Switch from parenteral to oral antibiotics for brain abscesses: a retrospective cohort study of 109 patients.

OBJECTIVES: Brain abscess is one of the most serious diseases of the CNS and is associated with high morbidity and mortality. With regard to the lack of data supporting an optimal therapeutic strategy, this study aimed to explore the prognostic factors of brain abscess, putting emphasis on the impact of therapeutic decisions. METHODS: We retrospectively included patients hospitalized for brain abscess during a period of 13 years. Comorbidities (Charlson scale), clinical presentation, microbiology culture, radiological features and therapeutic management were collected. Glasgow Outcome Scale (GOS) at 3 months and length of hospital stay were, respectively, the main and the secondary outcomes. Logistic regression was used to determine factors associated with outcome independently. RESULTS: Initial Glasgow Coma Scale (GCS) ≤14 and comorbidities (Charlson scale ≥2) were associated with poor neurological outcome while oral antibiotic switch was associated with better neurological outcome. Oral switch did not appear to be associated with an unfavourable evolution in the subset of patients without initial neurological severity (GCS >14) on admission. Duration of IV regimen and time to oral switch were associated with the length of inpatient stay. CONCLUSIONS: This study confirms the role of GCS and comorbidities as prognostic factors and presents reassuring data regarding the safety of oral switch for the antibiotic treatment of brain abscesses. Oral switch could prevent catheter-induced iatrogenic complications and allow a higher quality of life for patients.

Impact of baseline plasma HIV-1 RNA and time to virological suppression on virological rebound according to first-line antiretroviral regimen.

OBJECTIVES: We investigated the risk of virological rebound in HIV-1-infected patients achieving virological suppression on first-line combined ART (cART) according to baseline HIV-1 RNA, time to virological suppression and type of regimen. PATIENTS AND METHODS: Subjects were 10 836 adults who initiated first-line cART (two nucleoside or nucleotide reverse transcriptase inhibitors + efavirenz, a ritonavir-boosted protease inhibitor or an integrase inhibitor) from 1 January 2007 to 31 December 2014. Cox proportional hazards models with multiple adjustment and propensity score matching were used to investigate the effect of baseline HIV-1 RNA and time to virological suppression on the occurrence of virological rebound. RESULTS: During 411 436 patient-months of follow-up, risk of virological rebound was higher in patients with baseline HIV-1 RNA ≥100 000 copies/mL versus <100 000 copies/mL, in those achieving virological suppression in > 6 months versus <6 months, and lower with efavirenz or integrase inhibitors than with ritonavir-boosted protease inhibitors. Baseline HIV-1 RNA >100 000 copies/mL was associated with virological rebound for ritonavir-boosted protease inhibitors but not for efavirenz or integrase inhibitors. Time to virological suppression >6 months was strongly associated with virological rebound for all regimens. CONCLUSIONS: In HIV-1-infected patients starting cART, risk of virological rebound was lower with efavirenz or integrase inhibitors than with ritonavir-boosted protease inhibitors. These data, from a very large observational cohort, in addition to the more rapid initial virological suppression obtained with integrase inhibitors, reinforce the positioning of this class as the preferred one for first-line therapy.

Association between radiographic and functional outcome in vertebral osteomyelitis SPONDIMMO, a 6-month prospective multicenter cohort.

OBJECTIVES: This study aimed to describe radiographic and functional evolution over 6 months in a large cohort of VO patients. METHODS: We prospectively recruited patients with VO from 2016 to 2019 in 11 French centers. X-rays were performed at baseline, 3 months, and 6 months to assess progression using structural and static criteria. Functional impairment was evaluated using the Oswestry Disability Index (ODI) at 3 months and 6 months. RESULTS: Two hundred and twenty-two patients were included. Mean age was 67.8±14 years, mostly men (67.6%). After 3 months, there was a significant increase in vertebral fusion (16.4% vs 52.7%), destruction of vertebral bodies (10.1% vs 22.8%), and of all the static features (frontal angulation (15.2% vs 24.4%), segmental (34.6% vs 56%) and regional (24.5% vs 41%) kyphosis). From 3 to 6 months, among the different X-ray abnormalities, only the complete fusion progressed significantly (16.6% vs 27.2%). Median ODI showed significant improvement from 3 to 6 months (24, IQR [11.5-38] vs 16, IQR [6-34]). At 6 months, 14.1% of the patients had a severe disability, 2% a major disability. The persistence of vertebral destruction at 6 months was associated with a higher ODI (16, IQR [7.5-30.5] vs 27, IQR [11.5-44.5]). No differences in radiological progression were observed with immobilization using a rigid brace. CONCLUSION: Our study demonstrates structural and static radiographic progression after 3 months. Only the complete fusion progressed over the long-term. Functional impairment was associated with persistence of vertebral destruction.

