Investigation of CryptoPS LFA-positive sera in patients at risk of cryptococcosis.

Cryptococcal antigen (CrAg) is a capsule polysaccharide antigen that can be detected in the fluids of patients with cryptococcal infections. Cryptococcal Antigen Latex Agglutination System (CALAS), enzyme-linked immunosorbent assays (EIA), and lateral flow assay (LFA) are the main methods available. Two main commercial LFA kits are available: CryptoPS (Biosynex, Illkirch Graffenstaden, France) and CrAg LFA (IMMY, Inc. USA). In our lab, we prospectively used CryptoPS as a screening tool in serum for confirmed positive results with CALAS. We investigated the rigor of the CryptoPS test in serum in a multicentric evaluation over 3 years. To improve the specificity of CryptoPS in serum, we additionally implemented and evaluated a pretreatment protocol before CryptoPS testing. A total of 43 serum samples collected from 43 patients were investigated. We found that the CryptoPS assay is hampered by a high rate of false-positive results in serum with a high rate of CryptoPS-positive but CrAg LFA-negative and CALAS-negative sera in patients with no proof of Cryptococcus infection (n = 29). Using a simple pretreatment procedure (5 min incubation at 100°C and centrifugation) we were able to reverse false-positive results, suggesting that there could be interferent material present in the serum. Pretreatment also impacted the CryptoPS results (negative result) in two patients with the cryptococcal disease, one with isolated antigenemia and one with cryptococcal meningitis. Comparing the titers obtained with CALAS and CrAg LFA, we noticed that the titer obtained with CrAg LFA was almost 10-fold higher than those with CALAS. This study showed that Biosynex CryptoPS in serum could give false-positive results even in the absence of cryptococcal disease. These could be reduced by applying an easy pretreatment procedure to the serum before testing, with little but existing impact on the sensitivity.

Lateral flow assays are useful to detect the cryptococcal antigen in human fluids. We investigated CryptoPS-positive results and observed that true false-positive results occurred. The false-positive results can be reduced by applying an easy pretreatment procedure.

Native joint septic arthritis due to Clostridium tarantellae.

Clostridium is a diverse genus including more than 200 species involved in varied clinical presentations in infectious diseases. Septic arthritis caused by Clostridium sp. are however uncommon. We report here the first septic arthritis due to Clostridium tarantellae, formerly called Eubacterium tarantellae, in a patient under anti-TNF therapy.

Hepatitis B Virus-Hepatitis D Virus mother-to-child co-transmission: A retrospective study in a developed country.

BACKGROUND & AIMS: Hepatitis B Virus (HBV) DNA during chronic infection can reach levels at which mother-to-child (MTC) transmission frequently occurs despite passive-active immunization of newborns. Hepatitis D Virus (HDV) RNA can reach high levels, we assessed HBV/HDV MTC co-transmission. METHODS: Monocentric retrospective study (registered in ClinicalTrials.gov (NCT02044055)), after informed consent in HBV/HDV co-infected women pregnant between 01/01/2004 and 01/01/2015 in Paris, France. The children were tested when 24 months of age or older. RESULTS: Twenty-two (3%) of 742 HBV infected women, HDV co-infected, gave birth to 54 children during the study period. HBV DNA was above 5 Log10 I.U/mL in 10 pregnancies previous any treatment, with HDV RNA of less than 2.3 Log10 I.U/mL. HDV RNA was above 5 Log10 I.U/mL in eight pregnancies previous any treatment, with HBV DNA of less than 1.5 Log10 I.U/mL. Inverse patterns of HBV DNA and HDV RNA were observed in 17 of 35 (49%) pregnancies: 13 (76%) received no HBV treatment; four (24%) were treated. HBV DNA was under 5 Log10 I.U/mL in 46 of the 50 assessed women (92%) at birth. Of the 36 assessed children, given passive-active immunization, 24 (66%) were protected, 10 (28%) were neither infected nor protected, one was chronically HBV infected, and one had a past HBV infection. HDV Ab was negative in the 36 children. CONCLUSIONS: These results suggest that HBV/HDV MTC co-transmission is exceptional. Studies are needed, mainly in developing countries.

New Insights Into the Therapeutic Management of Varicella Zoster Virus Meningitis: A Series of 123 Polymerase Chain Reaction-Confirmed Cases.

