Development of Echinocandin Resistance in Clavispora lusitaniae during Caspofungin Treatment

International audienceClavispora lusitaniae is an opportunistic human pathogen responsible for 0.6 to 2% of candidemia. This species is intrinsically susceptible to echinocandins. Nevertheless, in this study, development of echinocandin resistance in C. lusitaniae isolates was observed during caspofungin treatment. This resistance resulted from missense mutation in the echinocandin target Fks1 gene

Evaluation of the (1,3)-beta-D-glucan assay for the diagnosis of neonatal invasive yeast infections

International audienceMost newborns in the neonatal intensive care unit (NICU) are premature and at risk of invasive fungal infections (IFIs). Invasive yeast infections (IYIs) are the most common fungal infections in this population. These infections are difficult to diagnose because symptoms are nonspecific, and the sensitivity of blood cultures is low. The serum (1,3)-beta-D-glucan (BDG) assay provides a reliable marker for the diagnosis of IFIs in adults with haematological malignancies. We assessed the diagnostic performance of this test in neonatal IYIs and its contribution to the monitoring of antifungal treatment. A retrospective study was performed in the NICU of the French University Hospital of Amiens from February 2012 to February 2014. Forty-seven neonates (33 males, 14 females) with a median gestational age of 30 weeks (IQR: 27-31) and median birth weight of 1200 g (IQR: 968-1700) were included and divided into three groups: 21 control neonates (CTRL), 20 neonates with probable IYI (PB), and six with proven IYI (PV). Median BDG levels were significantly higher in the global IYI group (PB + PV): 149 pg/ml (IQR: 85-364) vs. CTRL group: 39 pg/ml (IQR: 20-94) (P < .001). The optimal cut-off was 106 pg/ml (sensitivity 61.5%; specificity 81%). BDG levels decreased with antifungal treatment. BDG was detectable in cerebrospinal fluid, but the interest of this for diagnostic purposes remains unclear. Our results suggest that the BDG assay may be useful for the early identification of IYIs in neonates and for monitoring antifungal therapy efficacy

Painless Nodules on the Left Hand of a Kidney Transplant Recipient

International audienc

Molecular epidemiology of a Malassezia pachydermatis neonatal unit outbreak

International audienceThe non-lipid-dependent yeast Malassezia pachydermatis is predominantly zoophilic but occasionally colonizes the human skin. This yeast caused an outbreak in a neonatal iIntensive care unit (NICU). This study aimed to describe the molecular epidemiology of this M. pachydermatis outbreak. All the M. pachydermatis isolates collected at a French University Hospital from January 2012 to April 2013 were included in the study. M. pachydermatis isolates, sampled from various biological samples sites in 25 patients, were identified via MALDI-TOF mass spectrometry and typed using intergenic-spacer 1 (IGS1) nucleotide sequence polymorphisms analysis. By analyzing 90 IGS1 sequences (including 43 deposited in GenBank), we found that of the 186 M. pachydermatis isolates, 47 were viable for typing and all of them clustered within type 3; 78.7% clustered within the 3D subtype; the remaining clustered within three newly described subtypes: 3E (4.3%), 3F (8.5%) and 3 G (8.5%). No particular subtype was associated with a collection site or a particular time period. This first molecular investigation of a M. pachydermatis outbreak in neonates showed that multiple genotypes can colonize the same neonate patient by. The source of this polyclonal outbreak could not be identified. It stopped after infection control measures, including the prohibition of a lipid-rich moisturizing hand cream used by the health care staff, had been implemented

Home Environment as a Source of Life-Threatening Azole-Resistant Aspergillus fumigatus in Immunocompromised Patients

International audienceA case of fatal aspergillosis due to a TR46/Y121F/T289A azole-resistant Aspergillus fumigatus is reported. Environmental investigations at the patient's residence led to the recovery of TR46/Y121F/T289A isolates, genotypically indistinguishable from the clinical isolate, supporting for the first time the direct role of household as potential source of azole-resistant invasive aspergillosis

Prospective Observational Study on the Association Between Serum Mannose-Binding Lectin Levels and Severe Outcome in Critically Ill Patients with Pandemic Influenza Type A (H1N1) Infection

