Clin Microbiol Infect 2012; 18 (Suppl. 7): 38–52
Invasive candidiasis (IC) is a relatively common syndrome in neonates and children and is associated with significant morbidity and mortality. These ...guidelines provide recommendations for the prevention and treatment of IC in neonates and children. Appropriate agents for the prevention of IC in neonates at high risk include fluconazole (A‐I), nystatin (B‐II) or lactoferrin ± Lactobacillus (B‐II). The treatment of IC in neonates is complicated by the high likelihood of disseminated disease, including the possibility of infection within the central nervous system. Amphotericin B deoxycholate (B‐II), liposomal amphotericin B (B‐II), amphotericin B lipid complex (ABLC) (C‐II), fluconazole (B‐II), micafungin (B‐II) and caspofungin (C‐II) can all be potentially used. Recommendations for the prevention of IC in children are largely extrapolated from studies performed in adults with concomitant pharmacokinetic data and models in children. For allogeneic HSCT recipients, fluconazole (A‐I), voriconazole (A‐I), micafungin (A‐I), itraconazole (B‐II) and posaconazole (B‐II) can all be used. Similar recommendations are made for the prevention of IC in children in other risk groups. With several exceptions, recommendations for the treatment of IC in children are extrapolated from adult studies, with concomitant pharmacokinetic studies. Amphotericin B deoxycholate (C‐I), liposomal amphotericin B (A‐I), ABLC (B‐II), micafungin (A‐I), caspofungin (A‐I), anidulafungin (B‐II), fluconazole (B‐I) and voriconazole (B‐I) can all be used.
The aetiological agents of many invasive fungal infections are saprobes and opportunistic pathogens. Some of these fungi are darkly pigmented due to melanin production and traditionally have been ...named ‘dematiaceous’. The melanized fungi cause a wide array of clinical syndromes ranging from superficial to deep-seated infections. Diagnosis relies on histopathological examination of clinical specimens and on examination of cultures. Sequencing is recommended for accurate species identification, especially for unusual or newly described pathogens. In cases of mycetoma and chromoblastomycosis, pathognomonic histological findings are useful and the Fontana–Masson stain, specific for melanin, usually confirms the diagnosis. There are no standardized therapies but voriconazole, posaconazole and itraconazole demonstrate the most consistent in vitro activity against this group of fungi. Oral itraconazole has been considered the drug of choice, given the extensive clinical experience with this drug. However, voriconazole may presumably be superior for central nervous system infections because of its ability to achieve good levels in the cerebrospinal fluid. Posaconazole is a well-tolerated alternative drug, backed by less clinical experience but with excellent salvage treatment results after failure of other antifungals. Amphotericin B has been useful as alternative therapy in some cases. Combination antifungal therapy is recommended for cerebral abscesses when surgery is not possible and for disseminated infections in immunocompromised patients.
Clin Microbiol Infect 2012; 18 (Suppl. 7): 9–18
As the mortality associated with invasive Candida infections remains high, it is important to make optimal use of available diagnostic tools to ...initiate antifungal therapy as early as possible and to select the most appropriate antifungal drug. A panel of experts of the European Fungal Infection Study Group (EFISG) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) undertook a data review and compiled guidelines for the clinical utility and accuracy of different diagnostic tests and procedures for detection of Candida infections. Recommendations about the microbiological investigation and detection of candidaemia, invasive candidiasis, chronic disseminated candidiasis, and oropharyngeal, oesophageal, and vaginal candidiasis were included. In addition, remarks about antifungal susceptibility testing and therapeutic drug monitoring were made.
Summary
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.
Neonatal invasive candidiasis (NIC) is a leading cause of infection-related morbidity and mortality in preterm neonates. Several studies have shown that (1,3)-Beta-d-glucan (BDG) was accurate in ...detecting invasive fungal infection in adults, but studies in neonates are scarce. The aim was to obtain summary estimates of the accuracy of BDG detection in serum for the diagnosis of NIC.
We searched Medline, Embase, Clinicaltrials.gov, and Google Scholar (inception to July 2019). We checked the reference lists of included studies, clinical guidelines, and review articles. We included studies that assessed the accuracy of BDG against a reference standard that defined groups of patients with ordinal levels of NIC probability (e.g. proven, probable, possible) and included fungal blood culture. Participants were neonates suspected of having NIC. The intervention was BDG measurement in serum (Fungitell® assay). We assessed risk of bias and applicability using QUADAS-2. We used bivariate meta-analysis to produce summary estimates of diagnostic accuracy at prespecified positivity thresholds of 80 and 120 pg/mL. This study was registered with PROSPERO (CRD42018089545).
