Susceptibility to mycobacterial infection in VEXAS syndrome.

OBJECTIVES: VEXAS is a recently described acquired auto-inflammatory and hematologic syndrome caused by somatic mutations in UBA1. To date, VEXAS is not a recognized cause of acquired immunodeficiency. PATIENTS AND METHODS: Two of our 10 VEXAS patients developed a disseminated Mycobacterium avium infection. To shed light on this observation, we retrospectively studied all patients with disseminated non-tuberculous mycobacterial infections (NTMi) seen at our institution over 13 years. Inclusion criteria were a positive blood/bone marrow culture, or 2 positive cultures from distinct sites, or one positive culture with 2 involved sites. RESULTS: patient 1 presented with fever, rash, orbital cellulitis and lung infiltrates. Patient 2 presented with fever and purpura. In both cases, Mycobacterium avium was identified on bone marrow culture. Twenty cases of disseminated NTMi were reviewed. Among 11 HIV-negative patients, three had chronic immune-mediated disease; three had untreated myeloid neoplasm; two had VEXAS; one had undergone kidney transplantation; one had GATA-2 deficiency; and one had no identified aetiology. None had lymphoid neoplasia or had undergone bone marrow transplantation. HIV-negative cases had higher CD4 counts than HIV-positive patients (median CD4: 515/mm3  vs 38/mm3, p< 0.001). Monocytopenia was present in seven cases. At 2 years, six patients had died, including both VEXAS patients. DISCUSSION: VEXAS patients have an intrinsic susceptibility to disseminated NTMi, which may result from monocytic dysfunction. NTMi can mimic VEXAS flare. Clinicians should maintain a high suspicion for opportunistic infections before escalating immunosuppressive therapy. Further studies are needed to confirm and better decipher the herein reported observations.

Staphylococcus succinus Infective Endocarditis, France.

Infective endocarditis is a rare condition in humans and is associated with high illness and death rates. We describe a case of infective endocarditis caused by Staphylococcus succinus bacteria in France. We used several techniques for susceptibility testing for this case to determine the oxacillin profile.

Safety and Efficacy of Ceftaroline in Neonates With Staphylococcal Late-onset Sepsis: A Case Series Analysis.

Treatment of late-onset neonatal staphylococcal sepsis is sometimes challenging with feared side effects of vancomycin, increasing minimal inhibitory concentrations and questions about catheter management. In case of failure, ceftaroline was administered as a compassionate treatment in 16 infants (gestational age of less than 32 weeks and less than 28 postnatal days), whose first-line treatment failed. We report 11 successes and no severe adverse drug reactions. Larger data are required to confirm these encouraging results.

Xpert MTB/RIF Ultra Trace Results: Decision Support for the Treatment of Extrapulmonary Tuberculosis in Low TB Burden Countries.

OBJECTIVES: Extrapulmonary tuberculosis (EPTB) can be difficult to diagnose, especially in severe forms. The Xpert MTB/RIF Ultra test introduced an additional category called trace to reference very small amounts of Mycobacterium tuberculosis complex (MTBC) DNA. The objective of our multicenter study was to evaluate whether the trace result on an extrapulmonary (EP) sample is a sufficient argument to consider diagnosing tuberculosis and starting treatment, even in severe cases. METHODS: A retrospective, multicenter cohort study was conducted from 2018 to 2022. Patients strongly suspected of EPTB with a trace result on an EP specimen were included. Hospital records were reviewed for clinical, treatment, and paraclinical data. RESULTS: A total of 52 patients were included, with a severe form in 22/52 (42.3%) cases. Culture was positive for MTBC in 33/46 (71.7%) cases. Histological analysis showed granulomas in 36/45 (80.0%) cases. An Ultra trace result with a presumptive diagnosis of TB led to the decision to treat 41/52 (78.8%) patients. All patients were started on first-line anti-TB therapy (median duration of 6.1 months), with a favorable outcome in 31/35 (88.6%) patients. The presence of a small amount of MTBC genome in EPTB is a sufficient argument to treat patients across a large region of France.

