Prospective evaluation of Coris Influ-A&B Respi-Strip and of BinaxNOW Influenza A&B assay against viral culture and real-time PCR assay for detection of 2009 pandemic influenza A/H1N1v in Belgian patients.

PURPOSE: Evaluation of the performance of two rapid (15') antigen detection tests (RAT), BinaxNOW Influenza A&B and Coris Influ-A&B Respi-Strip for the detection of A(H1N1)v2009. STUDY DESIGN: Between July 2009 and November 2009, 4105 respiratory specimens from patients with influenza-like illness attending seven public hospitals in Brussels were prospectively examined by two immunochromatographic RAT, followed by viral culture and/or specific real-time RT-PCR. RESULTS: Samples consisted predominantly of nasopharyngeal aspirates (NPA-41%), nasopharyngeal (NPS-37%) and throat swabs (TS-14%). The sensitivity and specificity of Coris RAT and BinaxNOW RAT were 36.6% and 99.7%, and 47% and 98.7% respectively compared to culture; and 33.7% and 99.6%; and 46.5% and 98.8% compared to RT-PCR. Significant differences in sensitivity could be observed when splitting up the samples by sample type and patient's age. NPA gave by far the highest sensitivities: 51.1- 62% for Coris compared to culture and 62.6-78.4% for BinaxNOW. Sensitivities in paediatric NPS varied less between different hospitals (34-41.9%) being still much higher than in adult NPS (11.4-20%). TS resulted in unsatisfactory results: 13% sensitivity in children and 10.5% in adults. CONCLUSIONS: Both RAT showed excellent specificities, but insufficient sensitivities. Consequently, negative results should be confirmed. NPA are clearly superior to NPS orTS, and they stay the sample of choice for viral diagnosis.

An illustrated case of altered cellular immunity after autologous stem cell transplantation.

We report an unusual association of T-cell lymphoma, autologous stem cell transplantation and Progressive Multifocal Leukoencephalopathy.

Piperacillin-tazobactam monotherapy in high-risk febrile and neutropenic cancer patients.

Combination therapy with a beta-lactam plus an aminoglycoside has been the standard approach for treating febrile neutropenia for many years. More recently, beta-lactam monotherapy has also been shown to be a reliable and safe approach. In the present study, 763 eligible patients with fever and neutropenia received piperacillin-tazobactam monotherapy. On day 3, according to the study protocol, 165 patients with persistent fever who fulfilled the study entry criteria were randomised to receive vancomycin or a placebo. The success rate was 51% in the intention-to-treat analysis and 62% in the per-protocol analysis. The overall mortality rate was 8% (58/763), with only 18 (2.4%) deaths attributed to the initial or subsequent infection. Randomisation had no influence on the study endpoints. The adverse event rate was evaluated only in the patient population not included in the randomised part of the study. Among these patients, adverse events probably or definitely related to piperacillin-tazobactam therapy were uncommon, confirming the favourable safety profile of piperacillin-tazobactam. It was concluded that piperacillin-tazobactam could be considered as monotherapy for patients with high-risk febrile neutropenia.

Vancomycin versus placebo for treating persistent fever in patients with neutropenic cancer receiving piperacillin-tazobactam monotherapy.

This prospective, double-blind trial assessed whether the addition of a glycopeptide would be able to reduce the time to defervescence in neutropenic patients with cancer who had persistent fever 48-60 h after the initiation of empirical piperacillin-tazobactam monotherapy. Of 763 eligible patients, 165 with persistent fever were randomized to receive piperacillin-tazobactam therapy plus either vancomycin therapy or placebo. Defervescence was observed in 82 (95%) of 86 patients in the vancomycin group and in 73 (92%) of 79 patients in the placebo group (P=.52). The distributions of the time to defervescence were not statistically significant between the 2 groups (estimated hazard ratio, 1.03; 95% confidence interval, 0.75-1.43; P=.75). The number of additional episodes of gram-positive bacteremia and the percentage of patients for whom amphotericin B was empirically added to their therapy regimen were also similar in both groups. This study failed to demonstrate that the empirical addition of vancomycin therapy to the treatment regimen is of benefit to persistently febrile neutropenic patients with cancer.

Disseminated infection due to Cylindrocarpon (Fusarium) lichenicola in a neutropenic patient with acute leukaemia: report of a case and review of the literature.

