Pressure ulcer-related pelvic osteomyelitis: evaluation of a two-stage surgical strategy (debridement, negative pressure therapy and flap coverage) with prolonged antimicrobial therapy.

BACKGROUND: A two-stage surgical strategy (debridement-negative pressure therapy (NPT) and flap coverage) with prolonged antimicrobial therapy is usually proposed in pressure ulcer-related pelvic osteomyelitis but has not been widely evaluated. METHODS: Adult patients with pressure ulcer-related pelvic osteomyelitis treated by a two-stage surgical strategy were included in a retrospective cohort study. Determinants of superinfection (i.e., additional microbiological findings at reconstruction) and treatment failure were assessed using binary logistic regression and Kaplan-Meier curve analysis. RESULTS: Sixty-four pressure ulcer-related pelvic osteomyelitis in 61 patients (age, 47 (IQR, 36-63)) were included. Osteomyelitis was mostly polymicrobial (73%), with a predominance of S. aureus (47%), Enterobacteriaceae spp. (44%) and anaerobes (44%). Flap coverage was performed after 7 (IQR, 5-10) weeks of NPT, with 43 (68%) positive bone samples among which 39 (91%) were superinfections, associated with a high ASA score (OR, 5.8; p = 0.022). An increased prevalence of coagulase negative staphylococci (p = 0.017) and Candida spp. (p = 0.003) was observed at time of flap coverage. An ESBL Enterobacteriaceae spp. was found in 5 (12%) patients, associated with fluoroquinolone consumption (OR, 32.4; p = 0.005). Treatment duration was as 20 (IQR, 14-27) weeks, including 11 (IQR, 8-15) after reconstruction. After a follow-up of 54 (IQR, 27-102) weeks, 15 (23%) failures were observed, associated with previous pressure ulcer (OR, 5.7; p = 0.025) and Actinomyces spp. infection (OR, 9.5; p = 0.027). CONCLUSIONS: Pressure ulcer-related pelvic osteomyelitis is a difficult-to-treat clinical condition, generating an important consumption of broad-spectrum antibiotics. The lack of correlation between outcome and the debridement-to-reconstruction interval argue for a short sequence to limit the total duration of treatment.

Pristinamycin in the treatment of MSSA bone and joint infection.

OBJECTIVES: The aim of this study was to evaluate pristinamycin in the treatment of MSSA bone and joint infection (BJI). PATIENTS AND METHODS: A retrospective, single-centre cohort study (2001-11) investigated outcome in adults receiving pristinamycin for MSSA BJI and pristinamycin-related adverse events (AEs). RESULTS: One hundred and two MSSA BJIs were assessed in 98 patients [chronic infection, 33.3%; and orthopaedic device-related infection (ODI), 67.6%]. Surgery was performed in 77.5% of total cases, and in all but three ODIs, associated with antibiotic therapy of a median total duration of 29.2 weeks. Pristinamycin was prescribed as a part of the initial intensive treatment phase (29.4%) and/or included in final maintenance therapy (83.3%) at a dose of 47.6 (45.5-52.6) mg/kg/day for 9.3 (1.4-20.4) weeks. AEs occurred in 13.3% of patients, consisting of gastrointestinal disorder (76.9%) or allergic reaction (23.1%), leading to treatment interruption in 11 cases. AEs were related to daily dose (OR, 2.733 for each 10 additional mg/kg/day; P = 0.049). After a follow-up of 76.4 (29.6-146.9) weeks, the failure rate was 34.3%, associated with ODI (OR, 4.421; P = 0.006), particularly when the implant was retained (OR, 4.217; P = 0.007). In most patients, the pristinamycin companion drug was a fluoroquinolone (68.7%) or rifampicin (21.7%), without difference regarding outcome. CONCLUSIONS: Pristinamycin is an effective, well-tolerated alternative therapeutic option in MSSA BJI, on condition that a daily dosage of 50 mg/kg is respected.

Teicoplanin-based antimicrobial therapy in Staphylococcus aureus bone and joint infection: tolerance, efficacy and experience with subcutaneous administration.