Spine immobilization and neurological outcome in vertebral osteomyelitis SPONDIMMO, a prospective multicentric cohort.

OBJECTIVE: The aim of our study was to describe spine immobilization in a multicentric cohort of vertebral osteomyelitis (VO), and evaluate its association with neurological complications during follow-up. METHODS: We prospectively included patients from 2016 to 2019 in 11 centers. Immobilization, imaging, and neurological findings were specifically analyzed during a 6-month follow-up period. RESULTS: 250 patients were included, mostly men (67.2%, n=168). Mean age was 66.7±15 years. Diagnosis delay was 25 days. The lumbo-sacral spine was most frequently involved (56.4%). At diagnosis, 25.6% patients (n=64) had minor neurological signs and 9.2% (n=23) had major ones. Rigid bracing was prescribed for 63.5% (n=162) of patients, for a median of 6 weeks, with variability between centers (P<0.001). The presence of epidural inflammation and abscess on imaging was associated with higher rates of rigid bracing prescription (OR 2.33, P=0.01). Frailness and endocarditis were negatively associated with rigid bracing prescription (OR 0.65, P<0.01, and OR 0.42, P<0.05, respectively). During follow up, new minor or major neurological complications occurred in respectively 9.2% (n=23) and 6.8% (n=17) of patients, with similar distribution between immobilized and non-immobilized patients. CONCLUSION: Spine immobilization prescription during VO remains heterogeneous and seems associated inflammatory lesions on imaging but negatively associated with frailness and presence of endocarditis. Neurological complications can occur despite rigid bracing. Our data suggest that in absence of any factor associated with neurological complication spine bracing might not be systematically indicated. We suggest that spine immobilization should be discussed for each patient after carefully evaluating their clinical signs and imaging findings.

Hypermetabolic pulmonary lesions on FDG-PET/CT: Tularemia or neoplasia?

OBJECTIVES: Pulmonary tularemia is a rare and little-known disease, whose clinical and radiological presentation can be confused with those of much more frequent pathologies, such as lung cancer or B-cell lymphoma (46,000 and 5,000 new cases respectively per year in France). Furthermore, PET/CT is a powerful tool for the diagnosis of malignancies or the exploration of fever of unknown origin. The objective of this study was to describe the characteristics of pulmonary tularemia and to determine whether its PET/CT aspect could help distinguish it from neoplasia. METHODS: Retrospective observational study collecting all pulmonary tularemia cases for which a PET/CT was performed between 2016 and 2020. RESULTS: Twenty-seven cases of pulmonary tularemia were analyzed. The sex ratio was 4.4, and the median age was 60 years. Clinical manifestations were mainly represented by fever (n=23), arthralgia (n=7) and cough (n=6). PET/CT revealed intensely hypermetabolic mediastinal adenopathies in all cases, associated with parenchymal (n=20) or pleural (n=6) lesions, suggesting neoplastic pathology in 15 patients. Cytopuncture or lymph node biopsy was performed in 16 patients, revealing non-specific adenitis (n=8), necrotic epithelio-gigantocellular granuloma (n=3), or were non-contributory (n=5). All patients reported significant environmental exposure. The outcome was favorable for all patients, spontaneously for 8 of them and after antibiotic therapy with either doxycycline or ciprofloxacin for the other 19. CONCLUSIONS: Depending on the epidemiological setting, pulmonary tularemia may be considered an alternative diagnosis to lung cancer, lymphoma, or tuberculosis, in the presence of infectious symptoms and hypermetabolic pulmonary lesions and mediastinal lymphadenopathies on PET/CT.

Dalbavancin treatment for prosthetic joint infections in real-life: a national cohort study and literature review.

