Search

Voriconazole is an antifungal treatment with central neurotoxicity. Modifications of the electroretinogram can explain some of its visual complications: visual hallucination, blurred vision, altered visual perception or photophobia. However, reports from the literature or the French pharmacovigilance centers evoked toxic optic neuropathy due to voriconazole. The aim of this report is to analyze the role of voriconazole in the occurrence of toxic optic neuropathy or the role of the combination of voriconazole with other neurotoxic drugs.We report the case of a 15-year-old young boy treated with voriconazole and ethambutol for a severe lung infection due to aspergillosis and mycobacterium tuberculosis in the mucoviscidosis and pulmonary transplantation who developed a toxic optic neuropathy. A review of the literature on the role of ethambutol on the activity of CYP2C19 and its relationship with the serum concentration of voriconazole was conducted.In our patients, visual acuity recovered after discontinuation of voriconazole. Other cases of toxic optic neuropathy due to voriconazole were reported in pharmaco-vigilance databases, often in association with ethambutol.Ethambutol can reduce the activity of CYP2C19 leading to an increase of voriconazole concentration. Thus, it potentiates its risk of adverse event. Such mechanism leading to this neuro ophthalmological adverse effect would have an important clinical involvement. It would require a stricter monitoring and screening of patients treated by combination of neurotoxic molecules and VRZ to detect an adverse event.

Purpose The purpose of this study was first to evaluate the imaging-related cumulative post-transplantation radiation dose in cystic fibrosis (CF) lung transplantation (LT) recipients and second, to identify the occurrence and type of malignancies observed after LT. Materials and methods A total of 52 patients with CF who underwent LT at our institution between January 2001 and December 2006 with at least 3 years of survival were retrospectively included. There were 27 men and 25 women with a mean age of 24.4 ± 9.2 (SD) years (range: 7.6–52.9 years) at the time of LT. Calculation of cumulative effective and organ doses after LT were based on dosimetry information and acquisition parameters of each examination. Cumulative radiation doses were calculated until June 2016, but stopped at the time of de novomalignancy diagnosis, for patients developing the condition. Results Patients received a mean cumulative effective dose of 110.0 ± 51.6 (SD) mSv (range: 13–261.3 mSv) over a mean follow-up of 8.1 ± 3.6 (SD) years (range: 0.5–13.5 years), with more than 100mSv in 5 years in 19/52 patients (37%). Chest CT accounted for 73% of the cumulative effective dose. Mean doses to the lung, breast and thyroid were 152.8 ± 61.1 (SD) mGy (range: 21.2–331.6 mGy), 106.5 ± 43.2 (SD) mGy (range: 11.9–221.4 mGy) and 72.7 ± 31.8 (SD) mGy (range: 9.5–165.0 mGy), respectively. Nine out of 52 patients (17%) developed a total of 10 de novo malignancies, all but one attributable to immunosuppression after a mean post-transplantation follow-up period of 11.1 ± 3.5 (SD) years (range: 3.7–16.3 years). Six-month cumulative effective dose was not greater in patients with de novomalignancies than in those without de novomalignancies (28.9 ± 14.5 (SD) mGy (range: 13.0–53.4) vs 25.6 ± 15.3 (range: 5.0–69.7), respectively, P > 0.05). Conclusion The cumulative effective dose exceeded 100 mSv in 5 years in 37% of LT recipients, the reason why continuous efforts should be made to optimize chest CT acquisitions accounting for 73% of the radiation dose.