BACKGROUND: Staphylococci represent the first etiologic agents of bone and joint infection (BJI), leading glycopeptides use, especially in case of methicillin-resistance or betalactam intolerance. Teicoplanin may represent an alternative to vancomycin because of its acceptable bone penetration and possible subcutaneous administration. METHODS: Adults receiving teicoplanin for S. aureus BJI were included in a retrospective cohort study investigating intravenous or subcutaneous teicoplanin safety and pharmacokinetics. RESULTS: Sixty-five S. aureus BJIs (orthopedic device-related infections, 69 %; methicillin-resistance, 17 %) were treated by teicoplanin at the initial dose of 5.7 mg/kg/day (IQR, 4.7-6.5) after a loading dose of 5 injections 12 h apart. The first trough teicoplanin level (Cmin) reached the therapeutic target (15 mg/L) in 26 % of patients, only. An overdose (Cmin >25 mg/L) was observed in 16 % patients, 50 % of which had chronic renal failure (p = 0.049). Seven adverse events occurred in 6 patients (10 %); no predictive factor could be highlighted. After a 91-week follow-up (IQR, 51-183), 27 treatment failures were observed (42 %), associated with diabetes (OR, 5.1; p = 0.057), systemic inflammatory disease (OR, 5.6; p = 0.043), and abscess (OR, 4.1; p < 10-3). A normal CRP-value at 1 month was protective (OR, 0.2; p = 0.029). Subcutaneous administration (n = 14) showed no difference in pharmacokinetics and tolerance compared to the intravenous route. CONCLUSIONS: Teicoplanin constitutes a well-tolerated therapeutic alternative in S. aureus BJI, with a possible subcutaneous administration in outpatients. The loading dose might be increase to 9-12 mg/kg to quickly reach the therapeutic target, but tolerance of such higher doses remains to be evaluated, especially if using the subcutaneous route.

Pharmacokinetic/Pharmacodynamic Dosage Individualization of Suppressive Beta-Lactam Therapy Administered by Subcutaneous Route in Patients With Prosthetic Joint Infection.

Suppressive parenteral antibiotic therapy with beta-lactams may be necessary in patients with Gram-negative bone and joint infection (BJI). Subcutaneous drug administration can facilitate this therapy in outpatient setting, but there is limited information about this practice. We have developed an original approach for drug dosing in this context, based on therapeutic drug monitoring (TDM) and pharmacokinetic/pharmacodynamic (PK/PD) principles. The objective of this study was to describe our approach and its first results in a case series. We analyzed data from patients who received suppressive antibiotic therapy by subcutaneous (SC) route with beta-lactams as salvage therapy for prosthetic joint infection (PJI) and had TDM with PK/PD-based dose adjustment. Ten patients (six women and four men with a mean age of 77 years) were included from January 2017 to May 2020. The drugs administered by SC route were ceftazidime (n = 4), ertapenem (n = 4), and ceftriaxone (n = 2). In each patient, PK/PD-guided dosage individualization was performed based on TDM and minimum inhibitory concentration (MIC) measurements. The dose interval could be prolonged from twice daily to thrice weekly in some patients, while preserving the achievement of PK/PD targets. The infection was totally controlled by the strategy in nine out the 10 patients during a median follow-up of 1,035 days (~3 years). No patient acquired carbapenem-resistant Gram-negative bacteria during the follow-up. One patient presented treatment failure with acquired drug resistance under therapy, which could be explained by late MIC determination and insufficient exposure, retrospectively. To conclude, our innovative approach, based on model-based TDM, MIC determination, and individualized PK/PD goals, facilitates, and optimizes suppressive outpatient beta-lactam therapy administered by SC route for PJI. These encouraging results advocate for larger clinical evaluation.

Bone and Joint Infection Involving Corynebacterium spp.: From Clinical Features to Pathophysiological Pathways.

