipyretic medications in patients with severe sepsis or septic shock. To identify clinical and demographic factors associated with antipyretic medication administration in severe sepsis and septic shock. This single-center, retrospective, cohort study assessed febrile patients (temperature ≥ 38.3 °C) with gram-negative severe sepsis or septic shock at an 1111-bed academic medical center between January 2002 and February 2008. Patients were excluded if they had liver disease, acute brain injury, or allergy to acetaminophen. Generalized estimating equations were used to estimate the effect of clinical factors on treatment of patients with antipyretic medications. Although 76% of patients in this febrile cohort (n = 241) were prescribed an antipyretic agent, only 42% received antipyretic therapy; 95% of the doses were acetaminophen. Variables associated with antipyretic treatment were maximum body temperature (OR 2.11, 95% CI 1.53 to 2.89), time after sepsis diagnosis (OR 0.88, 95% CI 0.82 to 0.95), surgery during hospitalization (OR 0.49, 95% CI 0.31 to 0.80), death within 36 hours (OR 0.35, 95% CI 0.15 to 0.85), and mechanical ventilation (OR 0.58, 95% CI 0.34 to 0.98). Severity of illness factors, demographic factors, and patient treatment location did not predict who would receive antipyretic therapy. Most febrile episodes in patients with gram-negative severe sepsis or septic shock were not treated with antipyretic medications. Further studies are needed to demonstrate the effect of antipyretics on clinically relevant outcomes in severe sepsis and septic shock.

Piperacillin–Tazobactum Plus Amikacin Versus Ceftazidime Plus Amikacin as Empirical Therapy for Fever in Neutropenic Patients with Hematological Malignancies

Infections are one of the main cause of death in cancer patients particularly when granulocytopenia is present. A number of drugs have been used for the treatment of neutropenic patients with fever. Most published literature has shown piperacillin-tazobactum in combination with amikacin to be significantly more effective than ceftazidime plus amikacin in empirical treatment of febrile episodes in patients with neutropenia. In view of the reported literature we have tried this combination in our febrile neutropenic patients with haematological malignancies at PGIMS Rohtak. It was an open randomized trial. Patients were divided into two groups of 20 each. In the first group (group A) piperacillin-tazobactum (4+0.5 g 6 hourly) with single daily dose of amikacin 20mg/kg was given. In the second group (group B) ceftazidime 40mg/kg every 8 hourly with single daily dose of amikacin 20mg/kg was given. The most common site of infection was blood followed by urinary tract, respiratory tract and oral cavity. 13 (65%) patients in group A and 12 (60%) patient in group B showed clinical success. In our study however in our patients a better response was seen in patients with piperacillin-tazobactum+amikacin (65% vs. 60%). So it is recommended that piperacillin-tazobactum+amikacin should be given in febrile neutropenic patients with haematological malignancies.

Decreased incidence of febrile episodes with antibiotic prophylaxis in the treatment of decitabine for myelodysplastic syndrome

We analyzed the role of antibiotic prophylaxis during decitabine treatment for MDS. The primary endpoint was the incidence of febrile episodes. The total number of decitabine cycles given to 28 patients was 131, and febrile episodes occurred in 15 cycles (11.5%). Antibiotic prophylaxis was orally administered in 95 cycles (72.5%). Febrile episodes were significantly less frequent among patients who received antibiotic prophylaxis (7.4%) than in those without prophylaxis (22.2%) ( P = 0.017). In conclusion, antibiotic prophylaxis reduced the incidence of febrile episodes in patients who received decitabine treatment for MDS, especially at earlier cycles and in the presence of severe cytopenia.

Etanercept and anakinra can prolong febrile episodes in patients with hyperimmunoglobulin D and periodic fever syndrome

Hyperimmunoglobulin D and periodic fever syndrome (HIDS) is a rare, hereditary autoinflammatory condition, characterized by recurrent inflammatory episodes. There is no proven treatment for HIDS, but various drugs including, non-steroidal anti-inflammatory drugs, colchicine, steroids, statins and thalidomide have all been tried. Recently, some patients have demonstrated a good clinical response to either etanercept or anakinra. We report a case of a 10-year-old girl who experienced prolonged and severe inflammatory attacks, when she was treated with etanercept, and later with anakinra.

Bloodstream infections in cancer patients with febrile neutropenia

Bloodstream infections (bacteraemia) account for approximately 25–30% of febrile episodes in patients with febrile neutropenia (FN). In developed countries, Gram-positive pathogens predominate. Mortality is higher in Gram-negative bacteraemia. A recent study involving 2142 patients with FN was reviewed, including 168 patients with Gram-negative bacteraemia (mortality 18%), 283 patients with Gram-positive bacteraemia (mortality 5%) and 48 patients with polymicrobial bacteraemia (mortality 13%). Among patients who received prophylactic antibiotics, Gram-positive bacteraemia was far more common than Gram-negative bacteraemia (75% vs. 25%), compared with approximately 50% of each in patients without prophylactic antibiotics. Patients with a Multinational Association for Supportive Care in Cancer (MASCC) score <15 had a 36% mortality compared with 3% if the MASCC score was >21. The MASCC score may help risk stratification of patients with FN and bacteraemia, although these data require confirmation. In two series of patients from developing countries (Lebanon and Malaysia), Gram-negative bacteraemia was more common and mortality was higher. In developing countries, Gram-negative bacteraemia may be more frequent due to less use of prophylactic antibiotics and central lines. Laboratory markers may have predictive and prognostic value for bacteraemia in patients at the onset of FN, including mannose-binding lectin, interleukin (IL)-6, IL-8 and procalcitonin, but further studies are required before they can be recommended. New therapies are required to lower the mortality in patients with FN with a high risk for bacteraemia.