Background Homeostatic turnover of the extracellular matrix conditions the structure and function of the healthy lung. In lung transplantation, long-term management remains limited by chronic lung allograft dysfunction, an umbrella term used for a heterogeneous entity ultimately associated with pathological airway and/or parenchyma remodeling. Objective This study assessed whether the local cross-talk between the pulmonary microbiota and host cells is a key determinant in the control of lower airway remodeling posttransplantation. Methods Microbiota DNA and host total RNA were isolated from 189 bronchoalveolar lavages obtained from 116 patients post lung transplantation. Expression of a set of 11 genes encoding either matrix components or factors involved in matrix synthesis or degradation (anabolic and catabolic remodeling, respectively) was quantified by real-time quantitative PCR. Microbiota composition was characterized using 16S ribosomal RNA gene sequencing and culture. Results We identified 4 host gene expression profiles, among which catabolic remodeling, associated with high expression of metallopeptidase-7, -9, and -12, diverged from anabolic remodeling linked to maximal thrombospondin and platelet-derived growth factor D expression. While catabolic remodeling aligned with a microbiota dominated by proinflammatory bacteria (eg, Staphylococcus, Pseudomonas, and Corynebacterium), anabolic remodeling was linked to typical members of the healthy steady state (eg, Prevotella, Streptococcus, and Veillonella). Mechanistic assays provided direct evidence that these bacteria can impact host macrophage-fibroblast activation and matrix deposition. Conclusions Host-microbes interplay potentially determines remodeling activities in the transplanted lung, highlighting new therapeutic opportunities to ultimately improve long-term lung transplant outcome., Graphical abstract

Background The optimal management of Mycobacterium chelonae disease in immunocompromised patients remains unclear. A combination of antimicrobial agents is recommended as monotherapy with clarithromycin has been associated with clinical failures due to acquired resistance. Objectives We aim to report the efficacy and tolerability of linezolid in association with clarithromycin for the treatment of M. chelonae infections in immunocompromised patients. Methods We describe four immunocompromised patients treated by linezolid and clarithromycin for cutaneous M. chelonae disease. Results This combination was associated with rapid clinical efficacy in all patients with no relapse observed after a median follow-up of 2.25 years (1.4 years). However, this treatment was responsible for frequent adverse events including thrombocytopaenia, myalgia and mitochondrial toxicity. All adverse effects were reversible after linezolid discontinuation. Conclusions We therefore suggest linezolid/clarithromycin combination as the initial therapeutic strategy for M. chelonae skin infections in immunocompromised patients.

The safety and efficacy of amphotericin B lipid complex (ABLC) were evaluated in a retrospective study of 46 paediatric patients with invasive infections. The study included a large proportion of patients who were refractory to or intolerant of conventional antifungal therapy. The mean age of the children was 9.7 +/- 4.8 years. Primary underlying conditions included mainly haematopoietic stem cell transplantation, leukaemia and lung transplantation. The mean daily dose given was 4.11 mg/kg for a mean duration of 38.7 days. At the end of therapy, 38 of 46 (83%) patients responded successfully to treatment with ABLC, including 18 of 23 (78%) with aspergillosis and 17 of 19 (89%) with candidiasis. ABLC was well tolerated, with a low incidence of adverse events. The mean creatinine value was 74.5 microl/mol/l at baseline and 78.2 micromol/l at the end of therapy. These results support the use of ABLC in the treatment of invasive fungal infections in children, including patients who have previously failed, or are intolerant of, traditional antifungal regimens.

Pediatric lung transplantations (LTx) remains a small part of LTx performed worldwide. The majority of these Tx concerns young adolescents, transplantations in infants being anecdotic. We conducted a retrospective study of LTx in children and adolescents in one center in Paris from the beginning of the 90's to 2013.Data from Broussais then HEGP were collected retrospectively from 1990 to 2013: 380 LTx were reported in 368 patients including 111 LTx performed among children from 5 to 18 years of age (30%).One hundred and eleven patients received 121 LTx: 86 bilateral LTx, 13 combined lung-liver, 3 monopulmonary, 5 heart-lung and 4 combined heart-lung-liver Tx. Eighty-eight percent of the patients had cystic fibrosis. Median age was 14 years, weight 34 kg and height 144 cm. Median age of donors was 27 years, weight 60 kg and height 167 cm. Conditional survival for children was not different than adults: 72% at one year, 42% at 5 years, 37% at 10 years and 26% at 15 years. There was not overall early mortality after transplantation. Era graft survival was significantly higher after year 2000 (53% at 5 years vs 32% P=0.03).Lung transplantation among children under 18 years have similar outcome to those of adult patients.

