Alain Haloun

High prevalence of triazole resistance in Aspergillus fumigatus, especially mediated by TR/L98H, in a French cohort of patients with cystic fibrosis

OBJECTIVES Triazole resistance in Aspergillus fumigatus due to a single azole resistance mechanism (TR/L98H) is increasingly reported in European countries. Data from patients with cystic fibrosis (CF) are limited. Our study aimed to investigate the prevalence and molecular mechanisms of azole resistance in A. fumigatus in a cohort of patients with CF. METHODS Eighty-five A. fumigatus isolates from 50 CF patients, collected between January 2010 and April 2011, were retrospectively analysed for azole resistance using agar plates containing 4 mg/L itraconazole. MICs of itraconazole, voriconazole and posaconazole were determined according to EUCAST methodology for each isolate able to grow on this medium. Species identification was performed by sequencing of the β-tubulin gene. Sequencing analysis of the cyp51A gene and its promoter region was conducted. RESULTS Nine isolates (four patients, 8% prevalence) were able to grow on itraconazole-containing agar plates. Itraconazole resistance was confirmed by EUCAST methodology (MICs >2 mg/L). All isolates had mutations in the cyp51A gene at residues previously involved in azole resistance: L98H (n = 5), M220T (n = 4) and G54R (n = 1). One patient had three genetically distinct azole-resistant isolates identified during the study. The isolates with L98H that were recovered from three patients (6% prevalence) also had the 34 bp tandem repeat in the promoter region of cyp51A (TR/L98H) and displayed multiazole resistance. CONCLUSIONS We report an 8% prevalence of itraconazole resistance in CF patients in our centre, mostly driven by TR/L98H (6%). Our data confirm that TR/L98H occurs in France and can be highly prevalent in CF patients.

Disseminated Scedosporium/Pseudallescheria Infection after Double-Lung Transplantation in Patients with Cystic Fibrosis

ABSTRACT We report a case of disseminated Scedosporium/Pseudallescheria infection due to Pseudallescheria boydii sensu stricto after lung transplantation in a patient with cystic fibrosis. Dissemination occurred under voriconazole. Despite surgery and combination therapy with voriconazole, caspofungin, and terbinafine, the patient died 8 months after transplantation. Previously reported cases are reviewed.

Experience of extracorporeal membrane oxygenation as a bridge to lung transplantation in France

BACKGROUND Extracorporeal membrane oxygenation (ECMO) is increasingly used as a bridge to lung transplantation (LTx). However, data concerning this approach remain limited. METHODS We retrospectively reviewed the medical records of all patients in France who received ECMO as a bridge to LTx from 2007 to 2011. Post-transplant survival and associated factors were assessed by the Kaplan-Meier method and the Cox model. RESULTS Included were 36 patients from 11 centers. Indications for LTx were cystic fibrosis (CF) in 20 (56%), pulmonary fibrosis (PF) in 11 (30%), and other diagnoses in 5 (14%). ECMO was venovenous for 27 patients (75%) and venoarterial for 9 (25%). Mean follow-up was 17 months. Bridging to LTx was achieved in 30 patients (83%); however, only 27 patients (75%) survived the LTx procedure, and 20 (56%) were discharged from hospital. From ECMO initiation, 2-year survival rates were 50.4% overall, 71.0% for CF patients, 27.3% for PF patients, and 20.0% for other patients (p < 0.001). From LTx, 2-year survival rates were 60.5% overall, 71.0% for CF patients, 42.9% for PF patients, and 33.0% for other patients (p = 0.04). CONCLUSIONS Our study confirms that the use of ECMO as a bridge to LTx in France could provide a medium-term survival benefit for LTx recipients with critical conditions. Survival differed by underlying respiratory disease. Larger studies are needed to further define the optimal use of ECMO.

Fatal Invasive Infection with Fungemia Due to Microascus cirrosus after Heart and Lung Transplantation in a Patient with Cystic Fibrosis

ABSTRACT Scopulariopsis species are rarely but increasingly recognized as opportunistic pathogens in immunocompromised patients. We report on a patient suffering from cystic fibrosis who developed disseminated fungal infection due to a rare Scopulariopsis species, Microascus cirrosus, after heart and lung transplantation. Despite antifungal combination therapy with voriconazole and caspofungin, the patient died 4 weeks after transplantation. Diagnostic difficulties and optimal management of disseminated Scopulariopsis/Microascus infections are discussed.

