rifampin and Osteoarthritis

Topics: Adrenal Cortex Hormones; Adult; Animals; Antirheumatic Agents; Antiviral Agents; Arthritis, Juvenile; Arthritis, Rheumatoid; Child; Enzyme Inhibitors; Ganciclovir; Genetic Therapy; Haplorhini; Hormones; Humans; Injections, Intra-Articular; Methotrexate; Mice; Osmium Tetroxide; Osteoarthritis; Photochemotherapy; Rats; Rifampin; Somatostatin; Synovectomy; Synovitis; Time Factors

Levofloxacin plus rifampicin (L+R) is the treatment of choice for acute staphylococcal prosthetic joint infection (PJI) managed with debridement and implant retention (DAIR). Long courses have been empirically recommended, but some studies have suggested that shorter treatments could be as effective. Our aim was to prove that a short treatment schedule was non-inferior to the standard long schedule. An open-label, multicentre, randomised clinical trial (RCT) was performed. Patients with an early post-surgical or haematogenous staphylococcal PJI, managed with DAIR and initiated on L+R were randomised to receive 8 weeks of treatment (short schedule) versus a long schedule (3 months or 6 months for hip or knee prostheses, respectively). The primary endpoint was cure rate. From 175 eligible patients, 63 were included (52% women; median age, 72 years): 33 patients (52%) received the long schedule and 30 (48%) received the short schedule. There were no differences between the two groups except for a higher rate of polymicrobial infection in the long-schedule group (27% vs. 7%; P = 0.031). Median follow-up was 540 days. In the intention-to-treat analysis, cure rates were 58% and 73% in patients receiving the long and short schedules, respectively (difference -15.7%, 95% CI -39.2% to 7.8%). Forty-four patients (70%) were evaluable per-protocol: cure rates were 95.0% and 91.7% for the long and short schedules, respectively (difference 3.3%, 95% CI -11.7% to 18.3%). This is the first RCT suggesting that 8 weeks of L+R could be non-inferior to longer standard treatments for acute staphylococcal PJI managed with DAIR.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Debridement; Female; Humans; Levofloxacin; Male; Middle Aged; Osteoarthritis; Prosthesis Retention; Prosthesis-Related Infections; Rifampin; Time Factors; Treatment Outcome

Pharmacokinetics of clindamycin in combination with rifampicin or levofloxacin were prospectively evaluated for the oral treatment of severe staphylococcal osteo articular infections.. Thirty-four patients (25 males, 9 females), with a mean age of 52.4 ± 17 years (range, 24-81 years), were randomly assigned either to the clindamycin-rifampicin or to the clindamycin-levofloxacin arm (control), following surgical debridement and intravenous adapted treatment. Trough and peak serum concentrations of clindamycin were measured at day-1 (D1), D15 and D30 of oral treatment. Cure was evaluated at a minimum of one year after the initiation of treatment.. The oral treatment was interrupted in 4 cases because of adverse events. Mean trough and peak serum concentrations of clindamycin in the clindamycin-rifampicin arm were lower than in the clindamycin-levofloxacin arm during the time of oral antibiotic regimen (0.79 ± 0.3 μg/ml vs 4.7 ± 1.2 μg/ml, p < 0.001, and 3.48 ± 1.1 μg/ml vs 10.2 ± 1.8 μg/ml, p < 0.001, respectively). A consistent decrease in clindamycin serum concentration was observed at each time-point of follow-up. At a mean of 23 ± 7.8 months (range, 12-47 months), 24 patients were available for clinical evaluation. No difference could be detected in the cure rates between the groups.. Our results indicate a significant influence of rifampicin on clindamycin pharmacokinetics using the oral route. Clindamycin serum concentrations (trough and peak) were systematically below the recommended therapeutic ranges when associated with rifampicin, as opposed to the control. Considering the potential risk of selection of mutant resistant to clindamycin, we do not recommend the clindamycin-rifampicin combination in the oral treatment of severe staphylococcal osteoarticular infection, unless clindamycin serum concentration is thoroughly controlled. The study has been registered on the clinicaltrials.gov website under the number NCT 01500837.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Clindamycin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Osteoarthritis; Prospective Studies; Rifampin; Serum; Staphylococcal Infections; Treatment Outcome; Young Adult