Tacrolimus (TRL) is an immunosuppressive drug characterized by a narrow therapeutic index, low bioavailability, and pharmacokinetic variability. Intravenous (IV) TRL may be needed whenever the oral route is unavailable. The small amount of infusion formulation (5 mg/mL) results in a large dilution and need for careful technical management of the infusion. This study addressed the feasibility to provide sublingual (SL) as an alternative to IV. TRL for transplanted patients. In a substudy, we performed a retrospective analysis of 17 lung and heart transplant patients using SL TRL. It included therapeutic drug monitoring and 4 area under curve (AUC) measurements. Patients received SL TRL on a dose-to-dose basis from the oral formulation. The mean age of the subjects (14 male, 3 female) was 35.3 ± 15.6 years; 146 trough (C 0 ) samples were collected during the SL period (15.8 ± 20.6 days) showing a conformity level of 90.4%. Mean dose, C 0 , and AUC of SL tacrolimus were 0.116 ± 0.096 mg/kg, 12.9 ± 5 ng/mL, and 230 ± 74 ng · h/mL, respectively, with an average 1 hour time to peak concentration. Acute rejection episodes, renal toxicity, and drug interactions were not observed. This study supported the convenience of short-term SL TRL administration, even in unconscious patients. Further investigations are needed to validate the dose range of the SL route.

Summary Background and objective: Invasive pulmonary aspergillosis (IPA) is a serious cause of death among immune-compromised patients such as organ-transplant recipients. Recently, voriconazole has been approved for first-line therapy in IPA. Theoretically, optimal voriconazole blood level (superior to 1 mg/L according to recent studies) should be reached within 24 h. In practice, a significantly longer time seems to be needed in lung-transplant recipients. Therefore, caspofungin is now used in combination with voriconazole to provide cover against Aspergillus spp. infection during this gap. The first aim of this study was to investigate Aspergillus spp. infection treated with this combination and the atter’s tolerability. The median time for attainment of apparently active blood levels in lung transplant recipients were compared between those with cystic fibrosis and those without. Methods: Lung-transplant recipients who received a combination of voriconazole and caspofungin between 2002 and 2008 as primary therapy were identified retrospectively. The median number of days to reach active voriconazole blood levels was compared between cystic fibrosis and other patients by Student’s t-test. Statistical significance was defined by P-value

Oral ganciclovir (GCV) was replaced by prodrug valganciclovir (vGCV) for cytomegalovirus (CMV) prophylaxis. We assessed retrospectively (2005-2007) vGCV effectiveness and safety during prophylaxis and 4 months after, in heart (HTx) and lung transplantation (LTx), including lung transplant for cystic fibrosis (CFTx). Patients with stable renal function received vGCV 900 mg daily during 3-6 and 8-12 months in HTx and LTx. Effectiveness was assessed by antigenemia (pp65Ag) and a GCV therapeutic drug monitoring to document exposure. A total of 32 patients (11 HTx, 7 LTx, and 14 CFTx) received vGCV for 106+/-67 days in HTx versus 270+/-85 days in LTx and CFTx. Doses were 700+/-225, 915+/-60, and 820+/-150 mg/24 h in HTx, LTx, and CFTx showing acceptable mean trough GCV 0.75+/-0.5 mg/L. Two of 9 cases of neutropenia were attributable to vGCV. Three CMV donor-positive/recipient-negative CFTx patients presented positive pp65Ag; 2 developed CMV disease (6%). We found that vGCV 900 mg, adapted to renal function, was effective and safe for long CMV prophylaxis together with efficient exposure in thoracic transplantation.

