Convalescent plasma transfusion for immunocompromised viremic patients with COVID-19: A retrospective multicenter study.

This study aims to assess the safety, virological, and clinical outcomes of convalescent plasma transfusion (CPT) in immunocompromised patients hospitalized for coronavirus disease 2019 (COVID-19). We conducted a retrospective multicenter cohort study that included all immunosuppressed patients with COVID-19 and RNAemia from May 2020 to March 2023 treated with CPT. We included 81 patients with hematological malignancies (HM), transplants, or autoimmune diseases (69% treated with anti-CD20). Sixty patients (74%) were vaccinated, and 14 had pre-CPT serology >264 BAU/mL. The median delay between symptom onset and CPT was 23 days [13-31]. At D7 post-CPT, plasma PCR was negative in 43/64 patients (67.2%), and serology became positive in 25/30 patients (82%). Post-CPT positive serology was associated with RNAemia negativity (p < 0.001). The overall mortality rate at D28 was 26%, being higher in patients with non-B-cell HM (62%) than with B-cell HM (25%) or with no HM (11%) (p = 0.02). Patients receiving anti-CD20 without chemotherapy had the lowest mortality rate (8%). Positive RNAemia at D7 was associated with mortality at D28 in univariate analysis (HR: 3.05 [1.14-8.19]). Eight patients had adverse events, two of which were severe but transient. Our findings suggest that CPT can abolish RNAemia and ameliorate the clinical course in immunocompromised patients with COVID-19.

Long-term neuro-functional disability in adult patients with community-acquired bacterial meningitis.

PURPOSE: To investigate the prevalence of neuro-functional disability and its determinants 12 months after community-acquired bacterial meningitis (CABM) in adult patients. METHODS: In a prospective multicenter cohort study (COMBAT), all consecutive cases of CABM were enrolled and followed up for 12 months. Neuro-functional disability at 12 months was evaluated using a combination of the Glasgow Outcome Scale (functional disability), and the modified Rankin Disability Scale (physical disability). Factors associated with neuro-functional disability were identified by multivariate logistic regression. RESULTS: Among 281 patients, 84 (29.9%) patients exhibited neuro-functional disability at 12 months: 79 (28.1%) with functional disability and 51 (18.1%) with physical disability. Overall, 6 patients (2.1%) died during the follow-up. The most common pathogen identified was Streptococcus pneumoniae (131/272, 48.2%); 77/268 patients (28.7%) had a physical disability at hospital discharge. Factors independently associated with 12-month neuro-functional disability were a pneumococcal meningitis (adjusted OR = 2.8; 95% confidence interval (CI) = [1.3; 6.7]), the presence of a physical disability at hospital discharge (aOR = 2.3; 95%CI = [1.2; 4.4]) and the presence of behavioral disorders at hospital-discharge (aOR = 5.9; 95%CI = [1.6; 28.4]). Dexamethasone use was not significantly associated with neuro-functional disability (OR = 0.2; 95%CI = [< 0.1;1.3]). CONCLUSION: Neuro-functional disability is frequently reported 12 months after CABM. Detailed neurological examination at discharge is needed to improve the follow-up. TRIAL REGISTRATION: NCT01730690.

Compound heterozygous PKHD1 variants cause a wide spectrum of ductal plate malformations.

Ductal plate malformations (DPM) present with a wide phenotypic spectrum comprising Von Meyenburg complexes (VMC), Caroli disease (CD), Caroli syndrome (CS), and autosomal recessive polycystic kidney disease (ARPKD). Variants in PKHD1 are responsible for ARPKD and CS with a high inter- and intra-familial phenotypic variability. Rare familial cases of CD had been reported and exceptional cases of CD are associated with PKHD1 variants. In a family of three siblings presenting with a wide spectrum of severity of DPM, we performed whole exome sequencing and identified two PKHD1 compound heterozygous variants (c.10444G>A; p.Arg3482Cys and c.5521C>T; p.Glu1841Lys), segregating with the symptoms. Two compound heterozygous PKHD1 variants, including one hypomorphic variant, were identified in two other familial cases of DPM with at least one patient presenting with CD. This report widens the phenotypic variability of PKHD1 variants to VMC, and others hepatic bile ducts malformations with inconstant renal phenotype in adults and highlights the important intra-familial phenotypic variability. It also showed that PKHD1 might be a major gene for CD. This work adds an example of the contribution of exome sequencing, not only in the discovery of new genes but also in expanding the phenotypic spectrum of well-known disease-associated genes, using reverse phenotyping.

Infective endocarditis in the Pacific: clinical characteristics, treatment and long-term outcomes.

