This survey at a whole institution underlines the high number of cases of invasive aspergillosis among nonneutropenic patients, with an overall mortality rate that was significantly higher than that for neutropenic patients.
Pneumocystis jirovecii pneumonia (PCP) is a life-threatening infection in immunocompromised patients. Quantitative real-time PCR (qPCR) is more sensitive than microscopic examination for the detection of P. jirovecii but also detects colonized patients. Hence, its positive predictive value (PPV) needs evaluation. In this 4-year prospective observational study, all immunocompromised patients with acute respiratory symptoms who were investigated for PCP were included, totaling 659 patients (814 bronchoalveolar lavage fluid samples). Patients with negative microscopy but positive qPCR were classified through medical chart review as having retained PCP, possible PCP, or colonization, and their clinical outcomes were compared to those of patients with microscopically proven PCP. Overall, 119 patients were included for analysis, of whom 35, 41, and 43 were classified as having retained PCP, possible PCP, and colonization, respectively. The 35 patients with retained PCP had clinical findings similar to those with microscopically proven PCP but lower fungal loads (P < 0.001) and were mainly non-HIV-infected patients (P < 0.05). Although the mean amplification threshold was higher in colonized patients, it was not possible to determine a discriminant qPCR cutoff. The PPV of qPCR in patients with negative microscopy were 29.4% and 63.8% when considering retained PCP and retained plus possible PCP, respectively. Patients with possible PCP had a higher mortality rate than patients with retained PCP or colonization (63% versus 3% and 16%, respectively); patients who died had not received co-trimoxazole. In conclusion, qPCR is a useful tool to diagnose PCP in non-HIV patients, and treatment might be better targeted through a multicomponent algorithm including both clinical/radiological parameters and qPCR results.
Trichophyton verrucosum is a zoophilic dermatophyte, known as a causative agent of inflammatory mycoses of the skin and the scalp in humans. In this study, we reviewed all cases of T. verrucosum infection diagnosed in our laboratory over a 12-year period, to determine epidemiological and clinical characteristics. Among 18,340 samples analyzed, 5,186 cultured positive with dermatophytes (2674 patients), of which 64 samples (41 patients) were positive for T. verrucosum. Our data show that there was a strong influence of age on the type of lesion, with children and adults presenting more frequently with tinea capitis and skin infections, respectively (P < .0001). Infection of children and adults resulted more frequently from indirect and direct exposure to cattle, respectively (P < .01). We observed a marked increase of cases over the last 4 years, with a correlation of the number of cases and the mean annual rainfall (P < .05), suggesting that increasing humidity favors cattle infection, and thereby, human infection. Whether this increase is the consequence of climate changes remains to be determined but should be considered.
Pneumocystis jirovecii is a transmissible fungus with a high pulmonary tropism. The prevalence of P. jirovecii in patients with cystic fibrosis (CF) has been estimated in Germany at 7.4%, in Spain at 21.5% and in Brazil at 38.2%. Data on the prevalence of P. jirovecii in CF patients in France remain scarce, particularly in Brittany, where the prevalence of CF is high (from 1/1600 to 1/4500). Our objectives were to determine the prevalence of colonization of the airways by P. jirovecii in Brittany in CF patients monitored at the "Centre de Ressources et de Compétences de la Mucoviscidose (CRCM)" of Rennes compared to that previously observed at the CRCM of Roscoff-Brest. Sputa from 86 patients (178 specimens) followed in Rennes were analyzed retrospectively. The detection of P. jirovecii was performed using real-time PCR targeting the gene encoding the mitochondrial large subunit of ribosomal RNA. Pneumocystis jirovecii DNA was detected in 3/86 patients (3.5%) monitored at Rennes, whereas it had previously been detected in 1/76 patients (1.3%) monitored at Roscoff-Brest, thus showing an overall prevalence of 2.5% in Brittany. These results obtained from two Breton centers taken together show that P. jirovecii prevalence in patients with CF in Brittany is lower than those observed in Germany, Spain, Brazil or in other regions of France. This study is a preliminary step in determining the risk factors for P. jirovecii acquisition, its epidemiological and clinical significance in CF patients through a prospective multicenter study.
Aspergillus fumigatus
triazole resistance is an emerging concern for treating chronically infected/colonized patients. This study sought to evaluate the performance of PCR assays to detect
Aspergillus
fungi together with azole resistance in sputum samples from cystic fibrosis (CF) patients. In total, 119 sputum samples from 87 CF patients were prospectively processed for
Aspergillus
detection by means of mycological culture and four qPCR assays, 2 in-house methods and two commercial multiplex real-time PCR assays simultaneously detecting
Aspergillus
and the most relevant
cyp51A
gene mutations (MycoGENIE
®
and AsperGenius
®
). Azole susceptibility of
A. fumigatus
isolates was assessed using Etest
®
method and
cyp51A
gene mutation were characterized by sequencing. The overall rate of
Aspergillus
detection with the four qPCR assays ranged from 47.9 to 57.1%, contrasting with 42/119 (35.3%) positive cultures with
A. fumigatus
. The high sensitivity of PCR on sputum could then contribute to more effective grading of
Aspergillus
disease in CF patients. Five out of 41 isolated strains (12.2%) exhibited azole-resistant MIC patterns, three of which harbored
cyp51A
mutations and only 1/3 with the sequence TR
34
/L98H. Combined with culture, PCR assay achieved high sensitivity
Aspergillus
screening in CF samples. However,
cyp51A
targeting was only moderately effective for azole resistance monitoring, while
Aspergillus
resistance remains of great concern.
The purpose of this investigation was to characterize the management and prognosis of severe Pneumocystis jirovecii pneumonia (PJP) in human immunodeficiency virus (HIV)-negative patients. An observational cohort study of HIV-negative adults with PJP documented by bronchoalveolar lavage (BAL) through Gomori-Grocott staining or immunofluorescence, admitted to one intensive care unit (ICU) for acute respiratory failure, was undertaken. From 1990 to 2010, 70 patients (24 females, 46 males) were included, with a mean age of 58.6 ± 18.3 years. The mean Simplified Acute Physiology Score (SAPS)-II was 36.9 ± 20.4. Underlying conditions included hematologic malignancies (n = 21), vasculitis (n = 13), and solid tumors (n = 13). Most patients were receiving systemic corticosteroids (n = 63) and cytotoxic drugs (n = 51). Not a single patient received trimethoprim-sulfamethoxazole as PJP prophylaxis. Endotracheal intubation (ETI) was required in 42 patients (60.0 %), including 38 with acute respiratory distress syndrome (ARDS). In-ICU mortality was 52.9 % overall, reaching 80.9 % and 86.8 %, respectively, for patients who required ETI and for patients with ARDS. In the univariate analysis, in-ICU mortality was associated with SAPS-II (p = 0.0131), ARDS (p < 0.0001), shock (p < 0.0001), and herpes simplex virus (HSV) or cytomegalovirus (CMV) on BAL (p = 0.0031). In the multivariate analysis, only ARDS was associated with in-ICU mortality (odds ratio [OR] 23.4 [4.5-121.9], p < 0.0001). PJP in non-HIV patients remains a serious disease with high in-hospital mortality. Pulmonary co-infection with HSV or CMV may contribute to fatal outcome.
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