Voriconazole is a new second-generation fluconazole-derived triazole. With greater potency against susceptible species and a broader spectrum of activity than fluconazole, it is the treatment of choice for invasive pulmonary aspergillosis and other fungal infections (Fusarium, Scedosporium/Pseudalleschezria) is indicated in a visit Candida infections refractory to fluconazole. We describe 7 cases of photosensitivity during treatment with voriconazole in a setting of immunodepression.The patients comprised 5 women and 2 men with a mean age of 38 years (17-67 years). Five had undergone pulmonary transplantation for mucoviscidosis, one had undergone kidney transplantation for lupus nephroangiosclerosis and one was on long-term systemic steroid treatment for Sjögren's syndrome. All patients had very severe immunosuppression and were receiving voriconazole for pulmonary aspergillosis (6 cases) or Scedosporium infection (1 case). Photosensitization appeared within 5 weeks to 14 months after the start of treatment, and in all cases followed exposure to sun, occasionally at low levels. In all cases, cutaneous lesions rapidly disappeared on discontinuation of treatment.There have been reports in the literature, although rare, of photosensitivity with voriconazole. Patients must be informed of the possibility of this adverse effect and sun protection must be recommended when voriconazole is prescribed, particularly during periods of intensive exposure.

With a survival rate of 70% at 3 years, cardiac transplantation is the best treatment for end-stage heart disease. However, progressive development of graft atherosclerosis is frequent. Diagnosis of transplant coronary disease remains difficult and non-invasive tests have proved relatively insensitive. Therefore, coronary angiography performed annually is still the gold-standard test for the detection of heart transplant vasculopathy. We analyzed the records of 96 patients (82 men and 14 women) who were transplanted from 1986 to 1996. Mean age was 53 +/- 2.7 and time elapsed from transplantation was mean 5.3 +/- 10 years. All patients had rest myocardial TI 201 perfusion SPECT, followed by MIBI gated SPECT after exercise. MIBI gated SPECT allows simultaneous evaluation of perfusion, regional LV function and global ejection fraction. Angiocoronarography, performed in all patients during the six months following radionuclide investigation, showed the presence of coronary heart vasculopathy in nine (9.3%). Seven of these patients had abnormal dual isotope imaging and 2 of them had normal perfusion but altered LV regional function. Sensitivity of dual isotope scintigraphy was 77% and specificity was 97.7%. Dual isotope scintigraphy is helpful to detect coronary vasculopathy in heart transplant recipients and may reduce indications of angiocoronarography.

Cystic fibrosis is a recessive disease that causes changes in mucus secretions, affecting different systems: respiratory, digestive, pancreatic, hepatic; resulting in obstructions and secondary infections. Transplantation may be used for the most severe forms and is then complicated by the pediatric context, the existence of malabsorption and secondary infections and the type of transplantation (pulmonary and/or hepatic). The follow-up is characterized by pulmonary infections and pulmonary chronic rejection. In our experience, the initiation of the immunosuppressive treatment must avoid corticoids in the early post-transplantation days and have recourse to intravenous cyclosporin (CyA) 2 mg/kg/day, given on average for one month in an oral form. In case of persistent acute rejection, tacrolimus (FK 506) is instituted. Oral CyA (10-12 mg/kg/day) seems more sensitive to malabsorption syndrome than FK 506 (0.2 mg/kg/day). In both cases, the development of an inhibitory metabolic interaction in the presence of itraconazole must be taken into account: used against aspergillosis, itraconazole is metabolized as CyA and FK 506 by Cyt P450 3A4. The intensity of the interaction is twofold for CyA versus fivefold for FK 506. The strategy for the use of other recently available immunosuppressives such as mycophenolate is under evaluation.

