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.

Daptomycin > 6 mg/kg/day as salvage therapy in patients with complex bone and joint infection: cohort study in a regional reference center.

BACKGROUND: Even if daptomycin does not have approval for the treatment of bone and joint infections (BJI), the Infectious Diseases Society of America guidelines propose this antibiotic as alternative therapy for prosthetic joint infection. The recommended dose is 6 mg/kg/d, whereas recent data support the use of higher doses in these patients. METHODS: We performed a cohort study including consecutive patients that have received daptomycin >6 mg/kg/d for complex BJI between 2011 and 2013 in a French regional reference center. Factors associated with treatment failure were determined on univariate Cox analysis and Kaplan-Meier curves. RESULTS: Forty-three patients (age, 61 ± 17 years) received a mean dose of 8 ± 0.9 mg/kg/d daptomycin, for a mean 81 ± 59 days (range, 6-303 days). Most had chronic (n = 37, 86 %) implant-associated (n = 37, 86 %) BJI caused by coagulase-negative staphylococci (n = 32, 74 %). A severe adverse event (SAE) occurred in 6 patients (14 %), including 2 cases of eosinophilic pneumonia, concomitant with daptomycin Cmin >24 mg/L. Outcome was favorable in 30 (77 %) of the 39 clinically assessable patients. Predictors for treatment failure were age, non-optimal surgery and daptomycin withdrawal for SAE. CONCLUSIONS: Prolonged high-dose daptomycin therapy was effective in patients with complex BJI. However, optimal surgery remains the cornerstone of medico-surgical strategy; and a higher incidence of eosinophilic pneumonia than expected was recorded.

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.

A French multicentric study and review of pulmonary Nocardia spp. in cystic fibrosis patients.

Some bacterial species recovered from the airways of cystic fibrosis (CF) patients are indisputably associated with lung infections, whereas the clinical relevance of others, such as Nocardia spp., remains unclear. Sixteen French CF cases of colonization/infection with Nocardia spp. were reviewed in order to evaluate the epidemiology, the clinical impact and the potential treatment of these bacteria, and results were compared to those of the literature. Five Nocardia species were identified, Nocardia cyriacigeorgica being the major species (50 % of cases). At first isolation, Nocardia was the sole pathogen recovered in six patients. Seven patients presented pulmonary exacerbation. For 12 patients, antimicrobial treatment against Nocardia was started immediately, mainly based on cotrimoxazole (6 of the 12 cases). In this study, we highlight the heterogeneity of the clinical management of Nocardia spp. in CF. Guidelines for the clinical management of Nocardia infections in CF patients are proposed.

Antimicrobial-related severe adverse events during treatment of bone and joint infection due to methicillin-susceptible Staphylococcus aureus.

Prolonged antimicrobial therapy is recommended for methicillin-susceptible Staphylococcus aureus (MSSA) bone and joint infections (BJI), but its safety profile and risk factors for severe adverse events (SAE) in clinical practice are unknown. We addressed these issues in a retrospective cohort study (2001 to 2011) analyzing antimicrobial-related SAE (defined according to the Common Terminology Criteria for Adverse Events) in 200 patients (male, 62%; median age, 60.8 years [interquartile range {IQR}, 45.5 to 74.2 years]) with MSSA BJI admitted to a reference regional center with acute (66%) or chronic arthritis (7.5%), osteomyelitis (9.5%), spondylodiscitis (16%), or orthopedic device-related infections (67%). These patients received antistaphylococcal therapy for a median of 26.6 weeks (IQR, 16.8 to 37.8 weeks). Thirty-eight SAE occurred in 30 patients (15%), with a median time delay of 34 days (IQR, 14.75 to 60.5 days), including 10 patients with hematologic reactions, 9 with cutaneomucosal reactions, 6 with acute renal injuries, 4 with hypokalemia, and 4 with cholestatic hepatitis. The most frequently implicated antimicrobials were antistaphylococcal penicillins (ASP) (13 SAE/145 patients), fluoroquinolones (12 SAE/187 patients), glycopeptides (9 SAE/101 patients), and rifampin (7 SAE/107 patients). Kaplan-Meier curves and stepwise binary logistic regression analyses were used to determine the risk factors for the occurrence of antimicrobial-related SAE. Age (odds ratio [OR], 1.479 for 10-year increase; 95% confidence interval [CI], 1.116 to 1.960; P = 0.006) appeared to be the only independent risk factor for SAE. In patients receiving ASP or rifampin, daily dose (OR, 1.028; 95% CI, 1.006 to 1.051; P = 0.014) and obesity (OR, 8.991; 95% CI, 1.453 to 55.627; P = 0.018) were associated with the occurrence of SAE. The high rate of SAE and their determinants highlighted the importance of the management and follow-up of BJI, with particular attention to be paid to older persons, especially for ASP dosage, and to rifampin dose adjustment in obese patients.

Determinants of methicillin-susceptible Staphylococcus aureus native bone and joint infection treatment failure: a retrospective cohort study.

