Beyond the First Year: Epidemiology and Management of Late-Onset Opportunistic Infections After Kidney Transplantation.

Late opportunistic infections (OI) occurring beyond the first year after kidney transplantation (KT) are poorly described and not targeted by prophylactic strategies. We performed a ten-year retrospective monocentric cohort study describing epidemiology, risk factors and impact of late OI occurring 1 year after KT. We included clinically symptomatic OI requiring treatment besides BK virus nephropathy. Control groups included early OI occurring in the first year after KT, and KT recipients without OI since KT and alive with a functional allograft at 1 year. Among 1066 KT recipients, 185 (19.4%) presented a first episode of OI 21.0 (8.0-45.0) months after KT: 120 late OI (64.9%) and 65 early OI (35.1%). Late OI were mainly viral (N = 83, 69.2%), mostly herpes zoster (HZ) (N = 36, 43.4%). Pneumocystis represented most late fungal infections (N = 12/25, 48%). Compared to early OI, we reported more pneumocystis (p = 0.002) and less invasive aspergillosis (p = 0.01) among late OI. Patients with late OI were significatively younger at KT (54.0 ± 13.3 vs. 60.2 ± 14.3 years, p = 0.05). Patient and allograft survival rates between late OI and control groups were similar. Only age was independently associated with mortality. While late OI were not associated with higher mortality or graft loss, implementing prophylactic strategies might prevent such infections.

Tuberculosis in sickle cell disease patients.

OBJECTIVE: Tuberculosis (TB) disease has rarely been reported in patients with sickle cell disease, but it is associated with an increased risk of bacterial infections. In France, sickle cell disease is frequent in populations with the highest prevalence of TB disease. We aimed to highlight clinical aspects of TB disease in patients with sickle cell disease. PATIENTS AND METHODS: Over a 10-year period, we retrospectively included all adults with sickle cell disease who had a positive culture for Mycobacterium tuberculosis managed in the adult sickle cell center of Henri-Mondor hospital. Sickle cell patients with TB disease were matched for comparison to adults without hemoglobinopathy and with documented TB disease in a 1:2 ratio. Logistic regression mixed models were performed. RESULTS: Twelve patients with sickle cell disease and documented TB disease (median age: 29years; IQR [25-34]) were compared to 24 non-sickle cell patients (median age: 33years; IQR [27.5-38.5]). Baseline characteristics were similar between groups except for sickle cell disease. Ten of the 12 patients with sickle cell disease had pulmonary TB. TB disease characteristics were similar between sickle cell and non-sickle cell patients although sickle cell patients had fewer positive sputum smears for acid-fast bacilli (P=0.003) and fewer lung cavitations (P=0.03). CONCLUSIONS: TB disease in sickle cell patients was globally similar to non-sickle cell patients, even though less infectious. Regular follow-up in specialized centers might allow for earlier TB disease diagnosis in sickle cell patients.

Clinical description of the broad range of neurological presentations of COVID-19: A retrospective case series.

BACKGROUND: Neurological disorders associated with SARS-CoV-2 infection represent a clinical challenge because they encompass a broad neurological spectrum and may occur before the diagnosis of COVID-19. METHODS: In this monocentric retrospective case series, medical records from patients with acute neurological disorders associated with SARS-CoV-2 infection from medicine departments of an academic center in Paris area were collected between March 15th and May 15th 2020. Diagnosis of SARS-CoV-2 was ascertained through specific RT-PCR in nasopharyngeal swabs or based on circulating serum IgG antibodies. RESULTS: Twenty-six patients diagnosed with SARS-CoV-2 infection presented with neurological disorders: encephalitis (N=8), encephalopathy (N=6), cerebrovascular events (ischemic strokes N=4 and vein thromboses N=2), other central nervous system (CNS) disorders (N=4), and Guillain-Barré syndrome (N=2). The diagnosis of SARS-CoV-2 was delayed on average 1.6 days after the onset of neurological disorder, especially in case of encephalitis 3.9 days, encephalopathy 1.0 day, and cerebrovascular event 2.7 days. CONCLUSIONS: Our study confirms that COVID-19 can yield a broad spectrum of neurological disorders. Because neurological presentations of COVID-19 often occur a few days before the diagnosis of SARS-COV-2 infection, clinicians should take preventive measures such as patient isolation and masks for any new admission to avoid nosocomial infections. Anti-SARS-CoV2 antibody detection in RT-PCR SARS CoV-2 negative suspected cases is useful to confirm a posteriori the diagnosis of atypical COVID-19 presentations.

Molecular testing for respiratory pathogens in sickle cell disease adult patients presenting with febrile acute chest syndrome.