Described here is an unusual case of disseminated Cylindrocarpon lichenicola (Fusarium lichenicola) infection originating from a toenail lesion of a neutropenic woman with cellulitis of the foot and underlying acute leukaemia. A computed tomography scan of the chest showed multiple, ill-defined, nodular infiltrates with alveolar consolidation. The fungus was isolated from both the nail and the skin of the infected toe. Susceptibility testing revealed low minimum inhibitory concentrations for amphotericin B (0.78 micro g/ml) and voriconazole (1.56 micro g/ml) and high minimum inhibitory concentrations (>100 micro g/ml) for fluconazole, ketoconazole and itraconazole. The infection resolved after treatment with a total dose of 1 g of amphotericin B followed by oral itraconazole and bone marrow regeneration.

Vibrio cholerae bacteremia in a neutropenic patient with non-small-cell lung carcinoma.

Vibrio cholerae was isolated from the blood cultures of a neutropenic patient treated with chemotherapy for non-small-cell lung cancer. Attempts to isolate Vibrio spp. from a rectal swab and stool were unsuccessful. Piperacillin/tazobactam treatment resulted in eradication of the microorganism from the patient's blood. Although Vibrio spp. have occasionally been the source of infection in immunocompromised patients, this report describes the first case of non-0:1 Vibrio cholerae bacteremia in a neutropenic patient with a solid tumour.

Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus.

During the past several decades, there has been a steady increase in the frequency of opportunistic invasive fungal infections (IFIs) in immunocompromised patients. However, there is substantial controversy concerning optimal diagnostic criteria for these IFIs. Therefore, members of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group formed a consensus committee to develop standard definitions for IFIs for clinical research. On the basis of a review of literature and an international consensus, a set of research-oriented definitions for the IFIs most often seen and studied in immunocompromised patients with cancer is proposed. Three levels of probability are proposed: "proven," "probable," and "possible." The definitions are intended for use in the context of clinical and/or epidemiological research, not for clinical decision making.

Outpatient and home parenteral antibiotic therapy (OHPAT) in low-risk febrile neutropenia: consensus statement of a Belgian panel.

Febrile neutropenia requires adequate antibiotic treatment. A subgroup of patients are only at low risk for complications and could be treated at home/as outpatients (OHPAT) after a short initial admission for work up. This position paper by a Belgian panel of experts presents criteria defining low-risk in febrile neutropenia, gives an overview of the existing experience and examines the present obstacles to a more widespread use of OHPAT in this country.

[Infection and cancer: general information and specific questions]. / Infection et cancer: notions générales et questions actuelles.

The main risk factors of infectious complications in cancer patients result from immune deficiency more or less related to cancer. Prognosis is related to the type and grade of the underlying disease. Prospective studies should be conducted to update data on the frequency of infections, morbidity and mortality (expert agreement). Prospective studies are needed to follow the epidemiology in cancer patients, particularly in neutropenic patients (expert agreement). Prospective studies should be conducted to determine prognosis factors allowing precise recognition of "low-risk" neutropenic patients with fever who could benefit from home care (expert agreement). When infection is suspected, the first criterion determining the therapeutic attitude concern signs of gravity requiring emergency care (septic shock). Beyond this situation, the first criterion determining the therapeutic attitude is the severity of the neutropenia. Microbial diagnosis is essential for initiating and later adapting anti-infectious treatment as well as for assessing efficacy.

[Standards, options and recommendations for good practice in hemoculture in cancerology]. / Standards, Options et Recommandations pour une bonne pratique des hémocultures en cancérologie.

Excepting emergency and aplasia: two to three blood samples should be draw for culture an hour apart within a 24 period (standard). For emergency or aplasia: two to three blood samples should be drawn for culture before initiating early antibiotic therapy. The delay between samples drawn from different sites should be less than one hour (standard). For patients on antibiotics: four to six blood samples should be drawn for culture within 48 hours, outside ongoing antibiotic administration. If the patient is given corticosteroids, it is recommended to draw two or three blood samples in case of deterioration (agreement of the experts). Rigorous aseptic techniques must be used (standard). Culture media are chosen according to the institution's microbial ecology (standard). The volume of blood drawn should be adapted to the system used (standard). Culture positivity is determined at 24 to 48 hours.