Background: Varicella zoster virus (VZV) can reactivate and cause meningitis, but few studies have distinguished it from meningoencephalitis regarding treatment recommendations.The objective of this study was to assess the outcomes of a large series of patients with VZV meningitis according to their therapeutic management. Methods: We conducted a bicentric retrospective cohort study, in Paris, France, including all adult patients with a cerebrospinal fluid sample positive for VZV by polymerase chain reaction between April 2014 and June 2022. We distinguished meningitis from encephalitis according to the International Encephalitis Consortium criteria. Unfavorable outcome was defined as mortality or functional sequelae defined by a loss of 2 points on the modified Rankin Scale. Results: We included 123 patients with meningitis. Among them, 14% received no antivirals, while 20% were treated with oral valacyclovir alone, 41% with a short course of intravenous (IV) acyclovir before switch to valacyclovir, and 25% with a long course of IV acyclovir. Outcomes were favorable regardless of antiviral regimen. In multivariate analysis, only age, underlying immunosuppression, and cranial radiculitis appear to be predictive factors for longer IV therapy, based on the Akaike information criterion. Conclusions: In this study, patients with VZV meningitis had a good outcome, with no evidence of any impact of the treatment strategy. However, further studies are needed to support the possibility of milder treatment in immunocompetent patients, avoiding cost and side effects of IV acyclovir.

Outbreak of NDM-1-producing Klebsiella pneumoniae in the intensive care unit during the COVID-19 pandemic: Another nightmare.

An outbreak of Klebsiella pneumoniae producing the carbapenemase NDM-1 occurred in our ICU during the last COVID-19 wave. Twelve patients were tested positive, seven remained asymptomatic whereas 5 developed an infection. Resistome and in silico multilocus sequence typing confirmed the clonal origin of the strains. The identification of a possible environmental reservoir suggested that difficulties in observing optimal bio-cleaning procedures due to workload and exhaustion contributed to the outbreak besides the inappropriate excessive glove use.

Impact of a 24/7 multiplex-PCR on the management of patients with confirmed viral meningitis.

Objectives: The relevance of syndromic multiplex-PCR for the etiological diagnosis of meningitis or meningoencephalitis is still a matter of debate. Here, we studied the impact of a 24/7 multiplex-PCR on the management of patients consulting in the emergency department for suspicion of community-acquired meningitis. Methods: We conducted a single-center retrospective study at the Emergency department of Lariboisière University Hospital (Paris, France) including all patients suspected of meningitis. During period 1 (April 2014-March 2017), the molecular assays used for the detection of infectious agents in the cerebrospinal fluid (CSF) were performed during the daytime. During period 2 (April 2017-March 2019), multiplex-PCR (BioFire® Filmarray® Meningitis/Encephalitis Panel [ME], bioMérieux) was performed 24/7. Results: During the periods 1 and 2, 4 100 and 3 574 patients were included and 284 (6.9%) and 308 (8.6%) meningitis were diagnosed, respectively. During the periods 1 and 2, the most common causes of meningitis were enterovirus (23.9% and 29.5%), varicella zoster virus (10.2% and 6.8%) and herpes simplex virus-2 (4.2% and 8.1%). For patients with confirmed viral meningitis, a significant decrease was found between period 1 and period 2, respectively for the rate of hospitalization (73.9% vs 42.0%; p < 0.05), the length of stay (3[2­5] vs 2[1­3] days; p < 0.05), the empirical antiviral (26.1% vs 14.5%) and antibacterial administrations (29.3% vs 14.5%; p < 0.05). Conclusions: Multiplex-PCR is an important tool in the diagnosis of infectious meningitis in the emergency department and is relevant in the management of meningitis by screening for patients who do not require hospitalization and antibacterial therapy.

Reliability and Safety of Bedside Blind Bone Biopsy Performed by a Diabetologist for the Diagnosis and Treatment of Diabetic Foot Osteomyelitis.

OBJECTIVE: Bone biopsy (BB) performed by a surgeon or an interventional radiologist is recommended for suspicion of osteomyelitis underlying diabetic foot ulcer (DFU). To facilitate its practice, we developed a procedure allowing bedside blind bone biopsy (B4) by a diabetologist. RESEARCH DESIGN AND METHODS: We conducted a three-step observational study consisting of a feasibility and safety phase (phase 1) to assess the success and side effects of B4, a validity phase (phase 2) to compare DFU outcomes between positive (B4+) and negative (B4-) bone cultures, and a performance phase (phase 3) to compare B4 with the conventional surgical or radiological procedure basic bone biopsy (B3). Primary end points were the presence of bone tissue (phase 1) and complete DFU healing with exclusive medical treatment at 12 months (phases 2 and 3). RESULTS: In phase 1, 37 consecutive patients with clinical and/or radiological suspicion of DFU osteomyelitis underwent B4. Bone tissue was collected in all patients with few side effects. In phase 2, a B4+ bone culture was found in 40 of 79 (50.6%) participants. Among B4+ patients, complete wound healing after treatment was 57.5%. No statistical difference was observed with patients with B4- bone culture not treated with antibiotics (71.8%, P = 0.18). In phase 3, the proportion of patients with positive BB was lower in B4 (40 of 79, 50.6%) than in B3 (34 of 44, 77.3%, P < 0.01). However, complete healing was similar (64.6% vs. 54.6%, P = 0.28). No difference in rate of culture contamination was observed. CONCLUSIONS: B4 is a simple, safe, and efficient procedure for the diagnosis of DFU osteomyelitis with a similar proportion of healing to conventional BB.

