Factors Associated With Genotypic Resistance and Outcome Among Solid Organ Transplant Recipients With Refractory Cytomegalovirus Infection.

Genotypically resistant cytomegalovirus (CMV) infection is associated with increased morbi-mortality. We herein aimed at understanding the factors that predict CMV genotypic resistance in refractory infections and disease in the SOTR (Solid Organ Transplant Recipients) population, and the factors associated with outcomes. We included all SOTRs who were tested for CMV genotypic resistance for CMV refractory infection/disease over ten years in two centers. Eighty-one refractory patients were included, 26 with genotypically resistant infections (32%). Twenty-four of these genotypic profiles conferred resistance to ganciclovir (GCV) and 2 to GCV and cidofovir. Twenty-three patients presented a high level of GCV resistance. We found no resistance mutation to letermovir. Age (OR = 0.94 per year, IC95 [0.089-0.99]), a history of valganciclovir (VGCV) underdosing or of low plasma concentration (OR= 5.6, IC95 [1.69-20.7]), being on VGCV at infection onset (OR = 3.11, IC95 [1.18-5.32]) and the recipients' CMV negative serostatus (OR = 3.40, IC95 [0.97-12.8]) were independently associated with CMV genotypic resistance. One year mortality was higher in the resistant CMV group (19.2 % versus 3.6 %, p = 0.02). Antiviral drugs severe adverse effects were also independently associated with CMV genotypic resistance. CMV genotypic resistance to antivirals was independently associated with a younger age, exposure to low levels of GCV, the recipients' negative serostatus, and presenting the infection on VGCV prophylaxis. This data is of importance, given that we also found a poorer outcome in the patients of the resistant group.

Specificities of Meningitis and Meningo-Encephalitis After Kidney Transplantation: A French Retrospective Cohort Study.

Kidney transplant recipients develop atypical infections in their epidemiology, presentation and outcome. Among these, meningitis and meningoencephalitis require urgent and adapted anti-infectious therapy, but published data is scarce in KTRs. The aim of this study was to describe their epidemiology, presentation and outcome, in order to improve their diagnostic and management. We performed a retrospective, multicentric cohort study in 15 French hospitals that included all 199 cases of M/ME in KTRs between 2007 and 2018 (0.9 case per 1,000 KTRs annually). Epidemiology was different from that in the general population: 20% were due to Cryptococcus neoformans, 13.5% to varicella-zoster virus, 5.5% to Mycobacterium tuberculosis, and 4.5% to Enterobacteria (half of which produced extended spectrum beta-lactamases), and 5% were Post Transplant Lymphoproliferative Disorders. Microorganisms causing M/ME in the general population were infrequent (2%, for Streptococcus pneumoniae) or absent (Neisseria meningitidis). M/ME caused by Enterobacteria, Staphylococci or filamentous fungi were associated with high and early mortality (50%-70% at 1 year). Graft survival was not associated with the etiology of M/ME, nor was impacted by immunosuppression reduction. Based on these results, we suggest international studies to adapt guidelines in order to improve the diagnosis and the probabilistic treatment of M/ME in SOTRs.

Infectious complications in HIV-infected kidney transplant recipients.

Renal transplantation is now a viable alternative for dialysis in HIV-infected patients who achieve good immunovirological control with current antiretroviral therapy regimens available. However, there are few studies that analyze the incidence of post-transplant infections in this population. In this study, a retrospective analysis of data files of 24 HIV-infected kidney transplant (KT) recipients was undertaken, matched to 21 non-infected controls. All patients received induction with anti-interleukin-2 antibodies and were followed in the Pitié-Salpêtrière Hospital in Paris, France. The rate of incidence of post-transplant infections was 23.58 and 26.98/100 patient-years, in HIV-infected and HIV-negative groups (relative risk [RR]: 0.90; 95% confidence interval [CI]: 0.58-1.39; p = 0.63). In HIV-infected KT recipients, bacterial infections were the most frequent (67.7%), followed by viral (14.7%) and fungal and parasitic infections (8.8%). Similar trends were seen in the control group. Incidence of opportunistic infections was similar in HIV-infected KT recipients and controls (38.2 vs. 26.5%; p = 0.44). There were three post-transplant HIV reactivations in two patients, secondary to poor adherence to medication. HIV status did not influence survival, but infections increased the risk of unfavorable outcome. Incidence of post-transplant infections was similar in HIV-infected KT recipients and controls. Infections, but not HIV status, had adverse effects on patient and graft survival.