BACKGROUND: Differentiating acute chest syndrome (ACS) from community-acquired pneumonia (CAP) is challenging in adults presenting with major sickle cell disease (SCD) (semiological similarity, rare microbiological documentation). We aimed to assess the usefulness of nucleic acid amplification test (NAAT) for respiratory pathogens, in combination with standard bacteriological investigations, in febrile ACS adult patients presenting with major SCD. METHODS: We performed a prospective, monocentric, observational study of 61 SCD adults presenting with febrile ACS from February 2015 to April 2016. Systematic blood, urine, and respiratory specimens were collected, before antibiotic initiation, for culture, urinary antigen tests, serology, and NAAT for respiratory pathogens. RESULTS: A pathogen was detected in 12 febrile ACS (19.7%): four viruses (6.6%) (Rhinovirus; Influenza A/B), seven bacteria (11.4%) (S. aureus, S. pneumoniae, K. pneumoniae, L. pneumophila, M. pneumoniae), one mixed infection (1.6%) (S. aureus and Influenza B). NAAT only detected L. pneumophila in one case (serogroup 2). Apart from a significantly shorter antibiotic therapy duration (6.1 vs. 7.8 days, P=0.045), no difference was observed between undocumented and microbiologically-documented febrile ACS. CONCLUSION: Using NAAT for the detection of respiratory pathogens in adults presenting with SCD slightly improved the microbiological diagnostic of febrile ACS, although respiratory infections are not the main etiological factor.

Acute enteritis associated with Coxsackievirus A19 in a kidney transplant patient.

Diarrhea is a frequent complication after kidney transplantation, with an incidence rate between 22% and 51%. In many cases, the cause remains unknown. We describe here the first case, to our knowledge, of persistent diarrhea associated with Coxsackievirus A19 (CVA19) in a kidney transplant recipient. The patient was a 46-year-old man who received a deceased-donor kidney. He experienced delayed graft function because of donor kidney donation after circulatory determination of death. Maintenance immunosuppression consisted of low-dose cyclosporine, high-dose mycophenolate mofetil (MMF) (3 g/day), and prednisone (10 mg/day). He had severe diarrhea for 2 weeks associated with acute renal failure. No pathogens were found in the stool cultures. Enterovirus detection was positive by real-time polymerase chain reaction, and sequence analysis found CVA19 (from Enterovirus C group). Area under the curve of MMF was 48 mg.h/L. Because of the persistence of diarrhea, MMF was stopped and replaced by azathioprine. The diarrhea disappeared, but serum creatinine did not return to baseline. CVA19 rarely causes gastroenteritis. This case illustrates that MMF is not always the direct cause of diarrhea, and that new clinical infectious diseases will be detected with the expansion of molecular-based DNA diagnostics.

162 HIV-1 infected pregnant women and vertical transmission. Results of a prospective study.

BACKGROUND: Aim of this paper is to describe the changes over a 16-year period of the characteristics and management of HIV infected pregnant women. METHODS: Prospective study: analysis of data obtained from 162 women and 176 infants. Factors evaluated included: maternal socio-demographic level, immunological and virological parameters, antiretroviral therapy, mode of delivery, pregnancy outcome and babies follow-up. RESULTS: The proportion of women with heterosexual acquisition of infection has increased significantly from 13.5% in 1985-1989 to 47.1% in 1996-2001 (p<0.0005, Fisher's exact test), while the proportion acquiring HIV through injecting drugs has declined. Mean CD4 cell count at delivery was 535 x 106/l (+/-522.3 x 106/l). In 1990, 50% of mothers received antiretroviral therapy, rising significantly to 87.5% in 2000. The elective cesarean section was introduced in 1998 and its rate has increased to 75% in 2000. The vertical transmission rate changed from 9.5% in 1985-1989 to 14.3% in 1996-2000 (this difference was not statistically significant, Fisher's exact test). CONCLUSIONS: Social characteristics of the HIV-infected women have changed since the mid-1980s: in recent times women are having children at increasingly older ages and are more likely to know that they are HIV infected when they become pregnant. Antiretroviral therapy, elective caesarean delivery and avoidance of breastfeeding can reduce transmission of HIV, but the vertical transmission rate was unaffected by their use in our study and it remains high in comparison with rates reported from other studies.

Gram-positive bacterial resistance. A challenge for the next millennium.

Penicillin G was first used in 1941. Since then, the trend in bacterial infections has changed. New antibiotics have been developed and bacterial resistance has spread as a consequence. The spread of Gram positive resistant bacteria is related to an inappropriate use of antibiotics. Antibacterial agents are abused or overused in various fields: medicine itself, veterinary science and zootechnics. Now, at the beginning of the third millennium we have been forced to limit our therapeutic options in order to combat these insidious enemies. Selective antibiotic pressure on the microbial population, notably on enterococci and staphylococci, made these two pathogens recalcitrant to traditional chemotherapy. It is a matter of concern that today, vancomycin-resistant Enterococcus spp. (VRE) and vancomycin-intermediate and resistant Staphylococcus aureus (VISA and VRSA) are now being observed worldwide among emerging pathogens. Most pharmaceutical companies are today developing antimicrobial drugs that are active against Gram-positive bacteria. Quinupristin/dalfopristin and linezolid are the most promising drugs and are available only for serious infections; future agents being developed for multi-resistant Gram-positive infections include daptomycin and the glycyclines, although these are still in the development phase. Nevertheless, our group has had the opportunity to treat some serious infections with these drugs and the good results achieved are reported in this review.