Impact of a 24/7 Rapid Molecular Assay for Influenza Detection on the Prescription of Oseltamivir.

We assessed the impact of a rapid molecular assay for influenza detection whether outsourced or performed onsite 24/7 in a University Hospital in Paris, France. Shorter median time-to-results (16.8 vs 2.3 hours, P < .05) and an increased rate of adequate prescription of oseltamivir (76.6% vs 95.3%, P < .05) were observed.

Incidence, risk factors and outcome of multi-drug resistant Acinetobacter baumannii nosocomial infections during an outbreak in a burn unit.

BACKGROUND: Multidrug-Resistant Acinetobacter baumannii (MR-AB) can cause outbreaks in burn units. We aimed to study the incidence, risk factors and outcome of MR-AB infections in a burn unit (BU). METHODS: A prospective study was conducted from April to November, 2014 during an outbreak in a BU in Paris. Weekly surveillance cultures were performed to determine MR-AB colonization. MR-AB nosocomial infections, discharge or death without MR-AB infection were considered as competing events. To identify risk factors for MR-AB infection, baseline characteristics and time-dependent variables were investigated in univariate analyses using Cox models. RESULTS: Eighty-six patients admissions were analyzed during the study period. Among them, 15 (17%) acquired MR-AB nosocomial infection. Median time to infection was 22days (interquartile range: 10-26 days). Cumulative incidence of MR-AB infections was 15% at 28days (95% CI=8-24). Risk factors for MR-AB infection in univariate analysis were SAPS II (Hazard Ratio (HR):1.08; 95% CI:1.05-1.12; P<0.0001) and ABSI (Abbreviated Burn Severity Index) scores (HR:1.32; 95% CI:1.12-1.56; P=0.001), MR-AB colonization (HR:10.2; 95%CI:2.05-50.3; P=0.004), invasive procedures (ventilation, arterial and/or venous catheter) (P=0.0001) and ≥2 skin grafts (HR:10.2; 95% CI:1.76-59.6; P=0.010). MR-AB infection was associated with an increased risk of death (HR: 7.11; 95%CI: 1.52-33.2; P=0.013) and longer hospital stay with a median estimated increase of 10days (IQR: 6; 14). CONCLUSIONS: Incidence of MR-AB nosocomial infection was high during this outbreak, and was associated with prolonged hospitalization and increased risk of death. High patient severity scores, prior MR-AB colonization, invasive procedures and repeated skin grafts were associated with an increased risk of nosocomial infection.

Comparative dynamics of the emergence of fluoroquinolone resistance in staphylococci from the nasal microbiota of patients treated with fluoroquinolones according to their environment.

Fluoroquinolone-resistant staphylococci (FQRS) are primarily selected in the nasal microbiota during fluoroquinolone (FQ) treatment. To gain insight into the dynamics of the emergence of FQRS, 49 hospitalised patients (HPs) and 62 community patients (CPs) treated with FQs were studied. Nasal swabs were collected before (T0), at the end of (T1) and 1 month after (T2) FQ treatment. FQRS were identified by mass spectrometry. Antibiotic resistance was determined. Pre- and post-exposure staphylococci populations were compared phenotypically and by MLST to determine the origin of FQRS. At T0, 33/49 HPs (67%) and 24/62 CPs (39%) carried FQRS (OR=3.3, 95% CI: 1.4-7.9; P<0.001). Among patients with no FQRS at T0, 15/16 HPs (94%) and 16/38 CPs (42%) had FQRS detected at T1 and/or T2 (OR=19.6, 95% CI: 2.5-902; P<0.001). Among FQRS having emerged, co-resistance to meticillin was detected in 87% and 82% of HPs and CPs, respectively. No selection of resistance emerging from the initial microbiota was evidenced. FQRS showed decreased species diversity in favour of Staphylococcus haemolyticus and Staphylococcus epidermidis. As a consequence of FQ treatment, acquisition of FQRS in the nasal microbiota is frequent in the community and almost inevitable in hospitals. Acquisition from extranasal sites prevails. A restriction in species diversity in favour of more pathogenic and resistant species occurs. This highlights the major impact of FQ treatment on nasal microbiota, the role of the ecological environment in the emergence of FQRS, and the high-risk of dissemination of resistant staphylococci.

