rifampin and Osteomyelitis

Mycobacterium Avium Complex (MAC) is an established microbiologic cause of pulmonary disease, lymphadenitis, and disseminated disease in cases of advanced immune suppression. However, MAC manifesting as vertebral osteomyelitis is less common, and is particularly rare in the absence of Acquired Immunodeficiency Syndrome (AIDS). Prompt diagnosis of MAC vertebral osteomyelitis is challenging, but necessary to prevent serious morbidity or mortality.. We report a case of MAC osteomyelitis of the lumbar spine in a 70-year-old woman on extended duration corticosteroid therapy for systemic lupus erythematosus who presented with progressive back pain. Upon presentation, imaging revealed osteomyelitis of the lumbar spine with associated paraspinal abscess. Cultures from the surgical evacuation of the paraspinal abscess yielded no pathogen growth and she was therefore treated with empiric antibacterial therapy. Two weeks after her initial hospital discharge she represented with severe back pain and radiologic evidence of progressive disease in her lumbar spine. Two additional vertebral biopsies were required during her first 2 weeks of admission. MAC eventually grew from culture 14 days after collection. She was treated with ethambutol and rifampin and her symptoms resolved in 2 weeks, though therapy was continued for 12 months.. MAC is an unusual cause of vertebral osteomyelitis in patients with AIDS, but is exceedingly rare in those without severe immune compromise. Despite its rarity, it must be considered in cases of vertebral osteomyelitis that do not respond to empiric antibiotic therapy. Multiple biopsies may be necessary to obtain a diagnosis and avoid destructive infectious complications of an untreated infection.

Topics: Abscess; Aged; Anti-Bacterial Agents; Drug Therapy, Combination; Ethambutol; Female; Humans; Lumbosacral Region; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Osteomyelitis; Rifampin

We report the first Italian case of Mycobacterium chimaera disseminated infection in a patient with a history of cardiac surgery. The patient was initially diagnosed with sarcoidosis and started on immunosuppressive therapy. Ten months later she developed a vertebral osteomyelitis: M. chimaera was isolated from bone specimen. A review of the literature shows that M. chimaera infection occurs specifically in this population of patients, due to contamination of heater-cooler units used during cardiosurgery. Devices responsible for the transmission were produced by Sorin Group Deutschland. Mycobacterium chimaera infection should be included in the differential diagnosis for patients undergoing cardiac surgery.

Topics: Acinetobacter Infections; Aged; Bacteremia; Diagnostic Errors; Drug Therapy, Combination; Equipment Contamination; Female; Heart Valve Prosthesis Implantation; Heating; Humans; Linezolid; Lumbar Vertebrae; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Osteomyelitis; Postoperative Complications; Prednisone; Rifampin; Sarcoidosis; Spondylitis; Vertebroplasty; Water Microbiology

Brucellosis is the most common worldwide zoonosis which continues to remain a significant worldwide health problem and burden. Transmission usually occurs secondary to direct or indirect exposure to certain animals, but a major mode of transmission is the ingestion ofunpasteurized milk or milk products from infected animals. 'Ihe disease has a geographic distribution including the Mediterranean basin and Arabian Peninsula, India, Mexico, and parts of Central and South America. However, cases are seen in the United States in international travelers or due to ingestion ofusuallyimported, unpasteurized dairyproducts. Systemic infection with Brucella species can affect anyorgan, although focal forms ofbrucellosis do exist. We present a case of brucellar vertebral osteomyelitis.

Topics: Animals; Anti-Bacterial Agents; Brucella; Brucellosis; Doxycycline; Drug Therapy, Combination; Female; Gentamicins; Humans; Middle Aged; Osteomyelitis; Rifampin; Treatment Outcome

Bartonella henselae commonly involves the mononuclear phagocyte system (MPS), and its most common presentation is lymphadenitis. Rarely, it can cause isolated osteomyelitis. We present a case of a 3 year old with constitutional symptoms and new onset of limp. Previously reported cases of osteomyelitis due to B. henselae are also reviewed here, keeping the index case in mind.. We conducted a Medline search using MeSH subject headings Bartonella and osteomyelitis, limited to humans.. The index case is a 3-year-old female who had a subacute presentation with new-onset leg pain and fever. Subsequent imaging demonstrated osteomyelitis of the acetabulum. Multiple diagnostic attempts were unsuccessful, and the patient did not respond to empiric therapy. Despite indeterminate serology, the diagnosis of Bartonella osteomyelitis was eventually confirmed by PCR on bone biopsy of the lesion. The literature search revealed 48 publications, which were reduced to 28 when limiting articles to the English language and the pediatric population. After a report of 36 pediatric cases in 2007, there have been an additional 12 pediatric cases since 1998. Generally, these patients had a subacute presentation with relatively mild constitutional symptoms. Most commonly, bone involvement occurred as osteolytic lesions of the axial skeleton. Of the total 48 cases reported, only four reported involvement of the axial skeleton.. We present the first case, to our knowledge, of pediatric osteomyelitis of the pelvis due to B. henselae with indeterminate serologic and positive PCR results. Bartonella osteomyelitis should be included in the differential diagnosis when typical pathogens are not identified or if the patient is slow to respond to standard therapies. The sensitivity of tissue PCR for Bartonella osteomyelitis is now better than the current gold standard of serology, and new management guidelines may need to reflect this.

Topics: Acetabulum; Animals; Anti-Bacterial Agents; Azithromycin; Bartonella henselae; Biopsy; Child, Preschool; Female; Fever; Humans; Lymphadenitis; Osteomyelitis; Polymerase Chain Reaction; Rifampin; Sensitivity and Specificity; Treatment Outcome

Staphylococcus spp. causes more than half of all osteoarticular infections of native structures or implanted material. The ability of Staphylococcus spp. to persist within infected bone tissue and to produce a bacterial biofilm, most notably in infections of implanted material, can lead to treatment failures and microbiological relapses. Rifampin is a cornerstone of the treatment of staphylococcal osteoarticular infections, particularly those of implanted material. Rifampin is a bactericidal antibiotic that diffuses very well within bone tissue and bacterial biofilms. The mechanism of action is inhibition of bacterial DNA transcription to mRNA independently from bacterial division, which results in activity against even dormant Staphylococcus spp. organisms. However, the high risk of emergence of rifampin-resistant mutants requires the concomitant administration of another antibiotic. Several antibiotics are recommended in the French guidelines issued by the French-Speaking Society for Infectious Diseases (Société de Pathologie Infectieuse de Langue Française [SPILF]). Here, we discuss the results from in vitro, animal, and clinical studies that explain the advantages and drawbacks of each antibiotic used with rifampin to treat osteoarticular infections due to Staphylococcus spp.

Topics: Anti-Bacterial Agents; Arthritis, Infectious; Biofilms; Drug Therapy, Combination; Humans; Infections; Osteomyelitis; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus

Endovascular aneurysm repair (EVAR) is now an established method of treating abdominal aortic aneurysms. Endovascular stent graft infection is a rare complication of EVAR. Diagnosis can be difficult and subsequent management challenging as a significant number of patients are unfit for further surgery and, untreated, graft infection is almost inevitably fatal. We present a case of an infected EVAR graft complicated by vertebral osteomyelitis that was treated conservatively. We discuss the diagnostic and therapeutic difficulties encountered and review the current literature on this evolving subject.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Aortic Aneurysm, Abdominal; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Clindamycin; Drug Administration Schedule; Drug Therapy, Combination; Endovascular Procedures; Gentamicins; Humans; Lumbar Vertebrae; Male; Osteomyelitis; Prosthesis-Related Infections; Rifampin; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

Bacille Calmette-Guérin osteomyelitis in infants is a known complication of Bacille Calmette-Guérin vaccination. Treatment consists of antituberculosis chemotherapy after biopsy/curettage; however, in cases of Bacille Calmette-Guérin osteomyelitis extending to the growth plate and epiphysis, the extent and time of surgical treatment such as curettage/biopsy is unknown because of bone growth disturbances. This article presents a case of an infant with this type of Bacille Calmette-Guérin osteomyelitis at the proximal tibia. A metaanalytic review was performed for possible risk factors of its recurrence. In our patient, primary curettage of partial lesion, excluding the part extending to the growth plate and epiphysis, failed, and recurettage of the extended lesion involving the growth plate and epiphysis was required for its eradication, resulting in bone growth disturbance. In the metaanalysis, 7 literatures reporting 14 cases of Bacille Calmette-Guérin osteomyelitis extending to the growth plate and epiphysis were included. Although statistical analysis showed no significant risk factors associated with the recurrence, these cases showed high recurrence rate in approximately 55.6%, requiring reoperation. Generally, the smaller damage to the growth plate can minimize bone growth disturbance. Taken together, it is suggested that Bacille Calmette-Guérin osteomyelitis extending to the growth plate and epiphysis is associated with high recurrence rate, and early curettage of the entire lesion should be performed to eradicate it and avoid resulting complications.

Topics: Anti-Bacterial Agents; BCG Vaccine; Bone Substitutes; Curettage; Durapatite; Growth Plate; Humans; Infant; Isoniazid; Knee Joint; Male; Meta-Analysis as Topic; Osteomyelitis; Pyrazinamide; Recurrence; Reoperation; Rifampin; Tibia

Methicillin resistant Staphylococcus aureus (MRSA) infection has classically been associated with institutional health care settings such as hospitals and nursing homes.. This article presents a case of community acquired MRSA infection resulting in severe osteomyelitis of the humerus, followed by a brief discussion and literature review.. Over the past few years, more community acquired cases of MRSA have occurred. Methicillin resistant S. aureus usually infects skin and soft tissue. Occasionally, a life threatening infection occurs involving the blood, lungs, heart and bone.

Topics: Adolescent; Anti-Bacterial Agents; Diagnosis, Differential; Fusidic Acid; Humans; Humerus; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Osteomyelitis; Rifampin; Shoulder Pain; Staphylococcal Infections; Tomography, X-Ray Computed

A 79-year-old man with a history of deep vein thrombosis and pulmonary embolism received anticoagulation therapy with warfarin 5 mg daily for 8 months. He was diagnosed with osteomyelitis and underwent partial metatarsal resection of his right foot. After surgery, antibiotics were initiated, including ertapenem sodium 1 g intravenously every 24 hours, vancomycin 1400 mg intravenously every 24 hours, and rifampin 300 mg by mouth twice daily. Achieving a therapeutic level of anticoagulation was difficult despite escalating doses of warfarin, because of the interaction with rifampin. A 5- to 6-fold increase in warfarin dose was prescribed to reach therapeutic international normalized ratios (INRs), but even these increases were insufficient to maintain his INR in the therapeutic range. After rifampin was discontinued, warfarin doses were gradually reduced over the next 2 months. When concurrent warfarin-rifampin therapy is necessary, vigilant monitoring is imperative and significant increases in warfarin doses are likely.

Topics: Aged; Antibiotics, Antitubercular; Anticoagulants; Drug Administration Schedule; Drug Interactions; Drug Monitoring; Humans; International Normalized Ratio; Male; Nursing Assessment; Osteomyelitis; Postoperative Care; Pulmonary Embolism; Rifampin; Risk Assessment; Venous Thrombosis; Warfarin

Topics: Administration, Oral; Anti-Bacterial Agents; Anti-Infective Agents; Chronic Disease; Drug Therapy, Combination; Fluoroquinolones; Gram-Negative Bacterial Infections; Humans; Osteomyelitis; Rifampin; Staphylococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination

The authors report a case of symphysis pubis osteomyelitis due to Brucella. Such localisation seems not to have been reported before. Despite an initially bad observance of antibiotic treatment, evolution has finally been favourable. At two year follow-up, no functional or radiological sequellae was observed.

Topics: Adult; Brucellosis; Doxycycline; Drug Therapy, Combination; Humans; Male; Osteomyelitis; Pubic Symphysis; Radiography; Rifampin

The prevalence of diabetes mellitus continues to inexorably rise in the United States and throughout the world. Lower limb amputations are a devastating comorbid complication of diabetes mellitus. Osteomyelitis increases the risk of amputation fourfold and commonly presages death. Antimicrobial therapy for diabetic foot osteomyelitis (DFO) varies greatly, indicating that high quality data are needed to inform clinical decision making. Several small trials have indicated that the addition of rifampin to backbone antimicrobial regimens for osteomyelitis outside the setting of the diabetic foot results in 28 to 42% higher cure rates.. This is a prospective, randomized, double-blind investigation of the addition of 6 weeks of rifampin, 600 mg daily, vs. matched placebo (riboflavin) to standard-of-care, backbone antimicrobial therapy for DFO. The study population are patients enrolled in Veteran Health Administration (VHA), ages ≥18 and ≤ 89 years with diabetes mellitus and definite or probable osteomyelitis of the foot for whom an extended course of oral or intravenous antibiotics is planned. The primary endpoint is amputation-free survival. The primary hypothesis is that using rifampin as adjunctive therapy will lower the hazard rate compared with the group that does not use rifampin as adjunctive therapy. The primary hypothesis will be tested by means of a two-sided log-rank test with a 5% significance level. The test has 90% power to detect a hazard ratio of 0.67 or lower with a total of 880 study participants followed on average for 1.8 years.. VA INTREPID will test if a rifampin-adjunctive antibiotic regimen increases amputation-free survival in patients seeking care in the VHA with DFO. A positive finding and its adoption by clinicians would reduce lower extremity amputations and their associated physical and emotional impact and reduce mortality for Veterans and for the general population with diabetic foot osteomyelitis. Given that rifampin-adjunctive regimens are currently employed for therapy for the majority of DFO cases in Europe, and only in a small minority of cases in the United States, the trial results will impact therapeutic decisions, even if the null hypothesis is not rejected.. Registered January 6, 2017 at ClinicalTrials.gov, NCT03012529.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amputation, Surgical; Anti-Bacterial Agents; Antibiotic Prophylaxis; Diabetic Foot; Double-Blind Method; Female; Foot; Humans; Male; Middle Aged; Osteomyelitis; Placebos; Prospective Studies; Rifampin; Secondary Prevention; Veterans; Young Adult

Little is known about the optimal duration of antibiotic therapy for diabetic foot osteomyelitis (DFO). This study sought to compare the effectiveness of 6 versus 12 weeks of antibiotic therapy in patients with DFO treated nonsurgically (i.e., antibiotics alone).. This was a prospective randomized trial comparing 6- versus 12-week duration of antibiotic treatment. Remission of osteomyelitis during the monitoring period was defined as complete and persistent (>4 weeks) healing of the wound (if present initially), absence of recurrent infection at the initial site or that of adjacent rays, and no need for surgical bone resection or amputation at the end of a follow-up period of at least 12 months after completion of antibiotic treatment.. Forty patients followed at five French general hospitals were randomized between January 2007 and January 2009, with 20 treated for 6 weeks and 20 treated for 12 weeks with antibiotics. The two groups were comparable for all variables recorded at inclusion in the study. Remission was obtained in 26 (65%) patients, with no significant differences between patients treated for 6 versus 12 weeks (12/20 vs. 14/20, respectively; P = 0.50). We did not identify any significant parameters associated with patient outcome. Fewer patients treated for 6 weeks experienced gastrointestinal adverse events related to antimicrobial therapy compared with patients treated for 12 weeks (respectively, 15 vs. 45%; P = 0.04).. The present multicenter prospective randomized study provides data suggesting that 6-week duration of antibiotic therapy may be sufficient in patients with DFO for whom nonsurgical treatment is considered.