BACKGROUND: Although methicillin-susceptible Staphylococcus aureus (MSSA) native bone and joint infection (BJI) constitutes the more frequent clinical entity of BJI, prognostic studies mostly focused on methicillin-resistant S. aureus prosthetic joint infection. We aimed to assess the determinants of native MSSA BJI outcomes. METHODS: Retrospective cohort study (2001-2011) of patients admitted in a reference hospital centre for native MSSA BJI. Treatment failure determinants were assessed using Kaplan-Meier curves and binary logistic regression. RESULTS: Sixty-six patients (42 males [63.6%]; median age 61.2 years; interquartile range [IQR] 45.9-71.9) presented an acute (n = 38; 57.6%) or chronic (n = 28; 42.4%) native MSSA arthritis (n = 15; 22.7%), osteomyelitis (n = 19; 28.8%) or spondylodiscitis (n = 32; 48.5%), considered as "difficult-to-treat" in 61 cases (92.4%). All received a prolonged (27.1 weeks; IQR, 16.9-36.1) combined antimicrobial therapy, after surgical management in 37 cases (56.1%). Sixteen treatment failures (24.2%) were observed during a median follow-up period of 63.3 weeks (IQR, 44.7-103.1), including 13 persisting infections, 1 relapse after treatment disruption, and 2 super-infections. Independent determinants of treatment failure were the existence of a sinus tract (odds ratio [OR], 5.300; 95% confidence interval [CI], 1.166-24.103) and a prolonged delay to infectious disease specialist referral (OR, 1.134; 95% CI 1.013-1.271). CONCLUSIONS: The important treatment failure rate pinpointed the difficulty of cure encountered in complicated native MSSA BJI. An early infectious disease specialist referral is essential, especially in debilitated patients or in presence of sinus tract.

Staphylococcus lugdunensis prosthetic joint infection: A multicentric cohort study.

OBJECTIVES: To describe Staphylococcus lugdunensis prosthetic joint infection (PJI) management and outcome. METHODS: Adults with proven S. lugdunensis PJI were included in a multicentric retrospective cohort. Determinants for failure were assessed by logistic regression and treatment failure-free survival curve analysis (Kaplan-Meier). RESULTS: One hundred and eleven patients were included (median age 72.4 [IQR, 62.7-79.4] years), with a knee (n = 71, 64.0%) or hip (n = 39, 35.1%) PJI considered as chronic in 77 (69.4%) cases. Surgical management consisted in debridement, antibiotic with implant retention (DAIR; n = 60, 54.1%), two-stage (n = 28, 25.2%) or one-stage (n = 15, 13.5%) exchange. Total duration of antimicrobial therapy was 13.1 (IQR, 11.8-16.9) weeks. After a median follow-up of 99.9 (IQR, 53.9-178.1) weeks, 22 (19.8%) S. lugdunensis-related treatment failures were observed. Independent determinants for outcome were diabetes (OR, 3.741; p = 0.036), sinus tract (OR, 3.846; p = 0.032), DAIR (OR, 3.749; p = 0.039) and rifampin-based regimen (OR, 0.319; p = 0.043). Twenty-four (40.0%) of the 60 DAIR-treated patients experienced treatment failure, with hip location (OR, 3.273; p = 0.048), delay from prosthesis implantation (OR, 1.012 per month; p = 0.019), pre-surgical CRP level >115 mg/L (OR, 4.800; p = 0.039) and mobile component exchange (OR, 0.302; p = 0.069) constituting additional determinants of outcome. CONCLUSIONS: Staphylococcus lugdunensis PJI are difficult-to-treat infections, with pivotal roles of an optimal surgical management.

[Capnocytophaga canimorsus: atypical septicemic meningitis, approach to microbiological diagnosis and therapeutic impact]. / Capnocytophaga canimorsus : méningite septicémique atypique, démarche du diagnostic microbiologique et impact thérapeutique.

Meningitis and septicaemia due to Capnocytophaga canimorsus are extremely rare and described as emerging zoonoses because of their low incidence and prevalence, but also because of the challenges in bacterial identification, thus, the real number of cases is probably underestimated. We report the case of a 61-year-old man, with a history a chronic alcoholism, who developed, following a recent dog bite, meningitis with normoglycorachia and concomitant sepsis, and had a favorable outcome after intravenous probabilistic antibiotherapy combining ceftazidime and metronidazole. This association aimed to cover the risks represented by Pseudomonas spp and anaerobic bacteria, once the microorganisms commonly associated with meningitis were excluded using molecular biology tools. In addition to the unusual biological results (normoglycorachia and bacterial morphology after Gram staining), we present the biological diagnostic approach (molecular, biochemical and physical tools successively used to lead, by exclusion and confirmation, to this diagnosis), closely linked to the clinical expertise. This is, to our knowledge, the first described case of meningitis with normoglycorachia and septicaemia due to Capnocytophaga canimorsus successfully treated with ceftazidime and confirmed by identification by MALDI-TOF mass spectrometry.

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.