We included eight studies (465 participants). Of these, two were judged at low overall risk of bias. There was substantial variability across studies in the reference standards used. At a positivity threshold of 80 pg/mL, summary estimates of sensitivity and specificity of BDG were 89% (95% CI: 80–94%) and 60% (53–66%), respectively; summary sensitivity for detecting proven cases of NIC was 99% (93–100%). At a positivity threshold of 120 pg/mL, summary estimates of sensitivity and specificity were 81% (71–88%) and 80% (67–88%), respectively.
Because of high sensitivity, BDG seems promising to rule-out NIC. It might be too early to recommend its use because of the scarcity of reliable clinical data, heterogeneity in case definitions, and unstable accuracy estimates.
Background.Computed tomography (CT) of the chest may be used to identify the halo sign, a macronodule surrounded by a perimeter of ground-glass opacity, which is an early sign of invasive pulmonary ...aspergillosis (IPA). This study analyzed chest CT findings at presentation from a large series of patients with IPA, to assess the prevalence of these imaging findings and to evaluate the clinical utility of the halo sign for early identification of this potentially life-threatening infection. Methods.Baseline chest CT imaging findings from 235 patients with IPA who participated in a previously published study were systematically analyzed. To evaluate the clinical utility of the halo sign for the early identification and treatment of IPA, we compared response to treatment and survival after 12 weeks of treatment in 143 patients who presented with a halo sign and in 79 patients with other imaging findings. Results.At presentation, most patients (94%) had ⩾1 macronodules, and many (61%) also had halo signs. Other imaging findings at presentation, including consolidations (30%), infarct-shaped nodules (27%), cavitary lesions (20%), and air-crescent signs (10%), were less common. Patients presenting with a halo sign had significantly better responses to treatment (52% vs. 29%; P < .001) and greater survival to 84 days (71% vs. 53%; P < .01) than did patients who presented with other imaging findings. Conclusions.Most patients presented with a halo sign and/or a macronodule in this large imaging study of IPA. Initiation of antifungal treatment on the basis of the identification of a halo sign by chest CT is associated with a significantly better response to treatment and improved survival.
Background. Chronic disseminated candidiasis (CDC) is typically observed during neutrophil recovery in patients with acute leukemia and requires protracted antifungal therapy. Objective. Our ...objective was to document the efficacy and tolerance of corticosteroid therapy (CST) in patients with symptomatic CDC, including those who experienced fever and abdominal pain despite ongoing antifungal therapy. Methods. We performed a retrospective, multicenter study involving 10 pediatric and adult patients who experienced ongoing symptomatic CDC despite receipt of appropriate antifungal therapy for whom adjuvant oral CST was initiated. Results. All cases of CDC were proven or probable, as determined on the basis of the European Organization for Research and Treatment of Cancer-Mycosis Study Group definition criteria, and occurred in patients with leukemia. CDC-attributable clinical symptoms resolved with CST, which was started a mean of 33.8 days after antifungal therapy had been initiated. Fever and abdominal pain disappeared a median of 4–5 days, and serum fibrinogen and C-reactive protein levels returned to normal values within 14–30 days. The median duration of hospitalization after CST initiation was 8.8 days. Hepatosplenic microabscesses decreased or disappeared within a mean period of 107 days (range, 30–210 days). No relapses of CDC were observed during a median duration of follow-up of 6.5 years (range, 4–9 years). Conclusions. In children and adults who experience persistently symptomatic CDC despite ongoing receipt of antifungal therapy, CST involving a prednisone equivalent at a dosage of ⩾0.5 mg/kg per day for at least 3 weeks is associated with a prompt resolution of symptoms and of inflammatory response. These findings support the pathophysiological hypothesis that CDC belongs to the spectrum of fungus-related immune reconstitution inflammatory syndrome.