International audienceMannose-binding lectin (MBL) plays an important role in the innate immune response. In addition to activating the complement, MBL can induce cytokine production and contribute to a deleterious inflammatory response with severe A(H1N1)pdm09 virus infection. Our aim was to determine if serum MBL levels correlate with the risk of mortality in intensive care units (ICU) patients with A(H1N1)pdm09 infection. Prospective observational study was performed in ICU patients with acute respiratory distress syndrome due to influenza A(H1N1)pdm09 virus. Demographic characteristics and severity indices were recorded at ICU admission. MBL was assayed from blood drawn at influenza diagnosis within 24-48 h following the ICU admission. Outcomes were compared according to MBL levels. Results are expressed as median and interquartile range. Serum MBL levels were studied in 27 patients (age: 56 [IQR 29] years) with severe A(H1N1)pdm09 infection and in 70 healthy controls. Median admission SAPSII and SOFA scores were 49 [IQR 26] and 12 [IQR 5], respectively. Mortality rate after a 30-day was 37%. MBL was significantly higher in non-survivors (3741 [IQR 2336] ng/ml) vs survivors (215 [IQR 1307] ng/ml), p = 0.006, as well as control group (1814 [IQR 2250] ng/ml), p = 0.01. In contrast, MBL levels in survivors group were significantly lower than the controls group (215 [IQR 1307] ng/ml vs. 1814 [IQR 2250] ng/ml, p = 0.005). MBL cut-off > 1870 ng/ml had a sensitivity of 80% and a specificity of 88.2% for mortality [AUC = 0.82 (95% CI 0.63-0.94)]. Kaplan-Meier analysis demonstrated a strong association between MBL levels and mortality (log-rank 7.8, p = 0.005). MBL > 1870 ng/ml was independently associated with mortality (HR = 8.7, 95% CI 1.2-29.1, p = 0.007). This study shows that baseline MBL > 1870 ng/ml is associated with higher mortality in ICU patients with severe A(H1N1)pdm09 infection

The pharmacokinetic challenge of voriconazole therapy for cerebral aspergillosis in patients treated with ibrutinib

International audienceNo abstract availabl

PCR-based detection of Aspergillus fumigatus and absence of azole resistance due to TR 34 /L98H in a french multicenter cohort of 137 patients with fungal rhinosinusitis

International audienceFungal rhinosinusitis (FRS) has a worldwide distribution, comprises distinct clinical entities but is mostly due to Aspergillus among which Aspergillus fumigatus plays a major role in European countries. Although, there is accumulating evidence for the emergence of environmentally acquired-azole resistance in A. fumigatus (such as TR34 /L98H) in various clinical settings, there is few data for patients with FRS. In this study, we aimed to investigate the prevalence of A. fumigatus azole resistance due to TR34 /L98H in a multicentre cohort of patients with FRS. One hundred and thirty-seven patients with FRS admitted between 2002 and 2016 at four French medical centres were retrospectively enrolled. Clinical and mycological findings were collected. Aspergillus fumigatus and the TR34 /L98H alteration conferring azole resistance were investigated directly from clinical samples using the commercial CE-IVD marked MycoGENIE® A. fumigatus real-time PCR assay. Fungal ball was the more frequent clinical form (n = 118). Despite the presence of fungal hyphae at direct microscopic examination, mycological cultures remained negative for 83 out of the 137 patients (60.6%). The PCR assay proved to be useful allowing the identification of A. fumigatus and etiological diagnosis in 106 patients (77.4%) compared with 44 patients (32.1%) when using culture as the reference method. Importantly, neither TR34 nor L98H alterations were evidenced

Posttraumatic mucormycosis: a nationwide study in France and review of the literature

Data on clinical, mycologic characteristics, and outcome of posttraumatic mucormycosis are scarce and often limited to case reports. From the French nationwide "RetroZygo" study, we compared posttraumatic mucormycosis cases with other forms of mucormycosis. We also reviewed reports of posttraumatic mucormycosis in the English-language literature from 1993 to 2013. We included all proven or probable cases for which underlying condition, route of infection, surgical and antifungal treatments, and outcome were detailed. From our cohort, posttraumatic mucormycosis (n = 16) differed significantly from other forms (n = 85) by rarity of underlying disease (31.2% vs 81%, p < 0.0001), frequency of cutaneous localization (87% vs 7%, p < 0.0001), short time before diagnosis (4.5 vs 21 d, p = 0.0002), species involved (Apophysomyces elegans complex and Saksenaea vasiformis), surgical requirement (93.7% vs 47%, p = 0.0006) and better survival (87.5% vs 47.6% at day 90, p = 0.03). We studied 122 cases of posttraumatic mucormycosis through our literature review. Most frequently reported traumas were traffic (37%), domestic accidents (15.1%), or natural disasters (13.4%). Mucormycosis occurred after extensive soft-tissue damage in 47.5% cases, with symptoms occurring a median of 9.5 days after trauma with necrosis being reported in 76.2% cases. Dissemination was found in 9% of patients, and bacterial coinfection in 41%. Nineteen percent of cases occurred in the Middle East or in India where Apophysomyces elegans complex was the predominant species recovered. Awareness of mucormycosis as a cause of posttrauma soft-tissue infection is warranted, especially in cases of soil-contaminated wounds. Survival is higher than in other forms of mucormycosis, but morbidity remains high