Synovial calprotectin: A potentially useful biomarker for the diagnosis of Kingella kingae native arthritis.

Kingella kingae is a bacteria involved in developing arthritis in children. Its diagnosis remains difficult. We report a case for which a new biomarker, calprotectin measured in the synovial fluid, was strongly positive and a specific molecular test was the only way to diagnose it specifically.

Assessment of a fully automated RPR assay (Mediace RPR) for serological diagnosis and follow-up of syphilis: a retrospective study.

OBJECTIVES: This study assessed the Mediace RPR assay, an automated RPR (aRPR), for syphilis diagnosis and serological follow-up. METHODS: Serums from patients positively screened for syphilis between January 2017 and December 2019 were retrospectively selected. A focus was performed on patients with a serological follow-up after treatment and/or a reinfection. Serums were tested by both manual (mRPR) and aRPR tests. Categorical and Quantitative Agreements (CA and QA), and serological follow-up conclusions were analyzed. RESULTS: 236 serums from 85 patients (99% of male, 66% of HIV-infected) were included. The overall QA was 54.2%. CA was low (79.7%) especially for samples with low RPR titers. No prozone effect was observed. Serological follow-up after treatment led to similar conclusions, although aRPR titers often decreased faster. Over 26 episodes of reinfection, 4 (15.4%) were misdiagnosed with the aRPR. CONCLUSIONS: While the Mediace aRPR presents the advantages of an automated test, its poor sensitivity in low titers may limit its use.

A fatal case associated with Catabacter hongkongensis bacteremia in lung cancer patient: A case report.

Catabacter hongkongensis is a bacterium first isolated in 2007 and has since been detected in the blood of about fifteen patients with disease such as gastrointestinal malignancy, intestinal obstruction, or acute intestinal infection. We describe herein the case of a patient newly diagnosed with metastatic lung cancer, who died from a fatal infection possibly related to Catabacter hongkongensis bacteremia. By reviewing all cases reported in the literature, our case report supports that this infection is associated with a very high mortality in cancer patients.

Epidemiology and Clinical Impact of Respiratory Coinfections at Diagnosis of Pneumocystis jirovecii Pneumonia.

BACKGROUND: The role of respiratory coinfections at diagnosis of Pneumocystis jirovecii pneumonia (PcP) on clinical impact has been underestimated. METHODS: A retrospective observational study was conducted January 2011 to April 2019 to evaluate respiratory coinfections at diagnosis of PcP patients in 2 tertiary care hospitals. Coinfection was defined by identification of pathogens from P. jirovecii-positive samples. RESULTS: Of 7882 respiratory samples tested for P. jirovecii during the 8-year study, 328 patients with diagnosis of PcP were included. Mean age was 56.7 (SD 14.9) years, 193 (58.8%) were male, 74 (22.6%) had positive HIV serology, 125 (38.1%) had viral coinfection, 76 (23.2%) bacterial coinfection, and 90-day mortality was 25.3%. In the overall population, 90-day mortality was independently associated with solid tumor underlying disease (odds ratio [OR], 11.8; 95% confidence interval [CI], 1.90-78.0; P = .008), sepsis-related organ failure assessment score (SOFA) at admission (OR, 1.62; 95% CI, 1.34-2.05; P< .001), and cytomegalovirus (CMV) respiratory coinfection (OR, 3.44; 95% CI, 1.24-2.90; P = .02). Among HIV-negative patients, respiratory CMV coinfection was associated with worse prognosis, especially when treated with adjunctive corticosteroid therapy. CONCLUSIONS: Respiratory CMV coinfection at PcP diagnosis was independently associated with increased 90-day mortality, specifically in HIV-negative patients.

Management of patients with pulmonary mycobacteriosis in France: a multicenter retrospective cohort study.