OBJECTIVES: Dalbavancin is a long-lasting lipoglycopeptide active against Gram-positive bacteria, especially methicillin-resistant staphylococci. Few data are available on dalbavancin use for treatment of prosthetic joint infections (PJIs). We describe a cohort of patients treated for PJI with dalbavancin and review the literature regarding this condition. METHODS: All adult patients with PJI from the French dalbavancin national cohort from 1 June 2017 to 1 January 2019 were included. We collected clinical and microbiological characteristics and outcome through a standardised questionnaire. Clinical cure was defined as absence of clinical signs of infection at last visit. Failure was a composite criterion defined by persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment and/or death from infection. The literature review was performed using PubMed. RESULTS: Seventeen patients were included. Bacteria were identified in 16 cases: Staphylococcus aureus (n = 10), including methicillin-resistant S. aureus (n = 1); and coagulase-negative staphylococci (n = 10), including methicillin-resistant Staphylococcus epidermidis (n = 4). Sixteen patients (94.1%) had received antibiotic therapy prior to dalbavancin use (mean of 2.2 ± 1.3 lines). Clinical cure was achieved in 8/17 patients after a median follow-up of 299.0 (IQR 97.0-476.0) days. We reviewed all cases of PJI treated with dalbavancin available in the literature and the overall clinical cure was estimated at 73.1%. CONCLUSION: Our study and literature data suggest that use of dalbavancin in PJI could be considered, even as salvage therapy. Dalbavancin appears to be a safe and easy treatment for patients with staphylococcal PJIs.

A 60-Year-Old Woman With Recurrent Hemoptysis.

CASE PRESENTATION: A 60-year-old non-smoker white woman presented with a new episode of hemoptysis. She reported recurrent hemoptoic sputum in the past month. She had no relevant medical history, except presumed resolved bacterial pneumonia 1 year ago. She denied taking immunosuppressive treatment and was not exposed to lung irritants. She had not traveled recently. General health status was good. She denied fever, dyspnea, chest pain, and extra-pulmonary symptoms.

Listeria Endophthalmitis Cured With Linezolid in an Immunocompetent Farmer Woman: Hazard of a Sweep of a Cow's Tail.

We report the first case of an unexpected exogenous Listeria monocytogenes endophthalmitis in a previously healthy woman after a cow's tail's sweep, successfully treated with surgery and linezolid. It is the first case carried out with linezolid to treat Listeria endophthalmitis. Therefore, it may challenge the requirement for intravenous antibiotics for long-term treatment.

Outcome and prognostic factors of Pneumocystis jirovecii pneumonia in immunocompromised adults: a prospective observational study.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) remains a severe disease associated with high rates of invasive mechanical ventilation (MV) and mortality. The objectives of this study were to assess early risk factors for severe PJP and 90-day mortality, including the broncho-alveolar lavage fluid cytology profiles at diagnosis. METHODS: We prospectively enrolled all patients meeting pre-defined diagnostic criteria for PJP admitted at Nantes university hospital, France, from January 2012 to January 2017. Diagnostic criteria for PJP were typical clinical features with microbiological confirmation of P. jirovecii cysts by direct examination or a positive specific quantitative real-time polymerase chain reaction (PCR) assay. Severe PJP was defined as hypoxemic acute respiratory failure requiring high-flow nasal oxygen with at least 50% FiO2, non-invasive ventilation, or MV. RESULTS: Of 2446 respiratory samples investigated during the study period, 514 from 430 patients were positive for P. jirovecii. Of these 430 patients, 107 met criteria for PJP and were included in the study, 53 (49.5%) patients had severe PJP, including 30 who required MV. All patients were immunocompromised with haematological malignancy ranking first (n = 37, 35%), followed by solid organ transplantation (n = 27, 25%), HIV-infection (n = 21, 20%), systemic diseases (n = 13, 12%), solid tumors (n = 12, 11%) and primary immunodeficiency (n = 6, 8%). By multivariate analysis, factors independently associated with severity were older age (OR, 3.36; 95% CI 1.4-8.5; p < 0.05), a P. jirovecii microscopy-positive result from bronchoalveolar lavage (BAL) (OR, 1.3; 95% CI 1.54-9.3; p < 0.05); and absence of a BAL fluid alveolitis profile (OR, 3.2; 95% CI 1.27-8.8; p < 0.04). The 90-day mortality rate was 27%, increasing to 50% in the severe PJP group. Factors independently associated with 90-day mortality were worse SOFA score on day 1 (OR, 1.05; 95% CI 1.02-1.09; p < 0.001) whereas alveolitis at BAL was protective (OR, 0.79; 95% CI 0.65-0.96; p < 0.05). In the subgroup of HIV-negative patients, similar findings were obtained, then viral co-infection were independently associated with higher 90-day mortality (OR, 1.25; 95% CI 1.02-1.55; p < 0.05). CONCLUSIONS: Older age and P. jirovecii oocysts at microscopic examination of BAL were independently associated with severe PJP. Both initial PJP severity as evaluated by the SOFA score and viral co-infection predicted 90-day mortality. Alveolitis at BAL examination was associated with less severe PJP. The pathophysiological mechanism underlying this observation deserves further investigation.