Introduction: Corynebacteria represent often-neglected etiological agents of post-traumatic and/or post-operative bone and joint infection (BJI). We describe here clinical characteristics and bacteriological determinants of this condition. Methods: A retrospective cohort study described characteristics, outcome and determinants of treatment failure of all patients with proven Corynebacterium spp. BJI (i.e., ≥2 culture-positive gold-standard samples). Available strains were further characterized regarding their antibiotic susceptibilies, abilities to form early (BioFilm Ring Test®) and mature (crystal violet staining method) biofilms and to invade osteoblasts (gentamicin protection assay). Results: The 51 included BJI were mostly chronic (88.2%), orthopedic device-related (74.5%) and polymicrobial (78.4%). After a follow-up of 60.7 weeks (IQR, 30.1-115.1), 20 (39.2%) treatment failures were observed, including 4 Corynebacterium-documented relapses, mostly associated with non-optimal surgical management (OR 7.291; p = 0.039). Internalization rate within MG63 human osteoblasts was higher for strains isolated from delayed (>3 months) BJI (p < 0.001). Infection of murine osteoblasts deleted for the ß1-integrin resulted in a drastic reduction in the internalization rate. No difference was observed regarding biofilm formation. Conclusions: Surgical management plays a crucial role in outcome of BJI involving corynebacteria, as often chronic and device-associated infections. Sanctuarisation within osteoblasts, implicating the ß1 cellular integrin, may represent a pivotal virulence factor associated with BJI chronicity.

Linezolid in the Starter Combination for Multidrug-Resistant Tuberculosis: Time to Move on to Group Four?

Linezolid (LNZ), a group 5 antituberculous drug (unclear efficacy), was used in the starter regimens of 23 adults with multidrug-resistant tuberculosis. The LNZ-containing regimens were effective in achieving culture conversions and relapse-free outcomes. The most frequent LNZ-related side effect was neuropathy. We propose that LNZ should be reclassified among bactericidal second-line drugs.

Actinomycosis: etiology, clinical features, diagnosis, treatment, and management.

Actinomycosis is a rare chronic disease caused by Actinomyces spp., anaerobic Gram-positive bacteria that normally colonize the human mouth and digestive and genital tracts. Physicians must be aware of typical clinical presentations (such as cervicofacial actinomycosis following dental focus of infection, pelvic actinomycosis in women with an intrauterine device, and pulmonary actinomycosis in smokers with poor dental hygiene), but also that actinomycosis may mimic the malignancy process in various anatomical sites. Bacterial cultures and pathology are the cornerstone of diagnosis, but particular conditions are required in order to get the correct diagnosis. Prolonged bacterial cultures in anaerobic conditions are necessary to identify the bacterium and typical microscopic findings include necrosis with yellowish sulfur granules and filamentous Gram-positive fungal-like pathogens. Patients with actinomycosis require prolonged (6- to 12-month) high doses (to facilitate the drug penetration in abscess and in infected tissues) of penicillin G or amoxicillin, but the duration of antimicrobial therapy could probably be shortened to 3 months in patients in whom optimal surgical resection of infected tissues has been performed. Preventive measures, such as reduction of alcohol abuse and improvement of dental hygiene, may limit occurrence of pulmonary, cervicofacial, and central nervous system actinomycosis. In women, intrauterine devices must be changed every 5 years in order to limit the occurrence of pelvic actinomycosis.

[Atherosclerosis, multiple sclerosis, and Alzheimer's disease: what role for Herpesviridae?]. / Athérosclérose, sclérose en plaque et maladie d'Alzheimer: quel rôle pour les Herpesviridae?

Herpesviridae are ubiquitous, and are commonly involved in well identified diseases as genital herpes, chickenpox and herpes zoster, infectious mononucleosis, exanthem subitum... They are responsible for latent and chronic infections after primary infection. Atherosclerosis, multiple sclerosis, Alzheimer's disease are diseases which are very different, and for which pathogenesis remains unknown. Several authors have hypothesized that Herpesviridae could play a role in such diseases. The present paper reviews arguments not only in favour but also against such hypothesis. Any formal conclusion is impossible, and more extensive studies are warranted.