BACKGROUND: Recent studies report very low adherence of practitioners to ATS/IDSA recommendations for the treatment of nontuberculous mycobacteria pulmonary disease (NTM-PD), as well as a great variability of practices. Type of management could impact prognosis. METHODS: To evaluate management and prognosis of patients with NTM-PD cases with respect to ATS recommendations, we conducted a multicenter retrospective cohort study (18 sentinel sites distributed throughout France), over a period of six years. We collected clinical, radiological, microbiological characteristics, management and outcome of the patients (especially death or not). RESULTS: 477 patients with NTM-PD were included. Respiratory comorbidities were found in 68% of cases, tuberculosis sequelae in 31.4% of patients, and immunosuppression in 16.8% of cases. The three most common NTM species were Mycobacterium avium complex (60%), M. xenopi (20%) and M. kansasii (5.7%). Smear-positive was found in one third of NTM-PD. Nodulobronchiectatic forms were observed in 54.3% of cases, and cavitary forms in 19.1% of patients. Sixty-three percent of patients were treated, 72.4% of patients with smear-positive samples, and 57.5% of patients with smear-negative samples. Treatment was in adequacy with ATS guidelines in 73.5%. The 2-year mortality was 14.4%. In the Cox regression, treatment (HR = 0.51), age (HR = 1.02), and M. abscessus (3.19) appeared as the 3 significant independent prognostic factors. CONCLUSION: These findings highlight the adequacy between French practices and the ATS/IDSA guidelines. Treatment was associated with a better survival.

Assessment of a Multiplex LAMP Assay (Eazyplex® CSF Direct M) for Rapid Molecular Diagnosis of Bacterial Meningitis: Accuracy and Pitfalls.

Background: Automated molecular panels are attractive tools for improving early meningitis diagnosis. This study assessed the Eazyplex® CSF direct M panel (EP), a multiplex real-time Loop-Mediated Isothermal Amplification assay. Methods: From December 2016 to December 2019, cerebrospinal fluid (CSF) samples were routinely tested with the EP V1.0. CSF parameters and microbiological and clinical data were retrospectively collected. Results: Out of 230 CSF samples, the EP yielded positive, negative, and invalid results for 32 (13.9%) (16 N. meningitidis, nine S. pneumoniae, two S. agalactiae, two E. coli, two H. influenzae, one L. monocytogenes), 182 (79.1%), and 16 (7%) samples, respectively. Among the positive samples, 14 (44%) remained negative in culture (antibiotic therapy before lumbar puncture (n = 11), meningococcal meningitis (n = 3)). High CSF protein concentrations and cellularity were associated with LAMP inhibition, counteracted by centrifugation. The automated software yielded 13 false positive and five false negative results. Amplification curve analysis was necessary and enabled the attainment of positive (PPA) and negative percentage agreement and positive and negative predictive values of 91.4%, 100%, 100%, and 98.3%. Three false negative results remained (two E. coli and one N. meningitidis). E. coli presented the poorest PPA (50%). Conclusion: This work confirms the strong performance of the EP, of particular interest in cases of antibiotic therapy before lumbar puncture.

Treatment of Bone and Joint Tuberculosis in France: A Multicentre Retrospective Study.

BACKGROUND: Nine percent of all cases of tuberculosis are bone and joint tuberculosis (BJTB). BJTB occurs in two main forms: spinal (STB) and extraspinal (ESTB). The aim of this study was to compare STB with ESTB in terms of diagnosis, treatment and outcomes. METHODS: We collected demographic, clinical, microbiological, treatment duration and outcome data for patients with BJTB in a retrospective multicentre study over a 17-year period. RESULTS: Of the 116 patients included in the study, 69 (59.5%) had STB and 47 (40.5%) had ESTB. The median age was higher in the ESTB group. There were significantly more foreign-born patients in the STB group. The median time for diagnosis was longer for ESTB (6 months) than STB (4 months) (p = 0.017). Magnetic resonance imaging was highly reliable for the diagnosis. Direct examination and histology allowed the diagnosis to be made in more than 80% of cases. The median treatment duration of 12 months, regardless of the type of BJTB, was longer than recommended. A favourable outcome was achieved in 91.9% of cases. CONCLUSION: The management of BJTB remains challenging. An earlier diagnosis should be more effective, reducing the total duration of treatment and leading to better tolerance.