Treatment of Gram-positive osteoarticular infections requires an adequate surgical approach combined with intensive antimicrobial therapy. The aim of this study was to evaluate the safety and efficacy of a combined regimen of high-dose daptomycin and rifampicin, in patients with various types of Gram-positive osteoarticular infections.. This single centre, non-comparative, prospective study evaluated the safety and efficacy of a combined regimen of intravenous daptomycin (8 mg/kg/day) and oral rifampicin (600 mg/day) in patients with Gram-positive osteoarticular infections, with a minimal follow-up of one year. Creatine phosphokinase, transaminases, bilirubinaemia, and serum creatinine, were measured at baseline and regular intervals.. The median daily doses of daptomycin and rifampicin, administered for a median duration of 21 (range, 10-122) days to 16 patients (median age, 63.5 years; 11 males, five females) presenting with staphylococcal (n = 15) or streptococcal (n = 1) osteoarticular infections, were 8.15 (range, 6.6-8.9) mg/kg/day and 600 (range, 600-900) mg/day, respectively. The combined regimen of daptomycin and rifampicin was well tolerated by all except one patient, without requiring treatment adjustment or discontinuation. One patient developed allergic responses probably due to rifampicin after 42 days. Fifteen (94 %) patients showed favourable clinical and microbiological outcomes.. The combined regimen of high-dose daptomycin and rifampicin was well tolerated and may provide a useful alternative to standard glycopeptide therapy for Gram-positive osteoarticular infections.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Daptomycin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Osteoarthritis; Prospective Studies; Prosthesis-Related Infections; Rifampin; Treatment Outcome

Staphylococcus aureus may invade and persist intracellularly in prosthetic joint infections (PJIs). Despite optimized treatments with levofloxacin plus rifampin, the intracellular reservoir may lead to infection relapse. This study assessed the intracellular activity of levofloxacin and rifampin in an in-vitro model of human osteoblastic infection.. All regimes led to a significant decrease in CFU count compared with controls (1-2 log. Levofloxacin plus rifampin had good intracellular activity against S. aureus. However, from the intracellular perspective, the addition of rifampin to levofloxacin showed no benefit but could account for an increased number of SCVs.

Topics: Anti-Bacterial Agents; Cell Line; Colony Count, Microbial; Humans; Levofloxacin; Microbial Sensitivity Tests; Microbial Viability; Models, Theoretical; Osteoarthritis; Osteoblasts; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Topics: Anti-Bacterial Agents; Clindamycin; Female; Humans; Male; Osteoarthritis; Rifampin; Serum; Staphylococcal Infections

A majority of osteoarticular and implant-related infections are due to staphylococci and biofilm formation. Combined therapy including rifampicin is frequently recommended. Indeed, rifampicin penetrates biofilms and kills adherent staphylococci, but cannot be administered as monotherapy because of the rapid emergence of resistant mutants. While several antibiotic combinations including rifampicin have been implemented, evaluation of the clindamycin-rifampicin combination has been neglected, presumably because of the emergence of alternative combinations, such as quinolone-rifampicin, and the fear of potential antagonistic interactions. We report a limited series of 20 patients (3 immune-suppressed) with 6 arthroplasty infections, 4 other implant infections, 7 native arthritis, and 3 osteomyelitis, who were all successfully treated with this oral combination for >75% of the antibiotic course (median duration 45 days). The excellent outcomes obtained with this antimicrobial combination after a mean follow-up of 2.6 y (range 1.0-6.1 y) warrant further clinical and microbiological studies for implementing this regimen in routine practice.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Clindamycin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Osteoarthritis; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus; Treatment Outcome; Young Adult

Linezolid therapy has shown high rates of clinical success in patients with osteomyelitis and prosthetic joint infections caused by Gram-positive cocci. Recent studies have demonstrated that linezolid/rifampicin combination therapy prevents the emergence of rifampicin-resistant mutations in vitro. However, linezolid/rifampicin combination-related haematological and neurological toxicities have not been evaluated.. To assess the tolerability of prolonged linezolid/rifampicin combination therapy compared with other linezolid-containing regimens in patients with bone and joint infections.. We reviewed the medical records of 94 patients who had received linezolid for >4 weeks after bone and joint infections. Anaemia was defined as a ≥2 g/dL reduction in haemoglobin, leucopenia as a total leucocyte count <4 × 10(9)/L, and thrombocytopenia as a reduction in platelet count to <75% of baseline.. Anaemia was less frequent among patients on linezolid/rifampicin combination therapy than among patients on linezolid alone or in combination with other drugs (9.3%, 44% and 52%, respectively; P<0.01). In multivariate analysis, age and treatment group were independently associated with anaemia. Thrombocytopenia was reported in 44% of patients on linezolid/rifampicin combination therapy, in 48% of patients on linezolid alone and in 57.7% of patients on other linezolid-containing regimens. Age was the only variable associated with thrombocytopenia (P=0.019) in univariate analysis.. Linezolid/rifampicin combination therapy was associated with a significantly reduced incidence of anaemia among patients with bone and joint infections, but it did not have an effect on thrombocytopenia and peripheral neuropathy rates. Linezolid/rifampicin combination therapy was not associated with poor clinical outcomes.