Information on the species causing Candida peritonitis, their in vitro susceptibility, antifungal strategies in this setting and patient outcome is still scarce. AmarCand was a prospective, ...non-interventional study in 271 adult intensive-care unit (ICU) patients with proven invasive Candida infection who received systemic antifungal therapy (France, 2005–2006). Of these ICU patients, 93 (median age 65 years, simplified acute physiology score II 52) had Candida peritonitis, including 73 nosocomial peritonitis, 53 concomitant bacterial peritoneal infections and 26 candidaemias. Candida species were C. albicans (n = 63/108 isolates, 58%), C. glabrata (n = 22, 20%), C. krusei (n = 9), C. kefyr (n = 5), C. parapsilosis (n = 3), C. tropicalis (n = 3), C. ciferii (n = 2) and C. lusitaniae (n = 1). Of tested isolates, 28% were fluconazole-resistant or susceptible dose-dependent (C. albicans 3/32, C. glabrata 9/14, C. krusei 4/4). Empiric antifungal treatment was started 1 day (median) after peritonitis diagnosis, with fluconazole (n = 72 patients), caspofungin (n = 12), voriconazole (n = 3), amphotericin B (n = 2), or a combination (n = 4). Following susceptibility testing, empiric antifungal treatment was judged inadequate in 9/45 (20%) patients and modified in 30 patients (fluconazole was replaced by caspofungin (n = 14) or voriconazole (n = 4)). Mortality in ICU was 38% (35/93) and was not influenced by type of Candida species, fluconazole susceptibility, time to treatment, candidaemia, nosocomial acquisition, or concomitant bacterial infection. No specific factors for death were identified. In summary, a high proportion of fluconazole-resistant or susceptible dose-dependent strains was cultured. These results confirm the high mortality rates of Candida peritonitis and plead for additional investigation in this population. Antifungal treatment for severe cases of Candida peritonitis in ICU patients remains the standard care.
Human Metapneumovirus (HMPV) belongs to the Pneumoviridae family and is responsible for respiratory infections. Mild infections are well-recognized in children, while its precise impact in various ...categories of immunocompromised adults has not been well addressed.
We retrospectively studied HMPV infections in immunocompromised adults followed in two large French university medical centers.
We identified immunocompromised adults with positive HMPV Polymerase Chain Reaction (PCR) for 36 months and reviewed their medical charts. For lung transplant recipients (LTR), FEV1 was collected at baseline, during and after infection. Imaging was centralized and chest involvement was categorized by dominant CT patterns. We compared severe patients (requiring oxygen or ventilation) and non hypoxemic patients.
Seventy-two patients were included, 27 were LTR, 25 had a hematological malignancy or were hematopoietic stem cell recipients, 20 had another immunocompromised status. Twenty patients (28%) presented a hypoxemic infection, requiring hospitalization and intensive care units transfers in 50/72 (69.4%) and 9/72 (12.5%) respectively, with only one death. Hypoxemia was less pronounced in LTRs (p = 0.014). Finally, age and dyspnea remained independent factors associated with hypoxemia (p < 0.005). The most frequent radiological patterns were bronchopneumonia (34.2%) and bronchiolitis (39.5% and 64.3% in the overall population and in LTRs respectively, p = 0.045). FEV1 improved in LTRs at one month and 85% had recovered their baseline FEV1 within 6 months.
In immunocompromised adults, HMPV infections required frequent hospitalizations and ICU transfers, while mortality is low. In LTRs, bronchiolitis pattern was predominant with short and long-term favorable outcome.
•In immunocompromised adults, HMPV infections required frequent hospitalizations and ICU transfers, while mortality is low.•Most of the patients with an available CT-scan had evidence of airway infection such as bronchitis, bronchiolitis or bronchopneumonia.•In lung transplant recipients, bronchiolitis pattern was predominant.•A significant FEV1 loss during infection occurred in most of lung transplant recipients and a new CLAD was observed in 14%.
Mastocytosis is a heterogeneous disease characterized by mast cells accumulation in one or more organs. We have reported that depression is frequent in mastocytosis, but although it was already ...described, little is known about the prevalence and features of cognitive impairment. Our objective was to describe the prevalence and features of cognitive impairment in a large cohort of patients with this rare disease (n = 57; mean age = 45) and to explore the relations between memory impairment and depression. Objective memory impairment was evaluated using the 3(rd) edition of the Clinical Memory scale of Wechsler. Depression symptoms were evaluated using the Hamilton Depression Rating Scale. Age and education levels were controlled for all patients. Patients with mastocytosis presented high levels of cognitive impairment (memory and/or attention) (n = 22; 38.6%). Cognitive impairment was moderate in 59% of the cases, concerned immediate auditory (41%) and working memory (73%) and was not associated to depression (p≥0.717). In conclusion, immediate auditory memory and attention impairment in mastocytosis are frequent, even in young individuals, and are not consecutive to depression. In mastocytosis, cognitive complaints call for complex neuropsychological assessment. Mild-moderate cognitive impairment and depression constitute two specific but somewhat independent syndromes in mastocytosis. These results suggest differential effects of mast-cell activity in the brain, on systems involved in emotionality and in cognition.
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