The knowledge of long-term changes in the transplanted heart is still incomplete. Among these changes that could potentially have an adverse effect on long-term cardiac function, myocardial fibrosis is of great concern. The aim of this study was to investigate the possible influence of acute or chronic rejection on the development of myocardial fibrosis in cardiac allografts.We used light microscopic computer-assisted morphometry of collagen density in 200 right ventricular endomyocardial biopsy specimens taken routinely in 21 heart transplant recipients during a mean follow-up period of 36 months (range, 12 to 84). The 21 patients were divided into two groups according to the presence of chronic rejection assessed by coronary angiography. The first group consisted of 11 patients with no chronic rejection; the second group consisted of 10 patients with chronic rejection. Both groups were divided into four subgroups according to the highest grade of acute rejection reached during the follow-up period (subgroup 1, no acute rejection or grade 1A; subgroup 2, grade 1B; subgroup 3, grades 3A or 3B; subgroup 4, grade 4). Patients of both groups were selected on the basis of similarity patterns in clinical characteristics and mean follow-up time.Patients with no chronic rejection had relatively little variation in serial determinations of myocardial collagen density. During the prechronic and chronic phases in patients with chronic rejection, we found no overall increase in myocardial collagen density. In both the chronic rejection and no chronic rejection groups there was no consistent relationship between myocardial collagen density and severity of acute rejection. In both groups there were occasional strikingly elevated myocardial collagen density values that were well above the other serial determinations. These elevated values of collagen density were mainly a result of scars, the sequellae of prior myocyte damage, because neither interstitial nor perivascular fibrosis could be detected.During this long-term follow-up study of endomyocardial biopsy samples, we found no significant association between either acute or chronic rejection and the later increase in myocardial collagen density.

We investigated extracorporeal photochemotherapy--which consists of the collection of blood mononuclear cells by means of a cell separator, their exposure to ultraviolet A light in the presence of a photoactivatable molecule such as 8-methoxypsoralen, and their intravenous reinjection into the patient--for the treatment of an acute lung rejection episode in a severely infected patient, assuming that its mechanism of action is an immunomodulation rather than an actual immunosuppression.Three weeks after the simultaneous beginning of antiinfectious and extracorporeal photochemotherapy treatments, the patient improved clinically. Acute lung rejection was no longer detectable histologically 4 weeks after the beginning of extracorporeal photochemotherapy. Twenty-two months after the beginning of extracorporeal photochemotherapy (47 months after transplantation), the patient was living a normal life.We believe this treatment may be considered for further studies not only in acute lung rejection therapy when intensive immunosuppression is contraindicated but also as a means of rejection prevention.

Treatment of transplant rejection with muromonab CD3 (Orthoclone OKT3) may result in haemodynamic instability and pulmonary oedema, which would question its prophylactic use. The aim of this study was to the evaluate haemodynamic and respiratory tolerance of prophylactic treatment of cardiac rejection with OKT3.Prospective clinical study.Twelve patients, whose pulmonary arterial resistances before transplantation were less than 400 dyn.s.cm-5, with haemodynamic and respiratory stability during the 4 hours before OKT3 administration.Patients under preventive haemodynamic support with isoprenaline 0.05 micrograms.kg-1.min-1 and dopamine 3 micrograms.kg-1.min-1. Immunosuppressive treatment with azathioprine 5 mg.kg-1 at d0 and 3 mg.kg-1 at d1 and d2 and with methylprednisolone 720 mg at d0 and 240 mg at d1 and d2. OKT3, 5 mg administered i.v. at d0, d1, d2. Respiratory and haemodynamic variables were recorded prior to (T0), 30 min (T1) and 360 min (T2) after injection of OKT3.Neither clinical nor radiological changes were observed after the OKT3 injections. At d0, T2, the heart rate increased and PaO2 and SaO2 decreased. At d1 and d2, T1, PaO2 decreased, and QS2QT at T1 d2 increased by nearly 3%.OKT3 does not result in major circulatory and haematosis changes, provided patients are selected, especially free of pretransplantation pulmonary hypertension. Prior to the treatment with OKT3, they should be in a satisfactory haemodynamic and respiratory status and receive high doses of corticosteroids.

The increase of organ transplantations during the last decades conjointly with the prescription of heavy immunosuppressive drugs, has led to an increased incidence of new invasive aspergillosis (IA). This study is a report of the Broussais Hospital experience from 1968 to 1993 on kidney, heart and heart and lungs transplantations. It concerns 21 IA cases. Incidence was 0.5% for kidney, 4.5% for heart and 18% for heart and lungs transplantations. The most important risk factors were the increase of immunosuppressive therapy (66% of the cases), neutropenia (19%), and renovation of the hospital wards (36%). Lung was the most frequent site of infection (95% of the cases), clinical symptoms were no significant. Diagnosis procedures were realised on biopsy (23%) and on bronchoalveolar lavage (66%). Usual amphotericin B treatment was disappointing: mortality rate of 77%, the liposomal preparation of the drug seemed to be more efficient: mortality rate of 50%. Itraconazole appeared to be used in succession with a careful adaptation of posology. Prophylactic amphotericin B in a local way (sprays and aerosols) led to a good efficiency jointly with the patient isolation during constructions in the hospital area.