INTRODUCTION: Data on clinical characteristics and outcomes of infective endocarditis (IE) in the Pacific are scarce. METHODS: Retrospective hospital-based study in New Caledonia, a high-income country, on patients aged over 18 years with definite IE according to the modified Duke criteria (2005-2010). RESULTS: 51 patients were included: 31 (60.8%) men; median age of 52.4 years (IQR 33.0-70.0). Left-sided IE accounted for 47 (92.2%) patients: native valve IE in 34 (66.7%) and prosthetic valve IE in 13 (25.5%). The main underlying heart disease included: rheumatic valve disease in 19 (37.3%), degenerative heart valve disease in 12 (23.5%) and congenital heart disease in 6 (11.8%). Significant comorbidities (Charlson's score >3) were observed in 20 (38.7%) patients. Infection was community acquired in 43 (84.3%) patients. Leading pathogens included Staphylococcus aureus in 16 (31.4%) and Streptococcus spp in 15 (29.4%) patients. Complications were noted in 33 patients (64.7%) and 24 (47.1%) were admitted to the intensive care unit. Cardiac surgery was eventually performed in 22 of 40 (55.0%) patients with a theoretical indication. None underwent emergent cardiac surgery (ie, first 24 h); 2 (3.9%) were operated within 7 days; and 20 (39.2%) beyond 7 days. 11 (21.6%) patients died in hospital and 21 (42.9%) were dead after a median follow-up of 28.8 months (IQR 4.6-51.2). Two (3.9%) were lost to follow-up. CONCLUSIONS: In New Caledonia, IE afflicts relatively young patients with rheumatic heart disease, and carries high complication and mortality rates. Access to heart surgery remains relatively limited in this remote archipelago.

Changing patterns of disseminated gonococcal infection in France: cross-sectional data 2009-2011.

OBJECTIVES: Disseminated gonococcal infections (DGIs) are rare. We describe the characteristics of DGIs in France. METHODS: This is a 3-year retrospective analysis of DGI cases collected through two networks of microbiologists and infectious disease specialists in France between 2009 and 2011. DGI was defined either by the isolation of Neisseria gonorrhoeae from blood and synovial fluid or by the existence of a clinical syndrome consistent with DGI and the isolation of N gonorrhoeae from any site. We describe the epidemiological, clinical and microbiological characteristics and outcomes of DGIs. RESULTS: 21 patients (9 women, 12 men; 18-62 years old) were diagnosed with DGI. The number of DGI cases increased between 2009 and 2011. Two men who had sex with men were coinfected with HIV. We found 28 extragenital locations, including arthritis (14 cases), tenosynovitis (7), skin lesions (4), endocarditis (1), prostatitis (1) and pelvic inflammatory disease (1). Genital signs were present in five patients. The diagnosis was confirmed by cultures in 20 patients-blood (4), synovial fluid (11), genital (3), throat (1), urine (1)-and by molecular biology on a pharyngeal swab in 1 patient. Seven cases were resistant to fluoroquinolones. The patients were treated with ceftriaxone, associated with corticosteroids (two cases) and surgery (six cases). Four patients had joint sequelae. CONCLUSIONS: DGIs are increasing. Men seem to be at higher risk than women. Joint involvement was common. Microbiological diagnosis was based on culture, however molecular biology using pharyngeal swabs was helpful when cultures were negative.

Risk factors and predictors of severe leptospirosis in New Caledonia.

BACKGROUND: Leptospirosis is a major public health concern in New Caledonia (NC) and in other tropical countries. Severe manifestations of the disease are estimated to occur in 5-15% of all human infections worldwide and factors associated with these forms are poorly understood. Our objectives were to identify risk factors and predictors of severe forms of leptospirosis in adults. METHODS AND FINDINGS: We conducted a retrospective case-control study of inpatients with laboratory-confirmed leptospirosis who were admitted to two public hospitals in NC in 2008-2011. Cases were patients with fatal or severe leptospirosis, as determined by clinical criteria. This approach was meant to be pragmatic and to reflect the routine medical management of patients. Controls were defined as patients hospitalized for milder leptospirosis. Risk and prognostic factors were identified by multivariate logistic regression. Among the 176 patients enrolled in the study, 71 had criteria of severity including 10 deaths (Case Fatality Rate = 14.1%). Three risk factors were independently associated with severe leptospirosis: current cigarette smoking (OR = 2.94 [CI 1.45-5.96]); delays >2 days between the onset of symptoms and the initiation of antibiotherapy (OR = 2.78 [CI 1.31-5.91]); and Leptospira interrogans serogroup Icterohaemorrhagiae as the infecting strain (OR = 2.79 [CI 1.26-6.18]). The following post-admission laboratory results correlated with poor prognoses: platelet count ≤50,000/µL (OR = 6.36 [CI 1.79-22.62]), serum creatinine >200 mM (OR = 5.86 [CI 1.61-21.27]), serum lactate >2.5 mM (OR = 5.14 [CI 1.57-16.87]), serum amylase >250 UI/L (OR = 4.66 [CI 1.39-15.69]) and leptospiremia >1000 leptospires/mL (OR = 4.31 [CI 1.17-15.92]). CONCLUSIONS: To assess the risk of developing severe leptospirosis, our study illustrates the benefit for clinicians to have: i) the identification of the infective strain, ii) a critical threshold of qPCR-determined leptospiremia and iii) early laboratory results. In New Caledonia, preventative measures should focus on early presumptive antibacterial therapy and on rodent (reservoir of Icterohaemorrhagiae serogroup) control.