Rifampin-Resistant Cutibacterium (formerly Propionibacterium) namnetense Superinfection after Staphylococcus aureus Bone Infection Treatment.

After rifampin and levofloxacin treatment for a Staphylococcus aureus bone infection, a pyogenic granuloma due to a newly described Cutibacterium species, C. namnetense developed on the tibia former external fixator. This rifampin resistant bacterium, selected during treatment, harbored a mutation in the rpoB gene. This case illustrates the possible in vivo selection of resistant mutant most likely due to the bacterial burden and therefore the importance of adequate bone infection treatment.

Emergence of Nontuberculous Mycobacterial Lymphadenitis in Children After the Discontinuation of Mandatory Bacillus Calmette and GuÉrin Immunization in France.

Eighty-five children were diagnosed with culture-confirmed nontuberculous mycobacterial cervical lymphadenitis within the MYCOMED surveillance network from 2004 to 2013. The mean incidence sharply increased from 0.57 to 3.7 per 100,000 children per year, after the discontinuation of mandatory bacillus Calmette and Guérin immunization in 2007. Cases were documented as Mycobacterium avium (62.3%), Mycobacterium intracellulare (15.3%) and Mycobacterium lentiflavum (12.9%). Outcome was favorable in all, with or without surgery or antimycobacterial treatment.

In vitro emergence of fluoroquinolone resistance in Cutibacterium (formerly Propionibacterium) acnes and molecular characterization of mutations in the gyrA gene.

In vitro occurrence of levofloxacin (LVX) resistance in C. acnes and characterization of its molecular background were investigated. The mutation frequency was determined by inoculation of 108 cfu of C. acnes ATCC 11827 (LVX MIC = 0.25 mg/L) on LVX-containing agar plates. The progressive emergence of resistance was studied by a second exposure to increasing LVX concentrations. For mutants, the QRDR regions including the gyrA and parC genes were sequenced and compared to both C. acnes ATCC 11827 and C. acnes KPA171202 reference sequences (NC006085). The importance of the efflux pump system in resistance was investigated by using inhibitors on selected resistant mutants with no mutation in the QRDR. C. acnes growth was observed on LVX-containing plates with mutation frequencies of 3. 8 cfu × 10-8 (8 × MIC) and 1.6 cfu × 10-7 (4 × MIC). LVX resistance emerged progressively after one-step or two-step assays. In LVX-resistant isolates, the MIC ranged from 0.75 to >32 mg/L. Mutations were detected exclusively in the gyrA gene. Ten genotypes were identified: G99 C, G99 D, D100N, D100 H, D100 G, S101L, S101W, A102 P, D105 H and A105 G. Mutants S101L and S101W were always associated with a high level of resistance. Mutants with no mutation in the QRDR were more susceptible when incubated with an efflux pump inhibitor (phenyl-arginine ß-naphthylamide) only, suggesting, for the first time, the expression of such a system in C. acnes LVX-resistant mutants.

Draft Genome Sequence of an Erythromycin-Resistant Propionibacterium acnes Isolate Recovered from Folliculitis of the Scalp.

Propionibacterium acnes is now well-known and recognized for its implication in the pathogenesis of acne vulgaris. Here, we report the draft genome sequence of an erythromycin-resistant P. acnes strain isolated from a case of folliculitis of the scalp belonging to phylotype IA1 and sequence type 18 (ST18).

Draft Genome Sequences of Four Propionibacterium acnes Strains Isolated from Implant-Related Infections.

Propionibacterium acnes was previously described as a potential implant-related pathogen. Here, we report the draft genome sequence of four P. acnes strains, isolated from spine material, hip arthroplasty, and knee arthroplasty infections in France belonging to different sequence types (ST18, ST27, and ST36).