Background. The aim of our study was to assess the detection of circulating DNA from the most common species of Mucorales for early diagnosis of mucormycosis in at-risk patients. Methods. We retrospectively evaluated a combination of 3 quantitative polymerase chain reaction (qPCR) assays using hydrolysis probes targeting Mucor/Rhizopus, Lichtheimia (formerly Absidia), and Rhizomucor for circulating Mucorales detection. Serial serum samples from 10 patients diagnosed with proven mucormycosis (2–9 samples per patient) were analyzed. Results. No cross-reactivity was detected in the 3 qPCR assays using 19 reference strains of opportunistic fungi, and the limit of detection ranged from 3.7 to 15 femtograms/10 µL, depending on the species. DNA from Mucorales was detected in the serum of 9 of 10 patients between 68 and 3 days before mucormycosis diagnosis was confirmed by histopathological examination and/or positive culture. All the qPCR results were concordant with culture and/or PCR-based identification of the causing agents in tissue (Lichtheimia species, Rhizomucor species, and Mucor/Rhizopus species in 4, 3, and 2 patients, respectively). Quantitative PCR was negative in only 1 patient with proven disseminated mucormycosis caused by Lichtheimia species. Conclusion. Our study suggests that using specific qPCR targeting several species of Mucorales according to local ecology to screen at-risk patients could be useful in a clinical setting. The cost and efficacy of this strategy should be evaluated. However, given the human and economic cost of mucormycosis and the need for rapid diagnosis to initiate prompt directed antifungal therapy, this strategy could be highly attractive.
To assess the efficacy of a preemptive antifungal therapy in preventing proven candidiasis in critically ill surgical patients. Before/after intervention study, with 2-yr prospective and 2-yr historical control cohorts. Surgical intensive care unit (SICU) in a university-affiliated hospital. Nine hundred and thirty-three patients, 478 in the prospective group and 455 in the control group, with SICU stay > or =5 days. During the prospective period, systematic mycological screening was performed on all patients admitted to the SICU, immediately at admittance and then weekly until discharge. A corrected colonization index was used to assess intensity of Candida mucosal colonization. Patients with corrected colonization index > or =0.4 received early preemptive antifungal therapy (fluconazole intravenously: loading dose 800 mg, then 400 mg/day for 2 wks). End points of this study were the frequency of proven candidiasis, especially SICU-acquired candidiasis. During the retrospective period, 32 patients of 455 (7%) presented with proven candidiasis: 22 (4.8%) were imported and 10 (2.2%) were SICU-acquired cases. During the prospective period, 96 patients with corrected colonization index > or =0.4 of 478 received preemptive antifungal treatment and only 18 cases (3.8%) of proven candidiasis were diagnosed; all were imported infections. Candida infections occurred more frequently in the control cohort (7% vs. 3.8%; p = .03). Incidence of SICU-acquired proven candidiasis significantly decreased from 2.2% to 0% (p < .001, Fisher test). Incidence of proven imported candidiasis remained unchanged (4.8% vs. 3.8%; p = .42). No emergence of azole-resistant Candida species (especially Candida glabrata, Candida krusei) was noted during the prospective period. Targeted preemptive strategy may efficiently prevent acquisition of proven candidiasis in SICU patients. Further studies are being performed to assess cost-effectiveness of this strategy and its impact on selection of azole-resistant Candida strains on a long-term basis.
1 October 2010 in Antimicrobial Agents and Chemotherapy
The outcomes for 73 invasive fusariosis patients treated with voriconazole were investigated. Patients with proven ( n = 67) or probable ( n = 6) infections were identified from the voriconazole clinical database ( n = 39) and the French National Reference Center for Mycoses and Antifungals database ( n = 34). Investigator-determined success was a complete or partial response. Survival was determined from day 1 of voriconazole therapy to the last day known alive. Patients were 2 to 79 years old (median, 43 years), and 66% were male. Identified Fusarium species (62%) were F. solani , F. moniliforme , F. proliferatum , and F. oxysporum . Underlying conditions analyzed included hematopoietic stem cell transplant (HSCT; 18%), hematologic malignancy (HM; 60%), chronic immunosuppression (CI; 12%), or other condition (OC; 10%). Infection sites were brain (5%), disseminated excluding brain (67%), lungs/sinus (15%), and other (12%). Most patients (64%) were or had recently been neutropenic ( 0.05). Combination therapy (13 patients) was no better than treatment with voriconazole alone. Overall, 59% of the patients died (49% died of fusariosis), and 90-day survival was 42%. Site of infection influenced survival ( P = 0.02). Median survival (in days) by species was as follows: F. solani , 213; F. oxysporum , 112; Fusarium spp., 101; F. proliferatum , 84; F. moniliforme , 76. We conclude that voriconazole is a therapeutic option for invasive fusariosis.
Background. An increased incidence of alveolar echinococcosis (AE) in patients with immunosuppression (IS) has been observed; our aim was to study this association and its characteristics. Methods. Fifty AE cases with IS-associated conditions (ISCs) before or at AE diagnosis were collected from the French AE registry (1982–2012, 509 cases). There were 30 cancers, 9 malignant hematological disorders, 14 chronic inflammatory diseases, 5 transplants, and 1 case of AIDS; 9 patients had ≥2 ISCs. Characteristics of the 42 IS/AE cases and the 187 non-IS/AE cases diagnosed during the period 2002–2012 were statistically compared. Results. There was a significant increase in IS/AE cases over time. Risk factors did not differ between IS/AE and non-IS/AE patients. However, AE was more frequently an incidental finding (78% vs 42%) and was diagnosed at earlier stages (41% vs 23%) in IS/AE than in non-IS/AE patients. Serology was more often negative (14% vs 1%) and treatment efficacy was better (51% regression after 1-year treatment vs 27%) in IS/AE patients. All IS/AE patients but 7 took IS drugs; 7 received biotherapeutic agents. When not concomitant, AE occurred in IS patients within a 48-month median time period. Atypical presentation and abscess-, hemangioma-, and metastasis-like images delayed AE diagnosis in 50% of IS/AE patients, resulting in inappropriate treatment. Liver images obtained for 15 patients 1–5 years before diagnosis showed no AE lesions. Albendazole efficacy was good, but 19 of 48 treated patients experienced side effects. Conclusions. Patients with immunosuppression are at increased risk for occurrence, delayed diagnosis, and progression of AE.
We report 20 episodes of infection caused by acquired echinocandin-resistant Candida spp. harboring diverse and new Fksp mutations. For 12 patients, initial isolates (low MIC, wild-type Fksp sequence) and subsequent isolates (after caspofungin treatment, high MIC, mutated Fksp) were genetically related.