Trimethoprim/sulfamethoxazole for nocardiosis in solid organ transplant recipients: Real-life data from a multicentre retrospective study.

BACKGROUND: Little is known regarding the optimal management of nocardiosis among solid organ transplant (SOT) recipients. It is often suggested to avoid trimethoprim/sulfamethoxazole (TMP-SMX) monotherapy in heavily immunocompromised patients (such as SOT recipients) and/or in case of severe or disseminated nocardiosis. Our aim was to report our experience with TMP-SMX monotherapy in SOT recipients with nocardiosis. METHODS: Using data from a previously published European study, we assessed the incidence of adverse events in SOT recipients receiving TMP-SMX monotherapy and assessed its effectiveness. RESULTS: Thirty-one SOT recipients with nocardiosis were included, mostly kidney transplant recipients (20/31, 65%). Eleven (36%) had disseminated infection, and four (13%) had brain nocardiosis. Most patients had lung and/or pleural involvement (26/31, 84%). Daily dose of trimethoprim at initiation was 10 [6.4-14.8] mg/kg. The median estimated glomerular filtration rate at time of diagnosis of nocardiosis was 44 [30-62] ml/min/1.73 m². TMP-SMX was discontinued prematurely in one third of the patients (10/31, 32%, mostly for hematological toxicity [n = 3] or increased serum creatinine [n = 3]). Focusing on the 24 (77%) patients who completed at least 30 days of TMP-SMX monotherapy, 4 had late (>30 days) drug discontinuation, 1 experienced treatment failure, and 19 completed planned TMP-SMX monotherapy. Clinical outcome was favorable in these 19 patients, despite the fact that 8 (42%) had disseminated infection and 2 (11%) brain nocardiosis. Overall, all-cause 1-year mortality was 10% (3/31). CONCLUSIONS: TMP-SMX monotherapy appears to be effective for the treatment of most nocardiosis among SOT recipients. Interventional studies are needed to compare its safety and effectiveness with those of other regimens used to treat posttransplant nocardiosis.

COVID-19 Repeated Convalescent Plasma Collection: Analysis of 149 Donations from 88 French Military Health Workers.

BACKGROUND: Passive therapy with convalescent plasma (CP) could be an effective and safe treatment option in COVID-19 patients. Neutralizing antibodies present in CP generated in response to SARS-CoV-2 infection and directed against the receptor-binding domain of the spike protein are considered to play a major role in the viral clearance. CP infusion may also contribute to the modulation of the immune response through its immunomodulatory effect. We describe for the first time the effectiveness of a CP collection protocol from repeated donations in young patients. MATERIALS AND METHODS: We enrolled health service workers who experienced mild to moderate COVID-19 and from whom several donations have been collected. No minimal severity threshold and no biological cure criteria were required. Donors could return to a second plasma donation 14 days after the first donation. A minimal neutralizing antibody titer of 1:40 was considered for clinical use. RESULTS: Eighty-eight donors were included (median age 35 [28-48] years, 41 women), and 149 plasma products were collected. COVID-19 were mainly WHO stage 2 infections (96%). Among the 88 first donations, 76% had neutralizing antibody titers higher than or equal to 1:40. Eighty-eight percent of donors who came for a second donation had a neutralizing antibody titer of 1:40. Median durations were 15 (15-19) and 38 (33-46) days from the first to the second donation and from recovery to the second donation, respectively. Sixty-nine percent of donors who came for a third donation had a neutralizing antibody titer of 1:40. Median durations were 16 (13-37) and 54 (49-61) days from the second to the third donation and from recovery to the third donation, respectively. No significant difference was observed between the IgG ratio and the age of the donors or the time between recovery and donation. The average IgG ratio did not significantly vary between donations. When focused on repeated blood donors, no significant differences were observed either. CONCLUSION: The recruitment of young patients with a mild to moderate CO-VID-19 course is an efficient possibility to collect CP with a satisfactory level of neutralizing antibodies. Repeated donations are a well-tolerated and effective way of CP collection.