Topics: Amputation, Surgical; Anti-Bacterial Agents; Diabetic Foot; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluoroquinolones; Humans; Male; Middle Aged; Osteomyelitis; Prospective Studies; Rifampin; Treatment Outcome; Wound Healing

Oral therapies alternative to fluoroquinolones against staphylococcal chronic osteomyelitis have not been evaluated in comparative studies. Consecutive nonaxial Staphylococcus aureus chronic osteomyelitis cases were included in a comparative trial after debridement. Fifty patients were randomized: group A (n = 22) was treated with cloxacillin for 6 weeks intravenously plus 2 weeks orally (p.o.), and group B (n = 28) was treated with rifampin-cotrimoxazole for 8 weeks p.o. During follow-up (10 years), five relapses occurred: two (10%) in group A and three (11%) in group B. Foreign-body maintenance was associated with relapse (P = 0.016). Oral rifampin-cotrimoxazole treatment showed outcomes comparable to those for intravenous cloxacillin treatment.

Topics: Administration, Oral; Adult; Aged; Anti-Infective Agents; Cloxacillin; Drug Combinations; Female; Follow-Up Studies; Humans; Injections, Intravenous; Male; Middle Aged; Osteomyelitis; Rifampin; Staphylococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Both linezolid and cotrimoxazole are antibiotics that are well suited for oral therapy of bone and joint infections (BJI) caused by otherwise resistant Gram-positive cocci (GPC) (resistance to fluoroquinolones, maccolides, betalactamines). However, in this context, no data are currently available regarding the safety and tolerance of these antibiotics in combination with rifampicin. The objective of this study was to compare the efficacy and safety of a combination of rifampicin and linezolid (RLC) with those of a combination of rifampicin and cotrimoxazole (RCC) in the treatment of BJI. Between February 2002 and December 2006, 56 adult patients (RLC, n = 28; RCC, n = 28), including 36 with infected orthopaedic devices (RLC, n = 18; RCC, n = 18) and 20 with chronic osteomyelitis (RLC, n = 10; RCC, n = 10), were found to be eligible for inclusion in this study. Patients who discontinued antibiotic therapy within 4 weeks of commencing treatment were considered to represent cases of treatment failure and were excluded. Rates of occurrence of adverse effects were similar in the two groups, at 42.9% in the RLC group and 46.4% in the RCC group (p = 1.00), and led to treatment discontinuation in four (14.3%) RLC and six (21.4%) RCC patients. Cure rates were found to be similar in the two groups (RLC, 89.3%, RCC, 78.6%; p = 0.47). Prolonged oral RLC and RCC therapy were found to be equally effective in treating patients with BJI caused by resistant GPC, including patients with infected orthopaedic devices. However, the lower cost of cotrimoxazole compared with linezolid renders RCC an attractive treatment alternative to RLC. Further larger clinical studies are warranted to confirm these preliminary results.

Topics: Acetamides; Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Chronic Disease; Drug Therapy, Combination; Female; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Linezolid; Male; Middle Aged; Orthotic Devices; Osteomyelitis; Oxazolidinones; Prosthesis-Related Infections; Rifampin; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

The aim of this study was to assess the frequency of gastrointestinal side effects (GSE) and hepatotoxicity in patients treated with rifampicin for an osteoarticular infection and to determine if there is an association between rifampicin plasma concentrations and side effects. Rifampicin plasma concentrations were prospectively measured before (trough concentration, C(0)) and 2 +/- 0.5 h (peak concentration, C(2)) after drug intake. The presence of GSE, the alanine transferase (ALT) value, and concomitantly administered medications were recorded on the day rifampicin concentrations were measured. C(0) and C(2) were compared for differences regarding the presence or absence of side effects. Multivariate analysis was performed, with associated medications being taken into account. Seventy C(0) and 57 C(2) values were measured in 46 adults after a median treatment of 8 days (range, 1-179). Wide inter-individual variability was observed for C(0) and C(2). Thirteen (28%) patients reported GSE at least once. When GSE occurred, C(0) (median, 1 mg L(-1); range, 0.1-9.9 mg L(-1)) and C(2) (median, 10.3 mg L(-1); range, 1.8-40.3 mg L(-1)) were similar to C(0) (median, 0.6 mg L(-1); range, 0.1-10.3 mg L(-1)) and C(2) (median, 10.9 mg L(-1); range, 2.9-29.0 mg L(-1)) without GSE. The ALT value was more than normal in only three patients (6.5%) after rifampicin treatment began. The patients received no different associated medications whether or not GSE were present. Multivariate analysis showed no association between rifampicin plasma concentrations and GSE. GSE occur frequently in patients receiving rifampicin for osteoarticular infection but without an association with rifampicin plasma concentrations. Thus, therapeutic drug monitoring of rifampicin is irrelevant in the management of GSE.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Diarrhea; Digestive System; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Nausea; Osteomyelitis; Pilot Projects; Prospective Studies; Rifampin; Vomiting

We retrospectively evaluated the safety and effectiveness of colistin alone or in combination with other antimicrobials in eight diabetic patients with severe diabetic foot infections due to multidrug resistant (MDR) Pseudomonas aeruginosa, complicated in 4 cases by osteomyelitis. All patients received colistin after other ineffective antimicrobial treatment, when MDR P. aeruginosa strains were isolated by cultural examination and together with a multidisciplinary care approach including revascularization, surgical debridement and adequate offloading. The mean duration of therapy was 72 +/- 52.9 days. Six out of 8 patients (75%) successfully benefited from colistin therapy, while 2 patients failed and/or experienced side effects that led to discontinuation of therapy. Serious adverse events (i.e. acute renal failure and pulmonary edema) were observed in 1 patient. Our data allow us to conclude that colistin, alone or in combination with other antimicrobials, is safe and effective when administered as part of a multidisciplinary approach, to promote healing of diabetic foot infection due to MDR P. aeruginosa.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Combined Modality Therapy; Debridement; Diabetic Foot; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Middle Aged; Osteomyelitis; Pseudomonas Infections; Retrospective Studies; Rifampin; Treatment Outcome

A controlled trial of treatment of chronic osteomyelitis caused by Staphylococcus aureus compared nafcillin alone with nafcillin plus rifampin for a six-week period. Treatment was well tolerated, the only adverse effect being mild neutropenia in four of 18 patients; no toxicity was observed from rifampin. Eight of ten patients in the combined treatment group had a favorable clinical response (with follow-up of two to four years) as compared to four of eight in the nafcillin group (P = .2). Despite the failure to show a statistically significant advantage of rifampin plus nafcillin, we conclude that the combination, along with appropriate surgery, should be considered for patients with chronic staphylococcal osteomyelitis.

Topics: Administration, Oral; Blood Sedimentation; Chronic Disease; Clinical Trials as Topic; Combined Modality Therapy; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nafcillin; Neutropenia; Osteomyelitis; Random Allocation; Rifampin; Staphylococcal Infections; Time Factors

Topics: Clindamycin; Diabetes Mellitus; Diabetic Foot; Drug Monitoring; Humans; Osteomyelitis; Rifampin

BACKGROUND Foot ulcers are high-morbidity and debilitating complications of diabetes mellitus, and carry significantly increased rates of associated major amputations. They contribute to significantly worse quality of life. Osteomyelitis is a frequent complication of diabetic foot ulcers, since bacteria can contiguously spread from soft tissues to the bone, involving the cortex first and then the bone marrow. Unfortunately, clinically unsuspected osteomyelitis is frequent in persisting diabetic foot ulcers. It is associated with limb amputations and increased mortality. CASE REPORT We describe a 76-year-old man with long-standing insulin-treated type 2 diabetes, who experienced extensively drug-resistant Enterococcus faecalis diabetic foot myositis and osteomyelitis associated with sepsis. He was successfully treated with surgical debridement combined with the administration of teicoplanin plus rifampicin in the outpatient setting, completing, in total, a twelve-week course of antibiotic therapy. CONCLUSIONS Clinically unsuspected osteomyelitis in patients with persisting diabetic foot ulcers has been associated with infections from highly resistant bacteria. Early and accurate diagnosis of diabetic foot osteomyelitis, as well as proper therapeutic approach (antimicrobial and surgical), is of great importance to reduce the risk of minor and major amputations, septic shock leading to multiple organ failure, and overall mortality.

Topics: Aged; Anti-Bacterial Agents; Diabetes Mellitus, Type 2; Diabetic Foot; Enterococcus faecalis; Humans; Male; Myositis; Osteomyelitis; Outpatients; Pharmaceutical Preparations; Quality of Life; Rifampin; Teicoplanin

Topics: Animals; Anti-Bacterial Agents; Escherichia coli; Osteomyelitis; Polyesters; Rats; Rifampin; Silicates; Silicon Dioxide; Staphylococcal Infections; Staphylococcus aureus

The objective of this study was to evaluate the clinical outcomes and safety of clindamycin combination antibiotherapy for the treatment of erythromycin-resistant, lincosamide-susceptible bone and joint infections caused by Staphylococcus spp. Between January 2010 and September 2018, 46 patients with Staphylococcus spp. erythromycin-resistant, lincosamide-susceptible bone and joint infections were treated with clindamycin combination antibiotherapy for 6 to 12 weeks. The type of infection was prosthetic in 20 cases (43.5%), osteosynthetic device in 15 cases (32.6%), chronic osteomyelitis in 7 cases (15.2%), and arthritis in 4 cases (8.7%). The cure rate was 67.4% by intention to treat and 84.6% per protocol, with a median follow-up of 398 days (range 86-843). Only 2 relapses (5.1%) were observed in patients with chronic osteomyelitis; an acquired resistance to lincosamides developed in 1 case. Clindamycin combination therapy appears to be effective for the treatment of bone and joint infection caused by erythromycin-resistant, lincosamide-susceptible Staphylococcus spp.

Topics: Aged; Anti-Bacterial Agents; Arthritis, Infectious; Bone and Bones; Clindamycin; Drug Resistance, Bacterial; Drug Therapy, Combination; Erythromycin; Female; Humans; Joints; Male; Microbial Sensitivity Tests; Middle Aged; Osteomyelitis; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus; Staphylococcus aureus

Topics: Animals; Antibiotics, Antitubercular; Bacterial Load; Drug Evaluation, Preclinical; Fracture Healing; Fractures, Open; Hydrogels; Male; Methicillin-Resistant Staphylococcus aureus; Mice, Inbred C57BL; Osteomyelitis; Rifampin; Staphylococcal Infections

To report the case of an infant with infrequent cranial osteomyelitis as a complication of furuncular myiasis.. The patient was a 4-month-old male who presented to the emergency department with a nodular skull lesion with edema, tenderness, pain, and purulent drainage, as well as progress of the ulcerated lesion and evidence of larvae inside. Antibiotic treatment was initiated, and the patient was taken to the operating room to remove the larvae, but he had no symptomatic improvement. A skull radiograph was taken to visualize the osteolytic lesion, and a 3D computed tomography scan showed osteomyelitis of the external parietal surface. Antibiotic management readjustment continued for a total of six weeks, and a skin flap was used with clinical improvement.. Myiasis is defined as the infestation of vertebrates with fly larvae. In mammals, larvae can feed on host tissue and cause a wide range of infestations depending on their location in the body. The cranial osteomyelitis as a complication of myiasis described in this report seems to be an exceptional case.

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antitubercular; Clindamycin; Combined Modality Therapy; Follow-Up Studies; Humans; Imaging, Three-Dimensional; Infant; Larva; Male; Myiasis; Osteomyelitis; Patient Discharge; Radiography; Rifampin; Skull Neoplasms; Surgical Flaps; Tomography, X-Ray Computed

Topics: Anti-Bacterial Agents; Antibodies, Bacterial; Bartonella henselae; Bone Marrow; Cat-Scratch Disease; Child, Preschool; Female; Femur; Humans; Magnetic Resonance Imaging; Osteomyelitis; Pelvis; Rifampin; Treatment Outcome

Topics: Anti-Bacterial Agents; Antitubercular Agents; Azithromycin; Debridement; Deprescriptions; Drug Therapy, Combination; Ethambutol; Finger Joint; Fisheries; Fresh Water; Humans; Immunocompromised Host; Infliximab; Male; Metacarpophalangeal Joint; Middle Aged; Mycobacterium Infections, Nontuberculous; Mycobacterium marinum; Osteomyelitis; Rifampin; Spondylitis, Ankylosing; Synovectomy; Tenosynovitis; Tumor Necrosis Factor Inhibitors; Wrist Joint

In general, osteomyelitis is treated with antibiotics, and in severe cases, the inflammatory bone tissue is removed and substituted with poly (methyl methacrylate) (PMMA) beads containing antibiotics. However, this treatment necessitates re-surgery to remove the inserted PMMA beads. Moreover, rifampicin, a primary heat-sensitive antibiotic used for osteomyelitis, is deemed unsuitable in this strategy. Three-dimensional (3D) printing technology has gained popularity, as it facilitates the production of a patient-customized implantable structure using various biodegradable biomaterials as well as controlling printing temperature. Therefore, in this study, we developed a rifampicin-loaded 3D scaffold for the treatment of osteomyelitis using 3D printing and polycaprolactone (PCL), a biodegradable polymer that can be printed at low temperatures. We successfully fabricated rifampicin-loaded PCL 3D scaffolds connected with all pores using computer-aided design and manufacturing (CAD/CAM) and printed them at a temperature of 60 °C to prevent the loss of the antibacterial activity of rifampicin. The growth inhibitory activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), the representative causative organisms of osteomyelitis, was confirmed. In addition, we optimized the rifampicin-loading capacity that causes no damage to the normal bone tissues in 3D scaffold with toxicity evaluation using human osteoblasts. The rifampicin-releasing 3D scaffold developed herein opens new possibilities of the patient-customized treatment of osteomyelitis.

Topics: Anti-Bacterial Agents; Biocompatible Materials; Cell Line; Cell Proliferation; Drug Design; Escherichia coli; Hot Temperature; Humans; Microbial Sensitivity Tests; Osteoblasts; Osteomyelitis; Polymethyl Methacrylate; Printing, Three-Dimensional; Rifampin; Staphylococcus aureus; Tissue Scaffolds; Translational Research, Biomedical

The prevalence of diabetes continues to rise around the world. Diabetic foot is a serious complication of diabetes, and diabetic patients with diabetic foot osteomyelitis (DFO) have a fourfold increased risk of amputation, usually indicating death. Therefore, it is particularly important to seek a more effective treatment for DFO. The treatment of DFO varies from person to person, and antimicrobial therapies vary widely. A large number of clinical studies have shown that rifampicin adjuvant therapy can reduce the rate of amputation and mortality in DFO patients. However, there is no systematic summary of clinical evidence, which limits the clinical application of rifampicin. Therefore, we attempted to provide high-quality evidence for the clinical efficacy and safety of rifampin in the adjuvant treatment of DFO through this meta-analysis.. English literature is mainly searched in Cochrane Library, PubMed, EMBASE and Web of Science, while Chinese literature is from CNKI, CBM, VIP and Wangfang databases. At the same time, we will search clinical registration tests and gray literature. Two methodologically trained researchers will read the title, abstract, and full text, and independently select qualified literature based on inclusion and exclusion criteria. Binary data is expressed as relative risk, continuous data is expressed as mean difference or standard mean difference. The final data are synthesized using a fixed effect model or a random effect model, depending on the presence of heterogeneity. In the end, the patient's amputation rate and mortality were the main research indicators. Survival rate, HbA1c, serum creatinine, changes in ulcer area, and SF-36 quality of life assessment were used as secondary indicators. We will perform a sensitivity analysis to assess the stability of the results. Then the publication bias was evaluated by funnel plot analysis and Egger test. Finally, we will use a "recommendation grading, evaluation, formulation and evaluation" system to assess the quality of the evidence. All data analysis will be meta-analyzed by the statistical software RevMan software version 5.3.. This study will provide a high-quality comprehensive report on the effectiveness and safety of rifampicin in the treatment of DFO, and our findings will be published in peer-reviewed journals.. This systematic review and meta-analysis will provide a comprehensive summary and careful evaluation of rifampicin as an adjuvant treatment of DFO with a view to providing multiple options for clinical treatment of the disease. REGISTRATION NUMBER:: is INPLASY202040084.

