Mucormycosis treatment: Recommendations, latest advances, and perspectives.

Mucormycosis are life-threatening fungal infections especially affecting immunocompromised or diabetic patients. Despite treatment, mortality remains high (from 32 to 70% according to organ involvement). This review provides an update on mucormycosis management. The latest recommendations strongly recommend as first-line therapy the use of liposomal amphotericin B (≥5mg/kg) combined with surgery whenever possible. Isavuconazole and intravenous or delayed-release tablet forms of posaconazole have remained second-line. Many molecules are currently in development to fight against invasive fungal diseases but few have demonstrated efficacy against Mucorales. Despite in vitro efficacy, combinations of treatment have failed to demonstrate superiority versus monotherapy. Adjuvant therapies are particularly complex to evaluate without prospective randomized controlled studies, which are complex to perform due to low incidence rate and high mortality of mucormycosis. Perspectives are nonetheless encouraging. New approaches assessing relationships between host, fungi, and antifungal drugs, and new routes of administration such as aerosols could improve mucormycosis treatment.

Post-traumatic Curvularia sp. arthritis in an immunocompetent adult.

A 44-year-old woman, victim of a road accident in Mali was diagnosed with left knee arthritis. Joint effusion aspiration and subcutaneous surgical biopsies were positive for a melanized asexual ascomycete. Using microscopy and molecular biology, the fungus was identified as Curvularia sp. In vitro antifungal susceptibility was determined by the EUCAST broth microdilution reference technique and by E-test. The patient was treated with liposomal amphotericin B before posaconazole relay. Mycological samples obtained 10 days after starting the antifungal therapy by liposomal amphotericin B were negative in culture. Curvularia spp. are environmental fungi which can under certain conditions be pathogenic for humans.

Community-acquired pneumonia in the emergency department: an algorithm to facilitate diagnosis and guide chest CT scan indication.

OBJECTIVE: The aim was to create and validate a community-acquired pneumonia (CAP) diagnostic algorithm to facilitate diagnosis and guide chest computed tomography (CT) scan indication in patients with CAP suspicion in Emergency Departments (ED). METHODS: We performed an analysis of CAP suspected patients enrolled in the ESCAPED study who had undergone chest CT scan and detection of respiratory pathogens through nasopharyngeal PCRs. An adjudication committee assigned the final CAP probability (reference standard). Variables associated with confirmed CAP were used to create weighted CAP diagnostic scores. We estimated the score values for which CT scans helped correctly identify CAP, therefore creating a CAP diagnosis algorithm. Algorithms were externally validated in an independent cohort of 200 patients consecutively admitted in a Swiss hospital for CAP suspicion. RESULTS: Among the 319 patients included, 51% (163/319) were classified as confirmed CAP and 49% (156/319) as excluded CAP. Cough (weight = 1), chest pain (1), fever (1), positive PCR (except for rhinovirus) (1), C-reactive protein ≥50 mg/L (2) and chest X-ray parenchymal infiltrate (2) were associated with CAP. Patients with a score below 3 had a low probability of CAP (17%, 14/84), whereas those above 5 had a high probability (88%, 51/58). The algorithm (score calculation + CT scan in patients with score between 3 and 5) showed sensitivity 73% (95% CI 66-80), specificity 89% (95% CI 83-94), positive predictive value (PPV) 88% (95% CI 81-93), negative predictive value (NPV) 76% (95% CI 69-82) and area under the curve (AUC) 0.81 (95% CI 0.77-0.85). The algorithm displayed similar performance in the validation cohort (sensitivity 88% (95% CI 81-92), specificity 72% (95% CI 60-81), PPV 86% (95% CI 79-91), NPV 75% (95% CI 63-84) and AUC 0.80 (95% CI 0.73-0.87). CONCLUSION: Our CAP diagnostic algorithm may help reduce CAP misdiagnosis and optimize the use of chest CT scan.

Observational study of vaccination in cancer patients: How can vaccine coverage be improved?