Pregnancy and heart-lung transplantation

The purpose of this study was to report a single centers experience of 5 new pregnancies following heart-lung transplantation. These 5 pregnancies gave rise to 4 live births. Vaginal delivery occurred at a mean of 38 +/- 1 weeks of amenorrhea (range, 37-39 weeks) and the mean birth weight was 3,143 +/- 757 grams (range, 2,270-3,990 grams). Mean maternal forced expiratory volume in 1 second (%) before, during (sixth month), and after (1 year) pregnancy was 87 +/- 18, 87 +/- 22, and 88 +/- 17, respectively (p = NS). In conclusion, pregnancy after heart-lung transplantation can be associated with a good prognosis for mother and child.

Gallibacterium anatis Bacteremia in a Human

ABSTRACT We describe the first case of bacteremia due to Gallibacterium anatis. The patient, a 26-year-old woman, developed bacteremia and diarrhea. The origin of infection was possibly due to a diet contaminated by G. anatis in this highly immunocompromised patient.

Severe pulmonary hypertension leading to heart–lung transplantation and revealing breast cancer

To the Editors: Pulmonary tumour embolism is considered to be a rare cause of pulmonary hypertension. The incidence, studied in autopsy series, varies from 3 to 26% of patients with solid tumour [1]. It occurs most frequently in breast, stomach, lung, liver, prostate and pancreas adenocarcinoma [1]. The literature shows a male predominance and an average age of 52.4 yrs [2]. The signs are those of any pulmonary hypertension, occurring either during the history of a known neoplasia or as the first manifestation of malignancy. Pre-mortem diagnosis is difficult to confirm and definitive diagnosis is usually made on an autopsy study. Several studies have reported pulmonary wedge aspiration cytology performed during a right heart catheterisation as a useful pre-mortem diagnostic tool [3]. Treatment consists of treating the neoplasia. Specific treatment for pulmonary hypertension has not been evaluated. Most frequently, evolution leads to refractory right cardiac failure and death [4]. In rare cases improvement has been reported after chemotherapy [5] or endarterectomy [6]. Two mechanisms can be involved in the development of pulmonary hypertension in tumour pulmonary embolism: the first one is by mechanical occlusion of the small pulmonary arteries by multiple neoplastic microemboli, the second one is through development of pulmonary tumour thrombotic microangiopathy (PTTM) as a result of …

Total lung capacity size matching in fibrosis lung transplantation

Single (S) or bilateral (B) lung transplantation (LT) is offered for end stage, life-threatening pulmonary fibrosis (PF). Currently, no strong recommendation helps transplantation teams for choosing optimal total lung capacity (TLC) for size matching. We conducted a retrospective analysis of all LT performed in PF patients from 1988 to 2015 in Nantes University hospital, France, in order to study donor vs. recipient TLC. We defined transplanted BLT-TLC as follows: theoretic donor TLC minus lung volume surgical reduction, divided by theoretic recipient TLC. Transplanted SLT-TLC was similarly calculated, taking into account measured TLC of the remaining lung. 24 patients (46 ± 9 years, 10 SLT and 14 BLT) were included. Survival after transplantation for BLT, SLT and both was respectively 35.7%, 50% and 41.7% at 1 year, 21.5%, 10% and 16.7% at 5 years, with a median survival of 347 days for BLT and 272 days for SLT (p=0.38). Mean transplanted TLC was higher in BLT (86.4 ± 20.2% pred.) than in SLT (65.1 ± 7.2% pred.) (p = 0.007) and higher than recipient TLC measured / theoretic in BLT (54 ± 22%) and SLT (48 ± 10%) (p=0.038). Average lung volume reduction was 12.3% in BLT and was performed in 35.7% of BLT and 20% of SLT. When classifying patients according to different thresholds of transplanted TLC percentage (70% or 80% pred.), no mortality difference was observed in SLT, BLT or both groups. Taking into account surgical lung volume reduction, we report a lower transplanted TLC in BLT and SLT than the one suggested by Barnard et al. (Barnard J.B, J Heart Tranplant 2013;32:849-860). The best TLC size matching appears to be somewhere between measured and theoretic TLC recipient but has to be further explored.