Topics: Adjuvants, Pharmaceutic; Anti-Bacterial Agents; Diabetic Foot; Humans; Meta-Analysis as Topic; Osteomyelitis; Rifampin; Systematic Review as Topic

Owing to patient intolerance or drug interactions, alternative agents to rifampin are needed for management of staphylococcal periprosthetic joint infection. In the current study, we evaluated rifabutin, rifapentine and rifampin, with and without vancomycin, in a rat model of foreign body osteomyelitis.. Proximal tibiae were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and a Kirschner wire (K-wire) implanted in each. After 4 weeks of infection, rifampin, rifabutin, or rifapentine were administered, alone or with vancomycin. Tibiae and K-wires were cultured, and medians were reported as log10 colony-forming units (CFUs) per gram of bone or log10 CFUs per K-wire, respectively.. Rifampin, rifabutin or rifapentine administered with vancomycin yielded less MRSA from bones (0.10, 3.02, and 0.10 log10 CFUs/g, respectively) than did no treatment (4.36 log10 CFUs/g) or vancomycin alone (4.64 log10 CFUs/g) (both P ≤ .02). The K-wires of animals receiving no treatment or vancomycin monotherapy recovered medians of 1.76 and 2.91 log10 CFUs/g per K-wire, respectively. In contrast, rifampin, rifabutin and rifapentine administered with vancomycin yielded medians of 0.1 log10 CFUs per K-wire, respectively. Rifampin resistance was detected in a single animal in the rifampin monotherapy group.. Rifabutin or rifapentine with vancomycin were as active as rifampin with vancomycin against MRSA in rat foreign body osteomyelitis, suggesting that rifabutin and/or rifapentine may be alternatives to rifampin in the clinical management of staphylococcal periprosthetic joint infections.

Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Drug Therapy, Combination; Foreign Bodies; Male; Methicillin-Resistant Staphylococcus aureus; Osteomyelitis; Rats; Rats, Wistar; Rifabutin; Rifampin; Staphylococcal Infections; Vancomycin

Topics: Animals; Foreign Bodies; Methicillin-Resistant Staphylococcus aureus; Osteomyelitis; Rats; Rifabutin; Rifampin

Next-generation treatment strategies to treat osteomyelitis with complete eradication of pathogen at the bone nidus and prevention of emergence of drug resistance is a real challenge in orthopedics. Conventional treatment strategies including long-term adherence of patients to systemic antibiotic delivery, local delivery using nondegradable vehicles, and surgical debridement are not completely effective in achieving successful results. In this study, a broad-spectrum antibiotic, rifampicin (RFP), was incorporated into a biphasic nanohydroxyapatite (nHAP)/calcium sulfate ceramic carrier (NC) system.

Topics: Animals; Ceramics; Humans; Osteomyelitis; Rats; Rifampin; Staphylococcus aureus; Tibia

Bacillus Calmette-Guérin (BCG)-associated osteomyelitis is a rare adverse event following BCG vaccination, and there have been no previous reports of BCG-associated cervical spondylitis. Here, we describe the case of a 3-year-old immunocompetent girl who developed BCG-associated cervical spondylitis and was successfully treated by prompt surgical drainage of the abscess and administration of isoniazid and rifampicin for 9 months without sequelae.

Topics: Abscess; Antitubercular Agents; BCG Vaccine; Cervical Vertebrae; Child, Preschool; Female; Humans; Immunocompetence; Isoniazid; Mycobacterium bovis; Osteomyelitis; Rifampin; Spondylitis; Tuberculosis

The purpose of this study was to gather temporal trends on bacteria epidemiology and resistance of intraoperative bone culture from chronic ostemyelitis at an affiliated hospital in South China.. Records of patients with chronic osteomyelitis from 2003 to 2014 were retrospectively reviewed. The medical data were extracted using a unified protocol. Antimicrobial susceptibility testing was carried out by means of a unified protocol using the Kirby-Bauer method, results were analyzed according to Clinical and Laboratory Standards Institute definitions.. Four hundred eighteen cases met our inclusion criteria. For pathogen distribution, the top five strains were Staphylococcus aureus (27.9%); Pseudomonas aeruginosa (12.1%); Enterobacter cloacae (9.5%); Acinetobacter baumanii (9.0%) and Escherichia coli (7.8%). Bacterial culture positive rate was decreased significantly among different year-groups. Mutiple bacterial infection rate was 28.1%. One strain of Staphylococcus aureus was resistant to linezolid and vancomycin. Resistance of Pseudomonas aeruginosa stains to Cefazolin, Cefuroxime, Cefotaxime, and Cefoxitin were 100% nearly. Resistance of Acinetobacter baumanii stains against Cefazolin, Cefuroxime were 100%. Ciprofloxacin resistance among Escherichia coli isolates increased from 25 to 44.4%. On the contrary, resistance of Enterobacter cloacae stains to Cefotaxime and Ceftazidime were decreased from 83.3 to 36.4%.. From 2003 to 2014, positive rate of intraoperative bone culture of chronic osteomyelitis was decreased; the proportion of Staphylococcus aureus was decreased gradually, and our results indicate the importance of bacterial surveilance studies about chronic osteomyelitis.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Cefotaxime; China; Chronic Disease; Drug Resistance, Bacterial; Escherichia coli; Female; Hospitals; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Osteomyelitis; Pseudomonas aeruginosa; Retrospective Studies; Rifampin; Staphylococcus aureus; Young Adult

Among patients diagnosed with diabetes, the lifetime incidence of foot ulcers is 15%. Infection is a common complication of foot ulcers, and 20% to 60% of infections result in diabetic foot osteomyelitis (DFO). Current treatment guidelines do not endorse any specific antibiotic agent for DFO, but small clinical trials suggest the addition of rifampin to antimicrobial regimens results in improved cure rates for osteomyelitis.. To compare the clinical outcomes of patients treated for DFO in the Veterans Health Administration (VHA) with and without adjunctive rifampin.. This observational cohort study used VHA databases to identify index DFO cases from January 1, 2009, through December 31, 2013, and analyzed patients alive and without high-level amputation at 90 days after diagnosis in whom antibiotic therapy was initiated within 6 weeks of diagnosis. Patients with death or major amputation within 90 days of diagnosis, who were not treated with systemic antibiotics dispensed by the VHA within 6 weeks of diagnosis, or who were treated at facilities where rifampin was not dispensed for DFO were excluded. The retrospective cohort to inform the planning of a multisite randomized clinical trial was first investigated in spring 2015; retrospective analysis was performed from February 2017 through September 2019.. Patients initiating rifampin therapy within 6 weeks of the DFO diagnosis and receiving the drug for at least 14 days within 90 days of diagnosis were considered treated with rifampin. Patients not administered rifampin within 90 days of diagnosis served as the comparator group.. A combined end point of mortality or amputation within 2 years of diagnosis was analyzed. Differences in times to event were evaluated using log-rank tests. Differences in event rates were compared using χ2 tests and multivariable logistic regression.. The analysis population included 130 patients treated with rifampin and 6044 treated without rifampin (total of 6174; 6085 men [98.6%]; mean [SD] age, 64.9 [9.7] years). Lower event rates were observed among the rifampin group (35 of 130 [26.9%] vs 2250 of 6044 [37.2%]; P = .02). Patients treated with rifampin were younger (mean [SD] age, 62.2 [9.4] vs 64.9 [9.6] years), had fewer comorbidities (mean [SD] Charlson comorbidity index score, 3.5 [1.8] vs 4.0 [2.2]), had more infectious disease specialty consultations (63 of 130 [48.5%] vs 1960 of 6044 [32.4%]), and more often had Staphylococcus aureus identified in cultures (55 of 130 [42.3%] vs 1755 of 6044 [29.0%]) than patients not treated with rifampin. A logistic regression estimating the odds of events and controlling for these and other covariates yielded a significant association of rifampin (odds ratio, 0.65; 95% CI, 0.43-0.96; P = .04).. In this cohort study, patients administered rifampin experienced lower rates of death and amputation than patients not treated with rifampin, which remained significant after adjustment for confounders. These results coupled with existing evidence from small clinical trials suggest the addition of rifampin to current treatment regimens may be a useful antimicrobial option in the treatment of DFO.

Topics: Amputation, Surgical; Anti-Bacterial Agents; Diabetic Foot; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Osteomyelitis; Rifampin; Treatment Outcome; United States; Veterans Health Services

Empiric antibiotic therapy for suspected hematogenous vertebral osteomyelitis (HVO) should be initiated immediately in seriously ill patients and may be required in those with negative microbiological results. The aim of this study was to inform the appropriate selection of empiric antibiotic regimens for the treatment of suspected HVO by analyzing antimicrobial susceptibility of isolated bacteria from microbiologically proven HVO.. We conducted a retrospective chart review of adult patients with microbiologically proven HVO in five tertiary-care hospitals over a 7-year period. The appropriateness of empiric antibiotic regimens was assessed based on the antibiotic susceptibility profiles of isolated bacteria.. In total, 358 cases of microbiologically proven HVO were identified. The main causative pathogens identified were methicillin-susceptible Staphylococcus aureus (33.5%), followed by methicillin-resistant S. aureus (MRSA) (24.9%), Enterobacteriaceae (19.3%), and Streptococcus species (11.7%). Extended spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and anaerobes accounted for only 1.7% and 1.4%, respectively, of the causative pathogens. Overall, 73.5% of isolated pathogens were susceptible to levofloxacin plus rifampicin, 71.2% to levofloxacin plus clindamycin, and 64.5% to amoxicillin-clavulanate plus ciprofloxacin. The susceptibility to these oral combinations was lower in cases of healthcare-associated HVO (52.6%, 49.6%, and 37.6%, respectively) than in cases of community-acquired HVO (85.8%, 84.0%, and 80.4%, respectively). Vancomycin combined with ciprofloxacin, ceftriaxone, ceftazidime, or cefepime was similarly appropriate (susceptibility rates of 93.0%, 94.1%, 95.8%, and 95.8%, respectively).. Based on our susceptibility data, vancomycin combined with a broad-spectrum cephalosporin or fluoroquinolone may be appropriate for empiric treatment of HVO. Fluoroquinolone-based oral combinations may be not appropriate due to frequent resistance to these agents, especially in cases of healthcare-associated HVO.

Topics: Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacterial Infections; beta-Lactamases; Ciprofloxacin; Clindamycin; Drug Therapy, Combination; Empirical Research; Enterobacteriaceae; Female; Gene Expression; Humans; Levofloxacin; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Osteomyelitis; Retrospective Studies; Rifampin; Spine; Streptococcus; Vancomycin

Biocompatible polymers and ceramic materials have been identified as vital components to fabricate drug delivery and tissue engineering applications because of their high drug loading capability, sustained release and higher mechanical strength with remarkable in-vivo bioavailability. In the present work, initially we designed κ-carrageenan grafted with maleic anhydride and then reacted it with isoniazid drug (κ-Car-MA-INH). The polymeric system was cross linked with nanohydroxyapatite (NHAP) via electrostatic interaction followed by the addition of rifampicin (RF) and loaded to fabricate κ -Car-MA-INH/NHAP/RF nanocomposites. The chemical modification and interaction of drug with the polymeric-ceramic system were characterised by Fourier Transform Infrared spectroscopy (FT-IR). The zeta potential of the κ -Car-MA-INH/NHAP/RF nanocomposite was observed to be -20.04 mV using Zetasizer. The in vitro drug release studies demonstrated that the nanocomposite releases 76% of RF and 82% of INH in 12 days at pH 5.5. Scanning Electron Microscope analysis revealed the structural deformation of Staphylococcus aureus and Klebsiella pneumoniae upon treatment with this nanocomposite. By using ex-vivo studies combined with physio-chemical characterization methods on the erythrocytes, L929 and MG-63 cell lines, this composite was found to be biocompatible, non-cytotoxic and inducing cell proliferation with less significant hemolysis. Thus, our modified drug delivery nanocomposites afforded higher drug bioavailability with large potential for fabrication as long-acting drug delivery nanocomposites, especially with hydrophobic drugs inducing the growth of osteoblastic bone cells.

Topics: Animals; Antitubercular Agents; Carrageenan; Cell Line; Drug Delivery Systems; Drug Liberation; Durapatite; Erythrocytes; Hemolysis; Humans; Isoniazid; Klebsiella pneumoniae; Macrophages; Maleic Anhydrides; Mice; Nanocomposites; Osteoblasts; Osteomyelitis; Regeneration; Rifampin; Staphylococcus aureus; Tuberculosis

A 56-year-old woman, without any immunocompromising diseases, was referred to our hospital because of a recurrence of pyogenic spondylitis. Computed tomography revealed multiple osteolytic changes in the whole body. Vertebral magnetic resonance imaging revealed osteomyelitis and spondylitis. Mycobacterium scrofulaceum was detected in sputum cultures, in abscesses from the right knee, and in a subcutaneous forehead abscess. Therefore, the patient was diagnosed with disseminated Mycobacterium scrofulaceum infection. The patient was treated with rifampicin, ethambutol, and clarithromycin, which resulted in symptomatic relief and radiological improvement. We herein report a rare case of disseminated Mycobacterium scrofulaceum infection in an immunocompetent host.

Topics: Antitubercular Agents; Clarithromycin; Ethambutol; Female; Humans; Middle Aged; Mycobacterium Infections, Nontuberculous; Mycobacterium scrofulaceum; Osteomyelitis; Rifampin

Chronic osteomyelitis is a chronic inflammatory disease induced by bone infection. It may be limited to a single portion of bone or involve several areas such as marrow, cortical, periosteum and adjacent soft tissues. Being able to persist for weeks, months or even years, it remains a therapeutic challenge in spite of the important medical and surgical advances, with a prolonged and complex management given the nature of the surgical interventions and the antibiotherapies required. We report a case of chronic osteomyelitis treated by long-term suppressive antibiotic therapy, which may be a reasonable alternative to surgery in inoperable clinical situations, but taking into account the risks associated with it in terms of side effects and selection of resistant organisms, as well as the cost of treatment and the quality of life of the patient.. L’ostéomyélite chronique est une pathologie inflammatoire chronique induite par une infection osseuse. Elle peut être limitée à une seule portion d’os ou impliquer plusieurs zones telles que la moelle, la corticale, le périoste et les tissus mous adjacents. Pouvant persister pendant des semaines, des mois voire des années, elle reste un challenge thérapeutique en dépit des importantes avancées médicales et chirurgicales, avec une prise en charge prolongée et complexe compte tenu de la nature des interventions chirurgicales et des antibiothérapies requises. Nous rapportons un cas d’ostéomyélite chronique pris en charge par antibiothérapie suppressive au long cours, qui peut être une alternative raisonnable à la chirurgie dans des situations cliniques inopérables, mais en prenant en considération les risques qui y sont associés en termes d’effets secondaires et de sélection des germes résistants, ainsi que le coût du traitement et la qualité de vie du patient.