Topics: Acetamides; Adult; Aged; Aged, 80 and over; Anemia; Anti-Bacterial Agents; Arthritis, Infectious; Drug Therapy, Combination; Female; Humans; Incidence; Linezolid; Male; Middle Aged; Nervous System Diseases; Osteoarthritis; Oxazolidinones; Rifampin; Thrombocytopenia; Time Factors; Treatment Outcome

We report on a case of arthroscopic treatment of septic arthritis of the elbow joint in a 65-year-old man with an elbow endoprosthesis. Two months after arthroplasty of the elbow joint, the patient developed acute septic arthritis of the right elbow. Methicillin-sensitive Staphylococcus aureus was identified as the causative organism. Six days after the onset of symptoms, the patient was treated with a single arthroscopic procedure of the infected periprosthetic joint, including irrigation with 5 L of Ringer's lactate solution, debridement, and partial synovectomy with a 4.5-mm curved shaver. Intravenous antibiotic therapy was also used for 3 months including rifampicine and fucidic acid according to the intraoperative cultures. The acutely infected total elbow arthroplasty could be cured without removal of the endoprosthesis of the elbow. Ten months postoperatively, the patient remains free of symptoms and his blood rates are within normal limits.

Topics: Aged; Arthritis, Infectious; Arthroplasty, Replacement; Arthroscopy; Combined Modality Therapy; Debridement; Drug Therapy, Combination; Elbow Joint; Fusidic Acid; Humans; Isotonic Solutions; Joint Prosthesis; Male; Methicillin; Ossification, Heterotopic; Osteoarthritis; Prosthesis-Related Infections; Rifampin; Ringer's Lactate; Staphylococcal Infections; Staphylococcus aureus; Therapeutic Irrigation

Topics: Accidental Falls; Aged; Ankle Injuries; Antibiotics, Antitubercular; Antitubercular Agents; Drug Therapy, Combination; Female; Follow-Up Studies; Ganglionic Blockers; Humans; Isoniazid; Osteoarthritis; Pempidine; Rifampin; Time Factors; Tuberculosis, Osteoarticular

A case of septic arthritis caused by Corynebacterium amycolatum in a native hip joint occurred in an adult man following contralateral vascular graft sepsis, and was successfully treated with intravenous vancomycin followed by oral doxycycline and rifampicin. To the authors' knowledge, this is the only reported case of septic arthritis due to C. amycolatum.

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Arthritis, Infectious; Arthroplasty, Replacement, Hip; Corynebacterium; Corynebacterium Infections; Doxycycline; Drug Therapy, Combination; Femoral Artery; Hip Joint; Humans; Male; Middle Aged; Osteoarthritis; Rifampin; Vancomycin

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Brucellosis; Doxycycline; Drug Therapy, Combination; Female; Humans; Intervertebral Disc; Middle Aged; Osteoarthritis; Rifampin; Shoulder Joint; Spinal Cord Compression

Two hundred and sixty three patients with a diagnosis of brucellosis between January 1984 and December 1987 were studied prospectively. Sixty five patients (25%) developed osteoarticular complications. These patients had a more prolonged course than those with no complications. Spondylitis in 38 (58%) and sacroiliitis in 29 (45%) were the most prevalent. There were no significant laboratory, serological, or bacteriological differences between patients with and without osteoarticular complications. At diagnosis 47 patients (72%) showed radiographic abnormalities, commonly in axial sites but rarely in peripheral sites. Radionuclide bone scan was positive with no radiographic abnormalities in 17 (26%) of cases. Fifty seven patients received medical treatment alone, 51 (89%) being cured with a single course of treatment. Treatment failed or there was a relapse in six patients (11%), of whom five had spondylitis. Eight of the 65 patients (12%), all of whom had spondylitis and paravertebral or epidural abscesses, also required surgical treatment.