Change of procalcitonin predicts clinical outcome of febrile episodes in patients with hematological malignancies

Procalcitonin (PCT) was widely investigated in febrile neutropenia as an indirect marker of infection. Many institutions also use PCT as a tool to monitor the course of a febrile episode because increases in PCT values during the febrile episode were associated with development of complications. However, to date, no study systematically evaluated the accuracy of decreasing PCT values in predicting favorable outcomes of a febrile episode. The aim of this study was to evaluate the changes in PCT values after resolution of fever with regard to their predictive value of stable defervescence. PCT was studied prospectively in 94 febrile episodes of 35 patients with hematological malignancies. Sixty-seven episodes were associated with an increased level of PCT at the beginning. In these episodes, stable resolution of fever was significantly correlated with a decrease in PCT values. The best cut-off level to predict freedom from recurrence of fever for at least 5 days was <70% of the maximum PCT value on the second afebrile day. Out of 44 patient episodes with a subsequent decrease to <70%, only two patients had recurrent fever within the next 5 days, revealing a negative predictive value of 95%, p<0.001. Our study supports the value of PCT as a reliable tool to predict clinical outcome in febrile neutropenia.

Manejo del paciente con neutropenia de bajo riesgo y fiebre

For years the classical approach to febrile episodes in patients with chemotherapy-induced neutropenia consisted of hospital admission and intravenous administration of broad-spectrum antibiotics. However, since the end of the 1980s, it has been known that not all episodes of neutropenia carry the same risk of developing complications. These low risk febrile patients with neutropenia, that is, those without a clear focus of infection, without criteria for severe sepsis, and with an expected duration of neutropenia of less than 7-10 days, could benefit from outpatient oral antibiotic therapy or, failing this, from intravenous administration through a perfusion pump in the home. The present study analyzes the current situation of the new treatment modalities that aim to improve patients' quality of life and to optimize healthcare resources and costs.

Assessment of systemic inflammation markers to differentiate a stable from a deteriorating clinical course in patients with febrile neutropenia

In this study, we evaluated the predictive values of procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6) and serum amyloid A (SAA) for determining the clinical course in febrile neutropenic patients. Daily plasma analyses during the fever course were performed in 101 episodes with fever and chemotherapy-induced neutropenia (neutrophil count <0.5 x 10(9)/L). Procalcitonin (PCT) and IL-6 values were significantly higher in febrile episodes in patients who developed complications. Procalcitonin with a cut-off value of < or =0.4 ng/mL or IL-6 < or =50 pg/mL 3 d after fever onset indicated daily high negative predictive values (NPVs) (91-100%) for episodes with complications. No marker could predict deterioration; however, daily low plasma concentrations of PCT or IL-6 during the first 8 d of fever were found to be a good predictor of no subsequent complications in neutropenic patients and therefore to be a helpful tool for limiting anti-microbial therapy.

Empiric Antifungal Strategies for Acute Leukemia Patients

Fungal infections are significant pathogens in hematologic patients and remain an important cause of morbidity and mortality 1. Invasive fungal infections are difficult to diagnose and the practice of starting empirical antifungal therapy in persistently febrile and neutropenic patients apparently unresponsive to antibacterial therapy has become very frequent at cancer centers 2,3. Consequently efficacy assessment in these patients remains an important problem. Clinical endpoints used for the evaluation of efficacy include resolution of fever during neutropenia and survival. In addition, the endpoints of patients with severe (absolute neutrophil count 10 days), such as those with acute leukemia, may be poor compared to other hematological patients. Despite an expanded arsenal of antifungal drugs, amphotericin B remains the treatment of choice for empirical cases in severely immunocompromised patients, although adverse effects, particularly renal insufficiency, are limiting factors in achieving an effective dose. Lipid formulations such as AmBisome, the only true liposome, offer a better therapeutic index by circumscribing amphotericin B toxicity 4,5. In our study, performed between January 1999 and December 2002, we examined febrile episodes in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in order to evaluate the safety and efficacy of AmBisome in persistent fever of unknown origin (FUO) or in possible fungal infections, in patients intolerant or unresponsive to conventional amphotericin B. Antifungal prophylaxis was instituted at the onset of neutropenia (PMN <500/μl) using oral azoles (itraconazole 200 mg/day) and stopped when antiJournal of Chemotherapy Vol. 17 n. 1 (115-116) 2005