Topics: Aged; Anti-Bacterial Agents; Chronic Disease; Drug Administration Schedule; Floxacillin; Humans; Male; Minocycline; Osteomyelitis; Rifampin

Staphylococcal prosthetic joint infections (PJIs) are associated with biofilm formation, making them difficult to treat; if managed with debridement and implant retention, rifampin-based therapy is usually employed. Rifampin resistance potentially challenges PJI treatment. In investigating the effects of rifampin monotherapy on methicillin-resistant Staphylococcus aureus (MRSA) foreign-body osteomyelitis in rats, we previously demonstrated that rifampin resistance was selected but that it disappeared 14 days following rifampin monotherapy (1) and that rifampin resistance occurred less frequently following two rounds than following one round of rifampin monotherapy (2). Here, we compared rifampin monotherapy followed by rifampin-vancomycin combination therapy to rifampin-vancomycin combination therapy alone in experimental MRSA foreign-body osteomyelitis. Animals treated with rifampin monotherapy followed by rifampin-vancomycin combination therapy had decreased quantities of bacteria 14 days following treatment completion (P = 0.034) compared to those in animals treated with combination therapy alone. Additionally, some isolates recovered from animals treated with combination therapy alone, although still susceptible to rifampin, had higher MIC, minimum biofilm-inhibitory concentration (MBIC), and minimum biofilm-bactericidal concentration (MBBC) values than those of the inoculating strain. This suggests that rifampin may remain a feasible treatment option in foreign-body-associated orthopedic infections following the selection of rifampin resistance.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Drug Therapy, Combination; Foreign Bodies; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Osteomyelitis; Rats, Wistar; Rifampin; Staphylococcal Infections; Vancomycin

Infection after osteosynthesis is an important complication with significant morbidity and even mortality. These infections are often caused by biofilm-producing bacteria. Treatment algorithms dictate an aggressive approach with surgical debridement and antibiotic treatment. The aim of this study is to analyze the effect of such an aggressive standardized treatment regime with implant retention for acute, existing <3 weeks, infection after osteosynthesis.. We conducted a retrospective 2-year cohort in a single, level 1 trauma center on infection occurring within 12 months following any osteosynthesis surgery. The standardized treatment regime consisted of implant retention, thorough surgical debridement, and immediate antibiotic combination therapy with rifampicin. The primary outcome was success. Success was defined as consolidation of the fracture and resolved symptoms of infection. Culture and susceptibility testing were performed to identify bacteria and resistance patterns. Univariate analysis was conducted on patient-related factors in association with primary success and antibiotic resistance.. Forty-nine patients were included for analysis. The primary success rate was 63% and overall success rate 88%. Factors negatively associated with primary success were the following: Gustilo classification (P = 0.023), higher number of debridements needed (P = 0.015), inability of primary closure (P = 0.017), and subsequent application of vacuum therapy (P = 0.030). Adherence to the treatment regime was positively related to primary success (P = 0.034).. The described treatment protocol results in high success rates, comparable with success rates achieved in staged exchange in prosthetic joint infection treatment.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Clinical Protocols; Combined Modality Therapy; Debridement; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Fracture Fixation, Internal; Fractures, Bone; Humans; Male; Middle Aged; Osteomyelitis; Prosthesis Retention; Retrospective Studies; Rifampin; Surgical Wound Infection; Trauma Centers; Vancomycin; Young Adult

Linezolid is an effective antibiotic against most gram-positive bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus. Although linezolid therapy is known to result in thrombocytopenia, dosage adjustment or therapeutic drug monitoring of linezolid is not generally necessary. In this report, however, we describe the case of a 79-year-old woman with recurrent methicillin-resistant S. aureus osteomyelitis that was successfully treated via surgery and combination therapy using linezolid and rifampicin under therapeutic drug monitoring for maintaining an appropriate serum linezolid concentration. The patient underwent surgery for the removal of the artificial left knee joint and placement of vancomycin-impregnated bone cement beads against methicillin-resistant S. aureus after total left knee implant arthroplasty for osteoarthritis. We also initiated linezolid administration at a conventional dose of 600 mg/h at 12-h intervals, but reduced it to 300 mg/h at 12-h intervals on day 9 because of a decrease in platelet count and an increase in serum linezolid trough concentration. However, when the infection exacerbated, we again increased the linezolid dose to 600 mg/h at 12-h intervals and performed combination therapy with rifampicin, considering their synergistic effects and the control of serum linezolid trough concentration via drug interaction. Methicillin-resistant S. aureus infection improved without reducing the dose of or discontinuing linezolid. The findings in the present case suggest that therapeutic drug monitoring could be useful for ensuring the therapeutic efficacy and safety of combination therapy even in patients with osteomyelitis who require long-term antibiotic administration.

Topics: Aged; Anti-Bacterial Agents; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Knee; Linezolid; Methicillin-Resistant Staphylococcus aureus; Osteomyelitis; Patella; Rifampin; Staphylococcal Infections

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Osteomyelitis; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

Susceptibility to antibiotics is dramatically reduced when bacteria form biofilms. In clinical settings this has a profound impact on treatment of implant-associated infections, as these are characterized by biofilm formation. Current routine susceptibility testing of microorganisms from infected implants does not reflect the actual susceptibility, and the optimal antibiotic strategy for treating implant-associated infections is not established. In this study of biofilm formation in implant-associated osteomyelitis, we compared thein vitroandin vivoefficacy of selected antibiotics alone and in combination againstStaphylococcus aureus.We tested vancomycin, linezolid, daptomycin and tigecycline alone and in combination with rifampicin, vancomycin, linezolid and daptomycin againstS. aureusIn vitro, biofilm formation dramatically reduced susceptibility by a factor of 500-2000.In vivo, antibiotic combinations were tested in a murine model of implant-associated osteomyelitis. Mice were infected by inserting implants colonized withS. aureustrough their tibia. After 11 days, the animals were divided into different groups (five animals/group) and given 14 days of antibiotic therapy. All antibiotics resulted in a reduced bacterial load in the infected bone surrounding the implant. Overall, the most effective antibiotic combinations contained rifampicin. Combinations containing two non-rifampicin antibiotics were not more active than single drugs.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Daptomycin; Disease Models, Animal; Drug Resistance, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Linezolid; Mice; Microbial Sensitivity Tests; Osteomyelitis; Prostheses and Implants; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Vancomycin

We compared tedizolid alone and tedizolid with rifampin to rifampin and vancomycin plus rifampin in a rat model of methicillin-resistant Staphylococcus aureus (MRSA) foreign body-associated osteomyelitis. The study strain was a prosthetic joint infection-associated isolate. Steady-state pharmacokinetics for intraperitoneal administration of tedizolid, vancomycin, and rifampin were determined in uninfected rats. MRSA was inoculated into the proximal tibia, and a wire was implanted. Four weeks later, the rats were treated intraperitoneally for 21 days with tedizolid (n = 14), tedizolid plus rifampin (n = 11), rifampin (n = 16), or vancomycin plus rifampin (n = 13). Seventeen rats received no treatment. After treatment, quantitative bone cultures were performed. Blood was obtained for determination of drug trough concentrations in the tedizolid and tedizolid plus rifampin groups. The mean peak plasma concentration and mean area under the concentration-time curve from time zero to 24 h for tedizolid were 12 μg/ml and 60 μg · h/ml, respectively. The bacterial loads in all treatment groups were significantly lower than those in the control group; those in the tedizolid- plus rifampin-treated animals were not significantly different from those in the vancomycin- plus rifampin-treated animals. The range of mean plasma trough concentrations in the tedizolid group was 0.44 to 0.73 μg/ml. Although neither tedizolid nor vancomycin resistance was detected in isolates recovered from bones, rifampin resistance was detected in 10 animals (63%) in the rifampin group, 8 animals (73%) in the tedizolid plus rifampin group, and a single animal (8%) in the vancomycin plus rifampin group. Tedizolid alone or tedizolid combined with rifampin was active in a rat model of MRSA foreign body-associated osteomyelitis. The emergence of rifampin resistance was noted in animals receiving tedizolid plus rifampin.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Bone Wires; Disease Models, Animal; Drug Combinations; Drug Resistance, Bacterial; Foreign Bodies; Injections, Intraperitoneal; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Organophosphates; Osteomyelitis; Oxazoles; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections; Tibia; Vancomycin

Implant-associated methicillin-resistant Staphylococcus aureus (MRSA) infections are challenging to treat. We compared antimicrobial activities in a rat model of chronic osteomyelitis in the context of retention of the foreign body without débridement.. MRSA was inoculated into the proximal tibia and a wire implanted. Four weeks after infection, treatment with vancomycin 50 mg/kg every 12 h, tigecycline 14 mg/kg every 12 h, rifampin 25 mg/kg every 12 h, or the combination of vancomycin or tigecycline plus rifampin was administered intraperitoneally for 21 days.. MRSA was cultured from all tibias in the control group (median, 6.06 log10 CFU/g bone). Median bacterial counts (log10 CFU/g) at 48 h post-treatment were 6.16 for vancomycin (p = 0.753), 2.29 for vancomycin plus rifampin (p < 0.001), 5.90 for tigecycline (p = 0.270), 0.10 for tigecycline plus rifampin (p < 0.001), and 0.91 for rifampin (p = 0.044) treatment. Three deaths were observed in the tigecycline plus rifampin group. Median bacterial counts (log10 CFU/g) at two weeks post-treatment were 5.65 for vancomycin (p = 0.6), 4.05 for vancomycin plus rifampin (p = 0.105), 5.68 for tigecycline (p = 0.401), 4.05 for tigecycline plus rifampin (p = 0.028), and 5.98 for rifampin (p = 0.297) treatment.. Tigecycline plus rifampin resulted in a significant bacterial count decrease, an effect more prominent at 48 h than two weeks after treatment completion. Tigecycline was not well tolerated at the dose studied.

Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Humans; Male; Methicillin; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Minocycline; Osteomyelitis; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections; Tigecycline; Vancomycin

Topics: Anti-Bacterial Agents; Cutaneous Fistula; Drug Administration Schedule; Drug Interactions; Humans; Linezolid; Male; Osteomyelitis; Rifampin; Time Factors; Young Adult

Clindamycin, a lincosamide antibiotic with a good penetration into bone, is widely used for treating bone and joint infections by Gram-positive pathogens. To be active against Staphylococcus spp, its concentration at the infection site, C, must be higher than 2× the minimal inhibitory concentration (MIC). The aims of the work were to study the determinants of plasma clindamycin trough concentration, C min, especially the effect of co-treatment with rifampicin, and the consequences on clinical outcome.. An observational study was performed, involving patients hospitalized for a bone and joint infection who received clindamycin as part of their antibiotic treatment. Target C min was 1.7 mg/L, to reach the desired bone concentration/MIC >2, assuming a 30% diffusion into bone and MIC = 2.5 mg/L.. Sixty one patients (mean age: 56.8 years, 57.4% male) were included between 2007 and 2011. 72.1% underwent a surgery on a foreign material, and 91.1% were infected by at least a Gram-positive micro-organism. Median C min value was 1.39 mg/L, with 58% of the values below the threshold value of 1.7 mg/L. Median C min was significantly lower for patients taking rifampicin (0.46 vs 1.52 mg/L, p = 0.034). No patient with rifampicin co-administration reached the target concentration (maximal C min: 0.85 mg/L). After a median follow-up of 17 months (1.5-38 months), 4 patients relapsed, 2 died and 47 (88.7% of the patients with known outcome) were cured, independently of association with rifampicin.. This study shows the high inter-variability of plasma clindamycin concentration and confirms that co-treatment with rifampicin significantly decreases clindamycin trough concentrations.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Clindamycin; Drug Interactions; Drug Therapy, Combination; Female; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Osteomyelitis; Rifampin; Young Adult

Orthopedic foreign body-associated infections are often treated with rifampin-based combination antimicrobial therapy. We previously observed that rifampin-resistant and methicillin-resistant Staphylococcus aureus (MRSA) isolates were present 2 days after cessation of rifampin therapy in experimental foreign body osteomyelitis. Unexpectedly, only rifampin-susceptible isolates were detected 14 days after the completion of treatment. We studied two rifampin-resistant isolates recovered 2 days after treatment and one rifampin-susceptible isolate recovered 14 days after treatment. Growing these isolates alone in vitro or in vivo demonstrated no fitness defects; however, in mixed culture, rifampin-susceptible bacteria outcompeted rifampin-resistant bacteria. In vivo, two courses of rifampin treatment (25 mg/kg of body weight every 12 h for 21 days) yielded a greater decrease in bacterial quantity in the bones of treated animals 14 days following treatment than that in animals receiving a single course of treatment (P = 0.0398). In infections established with equal numbers of rifampin-resistant and rifampin-susceptible bacteria, one course of rifampin treatment did not affect bacterial quantities. Rifampin-resistant and rifampin-susceptible isolates were recovered both 2 days and 14 days following treatment completion; however, the proportion of animals with rifampin-resistant isolates was lower at 14 days than that at 2 days following treatment completion (P = 0.024). In untreated animals infected with equal numbers of rifampin-resistant and rifampin-susceptible bacteria for 4 weeks, rifampin-susceptible isolates were exclusively recovered, indicating the outcompetition of rifampin-resistant by rifampin-susceptible isolates. The data presented imply that although there is no apparent fitness defect in rifampin-resistant bacteria when grown alone, they are outcompeted by rifampin-susceptible bacteria when the two are present together. The findings also suggest that selected rifampin resistance may not persist in initially rifampin-susceptible infections following the discontinuation of rifampin.

Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Foreign Bodies; Male; Methicillin; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Osteomyelitis; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections

The purpose of this study was to investigate the curative effect of bone-like hydroxyapatite/poly amino acid (BHA/PAA) as a carrier for poly(lactic-co-glycolic acid)-coated rifapentine microsphere (RPM) in the treatment of rabbit chronic osteomyelitis induced by Staphylococcus aureus.. RPM was prepared through an oil-in-water emulsion solvent evaporation method, and RPM was combined with BHA/PAA to obtain drug-loaded, slow-releasing materials. Twenty-six New Zealand white rabbits were induced to establish the animal model of chronic osteomyelitis. After debridement, the animals were randomly divided into three groups (n=8): the experimental group (with RPM-loaded BHA/PAA), the control group (with BHA/PAA), and the blank group. The RPM-loaded BHA/PAA was evaluated for antibacterial activity, dynamics of drug release, and osteogenic ability through in vitro and in vivo experiments.. In vitro, RPM-loaded BHA/PAA released the antibiotics slowly, inhibiting the bacterial growth of S. aureus for up to 5 weeks. In vivo, at week 4, the bacterial colony count was significantly lower in the experimental group than in the control and blank groups (P<0.01). At week 12, the chronic osteomyelitis was cured and the bone defect was repaired in the experimental group, whereas the infection and bone defect persisted in the control and blank groups.. In vitro and in vivo experiments demonstrated that RPM-loaded BHA/PAA effectively cured S. aureus-induced chronic osteomyelitis. Therefore, BHA/PAA has potential value as a slow-releasing material in clinical setting. Further investigation is needed to determine the optimal dosage for loading rifapentine.