Extracorporeal photochemotherapy is a recently developed immunomodulator treatment against heart and lung graft rejection. The recipient's mononuclear cells are screened and irradiated with UV-A in the presence of 8-methoxy-psoralene (8-MOP), then reinjected. We treated 4 patients who had begun to reject their heart and/or lung grafts, with this technique, using one session per week for 4 weeks, followed by one session every 2 weeks for 2 months, then one session per month. In all cases, extracorporeal photochemotherapy appeared to improve the clinical and biological status of these patients. Episodes of rejection which could not be reversed with immunosuppressor treatment alone were controlled.

Immunoglobulin abnormalities in serum from 76 heart-transplant recipients were examined by cellulose acetate and agarose gel electrophoresis. Monoclonal components were typed by immunofixation. IgG, IgA, and IgM and total kappa and lambda light chains were quantified by immunonephelometry. We confirm that both monoclonal and oligoclonal immunoglobulin banding are common in serum from these patients. Of the 149 serum samples examined, 21 (15%) had one monoclonal component and 53 (35%) had two or more. These monoclonal immunoglobulins were generally present at a low concentration and were transient. The class of immunoglobulins most commonly involved was IgG (about sevenfold more numerous than IgM); monoclonal IgA components and free light chains were not detected. The nephelometric kappa/lambda and heavy chain/light chain ratios were poor indicators of these abnormalities. Immunoglobulin abnormalities were not correlated with the sex and age of recipients, the pre-existing cardiopathy, the time since transplantation, or plasma concentrations of cyclosporine, but did correlate with plasma immunoglobulin concentration, biopsy findings, and viral infections, especially cytomegalovirus (CMV). A monoclonal IgG purified from a patient with a high titer of anti-CMV antibodies did not react with CMV antigens. The origin of these immunoglobulin abnormalities is unclear. Our data suggest that the presence of monoclonal or oligoclonal banding in heart-transplant recipients is of limited prognostic significance.

To evaluate the incidence, risk factors and effects of systemic hypertension on renal function and left ventricular hypertrophy after heart transplantation, 85 recipients under triple drug low low dosage immunosuppressive therapy were studied. After a mean follow-up of 12.5 +/- 8.7 months, high incidence of hypertension was observed in 67% of the patient and 71% had developed de novo hypertension. None of the pre-transplant nor post-transplant cardiovascular risk factors were significantly associated with post-transplant hypertension. Faster deterioration of renal function, as assessed by intraindividual variations of serum creatinine values, was demonstrated in hypertensive patients and appeared as an early indicator of cyclosporine nephrotoxicity in patients at risk for hypertension. [table: see text] Serial (early, intermediate, late) echocardiographic evaluations demonstrated early increase in left ventricular mass and in fractional shortening in both hypertensive and normotensive heart transplant recipients with sustained enhanced contractility in hypertensive patients. [table: see text] Further studies will help to determine the exact relationship between cyclosporine dosages and hypertension, and their respective roles in the development of renal insufficiency and left ventricular hypertrophy after heart transplantation.