Risk factors for invasive pneumococcal disease in HIV-infected adults in France in the highly active antiretroviral therapy era.

Invasive pneumococcal diseases remain frequent and severe in HIV-infected subjects. To identify opportunities for prevention, we assessed risk factors of invasive pneumococcal diseases (IPD) in HIV-infected patients over a 10-year period in France. We performed a retrospective case-control study in a reference centre of HIV management in Paris. All HIV-infected patients having suffered from IPD between 2000 and 2011 were included. Control subjects were HIV-infected with no history of IPD or pneumonia, matched by date of diagnosis of HIV with controls. Two controls were randomly selected for each subject. In all, 42 HIV-infected patients presented 44 IPD episodes during the study period and were compared to 84 controls. In the multivariate analysis, patients with IPD were more likely than controls to have a Charlson Comorbidity Index ≥2 (adjusted OR = 7.07, 95% CI 1.99-25.1, p = 0.003), CD4-cell count <200/cells/µL (aOR = 6.93, 95% CI 1.80-26.7, p = 0.005), HIV-RNA viral load >400 copies/mL (aOR = 5.56, 95% CI 1.58-19.5, p = 0.007) and a non-European origin (aOR = 4.26, 95% CI 1.02-17.9, p = 0.047). HIV-infected patients with a higher burden of comorbidities, uncontrolled HIV replication, low CD4-cell counts and/or of non-European origin are at higher risk of developing IPD. Better screening for and management of HIV infection is necessary to reduce the risk of IPD.

Efficacy and safety of rilpivirine-based regimens in treatment-experienced HIV-1 infected patients: a prospective cohort study.

INTRODUCTION: Rilpivirine (RPV) is a new once-daily, non-nucleoside, reverse transcriptase inhibitor (NNRTI). In treatment-naïve patients, RPV has shown non-inferior antiviral activity to efavirenz but data in treatment-experienced patients are more limited. We assessed the efficacy and safety of RPV in treatment-experienced patients switching to a RPV-based regimen. METHODS: Between September 2012 and June 2013, all antiretroviral therapy (ART) experienced HIV-1 infected patients with a plasma HIV-RNA level <50 cp/mL, and switching to a RPV-based regimen, were enrolled in this prospective monocentric cohort study. Clinical and laboratory data were collected every 3 months to assess safety and efficacy. The primary endpoint was the proportion of patients with virologic success (HIV-RNA load <50 cp/mL) at 12 months using the FDA snapshot algorithm. RESULTS: A total of 281 patients (76% male, median age: 47 years, 56% MSM) were enrolled in this study. Median lymphocyte CD4 count at baseline was 640/mm(3). Patients have received ART for a median of 7 years and viral replication was fully suppressed for a median of 3 years. Before the switch, 39% patients were treated with NNRTI, 52% with protease inhibitor and 7% with integrase inhibitor-based regimens. Reasons for switch were simplification (176 cases), adverse events (AEs) (93 cases) and others (12 cases). At month 12 (database frozen on June 2014) in the snapshot analysis, 56% of patients met virologic success, 5% experienced virologic failure (n=14) and 39% had no data in the window period. In the LOCF analysis (using data from the previous available visit before month 12), 89% patients were suppressed, 5% had virologic failure and 6% had no data. Genotypic resistance analysis was performed in 7/14 patients at the time of virologic failure (3 of whom had previous NRTI/NNRTI resistance-associated mutations (RAMs)), and new NNRTI and NRTI RAMs emerged in 4 patients. RPV-based regimen was generally well tolerated and only 6% of patients discontinued treatment for AEs. Grade 2-4 treatment-related AEs occurred in 39 patients: 6 had rashes, 13 neuropsychiatric symptoms, 10 GI symptoms, 10 biological abnormalities. At month 12, significant changes from baseline were seen for total and LDL cholesterol (-0.5 and -0.28 mmol/L, respectively, p<0.05 for both), and plasma creatinine (+5.8 µmol/L, p<10-4). CONCLUSIONS: In patients fully suppressed on ART, switching to a RPV-based regimen in clinical practice was well tolerated and associated with few virologic failures.