Topics: Amino Acids; Animals; Anti-Bacterial Agents; Chronic Disease; Delayed-Action Preparations; Drug Carriers; Durapatite; Lactic Acid; Microspheres; Osteomyelitis; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Brucella is among the most common zoonotic diseases affecting humans. Although musculoskeletal involvement is seen in a large proportion of patients, the disease is often diagnosed late or misdiagnosed due to its subtle nature and rarity, and lack of awareness among clinicians. In this report, a 12-year-old girl was diagnosed with acute septic arthritis of the hip based on clinico-radiological features, and managed with standard treatment, including arthrotomy. However, the child did not respond to the treatment. Based on the histopathology and local endemicity, Brucella was suspected, and confirmed after serological testing. The child subsequently responded to treatment and, at latest follow-up at 1 year, had a full painless range of motion, with no relapse.

Topics: Acute Disease; Anti-Bacterial Agents; Arthritis, Infectious; Brucella melitensis; Brucellosis; Child; Doxycycline; Female; Femur; Gentamicins; Hip Joint; Humans; Osteomyelitis; Radiography; Rifampin

Topics: Anti-Bacterial Agents; Clindamycin; Female; Gram-Positive Bacterial Infections; Humans; Male; Osteomyelitis; Rifampin

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.

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Arthritis, Infectious; Bone and Bones; Discitis; Female; Fluoroquinolones; Humans; Hypokalemia; Inflammation; Jaundice, Obstructive; Joints; Male; Middle Aged; Osteomyelitis; Penicillins; Prosthesis-Related Infections; Retrospective Studies; Rifampin; Risk Factors; Staphylococcal Infections; Staphylococcus aureus

Topics: Antitubercular Agents; Aza Compounds; Bone Neoplasms; Diagnosis, Differential; Drug Therapy, Combination; Ethambutol; Fluorodeoxyglucose F18; Fluoroquinolones; Humans; Lung; Magnetic Resonance Imaging; Male; Middle Aged; Moxifloxacin; Osteomyelitis; Positron-Emission Tomography; Quinolines; Radiopharmaceuticals; Rifampin; Spine; Tomography, X-Ray Computed; Tuberculosis, Osteoarticular

Osteomyelitis due to Mycobacterium bovis Bacille Calmette-Guerin (BCG) often develops in patients with interferon-γ receptor 1 (IFNγR1) deficiency. In these patients, susceptibility appears to be caused by impaired interleukin-12- and IFNγ-mediated immunity. Here we report the case of a one-year-old girl with dominant partial IFNγR1 deficiency who suffered from lymphadenitis and multiple sites of osteomyelitis due to BCG infection. She was allergic to isoniazid and rifampicin--the prescribed standard treatment--and required prior desensitization therapy. She was subsequently treated with these drugs, but her symptoms did not improve. IFNγ therapy was added to the antitubercular therapy, increasing the serum level of IFNγ and leading to the resolution of the lymphadenitis and osteomyelitis. In conclusion, high dose IFNγ therapy in combination with antitubercular drugs led to resolution of BCG infection in a patient with dominant partial IFNγ deficiency.

Topics: Antitubercular Agents; Drug Therapy, Combination; Female; Gene Expression; Humans; Infant; Interferon-gamma; Interleukin-12; Isoniazid; Mycobacterium bovis; Osteomyelitis; Receptors, Interferon; Rifampin; Tuberculosis, Lymph Node; Virus Diseases

Orthopaedic implants are highly susceptible to infection. The aims of treatment of infection associated with internal fixation devices are fracture consolidation and prevention of chronic osteomyelitis. Complete biofilm eradication is not the primary goal, as remaining adherent microorganisms can be removed with the device after fracture consolidation. By contrast, in periprosthetic joint infection (PJI), biofilm elimination is required. Surgical treatment of PJI includes debridement with retention, one- or two-stage exchange and removal without reimplantation. In addition, prolonged antibiotic treatment, preferably with an agent that is effective against biofilm bacteria, is required. Rifampicin is an example of an antibiotic with these properties against staphylococci. However, to avoid the emergence of resistance, rifampicin must always be combined with another antimicrobial agent. With this novel treatment approach, orthopaedic implant-associated infection is likely to be eradicated in up to 80-90% of patients. Because most antibiotics have a limited effect against biofilm infections, novel prophylactic and therapeutic options are needed. Surface coating with antimicrobial peptides that reduce bacterial attachment and biofilm formation can potentially prevent implant-associated infection. In addition, quorum-sensing inhibitors are a novel therapeutic option against biofilm infections.

Topics: Anti-Bacterial Agents; Coated Materials, Biocompatible; Debridement; Fractures, Bone; Humans; Internal Fixators; Male; Middle Aged; Osteomyelitis; Prosthesis-Related Infections; Reoperation; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

To synthesize polydioxanone (PDS)-based drug delivery systems (hereafter referred to as "matrices") containing vancomycin (VANC) and/or rifampicin (RIF) and investigate their effect on the inhibition of biofilm growth containing osteomyelitis (OM)-associated pathogens.. PDS matrices were prepared by electrostatic spinning, and the drugs were incorporated as follows: group (G)1, 5wt%VANC; G2, 10wt%VANC; G3, 5wt%RIF; G4, 10wt%RIF; G5, 5wt%VANC+RIF; and G6, 10wt%VANC+RIF. A control group of pure PDS was also electrospun (G7). Biofilms formed by Staphylococcus aureus and S. epidermidis were grown on the electrospun matrices for 24 hours. The counts of viable cells were assessed after biofilm formation. The fiber morphology and biofilms were imaged using a scanning electron microscope.. G5 and G6 and pure PDS (G7) had the lowest and highest mean number of viable cell counts, respectively (P < .05). Small and isolated clusters of bacteria with no mature biofilm present were found on G6.. The results of the present study have provided evidence for the potential use of PDS-based matrices as an effective drug delivery system that could inhibit biofilm formation from OM-associated pathogens.

Topics: Anti-Infective Agents; Biofilms; Drug Carriers; Microbial Sensitivity Tests; Microscopy, Electron, Scanning; Osteomyelitis; Rifampin; Staphylococcus aureus; Staphylococcus epidermidis; Vancomycin

Appendicitis is a common cause of acute abdominal pain in children and is treated by an open or laparoscopic appendicectomy. Well documented post-operative complications include wound infection, intra-abdominal collection, and adhesional bowel obstruction. We present the rare case of right sacro-iliitis and iliac bone osteomyelitis in a 13 year old boy following an open appendicectomy for a perforated appendicitis.

Topics: Adolescent; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Appendectomy; Appendicitis; Ascitic Fluid; Ciprofloxacin; Clindamycin; Gram-Negative Bacteria; Humans; Laparotomy; Magnetic Resonance Imaging; Male; Metronidazole; Osteomyelitis; Rifampin; Rupture, Spontaneous; Sacroiliitis

Chronic flexor tenosynovitis in the hand caused by non-tuberculous mycobacterial (NTM) infection is uncommon. Although some authors have recommended combining surgical and drug therapy, there are few reports about the timing of drug administration after operation. The purpose of this retrospective study was to analyse the clinical outcome of the protocol, which consisted of extensive tenosynovectomy and drug therapy administered after culture results had been obtained. Four men and one woman were included. Average age was 57.4 years and average follow-up period was 46.7 months. Extensive tenosynovectomy was performed and surgical specimen was examined histopathologically and microbiologically. After a positive culture result had been obtained, three kinds of drugs were administered. Clinical outcome including infectious condition, range of motion, and grip strength was examined. All patients were immunocompetent and had no underlying disease. Three patients were diagnosed at first operation and two were diagnosed at second operation. The average period of drug therapy was 5.5 months. In four patients, infection resolved with combination therapy. In one patient with surgical treatment, only swelling remained. Osteomyelitis of the scaphoid was found in one patient to whom systemic steroid had been administered because of a negative culture result at first operation. For immunocompetent patients, flexor tenosynovitis in the hand caused by NTM was resolved with a combination of surgical and drug treatment. Drug treatment seemed to be essential after a reduction of the infectious lesion and the timing of administration was safe enough to resolve in four patients.

Topics: Adult; Aged; Anti-Bacterial Agents; Antitubercular Agents; Clarithromycin; Drug Therapy, Combination; Ethambutol; Female; Hand; Hand Strength; Humans; Immunocompetence; Isoniazid; Levofloxacin; Male; Middle Aged; Mycobacterium Infections, Nontuberculous; Mycobacterium kansasii; Mycobacterium marinum; Osteomyelitis; Range of Motion, Articular; Retrospective Studies; Rifampin; Scaphoid Bone; Synovectomy; Tenosynovitis

Primary pyomyositis is a rare bacterial infection of the skeletal muscle. Traditionally a tropical disease, it is increasingly described in westernised urban populations. The aetiology is due to transient bacteraemia in the presence of risk factors such as traumatised muscle, or immunocompromise. The condition presents in one of three stages, representing progression of disease severity. Intravenous antibiotic therapy is often sufficient for this disease at its early stage, but surgical drainage is necessary for advanced presentations. We report a severe case of stage 3 pyomyositis of the gluteus minimus, which led to Staphylococcus aureus sepsis, deranged liver function, acute kidney injury, autoanticoagulation and proximal femoral osteomyelitis in a healthy 64-year-old Caucasian man. This illustrates the potential severity of the disease, the life-threatening sequelae when diagnosis is delayed and the role of surgical drainage in averting the progression of systemic sepsis to end-organ dysfunction, disseminated intravascular coagulation and potentially death.

Topics: Anti-Bacterial Agents; Buttocks; Delayed Diagnosis; Drainage; Humans; Male; Middle Aged; Muscle, Skeletal; Osteomyelitis; Pyomyositis; Rifampin; Sepsis; Staphylococcal Infections; Vancomycin

We describe an outbreak of 5 osteoarticular infections among 24 daycare center attendees. Polymerase chain reaction revealed Kingella kingae in the joint fluid of 1 child and in 85% of throat samples from healthy contacts. Multilocus sequence typing performed on the joint fluid and carriage isolates identified an unique sequence type. Rifampin failed to eradicate K. kingae carriage.

Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Arthritis, Infectious; Carrier State; Child Day Care Centers; Disease Outbreaks; Humans; Infant; Kingella kingae; Multilocus Sequence Typing; Neisseriaceae Infections; Osteomyelitis; Pharynx; Polymerase Chain Reaction; Rifampin

Topics: Cicatrix; Clarithromycin; Debridement; Diabetes Mellitus, Type 2; Disease Susceptibility; Femoral Fractures; Fracture Fixation, Internal; Fractures, Closed; Humans; Male; Middle Aged; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Osteomyelitis; Osteotomy; Ribotyping; Rifampin; Surgical Wound Infection; Vancomycin

Methicillin-resistant Staphylococcus is a common cause of orthopaedic implant infections. In such cases, rifampicin is the antibiotic of choice, but it should not be administered alone to avoid the selection of resistant mutants. Linezolid has activity against resistant staphylococci and a high oral bioavailability; therefore, it could be a good option for combining with rifampicin. We describe 2 patients admitted to our hospital due to orthopaedic implant infections, who received combination therapy with linezolid and rifampicin. In both cases, the trough serum concentration of linezolid during rifampicin treatment was below the minimum inhibitory concentration required to inhibit the growth of 90% of organisms (MIC(90)) for staphylococci, but increased after rifampicin withdrawal. This finding suggests an interaction between rifampicin and linezolid, and a possible explanation is discussed.

Topics: Acetamides; Adult; Aged, 80 and over; Anti-Bacterial Agents; Drug Interactions; Female; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Osteomyelitis; Oxazolidinones; Prosthesis-Related Infections; Rifampin; Serum; Staphylococcal Infections

Topics: Antitubercular Agents; Biopsy; Carcinoma; Combined Modality Therapy; Diagnosis, Differential; Ethambutol; Female; Humans; Isoniazid; Lymphatic Diseases; Middle Aged; Mycobacterium tuberculosis; Osteolysis; Osteomyelitis; Pleural Effusion; Pleural Neoplasms; Pyrazinamide; Rifampin; Sputum; Sternum; Tomography, X-Ray Computed; Tuberculosis, Osteoarticular

This study was performed to describe clindamycin, administered either orally or intravenously, concentration-time courses to patients with osteomyelitis, to study the effects of different covariates on clindamycin pharmacokinetics and to simulate an optimized administration scheme.. Clindamycin concentrations were measured in 50 patients. A total of 122 plasma concentrations were available (58 from oral administration and 64 from i.v. infusion). A population pharmacokinetic model was developed with MONOLIX 4 software.. A one compartment model adequately described the data. Clindamycin clearance increased significantly with body weight (BW). The typical population estimates (interindividual variability) for clearance, volume of distribution and absorption rate constant were 16.2 l h(-1) (0.39), 70.2 l and 0.92 h(-1) , respectively. The bioavailability of the oral form was estimated to be 87.6%. According to BW, theoretical doses needed to reach a C(min) of 2 mg l(-1) were then calculated.. The current recommendation of 600 mg three times daily seems to be effective up to 75 kg but the dose should be raised to 900 mg three times daily thereafter. These assumptions should be prospectively confirmed.

Topics: Administration, Intravenous; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Biological Availability; Body Weight; Clindamycin; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Enzyme Inhibitors; Female; Humans; Male; Middle Aged; Models, Theoretical; Osteomyelitis; Retrospective Studies; Rifampin; Young Adult

To report a case of multidrug-resistant osteomyelitis successfully treated with telavancin, rifampin, and meropenem.. An 18-year-old male with spina bifida was treated primarily in the outpatient setting over the course of 133 days with multiple antimicrobials for a recurrent right calcaneal wound and osteomyelitis infection. Initial cultures were positive for methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus, which were treated with intravenous vancomycin 1 g every 12 hours, increased after 13 days to 1.5 g every 12 hours with addition of rifampin 300 mg twice daily, both of which were discontinued on day 22 due to leukopenia (white blood cell count 3.0 × 10(3)/μL) and neutropenia (absolute neutrophil count 0.2 × 10(3)/μL). Daptomycin 8 mg/kg/day was then initiated with rifampin 300 mg twice daily; treatment was discontinued after 49 days due to an elevated creatine kinase level of 1831 U/L (baseline 86). Intravenous meropenem 1 g every 8 hours was again initiated on day 83 following additional identification of quinolone-resistant Pseudomonas aeruginosa from the soft tissue of the right foot. Intravenous vancomycin 1 g every 12 hours was also restarted at this time for persistent coagulase-negative Staphylococcus and oral rifampin 300 mg twice daily was again added. Adverse events again required the discontinuation of vancomycin on day 91. The eventual drug therapy regimen consisted of telavancin 750 mg/day for 42 days, meropenem for 50 days, and oral rifampin for 50 days. At the end of treatment, the patient's right heel wound had almost completely closed. He was without recurrence or treatment-related adverse events at follow-up 1 year later.. Antimicrobial selection for osteomyelitis infections presents a challenge to the clinician due to patient intolerance, increasing antimicrobial resistance, and variable antimicrobial penetration at the site of infection. To our knowledge, this is the first case report of the successful use of a regimen including telavancin for the treatment of a recurrent, coagulase-negative Staphylococcus osteomyelitis infection.. In this complex case involving a polymicrobial infection of the right calcaneal bone and surrounding soft tissue, eventual drug therapy including telavancin, meropenem, and rifampin resulted in a successful clinical response.