Unique case report of a chromomycosis and Listeria in soft tissue and cerebellar abscesses after kidney transplantation.

BACKGROUND: Chromomycosis is a rare mycotic infection encountered in tropical and subtropical regions. The disease presents as a slowly-evolving nodule that can become infected with bacteria. Here, we describe a unique association of abscesses caused by a chromomycosis and Listeria monocytogenes in a kidney transplant recipient, and didactically expose how the appropriate diagnosis was reached. CASE PRESENTATION: A 49-year old male originating from the Caribbean presented a scalp lesion which was surgically removed in his hometown where it was misdiagnosed as a sporotrichosis on histology, 3 years after he received a kidney transplant. He received no additional treatment and the scalp lesion healed. One year later, an abscess of each thigh due to both F. pedrosoi and L. monocytogenes was diagnosed in our institution. A contemporary asymptomatic cerebellar abscess was also found by systematic MRI. An association of amoxicillin and posaconazole allowed a complete cure of the patient without recurring to surgery. Histological slides from the scalp lesion were re-examined in our institution and we retrospectively concluded to a first localisation of the chromomycosis. We discuss the possible pathophysiology of this very unusual association. CONCLUSION: In this case of disseminated listeriosis and chromomycosis, complete cure of the patients could be reached with oral anti-infectious treatment only.

[Cerebral vasculitis with aneurysms caused by varicella-zoster virus infection during AIDS: a new clinicoangiographical syndrome]. / Vascularite cérébrale avec sténoses et ectasies due au virus varicelle-zona au cours de l'infection par le VIH : une nouvelle entité compliquant le sida.

We describe three cases of cerebral angiopathy with aneurysms caused by a meningeal varicella-zoster virus infection occurring during AIDS. The clinical picture was rather stereotyped: severe immunocompromission due to HIV infection, ongoing multifocal cerebrovascular disease with territorial infarcts, lymphocytic meningitis with normal glucose content (two cases) or hypoglycorrhachia (one case), multifocal cerebral vasculopathy with narrowings and aneurysms, healing with or without neurological sequelae after intravenous aciclovir treatment. The diagnosis of varicella-zoster virus-induced angiopathy was ascertained by the positive specific PCR in the CSF in the three cases and by the results of the cerebromeningeal biopsy in one case. Although, varicella-zoster virus is already known as a cause of cerebral angiopathy both in the immunocompetent and the immunocompromised, these three cases are the first ever described of a particular angiopathy with narrowings and ectasias complicating AIDS. The infectious treatable cause and the risk of aggravation without treatment require early active oriented investigations in case of a patient with cerebrovascular disease occurring during HIV infection, including a CSF study with varicella-zoster PCR, to allow specific antiviral treatment. In our three cases, aciclovir intravenous treatment (30mg/kg per day) enabled VZ virus clearing from the CSF and stopped the course of the vasculopathy.

[Ovarian vein thrombophlebitis and post-partum fever]. / Thrombophlébite de la veine ovarienne et fièvre du post-partum.

INTRODUCTION: Ovarian vein thrombophlebitis (OVT) is a rare but potentially threatening complication of the postpartum period. Diagnosing it may be of some difficulty especially in case of symptoms mimicking appendicitis or pyelonephritis. EXEGESIS: We report 2 patients with postpartum right OVT. The clinical presentation included high grade fever, and pain, lumbar in one case, of the right flank in the other. Pulmonary embolism complicated both cases. CONCLUSION: Diagnostic and therapeutic management of OVT was transformed by progresses in medical imaging during the 1980's. However, optimal duration of anticoagulant treatment and secondary prevention indications have to be determined.

Tyrosine kinases wee1 and mik1 as effectors of DNA replication checkpoint control.

Cell cycle studies have revealed mechanisms that prevent cell division if DNA fails to be completely replicated or sustains damage. Here we focus on the evidence from yeast genetics that the wee1 and mik1 tyrosine kinases cooperate in the inhibitory phosphorylation of cdc2p, and the possibility that these kinases function in pathways that ensure the integrity of the genome prior to cell division. We also review the progress in cloning and analysing wee1-like tyrosine kinases from higher eukaryotes, and the evidence for and against their functioning in ensuring DNA replication prior to mitosis. Finally, we discuss the genes involved in these feedback controls and suggest that wee1p and mik1p might be the ultimate effectors that prevent mitosis when a checkpoint is triggered.