Topics: Adolescent; Adult; Aged; Brucellosis; Doxycycline; Drug Therapy, Combination; Female; Humans; Joints; Male; Middle Aged; Osteoarthritis; Prospective Studies; Rifampin; Sacroiliac Joint; Spine; Streptomycin

Rifampicin is a suitable drug for treating staphylococcal bone and articular infections, because high levels are obtained in the human tissues. The best oral dose is 600 mg 12 hourly. The serum levels range from 10 to 15 mg/l at the peak concentration and from 0.2 to 0.6 mg/l 8 h after oral administration of 600 mg. The ratio for cancellous bone/serum is 0.41 at 3 h and 0.39 at 12 h, and for cortical bone/serum is 0.20 at 3 h after a dose of 600 mg. In every case, tissue levels paralleled serum levels; cancellous bone levels are greater than the MIC of Staphylococcus aureus strains until 12 h after a dose of 600 mg. Rifampicin is always used in combination with another antibacterial substance. Results are excellent in most cases. The average duration of antibiotic treatment is 3 months for osteo-arthritis, 6 months for spondylitis and osteitis.

Topics: Adult; Aged; Bone and Bones; Diffusion; Drug Synergism; Female; Hip Prosthesis; Humans; Male; Middle Aged; Osteoarthritis; Rifampin; Staphylococcal Infections

Topics: Adolescent; Brucellosis; Doxycycline; Drug Therapy, Combination; Female; Humans; Osteoarthritis; Rifampin; Streptomycin

Tetracyclines are remarkably effective in brucellosis and give consistently good results. However, recurrences have been reported even after correct management. Combination therapy with tetracycline and streptomycin, advocated by the FAO/WHO, has improved results without giving complete satisfaction. Association of tetracycline with rifampicin suggested on sound theoretical grounds, has given promising results.

Topics: Acute Disease; Anti-Bacterial Agents; Brucellosis; Drug Therapy, Combination; Humans; Middle Aged; Osteoarthritis; Rifampin; Streptomycin; Tetracyclines; Time Factors

The authors emphasise the interest of identification of the germ during bone and joint infections, and recall the main data, often fragmentary, one the diffusion of antibiotics into bone. Concerning the practical use of antibiotics, they emphasise the necessity of basing their treatment on bacteriological examinations before choosing an association of two antibiotics, the effect of which will be regularly assessed by a study of the bactericidal power of the serum.

Topics: Aminoglycosides; Anti-Bacterial Agents; Arthritis, Infectious; Cephalosporins; Humans; Osteoarthritis; Penicillins; Rifampin; Tetracyclines

The authors discuss the present value of rifampicin in the treatment of human brucellosis on the basis of: 1) a bacteriological study of 42 strains of Brucella spp. (MIC's of rifampicin, tetracyclin, doxycyclin, minocyclin and streptomycin; results of doxycyclin-rifampicin and doxycyclin-streptomycin combinations), and 2) a clinical study of 38 cases of brucellosis treated with rifampicin, including 25 acute septicemias and 13 osteo-arthritis. Satisfactory results were observed in 92% of the cases with rifampicin alone, but one cannot state that the benefits are significant.

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Brucella; Brucellosis; Drug Therapy, Combination; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Middle Aged; Osteoarthritis; Pregnancy; Rifampin; Sepsis

Study of 26 cases of osteo-articular infections with an identified organism collected in a rheumatology department, has confirmed in the first place the increasing importance of gram negative organisms, compared with the staphylococcus which has always mainly predominated in this type of infection. In each case, the authors have made as complete a bacteriological study as possible, including antibiotic sensitivities, the measurement of the minimum inhibitory concentration of the antibiotics on the isolated strains, study of the bactericidal power in vitro of various combinations, and study of the inhibitory power of the serum on the organism. This study of the inhibitory power of the serum approximates most closely to testing the antibiotic activities in vivo, since one cannot make this assessment, in most cases, within the infective focus itself. Rifampicin, with the imperative condition that it is not used alone, is a major antibiotic in the osteo-articular infections, by reason of its very great activity against the staphylococcus, its excelent penetration into bone, and its ease of use. Other recognized anti-staphylococcal antibiotics behave in a more disappointing fashion. When the effectiveness of treatment is checked regularly by the inhibitory power of the serum, together with the other classical criteria of surveillance, cure of the infection as been achieved in every case.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Arthritis, Infectious; Bacteria; Blood Bactericidal Activity; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Osteoarthritis; Rifampin; Staphylococcus aureus