Febrile neutropenia in children.

Fever is frequent in neutropenic patients and often related to infection. Two major concepts, have contributed to the marked mortality decrease of those patients by the end of the 1960s: firstly, the duration and severity of neutropenia were the most important variables linked to infection and secondly, prompt administration of broad-spectrum antimicrobials empirically, was life-saving. At the same time it was universally admitted that a careful daily examination of all portals of entry for micro-organisms was mandatory and that laboratory and imaging investigations were needed at regular intervals, keeping constantly in mind the individual type and stage of immunosuppression. Through many studies, paediatricians contributed markedly in standardisation of management of febrile neutropenic patients. Neutropenic patients are not equally prone to infections, partly due to the underlying cancer, chemotherapy and co-morbidity factors. Neutropenic children are not only vulnerable to bacteria, fungi and viruses commonly encountered in adults, but also to common viruses and bacteria. Very few studies included a viral work-up. Epidemiological new trends are observed: Gram-positive bacteria and fungi are on the rise. Simplifying and shortening antibiotic regimens were made possible because new potent antibiotics were launched. Since the mid-1980s, many paediatric centres commonly discharge patients before complete bone marrow recovery, provided that patients meet certain low-risk criteria and do not exhibit any clinical or biological evidence of bacterial infection. However, a few prospective randomised studies have been conducted for assessing the safety of early antibiotics discontinuation and safe early discharge. The choice of oral agents up to now was complicated by the reluctance using fluoroquinolones in children. New challenges are numerous in terms of diagnostic tools, detection of epidemiological trends and emerging pathogens, identification and control of nosocomial threats including drug resistance, assessment of the real impact of prophylaxis, evaluation of new agents, the need for more accurate risk scoring systems, outpatient management and the necessity for an optimal use of resources.

[Standards, Options and Recommendations (SOR) for the surveillance and the prevention of cross infections in oncology. Fédération Nationale des Centres de Lutte Contre le Cancer]. / Standards, Options et Recommandations (SOR) pour la surveillance et la prévention des infections nosocomiales en cancérologie.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration 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 outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the prevention and the surveillance of cross infection in oncology. METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 106 independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS: 1) Criteria of infection status and nosocomiality defined by the Centers for Infectious Diseases (CDC) and Prevention and the Superior Council of Public Hygiene (CSHPF) are not adapted and have to be redefined in oncology. 2) The epidemiology of nosocomial infections in oncology is not well known but their incidence seems to be higher. Numerous risk factors of cross infections coexist in cancer patients, among which the duration and depth of neutropenia. 3) Surveillance and prevention of cross infection are compulsory and were taken into account in the accreditation of hospitals. Obligation is expressed in terms of means and results. 4) The objectives of the cross infection surveillance are to detect major problems and critic situations, to guide probabilistic antibiotic therapy and to assess the effectiveness of the infections control. The surveillance means consist in prevalence and incidence survey, punctually and continuously conducted. 5) The three specific behaviors to be adopted to prevent cross infections are to control: all the patients, infected patients carrying multiresistant bacteria, immunodepressed patients. 6) Standards of care have to be applied to a/l patients with cancer. 7) It is necessary to add particular septic cares for the patients infected with micro-organisms indicated on reference lists or carrying multiresistant bacteria. 8) The only objective of the protective isolation of immunodepressed cancer patients is to reduce the cross infection. There is no standard behavior for the indications and the modalities of protective isolation. The prevention behaviors to be taken are defined by expert agreements.

[Standards, Options, and Recommendations for the management of brief neutropenias. Fedération Nationale des Centres de Lutte Contre le Cancer]. / Standards, Options et Recommandations pour la prise en charge des neutropénies courtes.

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.

Imipenem versus targeted therapy in cancer patients.

In many instances, broad-spectrum antibiotics are initiated empirically in febrile cancer patients and continued for the whole duration of therapy. An alternative is to narrow the spectrum whenever the offending pathogen is identified. This study is aimed at comparing these two options. Non-neutropenic cancer patients with severe infections received empiric imipenem. After 72 h, those with microbiologically documented infection were randomized either to continue imipenem or to receive a targeted therapy. After 72 h of imipenem 76.1% were improved. After randomization, a higher efficacy was observed with imipenem (88.5 vs. 72.1%: P = 0.025). Bacterial and fungal superinfections were comparable. Costs were lower for targeted therapy in gram-positive infection and higher in gram-negative infection.

