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.

Mycobacterium tuberculosis prosthetic joint infections: A case series and literature review.

OBJECTIVES: We aimed to characterize diagnosis, management, and outcome of Mycobacterium tuberculosis prosthetic joint infections (PJI). METHODS: Cases of M. tuberculosis PJI documented in 7 referral French centers were retrospectively reviewed. Data were collected from medical files on a standardized questionnaire. We performed a literature review using the keywords 'prosthetic joint', and 'tuberculosis'. RESULTS: During years 1997-2016, 13 patients (8 males, 5 females, median age 79 years [range, 60-86]) had documented M. tuberculosis PJI, involving hip (n = 6), knee (n = 6), or shoulder (n = 1). Median time from arthroplasty to diagnosis was 9 years [0.4-20]. The diagnosis was obtained on joint aspirates (n = 9), or synovial tissue (n = 4). PCR was positive in all cases tested (5/5). Median duration of antituberculosis treatment was 14 months [6-32]). Nine patients underwent surgery: debridement (n = 4), resection arthroplasty (n = 3), and revision arthroplasty (1-stage exchange, n = 2). PJI was controlled in 12 patients. Seventeen additional cases of documented M. tuberculosis PJI have been reported, with a favorable outcome in 79% (11/14) of patients with no surgery, 85% (11/13) with debridement, 86% (19/22) with revision arthroplasty, and 81% (17/21) with resection (NS). CONCLUSIONS: M. tuberculosis PJI can be controlled with prolonged antituberculosis treatment in most cases, with or without surgical treatment.

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.

Vertebral osteomyelitis: an unusual presentation of Bartonella henselae infection.

OBJECTIVES: To report cases of cat scratch disease with vertebral osteomyelitis. METHODS: We describe clinical features, diagnostic, treatment, and outcome of 2 patients with vertebral osteomyelitis due to Bartonella henselae and provide a review of the relevant literature. RESULTS: A 47-year-old man was investigated for fever, splenomegaly, and cervical adenopathy. A lymphoma was suspected on the clinical picture, the laboratory tests, and the computed tomographic scan. [(18)F]-fluoro-2-deoxy-d-glucose-positron emission tomography detected splenic nodules and a hypermetabolic focus of C7 vertebral body compatible with a vertebral osteomyelitis on magnetic resonance imaging. B henselae infection was confirmed by polymerase chain reaction performed on lymph node biopsy. A 34-year-old woman was investigated for fever and right upper quadrant abdominal pain. She had consulted 2 weeks before for a unique lesion of right index and an axillar adenopathy that have improved spontaneously. A technetium bone scan performed 1 week later because of a thoracic backache demonstrated an increased uptake of the T6 vertebra. Vertebral magnetic resonance imaging was compatible with a T6 osteomyelitis. B henselae infection was confirmed by serology (seroconversion). Both patients were treated with rifampin and doxycycline and recovered within 3 months. CONCLUSIONS: B henselae vertebral osteomyelitis can involve immunocompetent adults. In the case of vertebral osteomyelitis with negative blood cultures, recent history of local lymphadenopathy and cat exposure must be investigated and B henselae serology must be performed. Nevertheless, even if serology is positive, vertebral biopsy is required to rule out other pathogens or malignancy. B henselae infection can be confirmed by polymerase chain reaction performed on vertebral or lymph node biopsy.

Bacteriophages can treat and prevent Pseudomonas aeruginosa lung infections.

Antibiotic-resistant bacteria threaten life worldwide. Although new antibiotics are scarce, the use of bacteriophages, viruses that infect bacteria, is rarely proposed as a means of offsetting this shortage. Doubt also remains widespread about the efficacy of phage therapy despite recent encouraging results. Using a bioluminescent Pseudomonas aeruginosa strain, we monitored and quantified the efficacy of a bacteriophage treatment in mice during acute lung infection. Bacteriophage treatment not only was effective in saving animals from lethal infection, but also was able to prevent lung infection when given 24 h before bacterial infection, thereby extending the potential use of bacteriophages as therapeutic agents to combat bacterial lung infection.

Systemic immune presentations of Coxiella burnetii infection (Q Fever).

OBJECTIVES: Q fever is a worldwide zoonosis caused by Coxiella burnetii. Its presentation can be atypical, delaying and complicating the diagnosis. We report 7 cases of Q fever mimicking vasculitis, systemic inflammatory disease, or auto-immune disorder. METHODS: Seven cases of Q fever diagnosed between 1995 and 2007 in Nantes University Hospital (France) are described. They occurred in a nonendemic region and were selected on the basis of initial clinical presentation suggesting systemic immune disease. C. burnetii was detected using indirect immunofluorescence serology. RESULTS: Q fever was acute in 4 of the 7 patients and chronic in 3. None had endocarditis. The initial presentations suggested Crohn's disease, Goodpasture's syndrome, polymyalgia rheumatica, adult-onset Still's disease, polyarteritis nodosa, giant-cell arteritis, and essential type II cryoglobulinemia. Two patients had antiphospholipid antibodies, 1 had transient IgG kappa monoclonal gammopathy, and 1 had polyclonal T CD8+ large granular lymphocyte expansion. CONCLUSION: Clinicians must be aware of the potential diagnosis of Q fever, and C. burnetii serology is a helpful diagnostic tool in the investigation of fever of unknown origin with atypical systemic symptoms suggesting vasculitis or inflammatory disease.

In vivo efficacy of moxifloxacin compared with cloxacillin and vancomycin in a Staphylococcus aureus rabbit arthritis experimental model.

We investigated the efficacies of moxifloxacin, cloxacillin, and vancomycin in a rabbit model of Staphylococcus aureus arthritis. No significant difference between therapeutic regimens was observed after a 7-day treatment. Oral moxifloxacin could be a suitable alternative to standard parenteral therapy for S. aureus arthritis.

In vitro and in vivo assessment of linezolid combined with ertapenem: a highly synergistic combination against methicillin-resistant Staphylococcus aureus.

Linezolid in combination with ertapenem showed in vitro synergy against methicillin-resistant Staphylococcus aureus strains. We confirmed this interaction in vivo by using a rabbit endocarditis experimental model and simulation of the human pharmacokinetics in animals for both antibiotics. Linezolid plus ertapenem exhibited highly synergistic activity in vivo after 4 days of treatment.