Topics: Adolescent; Aminoglycosides; Anti-Bacterial Agents; Coinfection; Drug Therapy, Combination; Humans; Lipoglycopeptides; Male; Meropenem; Osteomyelitis; Rifampin; Staphylococcal Infections; Thienamycins; Treatment Outcome

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) can cause osteomyelitis with severe sepsis and/or local complications in which a Panton-Valentine leukocidin (PVL) role is suspected. In vitro sub-MIC antibiotic effects on growth and PVL production by 11 PVL(+) MRSA strains, including the major CA-MRSA clones (USA300, including the LAC strain; USA400; and USA1000), and 11 PVL(+) methicillin-susceptible S. aureus (MSSA) strains were tested in microplate culture. Time-kill analyses with ceftobiprole at its MIC were also run with LAC. Efficacies of ceftobiprole (40 mg/kg of body weight subcutaneously [s.c.] four times a day [q.i.d.]) or vancomycin (60 mg/kg intramuscularly [i.m.] twice a day [b.i.d.]) alone or combined with rifampin (10 mg/kg b.i.d.) against rabbit CA-MRSA osteomyelitis, induced by tibial injection of 3.4 × 10(7) CFU of LAC, were compared. Treatment, started 14 days postinoculation, lasted 14 days. In vitro, 6/11 strains cultured with sub-MICs of ceftobiprole produced 1.6- to 4.8-fold more PVL than did the controls, with no link to specific clones. Rifampin decreased PVL production by all tested strains. In time-kill analyses at the LAC MIC (0.75 mg/liter), PVL production rose transiently at 6 and 8 h and then declined 2-fold at 16 h, concomitant with a 2-log(10)-CFU-count decrease. In vivo, the mean log(10) CFU/g of bone for ceftobiprole (1.44 ± 0.40) was significantly lower than that for vancomycin (2.37 ± 1.22) (P = 0.034), with 7/10 versus 5/11 bones sterilized, respectively. Combination with rifampin enhanced ceftobiprole (1.16 ± 0.04 CFU/g of bone [P = 0.056], 11/11 sterile bones) and vancomycin (1.23 ± 0.06 CFU/g [P = 0.011], 11/11 sterile bones) efficacies. Ceftobiprole bactericidal activity and the rifampin anti-PVL effect could play a role in these findings, which should be of interest for treating CA-MRSA osteomyelitis.

Topics: Animals; Anti-Bacterial Agents; Bacterial Toxins; Cephalosporins; Colony Count, Microbial; Community-Acquired Infections; Exotoxins; Female; Leukocidins; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Mutation; Osteomyelitis; Rabbits; Rifampin

Choice of pins, drills, and drilling technique can result in heat generation leading to thermal necrosis of bone. This has been reported frequently in internal as well as in external fixation. This publication is the first report of a patient having osteomyelitis of the proximal tibia due to thermal necrosis following tracker pin placement in computer-navigated total knee arthroplasty.

Topics: Anti-Bacterial Agents; Arthroplasty, Replacement, Knee; Bone Nails; Floxacillin; Hot Temperature; Humans; Knee Joint; Knee Prosthesis; Male; Middle Aged; Necrosis; Osteoarthritis, Knee; Osteomyelitis; Prosthesis-Related Infections; Radiography; Rifampin; Surgery, Computer-Assisted; Tibia; Treatment Outcome

Rifampin monotherapy was compared to the combination of linezolid or vancomycin with rifampin in an experimental rat model of methicillin-resistant Staphylococcus aureus (MRSA) chronic foreign body osteomyelitis. MRSA was inoculated into the proximal tibia, and a titanium wire was implanted. Four weeks after infection, rats were treated intraperitoneally for 21 days with rifampin alone (n = 16), linezolid plus rifampin (n = 14), or vancomycin plus rifampin (n = 13). Thirteen animals received no treatment. At completion of treatment, qualitative cultures of the wire and quantitative cultures of the bone (reported as median values) were performed. Quantitative cultures from the control, rifampin monotherapy, linezolid-plus-rifampin, and vancomycin-plus-rifampin groups revealed 4.54, 0.71, 0.10, and 0.50 log₁₀ CFU/gram of bone, respectively. The bacterial load was significantly reduced in all treatment groups compared to that in the control group. Rifampin resistance was detected in isolates from 10, 2, and 1 animal in the rifampin, linezolid-plus-rifampin, and vancomycin-plus-rifampin groups, respectively. Cultures of the removed wire revealed bacterial growth in 1 and 2 animals in the rifampin and linezolid-plus-rifampin groups, respectively, with no growth in the vancomycin-plus-rifampin group and growth from all wires in the untreated group. In conclusion, we demonstrated that combination treatment with linezolid plus rifampin or vancomycin plus rifampin is effective in an animal model of MRSA foreign body osteomyelitis in the context of retention of the infected foreign body.

Topics: Acetamides; Animals; Foreign Bodies; Linezolid; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Osteomyelitis; Oxazolidinones; Rats; Rats, Wistar; Rifampin; Vancomycin

Pyogenic Spinal Infection (PSI) is an uncommon disorder encompassing a broad spectrum of diseases including septic spondylodiscitis, osteomyelitis, epidural and paravertebral abscess formation. Presentation can be vague and highly variable but usually includes back pain and fever. Whilst predisposing factors, such as trauma and diabetes can often be identified a pathogenic organism may not be identified in up to a half of all cases leading to significant delay in both accurate diagnosis and effective treatment. Precise spinal imaging is essential and includes plain X-ray, CT and preferably MRI. The treatment of PSI can be conservative (including antibiotics); however, spinal surgery may be required for the complications in up to 50% of cases, with varying degrees of success. We present a challenging case of PSI encountered in a locally-employed 42-year-old Bangladeshi civilian working in Iraq. Despite obvious resource limitations available within a Role 2 Field Hospital, clinical suspicion coupled with repeat spinal CT was pivotal in obtaining the diagnosis. The patient was repatriated to Bangladesh for MRI and definitive surgical treatment.

Topics: Adult; Anti-Bacterial Agents; Antibiotics, Antitubercular; Bangladesh; Floxacillin; Humans; Iraq; Low Back Pain; Magnetic Resonance Imaging; Male; Osteomyelitis; Rifampin; Spinal Diseases; Tomography, X-Ray Computed

Topics: Anti-Bacterial Agents; Humans; Joint Prosthesis; Osteomyelitis; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections

Buruli ulcer (BU), a disease caused by Mycobacterium ulcerans, leads to the destruction of skin and sometimes bone. Here, we report a case of severe multifocal BU with osteomyelitis in a 6-year-old human immunodeficiency virus (HIV)-negative boy. Such disseminated forms are poorly documented and generally occur in patients with HIV co-infection. The advent of antibiotic treatment with streptomycin (S) and rifampin (R) raised hope that these multifocal BU cases could be reduced. The present case raises two relevant points about multifocal BU: the mechanism of dissemination that leads to the development of multiple foci and the difficulties of treatment of multifocal forms of BU. Biochemical (hypoproteinemia), hematological (anemia), clinical (traditional treatment), and genetic factors are discussed as possible risk factors for dissemination.

Topics: Anti-Bacterial Agents; Buruli Ulcer; Child; Humans; Male; Osteomyelitis; Rifampin; Streptomycin

Topics: Adolescent; Age Distribution; Aged; AIDS-Related Opportunistic Infections; Amikacin; Anti-Infective Agents; Buruli Ulcer; Child; Combined Modality Therapy; Debridement; Drug Therapy, Combination; Female; Humans; Metronidazole; Mycobacterium ulcerans; Osteomyelitis; Rifampin; Streptomycin

Daptomycin exhibits rapid bactericidal activity against Gram-positive organisms, including meticillin-resistant Staphylococcus aureus (MRSA). Daptomycin in combination with rifampicin needs to be assessed in bone infection. An MRSA acute osteomyelitis model was used. Daptomycin and vancomycin were compared, alone or in combination with rifampicin, over 4 days. Surviving bacteria were counted in bone, bone marrow and joint fluid. Vancomycin and daptomycin as single therapies were ineffective, but both combinations were significantly more effective than the corresponding monotherapy. Combination of daptomycin and rifampicin could prevent S. aureus from developing resistance. This combination could be a useful alternative to treat MRSA osteomyelitis at an early stage.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Bone and Bones; Bone Marrow; Daptomycin; Disease Models, Animal; Drug Therapy, Combination; Female; Joints; Methicillin-Resistant Staphylococcus aureus; Osteomyelitis; Rabbits; Rifampin; Staphylococcal Infections; Treatment Outcome; Vancomycin

Non-tuberculous mycobacteria (NTM) are an unusual cause of osteomyelitis in immunocompetent children. Diagnosis is often difficult due to the paucity of clinical symptoms and a subtle course of the disease. NTM comprise a group of about 91 identified species of environmental mycobacteria that cause infections most frequently in immunocompromised individuals or in patients with predisposing factors. Cervical lymphadenitis is the most common presentation of NTM infection in children. Invasive and recurrent infections with these organisms have been associated with a genetic defect of the interferon gamma-receptor. We report a 3-year-old immunocompetent girl who presented a NTM osteomyelitis of the left femur. Four months before she had been treated with medical and surgical therapy for a mycobacterium avium complex cervical lymphadenitis. Polymerase chain reaction assay on bone aspirate specimens confirmed the diagnosis of mycobacterium avium osteomyelitis. The patient was treated successfully with clarithromycin and rifampicin for 6 months.

Topics: Anti-Bacterial Agents; Arthralgia; Child, Preschool; Clarithromycin; Drug Therapy, Combination; Female; Humans; Immunocompetence; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Osteomyelitis; Rifampin; Treatment Outcome

A 72-year-old man presented with a 6-month history of low back and leg pain. Past medical history revealed transurethral resection of bladder cancer followed by multiple intravesical BCG instillation 12 years ago. Imaging studies of the thoracolumbar spine showed osteolysis of the L3 and L4 vertebrae and the associated intervertebral disc space, and a large soft tissue mass with signal abnormalities suggesting of an abscess. CT-guided needle biopsy showed Mycobacterium bovis infection. A triple anti-tuberculous chemotherapy regimen including isoniazid, rifampicin, and ethambutol was administered for 12 months. Surgical treatment included drainage of the abscess and L2-L5 spinal instrumentation and fusion. Intravesical BCG therapy may be complicated by late disseminated disease to the bone even many years after initial BCG therapy. Patients having BCG therapy should be closely evaluated thereafter for the possibility of hematogenous spread of mycobacteria to distant sites.

Topics: Administration, Intravesical; Aged; Antitubercular Agents; BCG Vaccine; Drug Therapy, Combination; Epidural Abscess; Ethambutol; Humans; Isoniazid; Lumbar Vertebrae; Male; Mycobacterium bovis; Osteolysis; Osteomyelitis; Rifampin; Spinal Fusion; Treatment Outcome; Tuberculosis, Spinal

Methicillin-resistant Staphylococcus aureus (MRSA) is a type of Staphylococcus that is resistant to certain antibiotics, such as methicillin, oxacillin, penicillin, and amoxicillin. This nosocomial pathogen has become a great threat in hospitals globally. Up to 40% of the normal population carries S. aureus in the anterior nares, and this rate is often higher in hospitalized patients and their attendants. This case report presents a patient with serious MRSA osteomyelitis of the mandible demonstrating purulent discharge. The patient failed to recover despite prolonged postoperative treatment and the administration of several antibiotics. There was a resulting nonunion along with chronic MRSA infection. The treatment protocol involved a multimodal approach with parenteral clindamycin infusion, local rifampicin irrigation, and intermaxillary fixation of the jaws.

Topics: Adult; Anti-Bacterial Agents; Bone Plates; Clindamycin; Fracture Fixation, Internal; Humans; Infusions, Intralesional; Male; Mandibular Diseases; Mandibular Fractures; Methicillin-Resistant Staphylococcus aureus; Osteomyelitis; Prosthesis-Related Infections; Reoperation; Rifampin; Staphylococcal Infections; Therapeutic Irrigation; Treatment Outcome

Topics: Animals; Anti-Infective Agents; Drug Delivery Systems; Drug Resistance, Bacterial; Minocycline; Osteomyelitis; Prosthesis-Related Infections; Rabbits; Rifampin; Staphylococcal Infections

We describe a case of a 10 year old patient who presented with intermittent fever and pain in the pelvis and elbow region. From the history, imaging and laboratory tests, a diagnosis of Brucella sacroiliitis and elbow osteoarthritis was made. The patient was given an antibiotic treatment for 3 months with a progressive improvement of symptoms to complete recovery, and normalization of imaging and laboratory findings.

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Arthritis, Infectious; Brucella melitensis; Brucellosis; Child; Doxycycline; Drug Therapy, Combination; Female; Gentamicins; Humans; Humerus; Osteomyelitis; Rifampin; Sacroiliac Joint; Treatment Outcome

Drug-induced thrombocytopenia is a challenging diagnosis in the clinical practice because of the many drugs or alternative causes that may be implicated. Exact identification of such drug(s) is required to guide future management and avoid re-exposure. We describe two cases of isolated thrombocytopenia in which cytometric analysis, a readily available technique, allowed the identification of the causative drug in the context of complex therapies (rifampicin and abciximab causing late onset thrombocytopenia).

Topics: Abciximab; Angioplasty, Balloon, Coronary; Anti-Bacterial Agents; Antibodies, Monoclonal; Anticoagulants; Autoantibodies; Ciprofloxacin; Drug Therapy, Combination; Flow Cytometry; Humans; Immunoglobulin Fab Fragments; Immunoglobulin G; Male; Middle Aged; Myocardial Infarction; Osteomyelitis; Purpura, Thrombocytopenic, Idiopathic; Rifampin

Mycobacterium szulgai is a pathogenic organism that most frequently causes pulmonary infection and may rarely result in disseminated disease in immunocompromised individuals. We report a case of multifocal osteomyelitis and cutaneous lesions due to M. szulgai in a patient with chronic lymphocytic leukemia. The successful treatment of multifocal osteomyelitis was accomplished using isoniazid, rifampin, and ethambutol.

Topics: Aged; Antitubercular Agents; Drug Therapy, Combination; Ethambutol; Female; Humans; Isoniazid; Leukemia, Lymphocytic, Chronic, B-Cell; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Osteomyelitis; Rifampin

Dental infections are associated with a range of serious complications. The orofacial region provides potential spaces in the tissue that infections of dental origin can occupy. We describe the subtemporal extension of a dental infection, the late development of cranial osteomyelitis, and its surgical management.