BACKGROUND: Chemotherapy increases the risk of infections, often severe, and some of them are vaccine-preventable infections. We aimed to assess vaccination coverage and associated factors in oncology and hematology patients. METHODS: Consecutive adult patients followed in a French university hospital for hematological malignancy or solid cancer voluntarily completed an anonymous questionnaire in September and October 2016. It included questions on underlying disease, chemotherapy, flu, and pneumococcal vaccination uptakes, and attitudes toward vaccination. Factors associated with vaccination uptake were assessed by multivariate logistic regression. RESULTS: The response rate was 41.9% (N=671) among 1,600 questionnaires distributed; 232 patients had underlying hematological malignancy and 439 had solid cancer. Half of the patients were aged over 65 years. Chemotherapy was ongoing or discontinued for less than one year in 74.7% of patients. In patients aged <65 years undergoing chemotherapy, flu vaccination rate was 19.9% whereas patients aged >65 years had coverage of 47%. Pneumococcal vaccine uptake was 7.3%. However, 64.7% of patients were favorable to vaccination. Vaccine uptake was associated with age >65 years (OR 4.5 [2.9-7.0]), information about vaccination delivered by the family physician (OR 12.9 [5.5-30.1]), follow-up in hematology unit (OR 2.0 [1.3-3.1]), and positive opinion about vaccination (OR 2.0 [1.3-3.1]). CONCLUSION: Despite specific recommendations regarding immunocompromised patients, anti-pneumococcal and flu vaccinations were rarely conducted, even in elderly patients. Targeted information campaigns to family physicians, oncologists, and patients should be implemented to improve vaccine coverage in patients with underlying malignancies.

Vaccination of cancer patients treated with chemotherapy: A survey among general practitioners.

OBJECTIVES: Despite specific recommendations issued by the French Public Health Council (Haut Conseil de Santé Publique), the vaccination coverage of patients with cancer or malignant blood disease remains insufficient. The aim of this study was to assess the vaccination of chemotherapy patients by their general practitioner (GP). METHODS: A survey was conducted between March and July 2017 in 4 French departments to describe the immunization practices of GPs for their chemotherapy patients and provide solutions to help to increase the vaccination rate. RESULTS: Of the 1610 GPs who received the questionnaire, 287 (17.8%) returned a usable form; 92.6% were globally pro-vaccine. One third of GPs (37.3%) declared that they vaccinated all their chemotherapy patients. The GPs (n=180) who never or only sometimes vaccinated their chemotherapy patients mainly voiced concerns about not being properly trained (45.6%) and the lack of easily available information on vaccination (35.0%). Three-quarters (n=212; 74%) of the GPs wanted to improve their level of medical knowledge via continuing education (52.4%) or by reading guidelines available on-line (39.6%). GPs suggested that a specific vaccination schedule be included in the letter they receive from the cancer specialist (72.8%) and that patient awareness be increased (50.5%). CONCLUSIONS: GPs are in favor of the vaccination of cancer patients. The main obstacles stated are the lack of education and the lack of easily available information. Vaccination coverage could be increased by improving the doctor-to-doctor relation between GPs and cancer specialists.

Mycobacterium avium complex disseminated infection in a kidney transplant recipient.

Mycobacterium avium-intracellulare complex (MAC) infections are well known in immunocompromised patients, notably in human immunodeficiency virus infection, but remain scarcely described in kidney transplantation. Moreover, cutaneous involvement in this infection is very unusual. We describe here a disseminated infection caused by MAC in a kidney transplant recipient revealed by cutaneous lesions. This case highlights the need for an exhaustive, iterative microbiologic workup in the context of an atypical disease presentation in a renal transplant patient, regardless of the degree of immunosuppression.

Dimorphic fungal osteoarticular infections.

The objective of this investigation was to review the clinical manifestations, management, and outcome of osteoarticular infections caused by dimorphic fungi. We exhaustively reviewed reports of bone and joint infections caused by dimorphic fungi published between 1970 and 2012. Underlying conditions, microbiological features, histological characteristics, clinical manifestations, antifungal therapy, and outcome were analyzed in 222 evaluable cases. Among 222 proven cases (median age 41 years [interquartile range (IQR) 26-57]), 73 % had no predisposing condition. Histopathology performed in 128 (57 %) cases and culture in 170 confirmed diagnosis in 63 % and 98 % of the cases, respectively. Diagnosis was obtained from an extra-osteoarticular site in 16 cases. The median diagnostic time was 175 days (IQR 60-365). Sporothrix schenckii was the most frequent pathogen (n = 84), followed by Coccidioides immitis (n = 47), Blastomyces dermatitidis (n = 44), Histoplasma capsulatum (n = 18), Paracoccidioides brasiliensis (n = 16), and Penicillium marneffei (n = 13). Arthritis occurred in 87 (58 %) cases and osteomyelitis in 64 (42 %), including 19 vertebral osteomyelitis. Dissemination was reported in 123 (55 %) cases. Systemic antifungal agents were used in 216 (97 %) patients and in combination with surgery in 129 (60 %). Following the Infectious Diseases Society of America (IDSA) guidelines, a successful initial medical strategy was observed in 97/116 (84 %) evaluable cases. The overall mortality was 6 %, and was highest for P. marneffei (38.5 %). This study demonstrates that dimorphic osteoarticular infections have distinctive clinical presentations, occur predominantly in apparently immunocompetent patients, develop often during disseminated disease, and may require surgical intervention.