Reactivation of Epstein-Barr virus among intensive care patients: a prospective observational study.

PURPOSE: Herpesvirus reactivation has been documented among patients in the intensive care unit (ICU) and is associated with increased morbidity and mortality, particularly for cytomegalovirus (CMV). Epstein-Barr virus (EBV) has been poorly studied despite >95% of the population being seropositive. Our preliminary study suggested an association between EBV reactivation and increased morbidity and mortality. This study aimed to investigate this association among patients admitted to the ICU. METHODS: In this multicenter prospective study, polymerase chain reaction was performed to quantify EBV in patients upon ICU admission and then twice a week during their stay. Follow-up was 90 days. RESULTS: The study included 129 patients; 70 (54.3%) had EBV reactivation. On day 90, there was no difference in mortality rates between patients with and without reactivation (25.7% vs 15.3%, p = 0.22). Patients with EBV reactivation at admission had increased mortality compared with those without reactivation and those with later reactivation. EBV reactivation was associated with increased morbidity. Patients with EBV reactivation had fewer ventilator-free days at day 28 than those without reactivation (18 [1-22] vs. 21 days [5-26], p = 0.037) and a higher incidence of acute respiratory distress syndrome (34.3% vs. 17%, p = 0.04), infections (92.9% vs. 78%, p = 0.03), and septic shock (58.6% vs. 32.2%, p = 0.004). More patients with EBV reactivation required renal replacement therapy (30% vs. 11.9%, p = 0.02). EBV reactivation was also associated with a more inflammatory immune profile. CONCLUSION: While EBV reactivation was not associated with increased 90-day mortality, it was associated with significantly increased morbidity.

[Malaria in 2022: clinical and therapeutic aspects]. / Le paludisme en 2022 : aspects cliniques et thérapeutiques.

In 2022 as in 1884, the clinical presentation of uncomplicated malaria is unspecific: fever of variable intensity, continuous or rhythmic, chills, flu syndrome, headache, respiratory and digestive disorders. At any time, it can evolve into a severe form (ex-pernicious attack or cerebral malaria) or even lethal. By reading again Alphonse Laveran's book on malarial fevers, we realized to what extent the observations made at that time allowed for a methodical and orderly description of the clinical forms of malaria, very close to what we can still observe today. No symptom or sign is pathognomonic of the disease. Only the detection of plasmodia or "malaria microbes" by direct or immuno-chromatographic methods allows for diagnostic confirmation, which is a prerequisite for the implementation of a curative treatment.Serendipity, synthetic chemistry and traditional medicine are the three methods that led to the discovery and large-scale production of antimalarial drugs. Serendipity for quinine, synthetic chemistry for chloroquine, and research conducted around traditional Chinese medicine for artemisinin and its derivatives. The latter have marked a real revolution in the management of malaria, both in its uncomplicated and severe forms. However, as with other antimalarial drugs, its medium- and long-term efficacy is compromised by the emergence and spread of resistance in malaria parasites, particularly P. falciparum. The control and eradication of malaria therefore require continued research in both prevention and therapy.The disease so well described by Alphonse Laveran has not yet said its last word….

Reasons for stopping Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC): A retrospective study to improve future patient selection.