Improved Laboratory Diagnosis of Bacterial and Fungal Infections in Patients with Hematological Malignancies using PCR and Ribosomal RNA Sequence Analysis

During October 1999 to November 2000, 98 blood culture specimens from the same number of febrile episodes originating from 49 patients with hematological malignancies were examined for the presence of eubacteria and fungi based on 16S rRNA gene and the 5.8, 18 and 28S rRNA combined with in vitro PCR amplification and sequencing, in addition to conventional blood culture laboratory techniques. Nineteen of the samples were associated with positive blood cultures. Eubacterial (16S rRNA) PCR detected bacterial DNA in 26 febrile episodes, i.e. in an additional 7 febrile episodes than blood-culture alone. The species identified by partial 16S rRNA gene sequencing were as follows Staphylococcus spp (n = 6), Staphylococcus epidermidis (n = 5), Acinetobacter spp (n = 5), Escherichia coli (n = 2), Enterobacter agglomerans (n = 2), Campylobacter spp (n = 1), Citrobacter spp (n = 1), Corynebacterium spp (n = 1), Enterobacter faecium (n = 1), Ralstonia spp (n = 1), Acidovorax spp. (n = 1) and Stenotrophomonas maltophilia (n = 1). Gram-positive bacteria were found in 12/27 (44.6%) and gram-negative bacteria were found in 15/27 (55.6%). After optimization of a PCR-based fungal detection method, none of the febrile episodes were shown to be attributable to fungi. The results of this study suggest that fungi are not common causal agents of febrile episodes in patients with a hematological malignancy at this centre and that molecular techniques can augment cultural methods in the diagnosis of causal agents of bacteremia in patients, so that appropriate antibiotic regimens may be commenced in patients with culture-negative episodes of infection.

The effect of ketorolac on postoperative febrile episodes in patients after abdominal myomectomy

Objective: Our purpose was to determine whether administering the anti-inflammatory agent ketorolac after abdominal myomectomy reduces the incidence of febrile episodes. Study Design: This prospective, randomized, double-blinded, placebo-controlled clinical investigation compared administering ketorolac 15 mg intravenously every 6 hours beginning in the recovery room with saline solution administered in the same regimen in 122 patients undergoing abdominal myomectomy in a large, urban academic medical center. The primary outcome was fever >101.0°F in the postoperative period. Results were analyzed by χ2 analysis, independent samples t test, and logistic regression. Results: Data were analyzed on 112 patients, with 56 in the treatment group and 56 in the placebo group. After confounding factors were controlled with logistic regression, the data revealed a statistically significant reduction in febrile episodes in the ketorolac-treated group (27%) compared with the saline solution-treated group (41%) (P =.04). Conclusion: Treatment with ketorolac after abdominal myomectomy results in a statistically significant reduction in the rate of febrile episodes. (Am J Obstet Gynecol 2002;187:1450-5.)

Nonneutropenic febrile episodes associated with docetaxel-based chemotherapy in patients with solid tumors.

Docetaxel is associated with severe lymphopenia and increased incidence of nonneutropenic infection. This study investigated the incidence of nonneutropenic infections and/or febrile episodes in patients with solid tumors receiving frontline docetaxel-based chemotherapy. Chemotherapy-naive patients with solid tumors treated with docetaxel-based chemotherapy were studied prospectively for the development of nonneutropenic infections. During a 2-year period, 680 cancer patients enrolled in 24 protocols received 2867 cycles of docetaxel-containing chemotherapy. Fifty-three patients (7.8%) developed nonneutropenic infections and/or febrile episodes. The most common of these were pulmonary infections (n = 25), Pneumocystis carinii interstitial pneumonias (n = 5), and candidal (n =11), herpetic (n =4), and cytomegaloviral (n =3) infections. Thirty-six patients (68%) had severe lymphopenia (< 900 cells per deciliter) and 49 (92%) had less than 400 CD4(+) cells per deciliter. Patients with a low CD4(+) cell count (</= 200 cells per deciliter) had a significantly higher probability to develop opportunistic than common infections (P = 0.002). The incidence of nonneutropenic infections and/or febrile episodes was significantly higher in patients treated with docetaxel/gemcitabine (18.3%; P = 0.0001) and docetaxel/CDDP (11.7%; P = 0.012) than in those treated with docetaxel alone (3.6%). Conversely, 175 patients who received 752 cycles of chemotherapy with paclitaxel-containing regimens and 410 patients who received 2174 cycles with nontaxane-based regimens developed 6 (3.4%; p=0.042) and 12 (3%; p=0.001) nonneutropenic infections, respectively. Less than 10% of the patients of the two latter groups were lymphopenic. The risk of nonneutropenic infection in patients receiving docetaxel-based chemotherapy was 2.38 and 2.8 times higher than in patients receiving paclitaxel and nontaxane-based chemotherapy, respectively. Patients treated with docetaxel-based chemotherapy are at increased risk of developing nonneutropenic infections. This may be related, at least partly, to severe postchemotherapy CD4(+) lymphopenia.