Topics: Abscess; Anti-Bacterial Agents; Bacteroides fragilis; Bacteroides Infections; Cephradine; Drainage; Female; Focal Infection, Dental; Humans; Middle Aged; Osteomyelitis; Rifampin; Temporal Bone

The adequate treatment of methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis has intrigued clinicians for some time. As the resistance of these pathogens, coupled with the increase in community-acquired cases, continues steadily to rise, clinicians are finding it useful to employ multi-modal approaches for efficacious treatment. The authors present a single case report of a patient with recurrent MRSA osteomyelitis, lumbar paraspinal and epidural abscess. He was found to have decreased muscle strength and was hyporeflexic in the involved extremity. Serum testing demonstrated MRSA bacteremia. Neuroimaging studies revealed evidence of paraspinal abscess and a presumed herniated nucleus pulposus at the L5/S1 interspace with significant nerve root compromise. Despite antimicrobials, his symptoms persisted, necessitating surgical exploration. At surgery, paraspinal and epidural abscesses were encountered and debrided; however, no herniated disc was visualized. This case demonstrates the diagnostic and therapeutic dilemmas with which these lesions present. We postulate that the MRSA osteomyelitis/discitis pathogens were walled off in the disc space and subsequently inoculated the soft tissues with ensuing bacteremia. We concur that antimicrobial treatment should be the first line of therapy for these patients; however, surgical debridements and cautious spinal instrumentation should be employed where appropriate.

Topics: Abscess; Acetamides; Adult; Anti-Bacterial Agents; Bacteremia; Debridement; Drug Therapy, Combination; Humans; Intervertebral Disc Displacement; Laminectomy; Linezolid; Lumbar Vertebrae; Male; Methicillin Resistance; Osteomyelitis; Oxazolidinones; Recurrence; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Time Factors; Treatment Outcome; Vancomycin

We hypothesized that regimens with an early switch to oral antibiotics are as effective as prolonged parenteral regimens for staphylococcal osteomyelitis.. We retrospectively reviewed records of adult patients with osteomyelitis caused by Staphylococcus aureus as determined by sterile site cultures, who had at least 6 months of follow-up post-therapy. The population was divided into two treatment groups: (1) an intravenous group (i.v.) that received > or = 4 weeks of parenteral therapy, and (2) a switch group that received < 4 weeks of intravenous followed by oral therapy.. A total of 72 patients (36 in each group) were identified with groups evenly matched for demographic and clinical characteristics. The overall apparent cure rate was 74%; 69% for the i.v. group and 78% for the switch group (P=0.59). Apparent cure rates were similar regardless of duration of intravenous therapy: 83% < 2 weeks, 72% 2-4 weeks, 75% 4-6 weeks and 66% > or = 6 weeks (P=0.68). Among the 39 patients who received rifampin-based combinations, those treated simultaneously with vancomycin and rifampin did significantly worse than those who received other rifampin combinations (P<0.02). Overall, MRSA infections responded poorly compared to MSSA (65% apparently cured versus 83%). However, 11/14 (79%) MRSA patients who received rifampin combinations, other than vancomycin and rifampin simultaneously, were apparently cured.. Overall outcomes did not differ significantly between i.v. and switch groups. Given the markedly lower costs and ease of administration, prolonged oral regimens after initial intravenous therapy may be a preferred regimen for staphylococcal osteomyelitis.

Topics: Administration, Oral; Anti-Bacterial Agents; Cohort Studies; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Male; Methicillin Resistance; Middle Aged; Osteomyelitis; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Vancomycin

Since device colonization is a prelude to infection, an antimicrobial-coated device that reduces bacterial colonization can potentially protect against infection. The objective of this animal study was to assess the efficacy of a coating with minocycline and rifampin to prevent colonization of a grit-blasted titanium implant and subsequent osteomyelitis.. Twenty-five rabbits underwent implantation of a titanium-alloy pin, either coated with minocycline and rifampin (thirteen rabbits) or uncoated (twelve rabbits), into the right femoral medullary canal. The implanted devices were inoculated with 500 CFU (colony-forming units) of Staphylococcus aureus prior to wound closure. The rabbits were killed one week later, and the removed device, femoral bone, a specimen obtained by swabbing the track surrounding the device, and blood were cultured. The rates of device colonization, osteomyelitis, and device-related osteomyelitis were compared between the two groups of rabbits.. The antimicrobial-coated devices had a significantly lower rate of colonization than the uncoated devices (five of thirteen compared with twelve of twelve, p = 0.0016) and were associated with significantly lower rates of osteomyelitis (six of thirteen compared with twelve of twelve, p = 0.005) and device-related osteomyelitis (five of thirteen compared with twelve of twelve, p = 0.0016). Bacteremia did not develop in any rabbit.. Orthopaedic devices coated with minocycline and rifampin significantly protected against device colonization and infection due to Staphylococcus aureus in this in vivo rabbit model.. It is possible that orthopaedic devices coated with this unique combination of antimicrobial agents may protect against the development of clinical infection in humans.

Topics: Animals; Anti-Infective Agents; Drug Delivery Systems; Minocycline; Osteomyelitis; Prosthesis-Related Infections; Rabbits; Rifampin; Staphylococcal Infections

This study was designed to investigate the role of hypermutability of Staphylococcus aureus on bacterial fitness and antibiotic resistance in a model of chronic bone infection. An isogenic pair of strains, S. aureus RN4220 and its mutator counterpart inactivated in the mutL gene were used in a rat model of osteomyelitis of the tibia. The effect of the mutator phenotype in the emergence of antibiotic resistance was assessed in rats infected by each strain separately and treated with rifampicin for 5 days. No difference between the two strains was found in bacterial growth in vitro and in bacterial survival in the animal model, indicating no fitness defect in the mutator strain. In competition studies performed in rats coinfected with the two strains at a same ratio and sacrificed at different times from day 3 to day 42 postinoculation, the mutator strain was clearly disadvantaged because it was found in all rats and at all study times at lower counts (P<0.05 from day 14 to day 42). Two of the 16 rats infected by the mutator strain and none of the 14 rats infected by the wild-type strain had acquired rifampicin-resistant mutants (P=0.4). Data suggest that the S. aureus mutator phenotype was associated with a decreased bacterial fitness in vivo and did not confer significant advantage in the acquisition of antibiotic resistance in a model of chronic bone infection.

Topics: Adenosine Triphosphatases; Animals; Bacterial Proteins; Bone and Bones; Colony Count, Microbial; Drug Resistance, Bacterial; Gene Deletion; Microbial Sensitivity Tests; Mutagenesis, Insertional; Osteomyelitis; Rats; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Survival Analysis

Staphylococcus aureus is responsible for 80% of human osteomyelitis. It can invade and persist within osteoblasts. Antibiotic resistant strains of S. aureus make successful treatment of osteomyelitis difficult.. antibiotic sensitivities of S. aureus do not change after exposure to the osteoblast intracellular environment. Human and mouse osteoblast cultures were infected and S. aureus cells were allowed to invade. Following times 0, 12, 24, and 48 h ( +/- the addition of erythromycin, clindamycin, and rifampin at times 0 or 12 h), the osteoblasts were lysed and intracellular bacteria enumerated. Transmission electron microscopy was performed on extracellular and intracellular S. aureus cells. In mouse osteoblasts, administration of bacteriostatic antibiotics at time 0 prevented the increase in intracellular S. aureus. If the antibiotics were delayed 12 h, this did not occur. When rifampin (bactericidal) was introduced at time 0 to human and mouse osteoblasts, there was a significant decrease in number of intracellular S. aureus within osteoblasts compared to control. If rifampin was delayed 12 h, this did not occur. Significant time-dependent S. aureus structural changes were observed after exposure to the osteoblast intracellular environment. These studies demonstrate that once S. aureus is established intracellularly for 12 h, the bacteria are less sensitive to antibiotics capable of eukaryotic cell penetration (statistically significant). These antibiotic sensitivity changes could be due in part to the observed structural changes. This leads to the rejection of our null hypotheses that the antibiotic sensitivities of S. aureus are unaltered by their location.

Topics: Animals; Cells, Cultured; Drug Resistance, Bacterial; Erythromycin; Gentamicins; Humans; Mice; Microscopy, Electron, Transmission; Osteoblasts; Osteomyelitis; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Time Factors

Topics: Administration, Oral; Adolescent; Aged; Anti-Bacterial Agents; Clindamycin; Community-Acquired Infections; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Femur; Fusidic Acid; Hip Prosthesis; Humans; Male; Methicillin Resistance; Osteomyelitis; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Time Factors

The evaluation of the safety and effectiveness of colistin in association with rifampin and imipenem in 1 diabetic patient with severe diabetic foot infection (DFI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa, complicated by osteomyelitis, is presented in this "Case Report". The patient received colistin after other ineffective antimicrobial treatment when an MDR P aeruginosa strain was isolated by cultural examination, together with a multidisciplinary care approach including surgical debridement and adequate offloading. The efficacy of combination colistin plus rifampin plus imipenem was observed with a checkerboard method and bactericidal activity of the serum. The patient received colistin combination therapy for 6 weeks with cure of the infection and without renal toxicity. These data suggest that colistin, in combination with rifampin and imipenem, is safe and effective, in promoting healing in DFI due to MDR P aeruginosa and suggest the need for controlled clinical studies.

Topics: Aged; Anti-Bacterial Agents; Colistin; Diabetic Foot; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Follow-Up Studies; Humans; Imipenem; Male; Metatarsal Bones; Osteomyelitis; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin

Staphylococcus aureus is the most common organism isolated in osteomyelitis. Methicillin-resistant S. aureus (MRSA) infections are particularly difficult to treat. We evaluated the efficacy of tigecycline and vancomycin with and without rifampicin in a rabbit model of MRSA osteomyelitis.. A 28 day antibiotic therapy with a subcutaneous injection of tigecycline (14 mg/kg twice daily), with and without oral rifampicin (40 mg/kg twice daily); or subcutaneous administration of vancomycin (30 mg/kg twice daily), with and without oral rifampicin (40 mg/kg twice daily) were compared. Osteomyelitis was induced with an intramedullary injection of 10(6) colony-forming units of MRSA. Infected rabbits were randomly divided into six groups: tigecycline, tigecycline with oral rifampicin, vancomycin, vancomycin with oral rifampicin, and no treatment control and tigecycline bone penetration groups. Treatment began 2 weeks after infection. After 4 weeks of therapy, the rabbits were left untreated for 2 weeks. Rabbits were then euthanized, and the tibias were harvested. The bones were cultured, and bacterial counts of MRSA were performed.. Rabbits that received tigecycline and oral rifampicin therapy (n=14) showed a 100% infection clearance. Rabbits treated with tigecycline (n=10) showed a 90% clearance. Rabbits treated with vancomycin and oral rifampicin (n=10) also showed a 90% clearance. Rabbits treated with vancomycin (n=11) showed an 81.8% clearance. Untreated controls (n=15) demonstrated only a 26% clearance. For the tigecycline bone penetration group, the bone concentrations of tigecycline in the infected tibia were significantly higher than the non-infected ones.. Tigecycline may be an effective alternative to vancomycin in the treatment of MRSA osteomyelitis.

Topics: Animals; Bone and Bones; Disease Models, Animal; Drug Therapy, Combination; Methicillin Resistance; Minocycline; Osteomyelitis; Rabbits; Radiography; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Tigecycline; Vancomycin

In this report, a 27 years old male patient diagnosed to have skin and bone tuberculosis (TB) has been presented. The patient admitted to the hospital with the complaints of fever, weight loss and night sweats. Patient's history revealed that following a trauma a skin lesion in the right ankle was developed and this was followed by the development of many lesions in different parts of the body. The lesions persisted despite the use of various antibiotics since a year. It has been recorded that his father has already been receiving anti-tuberculosis treatment. Osteomyelitis was detected in the distal part of right tibia by computerized tomography, and Mycobacterium tuberculosis was isolated from the specimens of skin lesion. The patient was immunocompetent, and there was no pulmonary involvement. Isoniazid (INAH), rifampin (RIF), ethambutol and morphozinamid therapy has been started and completed to 12 months with INAH and RIF. In the post-treatment follow-up of patient for one year, no relapse was detected. As a result, tuberculosis should be considered in patients with persistent skin lesions especially in endemic countries.

Topics: Adult; Antitubercular Agents; Drug Therapy, Combination; Humans; Immunocompetence; Isoniazid; Male; Osteomyelitis; Pyrazines; Rifampin; Tibia; Tomography, X-Ray Computed; Tuberculosis, Cutaneous; Tuberculosis, Osteoarticular

Topics: Adult; Amikacin; Anti-Bacterial Agents; Clarithromycin; Drug Resistance, Bacterial; Female; Humans; Mandibular Diseases; Mycobacterium chelonae; Mycobacterium Infections, Nontuberculous; Osteomyelitis; Rifampin; Root Canal Therapy

Kingella kingae often colonizes the oropharyngeal and respiratory tracts of children but infrequently causes invasive disease. In mid-October 2003, 2 confirmed and 1 probable case of K kingae osteomyelitis/septic arthritis occurred among children in the same 16- to 24-month-old toddler classroom of a child care center. The objective of this study was to investigate the epidemiology of K kingae colonization and invasive disease among child care attendees.. Staff at the center were interviewed, and a site visit was performed. Oropharyngeal cultures were obtained from the staff and children aged 0 to 5 years to assess the prevalence of Kingella colonization. Bacterial isolates were subtyped by pulsed-field gel electrophoresis (PFGE), and DNA sequencing of the 16S rRNA gene was performed. A telephone survey inquiring about potential risk factors and the general health of each child was also conducted. All children and staff in the affected toddler classroom were given rifampin prophylaxis and recultured 10 to 14 days later. For epidemiologic and microbiologic comparison, oropharyngeal cultures were obtained from a cohort of children at a control child care center with similar demographics and were analyzed using the same laboratory methods. The main outcome measures were prevalence and risk factors for colonization and invasive disease and comparison of bacterial isolates by molecular subtyping and DNA sequencing.. The 2 confirmed case patients required hospitalization, surgical debridement, and intravenous antibiotic therapy. The probable case patient was initially misdiagnosed; MRI 16 days later revealed evidence of ankle osteomyelitis. The site visit revealed no obvious outbreak source. Of 122 children in the center, 115 (94%) were cultured. Fifteen (13%) were colonized with K kingae, with the highest prevalence in the affected toddler classroom (9 [45%] of 20 children; all case patients tested negative but had received antibiotics). Six colonized children were distributed among the older classrooms; 2 were siblings of colonized toddlers. No staff (n = 28) or children aged <16 months were colonized. Isolates from the 2 confirmed case patients and from the colonized children had an indistinguishable PFGE pattern. No risk factors for invasive disease or colonization were identified from the telephone survey. Of the 9 colonized toddlers who took rifampin, 3 (33%) remained positive on reculture; an additional toddler, initially negative, was positive on reculture. The children of the control child care center demonstrated a similar degree and distribution of K kingae colonization; of 118 potential subjects, 45 (38%) underwent oropharyngeal culture, and 7 (16%) were colonized with K kingae. The highest prevalence again occurred in the toddler classrooms. All 7 isolates from the control facility had an indistinguishable PFGE pattern; this pattern differed from the PFGE pattern observed from the outbreak center isolates. 16S rRNA gene sequencing demonstrated that the outbreak K kingae strain exhibited >98% homology to the ATCC-type strain, although several sequence deviations were present. Sequencing of the control center strain demonstrated more homology to the outbreak center strain than to the ATCC-type strain.. This is the first reported outbreak of invasive K kingae disease. The high prevalence in the affected toddler class and the matching PFGE pattern are consistent with child-to-child transmission within the child care center. Rifampin was modestly effective in eliminating carriage. DNA sequence analysis suggests that there may be considerable variability within the species K kingae and that different K kingae strains may demonstrate varying degrees of pathogenicity.