[Recommendations for the use of diagnostic testing in low respiratory infections in children older than three months]. / Recommandations sur l'utilisation des nouveaux outils diagnostiques étiologiques des infections respiratoires basses de l'enfant de plus de trois mois.

Recommendations for the use of diagnostic testing in low respiratory infection in children older than 3 months were produced by the Groupe de Recherche sur les Avancées en Pneumo-Pédiatrie (GRAPP) under the auspices of the French Paediatric Pulmonology and Allergology Society (SP(2)A). The Haute Autorité de santé (HAS) methodology, based on formalized consensus, was used. A first panel of experts analyzed the English and French literature to provide a second panel of experts with recommendations to validate. Only the recommendations are presented here, but the full text is available on the SP(2)A website.

Lower Respiratory Tract Infection in a Renal Transplant Recipient: Do not Forget Metapneumovirus.

Human metapneumovirus (hMPV) is emerging as a cause of a severe respiratory tract infection in immunocompromised patients. hMPV pneumonia has only been seldom reported in nonpulmonary solid organ transplanted patients, such as renal transplant recipients. We report here a case of a 39-year-old patient presenting with fever, cough, and interstitial opacities on CT scan diagnosed as a nonsevere hMPV pneumonia 11 years after a renal transplantation. Infection resolved spontaneously. Differential diagnosis with Pneumocystis pneumonia was discussed. We review the medical literature and discuss clinical presentation and detection methods that can be proposed in solid organ transplant recipients.

Diabetes and mucormycosis: a complex interplay.

Mucormycosis is a life-threatening invasive fungal infection that arises particularly in diabetic patients with or without other underlying conditions such as haematological malignancies or the need for solid-organ transplantation. Rhino-orbito-cerebral involvement is the primary site of mucormycosis, but the paucity of signs may be a cause of delayed diagnosis. Thus, any case of documented non-bacteriological sinusitis in diabetic patients, even without ketoacidosis, should prompt suspicion of a mucormycosis diagnosis. To optimalize information for clinicians in charge of diabetic patients, this extensive review of the literature was carried out to provide an overview of mucormycosis specificities, epidemiology and pathophysiology in the setting of diabetes.

New insights into hepatosplenic candidosis, a manifestation of chronic disseminated candidosis.

Chronic disseminated candidosis, often referred to as hepatosplenic candidosis (HSC), is an infection due to Candida spp. that mainly involves the liver and spleen. HSC occurs mostly in patients after profound and prolonged neutropenia, which is more often seen in patients with acute haematological malignancies. The incidence of HSC ranges from 3% to 29% in patients suffering from Acute Leukaemia. However, it is now seen less frequently with the widespread use of antifungal agents as prophylaxis or as preemptive therapy. Early and adequate diagnosis and treatment of HSC are crucial, as treatment delays can negatively affect the prognosis of the underlying condition. The pathogenesis is not well understood, but it is believed that it may be due to an unbalanced adaptive immune response that leads to an exacerbated inflammatory reaction, resulting in an Immune Reconstitution Inflammatory Syndrome. In this context, new therapeutic approaches such as the use of adjuvant high-dose corticosteroids have been shown beneficial. This article will focus on the clinical, diagnostic and therapeutic aspects of HSC and provide an accurate review of recent pathophysiological data.