A Phase I Determination of Azithromycin in Plasma during a 6-Week Period in Normal Volunteers after a Standard Dose of 500mg Once Daily for 3 Days.

OBJECTIVES: The pharmacokinetics of azithromycin were evaluated in 12 healthy volunteers. METHODS: This was an open study in 12 healthy male subjects. Participants received a single dose of 2 x 250mg azithromycin (two azithromycin capsules) administered orally in the fasting state with 240ml water on three consecutive days. RESULTS: After oral intake of two capsules of 250mg azithromycin over three consecutive days (the normal treatment regimen in adults), azithromycin was present in measurable levels in plasma (>5 microg/L) for 7 to 17 days after the beginning of treatment. The apparent elimination half-life was very long (observed range: 49 to 108 hours, i.e. about 2 to 4.5 days). From the results in plasma, one can extrapolate that the azithromycin concentration would remain above 1 microg/L (corresponding to concentrations in tissues above 0.1 mg/L) for up to 15 to 30 days following treatment. The elimination half-life of azithromycin (average of 76 hours) was in agreement with values of depletion rates in tissues corresponding to a half-life of 60 to 72 hours. CONCLUSION: In conclusion, the utility of the long exposure of patients with benign respiratory infections to azithromycin and to subinhibitory concentrations of azithromycin should be questioned.

Epidemiology of infections in the adult medical intensive care unit of a cancer hospital.

A prospective collection of positive antimicrobial cultures was performed over 12 consecutive months in the medical intensive care unit of a cancer hospital. In all, 144 infections and 163 pathogens were documented during 87 of the 528 admissions. Lung, urinary, ENT (ear, nose and throat) infections and bacteraemia were the most frequently documented. Staphylococcus species, Streptococcus species, Escherichia coli, Klebsiella species and Pseudomonas species were the most common pathogens. Gram-positive strains were observed predominantly during monomicrobial bacteraemia (48.9%). Methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE) were found in 58% and 92% of the isolated strains respectively. No particular outbreak was identified. A further prospective study will be necessary to evaluate the impact of the antibiotic use on the selection of resistant strains in our ICU.

Monotherapy with meropenem versus combination therapy with ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto Infection Program.

Combinations of beta-lactams plus aminoglycosides have been standard therapy for suspected infections in granulocytopenic cancer patients, especially those with profound long-lasting granulocytopenia. With the advent of new broad-spectrum bactericidal antibiotics such as extended-spectrum cephalosporins or carbapenems, the need to combine beta-lactams with aminoglycosides became more controversial. The objective of this prospective randomized multicenter study was to compare the efficacy, safety, and tolerance of meropenem monotherapy with those of the combination of ceftazidime plus amikacin for the empirical treatment of fever in granulocytopenic cancer patients. Of 1,034 randomized patients, 958 were assessable in the intent-to-treat analysis for response to antibacterial therapy, including 483 in the meropenem group and 475 in the ceftazidime-plus-amikacin group. The median durations of neutropenia were 16 and 17 days, respectively. A successful outcome was reported in 270 of 483 (56%) patients treated with monotherapy compared with 245 of 475 (52%) patients treated with the combination group (P = 0.20). The success rates in the monotherapy group and the combination group were similar by type of infection (single gram-negative bacteremia, single gram-positive bacteremia, clinically documented infection, and possible infection). The occurrence of further infections assessed in patients for whom the allocated regimen was not modified did not differ between the two groups (12% in both groups). Mortality due to the presenting infection or further infection was relatively low (8 patients treated with the monotherapy compared with 13 patients treated with the combination). A total of 1,027 patients were evaluable for adverse events; the proportion of those who developed adverse effects was similar between the two groups (29% in both groups), and only 19 (4%) patients in the monotherapy group and 31 (6%) in the combination group experienced an adverse event related or probably related to the study drug. Allergic reactions were the only reason for stopping the protocol antibiotic(s) (3 and 5 patients, respectively). This study confirms that monotherapy with meropenem is as effective as the combination of ceftazidime plus amikacin for the empiric treatment of fever in persistently granulocytopenic cancer patients, and both regimens were well tolerated.