The number of patients who survive heart transplantation has considerably increased in recent years, but mortality during the first 3 months still reaches 10 to 20 p. 100 depending on the authors. Among the various causes of death, acute graft deficiency due to pulmonary arterial hypertension plays an important role. In most cases, pulmonary vascular resistance has been misevaluated or its progress has not been foreseen. Between January 1985 and June 1988, 96 heart transplantations were performed at the Broussais Hospital, Paris. We thought that pulmonary vascular resistance could be better evaluated by using dobutamine to mimick transplantation and to assess pulmonary pressure and resistance variations associated with the increase in cardiac output. High doses of dobutamine ranging from 10 to 30 mcg/kg/min were administered to bring the basal cardiac output level up to the theoretical output level or to increase it by 50 p. 100. The 96 patients who had heart transplantation during the aforementioned period were divided into two groups: group I comprised 35 patients who were transplanted before dobutamine was used, while group II comprised 61 patients for whom the dobutamine test was always considered. The mortality rate was 11.75 p. 100 (4/35) in group I and nil in group II as regards death from pulmonary arterial hypertension (p = 0.04). We demonstrate that a single resistance value is not reliable, even when it is normal, when the cardiac output is low. Furthermore, there is no threshold value for contraindication, and indexing resistance alters the scale of values but does not enable normality to be defined. By using the dobutamine test we were able to reduce considerably the mortality due to pulmonary arterial hypertension and also to exclude orthotopic transplantation in some patients.

Gastrointestinal involvement has been reported in 12-21% of post-transplant lymphoproliferative disorders but is unusual in the setting of heart transplantation. We report four post-transplant lymphoproliferative disorders observed among the 174 heart transplant recipients of our series, all of which were primary malignant lymphomas of and confined to the digestive tract. The mean onset time from transplantation was 22 months. Small intestine lesions were present in all four patients, with gastric involvement in one. Histologically, the tumour was monomorphic of immunoblastic type in one case and polymorphic in the three other cases. Analysis of cytoplasmic immunoglobulins demonstrated the presence of a major monoclonal subset in all patients. Epstein-Barr virus genome was found in numerous tumour cells by in situ hybridization. The exclusive localization to the digestive tract and the lymphoepithelial lesions observed in two cases suggest that these lymphoproliferations might originate from mucosa-associated lymphoid tissue.

Preliminary results of this study were presented at the European Congress of Clinical Microbiology and Infectious Diseases, Helsinki, Finland, 16-19 May 2009; International audience; Mycobacterium genavense, a nontuberculous mycobacteri-um, led to devastating infections in patients with acquired immunode-ficiency syndrome (AIDS) before highly active antiretroviral therapy (HAART) was available, as well as in other immunocompromised patients. We conducted the current study to describe the features of this infection in patients infected with human immunodeficiency virus (HIV) in the HAART era and in non HIV-infected patients. We conducted a retrospective cohort survey in France. All patients with M. genavense infection diagnosed from 1996 to 2007 at the National Reference Center, Institut Pasteur, Paris, were identified and their clinical, laboratory, and microbiologic data were centralized in a single database. Twenty-five cases of M. genavense infection originating from 19 centers were identified. Twenty patients had AIDS, 3 had solid organ transplantation, and 2 had sarcoidosis. Sixty-four percent (n = 16) were male, mean age was 42 years, and median CD4 count was 13/mm 3 (range, 0Y148/mm 3) in patients with AIDS. Twenty-four patients had disseminated infection with fever (75%, n = 18), weight loss (79%, n = 19), abdominal pain (71%, n = 17), diarrhea (62.5%, n = 15), splenomegaly (71%, n = 17), hepatomegaly (62.5%, n = 15), or abdominal adenopathy (62.5%, n = 15). M. genavense was isolated from the lymph node (n = 13), intestinal biopsy (n = 9), blood (n = 6), sputum (n = 3), stool (n = 3), and bone marrow (n = 5). Eleven patients (44%) died, 8 (32%) were considered cured with no residual symptoms, and 6 (24%) had chronic symptoms. The 1-year survival rate was 72%. The prognosis of M. genavense infection in HIV-infected patients has dramatically improved with HAART. Clinical presentations in HIV and non-HIV immunocompromised patients were similar. (Medicine 2011;90: 223Y230) Abbreviations: AFB = acid-fast bacilli, AIDS = acquired immuno-deficiency syndrome, HAART = highly active antiretroviral therapy, HIV = human immunodeficiency virus, SOT = solid organ transplant.