To improve the prognosis and maintain quality of life in patients with peritoneal metastasis (PM), a novel treatment has been introduced-pressurized intraperitoneal aerosol chemotherapy (PIPAC). The majority of teams propose at least 3 PIPAC procedures. However, for many patients PIPAC is stopped after only one or two procedures. The aim of this study was to identify the reasons for stopping PIPAC after only one or two procedures and to establish a profile of poor candidates. This retrospective, multicenter cohort study included all patients who underwent PIPAC in three French expert centers between 2015 and 2021. A total of 268 PIPAC procedures were performed in 89 patients. Of them, 48.3% of patients underwent fewer than three procedures: 28.1% had one, 20.2% two and 51.7% three or more PIPAC procedures. The main reason for stopping PIPAC, regardless of the number of procedures, was disease progression, in 55.8% of cases. Other reasons for stopping PIPAC were non-access to the abdominal cavity (7.9%), conversion to cytoreductive surgery (13.5%), post-PIPAC adverse events (7.9%), patients' wishes (10.1%) and death (2.2%). In univariate analysis, patients who received fewer than three PIPACs less frequently had chemotherapy beforehand (91% vs 100%, p = 0.05), less frequently had bimodal treatment (70% vs 87%, p = 0.04), had more ascites (median 80 ml vs 50 ml, p = 0.05) and more frequently had carcinomatosic ascites (48.8% vs 23.9%, p < 0.01). Performing PIPAC alone in chemotherapy-naïve patients with ascites should be avoided.

Abbott® ID NOW™ COVID-19 rapid molecular assay versus Hologic® Panther Aptima™ SARS-CoV-2 assay in nasopharyngeal specimens: results from 1-year retrospective study in an emergency department.

We compared ID Now™ and Hologic® Panther Aptima™ for the detection of SARS-COV-2. ID Now™ showed a positive and negative percent agreement of 86.9% and 99.7% respectively. This facilitates faster clinical decision-making, along with the rapid implementation of infection control measures, and improvement of patient flow in the emergency department toward inpatient wards.

Renal abscess caused by Panton-Valentine leukocidin-producing Staphylococcus aureus: report of an unusual case and review of the literature.

BACKGROUND: Renal abscesses are rare and mainly caused by an ascending infection due to Gram-negative microorganisms. We report the first case of a renal abscess caused by Panton-Valentine leukocidin-producing Staphylococcus aureus in an immunocompetent patient, and we present a comprehensive review of the literature. CASE PRESENTATION: A 20-year-old immunocompetent woman had a 2-month history of left-sided back pain, fever and urinary symptoms. Urinalysis showed leukocyturia (19,000/mm3) without bacteriuria. Intravenous cefotaxime treatment was initiated. A computed tomographic scan showed a large abscess in the left kidney. Computed tomographic percutaneous drainage was done and cultures of abscess and blood grew methicillin-susceptible Panton-Valentine leukocidin-producing Staphylococcus aureus. Treatment was switched to cefazoline and then to clindamycin for 21 days. The patient quickly improved and the abscess was completely resolved 6 months after end of antibiotic treatment. CONCLUSION: To our knowledge, this is the first report of a renal abscess caused by Panton-Valentine leukocidin-producing Staphylococcus aureus. Treatment with percutaneous drainage and an antibiotic with toxin inhibiting effect was successful.

Invasive Nocardiosis: Disease Presentation, Diagnosis and Treatment - Old Questions, New Answers?

Nocardia spp. is an environmental filamentous Gram-positive bacterium that may cause infections in humans and, despite recent progress, many challenges remain regarding the management of nocardiosis. This review aims at describing most recently published data regarding the diagnosis, treatment and follow-up of patients with invasive nocardiosis. As nocardiosis mainly affects patients with cell-mediated immunity defects, a comprehensive workup is mandatory in case of invasive nocardiosis occurring in "apparently healthy patients". Indeed, invasive nocardiosis might reveal an unknown primary immunodeficiency or the presence of anti-GM-CSF autoantibodies. Even if the diagnosis of nocardiosis mostly relies on direct examination and bacterial culture, a genus-specific PCR may be used for the detection of Nocardia, when directly performed on a clinical sample. Brain imaging should always be performed, even in the absence of neurological symptoms. Cotrimoxazole (trimethoprim/sulfamethoxazole), linezolid, parenteral cephalosporins, carbapenems and amikacin may be used as initial antibiotics to treat nocardiosis. Cotrimoxazole or linezolid can be used as monotherapy in selected patients without brain involvement. Although treatment duration has historically been set to at least 6 months in the absence of central nervous system involvement, shorter durations (<120 days) seem to be associated with a favourable outcome.