Risk factors for carbapenem-resistant Acinetobacter baumannii infections at a tertiary care hospital in New Caledonia, South Pacific.

In New Caledonia, South Pacific, Acinetobacter baumannii is a nosocomial pathogen. OXA-23 carbapenem-resistant A. baumannii (CRAB) has been ranked third among all multidrug-resistant (MDR) bacteria at the main hospital of Nouméa in New Caledonia (24.8%, 50/202 isolates). In the present study, risk factors and outcomes for 50 patients with CRAB infection were compared with those of 152 patients infected with other MDR bacteria. Independent risk factors for infection with CRAB were respiratory ward admission (odds ratio 2.8, 95% confidence interval 1.1-7.1) and previous treatment with quinolones, ß-lactams and anti-MRSA antibiotics. The 30-day mortality was higher for CRAB infections compared with other MDR infections (14% vs 3.3%, p = 0.006). These findings highlight the importance of knowing specific local characteristics relating to the ecology and patterns of resistance of MDR bacteria so as to avoid the emergence of unexpected pan-resistant bacteria.

In-hospital mortality of infective endocarditis: prognostic factors and evolution over an 8-year period.

Infective endocarditis (IE) remains severe. Few predictors of prognosis have been identified. It is not known whether mortality of IE has decreased during recent decades. 559 definite cases of IE were collected in a prospective population-based survey in 1999 in France. In-hospital death rate was 17%. It was lower in operated patients (14.4% vs 19.3%), although not significantly so. In multivariate analysis, the following variables were independent and significant predictors of mortality: history of heart failure (odds ratio: 2.65), history of immunosuppression (OR: 3.34), insulin-requiring diabetes mellitus (OR: 7.82), left-sided IE (OR: 1.97), heart failure (OR: 2.19), septic shock (OR: 4.33), lower Glasgow coma scale score (OR: 4.09), cerebral haemorrhage (OR: 9.46), and higher C-reactive protein level (OR: 2.60). Adjusted mortality was significantly lower in 1999 than in 1991 (22%): OR: 0.64 (p = 0.03). Thus, in a large and unselected cohort of patients hospitalized for IE in 1999, in-hospital mortality rate was lower than in 1991. Multivariate analysis identified factors classically known as having an impact on mortality. However, other factors, such as age and responsibility of Staphylococcus aureus, were not retained in the model.

Melioidosis in New Caledonia.

Recognized melioidosis-endemic areas are widening. In the South Pacific, melioidosis is endemic in New Caledonia, northern Australia, and Papua New Guinea. We report the first 4 documented cases of human melioidosis from New Caledonia. Molecular typing of 2 Burkholderia pseudomallei isolates suggests a link to Australian strains.

Frequent carriage of Panton-Valentine leucocidin genes by Staphylococcus aureus isolates from surgically drained abscesses.

Between 1 February and 15 April 2002, 95 patients were admitted to Gaston Bourret Territorial Hospital (New Caledonia, France) for drainage of community-acquired soft tissue abscesses. Staphylococcus aureus was detected in 68 cases (72%). Two-thirds of the patients with S. aureus infection had furuncles, which were located on the limbs in 82% of cases. The median interval between symptom onset and hospital admission was 5.7 days. Three-quarters of the patients were Melanesians living in tribes. Fifty-four S. aureus isolates were screened for toxin genes. Panton-Valentine leucocidin (PVL) genes were detected in 48 isolates (89%), the exfoliative toxin A gene was detected in 1 isolate, and no toxin genes were detected in 4 isolates. S. aureus nasal carriage was detected in 39.7% of patients with S. aureus infections. Two infecting S. aureus strains and two nasal carriage strains were resistant to methicillin. Comparative pulsed-field gel electrophoresis, performed in 16 cases, showed that five of six patients with PVL-positive nasal carriage strains were infected by the same strains. In contrast, 8 of 10 patients with PVL-negative nasal carriage strains were infected by PVL-positive strains. PVL genes thus appear to be a major virulence factor in both primary and secondary S. aureus skin infections.

Endocarditis in patients with a permanent pacemaker: a 1-year epidemiological survey on infective endocarditis due to valvular and/or pacemaker infection.

To describe characteristics of infective endocarditis (IE) in pacemaker (PM) recipients, including the annual incidence and exact localization of IE on PM leads, cardiac valves, or both, we prospectively analyzed 45 PM recipients from a group of 559 patients with definite IE who responded to a population-based survey conducted in France in 1999. Thirty-three patients had definite PM-lead IE (group I), and 12 had valvular IE without evidence of PM involvement (group II). The valvular structure was involved in almost two-thirds of IE cases among PM recipients. Of the 28 patients (62%) with valvular IE, 10 group I patients had tricuspid involvement, and 6 group I patients had left heart-valve involvement. The most frequent causative organisms in groups I and II were staphylococci (82%) and streptococci (50%), respectively. The incidence of age- and sex-standardized IE was 550 cases/million PM recipients per year. The incidence of IE with PM involvement is between that of valvular IE in the general population and prosthetic valve IE.