French national cohort of first use of dalbavancin: A high proportion of off-label use.

Dalbavancin is a glycopeptide antibiotic with a long half-life, recently marketed in Europe for skin and soft-tissue infections (SSTIs), but its real-life use is not well known. The aim of this study was to describe all first prescriptions in France over an 16-month period. A retrospective study on all adult patients receiving at least one dose of dalbavancin from 1 June 2017 to 31 September 2018 was performed (75 patients from 29 French hospitals). Data were collected via a standard questionnaire. Failure was defined as persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment, and/or death from infection. The main indications were bone and joint infection (BJI) (64.0%), endocarditis (25.3%), and SSTI (17.3%). The main bacteria involved were Staphylococcus aureus (51.4%), including methicillin-resistant S. aureus (MRSA) (19.4%), and coagulase-negative staphylococci (44.4%). Median minimum inhibitory concentrations (MICs) for staphylococci to vancomycin and dalbavancin ranged from 0.875-2.0 mg/L and 0.032-0.064 mg/L, respectively. Dalbavancin was used after a mean of 2.3 ± 1.2 lines of antimicrobial treatment. The main treatment regimens for dalbavancin were a two-dose regimen (1500 mg each) in 38 cases (50.7%) and a single-dose regimen (1500 mg) in 13 cases (17.3%). Overall, at the patient's last visit, clinical cure was observed in 54/68 patients, whilst failure was observed in 14/68 patients. First use of dalbavancin in France was mostly off-label. Most were due to BJI, often as rescue therapy for severe infections. Even in off-label situations, dalbavancin appears safe and effective.

Optimizing the virological success of tenofovir DF/FTC/rilpivirine in HIV-infected naive and virologically suppressed patients through strict clinical and virological selection.

BACKGROUND: Tenofovir DF/FTC/rilpivirine (TDF/FTC/RPV) is a single tablet regimen considered as safe and efficacious in HIV population as long as food requirements, concomitant PPI administration, and compromised antiviral activity have been carefully reviewed. We evaluated TDF/FTC/RPV in a real-life setting with focus on clinical and virological outcomes. METHODS: OCEAN II is a prospective, two-centre observational study. From September 2012 to December 2013, antiretroviral-naive patients with HIV RNA <100,000 copies/mL or wishing to switch for simplification were considered for TDF/FTC/RPV. A systematic review of potential obstacles to TDF/FTC/RPV administration was undertaken during a multidisciplinary meeting, including DNA genotyping to detect archived RPV and/or NRTI-associated resistance mutations if historical RNA resistance testing was lacking. RESULTS: TDF/FTC/RPV was considered for 480 patients, however was not offered to 194 patients (40%), mainly because of risk of insufficient virological efficacy, issues on adherence, patient refusal, meal constraint, or PPI therapy. A total of 286 patients (269 in maintenance; 17 ART-naive) received TDF/FTC/RPV. After a median follow-up of 30 months, virological failure occurred in five patients (1.7%) without the emergence of resistance mutations. Discontinuation of TDF/FTC/RPV occurred in 98 patients, due to adverse events in 43 patients (44%) and non-safety reasons in 55 patients (56%). No grade three-fourth adverse events occurred. CONCLUSION: In this real-life experience, cohort consisting primarily of virologically suppressed patients, TDF/FTC/RPV usually maintained virologic suppression. Discontinuation of therapy because of intolerability was due to mild adverse events. Strict clinical and virological screening probably explained the low rate of virological failure.