Home-based pulmonary rehabilitation in idiopathic pulmonary fibrosis.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a severe chronic lung disease. Pulmonary rehabilitation could improve the quality of life of patients with this condition. METHODS: We prospectively evaluated the impact of an 8-week home-based pulmonary rehabilitation programme over 10 months in stable patients suffering from IPF. Exercise capacity, pulmonary function, dyspnoea and quality of life were analyzed before and after the rehabilitation programme. RESULTS: Seventeen patients were included and 13 completed the study. Mean functional vital capacity (FVC) was 2.15±0.79L and mean diffusing capacity for carbon monoxide (DLCO) was 7.81±3.99mL/min/mmHg. Six patients were treated with low dose oral steroids (20mg/day of prednisone) with or without immunosuppressive treatments; six were taking part in therapeutic trials. Mean endurance time (7.4±9.1 min vs. 14.1±12.1 min; P=0.01), number of steps per minute on a stepper (322±97 vs. 456±163; P=0.026), six-minute walk distance relative to heart rate (HR) (11±6 vs. 17±12; P=0.006), exercise dyspnoea (P=0.026), sensation of physical limitation on the SF-36 (25%±26 vs. 49%±38; P=0.047) and four out of seven visual analogue scales were significantly improved after rehabilitation. In contrast, no significant difference was observed in resting pulmonary function or in other items on quality of life questionnaires. CONCLUSION: A home-based programme of pulmonary rehabilitation is feasible in IPF patients. It significantly improved endurance parameters and physical limitation in this patient group without changing pulmonary function.

[Home-based pulmonary rehabilitation in idiopathic pulmonary fibrosis]. / Réhabilitation respiratoire à domicile au cours de la fibrose pulmonaire idiopathique.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a severe chronic lung disease. Pulmonary rehabilitation could improve the quality of life of patients with this condition. METHODS: We prospectively evaluated the impact of an 8 week home-based pulmonary rehabilitation program over 10 months in stable patients suffering from IPF. Exercise capacity, pulmonary function, dyspnea and quality of life were analyzed before and after the rehabilitation program. RESULTS: 17 patients were included and 13 completed the study. Mean FVC was 2.15+/-0.79 L and mean DLCO was 7.81+/-3.99 ml/min/mmHg. Six patients were treated with low dose oral steroids ($20 mg/day of prednisone) with or without immunosuppressive treatments; 6 were taking part in therapeutic trials. Mean endurance time (7.4+/-9.1 min vs 14.1+/-12.1 min; p<0,01), number of beats per minute on a stepper (322+/-97 vs 456+/-163; p=0.026), 6 min walking distance to heart rate ratio (11+/-6 vs 17+/-12; p=0.006), exercise dyspnea (p=0.026), sensation of physical limitation at the SF-36 (25%+/-26 vs 49%+/-38; p=0.047) and 4 out of 7 visual analog scales were significantly improved after rehabilitation. In contrast, no significant difference was observed in resting pulmonary function or in other items of quality of life questionnaires CONCLUSION: A home-based program of pulmonary rehabilitation is feasible in IPF patients. It significantly improves endurance parameters and physical limitation in this patient group without changing pulmonary function.

[Ventilator-associated pneumonia and chronic obstructive pulmonary disease]. / Pneumonies acquises sous ventilation mécanique invasive et bronchopneumopathie chronique obstructive.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a common pulmonary and systemic inflammatory disease. Patients with COPD frequently require mechanical ventilation for acute exacerbations. BACKGROUND: The incidence of ventilator-associated pneumonia (VAP) in COPD patients varies from 6 to 33%. Tracheo-bronchial colonisation, local and systemic immuno-supression and frequent antibiotic treatment are factors predisposing to VAP in these patients. Gram negative bacilli are commonly isolated in COPD patients with VAP. Pseudomonas aeruginosa reported to be the most common. The diagnosis of VAP can be difficult in patients with COPD because of the low sensitivity of the portable chest radiograph. VAP is associated with higher mortality rates, longer duration of mechanical ventilation and ITU stay in patients with COPD. Initial antibiotic treatment should be based on recent guidelines and should take account of frequent prior hospitalisation and antibiotic treatment which are well known risk factors for multidrug resistant bacteria. Preventative measures recommended for the general population should be applied to COPD patients. In the absence of contraindications the use of non-invasive ventilation is recommended to reduce the risk of VAP. VIEWPOINT AND CONCLUSION: Future studies should better determine the incidence of VAP in COPD, improve the diagnostic approach and determine the effects of treating malnutrition, chronic tracheobronchial colonisation and limiting antibiotic and corticosteroid treatment on the incidence of VAP.