Topics: Anti-Bacterial Agents; Arthritis, Infectious; Child Day Care Centers; Child, Preschool; Disease Outbreaks; Electrophoresis, Gel, Pulsed-Field; Humans; Infant; Kingella kingae; Minnesota; Neisseriaceae Infections; Oropharynx; Osteomyelitis; Respiratory Tract Infections; Rifampin; Sequence Analysis, DNA

Topics: Antitubercular Agents; Child, Preschool; Diagnosis, Differential; Drug Therapy, Combination; Ethambutol; Female; Gait Ataxia; Humans; Isoniazid; Osteomyelitis; Physical Examination; Pyrazinamide; Rifampin; Tuberculosis, Spinal

Disseminated Mycobacterium avium intercellulare (MAI) infection is rare in non-AIDS patients. We report a 60-year-old woman with chronic lung disease who developed vertebral osteomyelitis due to MAI. She was treated successfully with combined therapy consisting of rifampin, ethambutol, and clarithromycin.

Topics: Clarithromycin; Drug Therapy, Combination; Ethambutol; Female; Humans; Middle Aged; Mycobacterium avium-intracellulare Infection; Osteomyelitis; Rifampin; Thoracic Vertebrae

A case report of cervical osteomyelitis possibly associated with a Zenker's diverticulum perforation.. To present clinical, radiologic, and surgical findings of a cervical osteomyelitis due to a Zenker's diverticulum perforation.. A 56-year-old patient was in an intensive care unit for a severe head injury. He was fed via a nasogastric tube. Four months later he developed a pyogenic cervical vertebral infection.. Plain films and magnetic resonance imaging showed a diffuse cervical osteomyelitis. Investigation of his dysphagia revealed a Zenker's diverticulum.. After administration of antibiotics and surgical treatment of the diverticulum, the cervical infection resolved. Plain films and magnetic resonance imaging showed healing with vertebral fusion.. Cervical osteomyelitis is uncommon. Only one case of direct contamination leading to cervical vertebral osteomyelitis after esophageal perforation has been previously described. Direct contamination of the prevertebral soft tissues by bacteria traveling through the fistula may have occurred. The development of vertebral osteomyelitis in this case is consistent with the hypothesis of direct contamination. Management relies on appropriate antimicrobial therapy and surgical management of the diverticulum. The association of Zenker's diverticulum with vertebral osteomyelitis and discitis is a unique, previously undescribed situation.

Topics: Anti-Infective Agents; Antibiotics, Antitubercular; Cervical Vertebrae; Fistula; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Ofloxacin; Osteomyelitis; Rifampin; Spinal Diseases; Suppuration; Tomography, X-Ray Computed; Zenker Diverticulum

Seventeen diabetic patients with moderate to mild foot lesions associated with 20 osteomyelitic bones diagnosed by both bone scan and bone biopsy received rifampicin plus ofloxacin for a median duration of 6 months. Cure was defined as disappearance of all signs and symptoms of infection at the end of the treatment and absence of relapse during follow up. At the end of the treatment period, cure was achieved in 15 patients (88.2%) and was maintained in 13 patients (76.5%) at the end of an average post-treatment follow-up of 22 months. No serious drug-related adverse events were recorded.

Topics: Administration, Oral; Aged; Anti-Infective Agents; Antibiotics, Antitubercular; Bacterial Infections; Chronic Disease; Diabetic Foot; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Ofloxacin; Osteomyelitis; Rifampin; Treatment Outcome

Topics: Adult; Anti-Bacterial Agents; Appendicitis; Drug Therapy, Combination; Enterocolitis; Humans; Male; Nafcillin; Neutropenia; Osteomyelitis; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Tibial Fractures

A rabbit model for Staphylococcus aureus osteomyelitis was used to compare 28-day combination antibiotic therapy using oral rifampin (40 mg/kg, twice daily) plus oral azithromycin (50 mg/kg, once per day), oral clarithromycin (80 mg/kg, twice daily), or parenteral nafcillin (30 mg/kg, four times daily). The left tibial metaphysis of New Zealand White rabbits was infected with Staphylococcus aureus. Grades 3 to 4 osteomyelitis (according to the Cierny-Mader classification system) development in the rabbits was confirmed radiographically. After antibiotic therapy regimens of 28 days, all tibias from controls that were infected but left untreated (n = 10) revealed positive cultures for Staphylococcus aureus at a mean concentration of 2.8 x 10(4) colony forming units/g bone. The rifampin plus clarithromycin (n = 15) and rifampin plus azithromycin (n = 15) groups showed significantly lower percentages of positive Staphylococcus aureus infection (20% and 13.3%, respectively) and bacterial concentrations (3.5 x 10(1) and 1.75 x 10(1) colony forming units/g bone, respectively). The osteomyelitic tibias of the nafcillin plus rifampin treated group (n = 7) showed no detectable Staphylococcus aureus infection (significantly lower than controls). The differences observed for bone bacterial concentrations and sterilization percentages between the antibiotic treated groups were not statistically significant. Although fluoroquinolones (including ofloxacin and ciprofloxacin) are the agents usually prescribed with rifampin, increasing resistance has been observed. Although macrolides traditionally are not used in the treatment of osteomyelitis, the results of this study indicate that azithromycin and clarithromycin may be attractive partners for rifampin for the treatment of Staphylococcus aureus osteomyelitis in humans.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Azithromycin; Biological Availability; Clarithromycin; Colony Count, Microbial; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Nafcillin; Osteomyelitis; Rabbits; Rifampin; Staphylococcal Infections; Tibia; Treatment Outcome

We report a case of Mycobacterium bovis BCG vertebral osteomyelitis in a 79-year-old man 2.5 years after intravesical BCG therapy for bladder cancer. The recovered isolate resembled M. tuberculosis biochemically, but resistance to pyrazinamide (PZA) rendered that diagnosis suspect. High-pressure liquid chromatographic studies confirmed the diagnosis of M. bovis BCG infection. The patient was originally started on a four-drug antituberculous regimen of isoniazid, rifampin, ethambutol, and PZA. When susceptibility studies were reported, the regimen was changed to isoniazid and rifampin for 12 months. Subsequently, the patient was transferred to a skilled nursing facility for 3 months, where he underwent intensive physical therapy. Although extravesical adverse reactions are rare, clinicians and clinical microbiologists need to be aware of the possibility of disseminated infection by M. bovis BCG in the appropriate setting of clinical history, physical examination, and laboratory investigation.

Topics: Administration, Intravesical; Aged; Antitubercular Agents; BCG Vaccine; Drug Therapy, Combination; Ethambutol; Humans; Isoniazid; Male; Mycobacterium bovis; Osteomyelitis; Pyrazinamide; Rifampin; Tuberculosis, Spinal; Urinary Bladder Neoplasms

Topics: Aged; Anti-Infective Agents; Antibiotics, Antitubercular; Ciprofloxacin; Femur; Humans; Male; Muscle, Skeletal; Myositis; Osteomyelitis; Recurrence; Rifampin; Staphylococcal Infections

Disseminated extrapulmonary tuberculosis is uncommon in no immunocompromised hosts. We described the case of a 68-year-old HIV seronegative man, who presented with a 5 months history of constitutional symptoms, generalized lymphadenopathy, evening fever, osteomyelitis of the left fibula and cutaneous lesions (papules and pustules). There was neither clinical nor radiological evidence of pulmonary involvement. On the basis of bacteriological and pathological findings the diagnosis of disseminated extrapulmonary tuberculous was made.

Topics: Aged; Antibiotics, Antitubercular; Antitubercular Agents; Fibula; Follow-Up Studies; HIV Seronegativity; Humans; Isoniazid; Male; Osteomyelitis; Pyrazinamide; Rifampin; Time Factors; Tomography, X-Ray Computed; Tuberculosis, Cutaneous; Tuberculosis, Lymph Node; Tuberculosis, Osteoarticular

Oral antibiotic therapy achieves clinical and bacteriological cure of the adult bacterial osteomyelitis associated or not to orthopedic implant.. We carried out a prospective study, with follow-up at 24 months, of patients with adult bacterial osteomyelitis, that were initially treated with parenteral antibiotic therapy for a week, followed with oral antibiotic therapy during 2 to 6 months, depending on the absence or presence or orthopedic implant, respectively.. 37 patients presented 44 episodes of adult bacterial osteomyelitis, 34 of them in presence of orthopedic implant. The most frequent causative microorganism was S. aureus (44%), followed by coagulase-negative Staphylococcus (29%). The oral antibiotic therapy most frequently employed was the combination cotrimoxazole-rifampin, followed by ciprofloxacin-rifampin. The clinical and bacteriologic cure were 85%, 82% in the group with orthopedic implant. 82% required surgical intervention.. The oral antibiotic therapy, preceded by a short parenteral therapy, can get high rates of clinical and bacteriological cure in the adult's bacterial osteomyelitis.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Antibiotics, Antitubercular; Bacterial Infections; Ciprofloxacin; Combined Modality Therapy; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Osteomyelitis; Prospective Studies; Rifampin; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

We describe a case of osteomyelitis due to Mycobacterium haemophilum in a cardiac transplant recipient and review the two other reported cases of M. haemophilum infection in cardiac transplant patients. Our patient had an excellent response to a prolonged course of therapy with clarithromycin and rifampin. We examine in detail the interactions between these two antibiotics and cyclosporine, including the apparently offsetting effects of clarithromycin/rifampin combination therapy on blood levels of cyclosporine.

Topics: Adult; Clarithromycin; Cyclosporine; Drug Interactions; Drug Therapy, Combination; Heart Transplantation; Humans; Immunosuppressive Agents; Male; Mycobacterium haemophilum; Mycobacterium Infections; Osteomyelitis; Rifampin

The purpose of the present study was to evaluate the combination of azithromycin and rifampicin on experimental chronic osteomyelitis due to Staphylococcus aureus. Alterations in bone bacterial titre, activity of tumour necrosis factor (TNF), a cytokine implicated in inflammation-induced bone pathology, and histopathological changes during infection and following antibiotic treatment were evaluated. Rats were infected with S. aureus by direct tibial inoculation and then randomized 56 days after infection to receive saline treatment or a combination of azithromycin and rifampicin (50 mg/kg po and 25 mg/kg sc respectively) once daily for 21 days. The combination of azithromycin and rifampicin was successful as determined by dramatic reduction in bone bacterial counts (approximately log 4 cfu), but regrowth of the organisms occurred suggesting that the duration of treatment was insufficient. TNF alpha mRNA and TNF activity were constantly elevated by approximately 20- and >200-fold, respectively, and remained elevated irrespective of antimicrobial treatment. Bone histology revealed extensive increase in bone turnover in both the infected and antibiotic treated bones with no difference being observed between the groups. This suggests that, in infected bone, the elevated TNF levels observed may be directly related to the bone pathology and both remain largely unchanged despite potent antibiotic therapy.

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antitubercular; Azithromycin; Bone and Bones; Chronic Disease; Disease Models, Animal; Drug Therapy, Combination; Osteomyelitis; Rats; Rifampin; RNA, Messenger; Staphylococcus aureus; Tumor Necrosis Factor-alpha

To evaluate the efficacy and safety of cotrimoxazol plus rifampicin in staphylococcal osteoarticular infection.. Open, non-comparative study of adult hospitalized patients with documented staphylococcal bone infection.. From Feb 1989 to Dec 1993 28 episodes of staphylococcal bone infection were treated in 14 men and 13 women; the mean age was 48 +/- 21 years (range, 11-84). They received cotrimoxazol (7 mg/kg/day of trimethoprim) plus rifampicin (600-1200 mg/day), both orally, every 8 to 12 h with a mean duration of treatment of 34.2 +/- 8.2 days (range, 21 to 55 days). This antibiotic regimen was initiated at the same time that appropriate surgery for each specific condition was undertaken. Diagnoses were postsurgical osteomyelitis (10 cases), infected total hip prostheses (4 cases, one with 2 episodes), osteomyelitis secondary to external pin fixation (5 cases), soft tissue infections linked to orthopedic implants (3 cases), two cases of metatarsal osteomyelitis (one diabetic foot and one patient with polineuropathy), and one case each of chronic osteomyelitis of femur, hematogenous lumbar spondylitis and posttraumatic osteomyelitis. Four patients had bacteremia. The duration of the infection, prior to surgery was less than one month in 12 episodes, 1 month to 2 years in 14, and in 2 cases, of 10 and 13 years, respectively. In 23 episodes the causal agent was Staphylococcus aureus and in 5 cases it was coagulase-negative staphylococci. Patients had received previous parenteral therapy with other antimicrobials during 2-40 days (X: 18.6 +/- 10.2 days). All patients but one had resolution of the infection and are currently asymptomatic 6 months to 5 years posttreatment in the 21 evaluable cases (X: 38 +/- 13.1 months). Five patients had adverse effects secondary to the antibiotic combination and in three these were severe enough to discontinue the antimicrobials. In no case of the 11 patients with post-treatment control cultures were staphylococci recovered from the wound.. The combination of cotrimoxazole plus rifampicin, both given orally, was highly effective in this selected group of patients. This combination should be considered as a useful alternative therapy of staphylococcal bone infection and deserves further study.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Child; Drug Therapy, Combination; Female; Humans; Lumbar Vertebrae; Male; Middle Aged; Osteomyelitis; Postoperative Complications; Retrospective Studies; Rifampin; Spondylitis; Staphylococcal Infections; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Brucellosis; Doxycycline; Drug Therapy, Combination; Humans; Ilium; Male; Osteomyelitis; Psoas Abscess; Rifampin; Sacroiliac Joint; Streptomycin

Primary vertebral osteomyelitis in a rare presentation of pneumococcal infection especially in an asymptomatic patient with no primary focus of infection. This report describes a patient who presented with lower back pain in which the magnetic resonance imaging showed little evidence of L1 and L2 vertebral body destruction. Cultures from these vertebral bodies grew penicillin and third-generation resistant pneumococcus. The patient was treated successfully with 6 weeks of vancomycin and rifampin.

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Drug Resistance, Multiple; Drug Therapy, Combination; Female; Humans; Middle Aged; Osteomyelitis; Pneumococcal Infections; Rifampin; Spinal Diseases; Streptococcus pneumoniae; Vancomycin

We report on three Italian children who presented with unilateral ankle tuberculosis (TB) consecutively during a short time period and in the same geographical area. A 6-year-old-girl with a family history of TB had limited mobility of the right leg at age 9 months; Mantoux test and radiographs at that age yielded normal findings. When severe right tibiotarsal swelling, reddening, pain and restriction of motion became apparent at age 4.6 years, the typical lesions of TB were evident on radiographs and computed tomographic (CT) scans. Mantoux test and synovial biopsy confirmed TB. A three-drug regimen of treatment proved useless: articular cartilage destruction and diffuse osteosclerosis ensued. Only a four-drug prolonged regimen of treatment proved to be somewhat effective. A 5-year-old girl had a 6-month history of painless swelling and limited mobility of the ankle; radiographs and CT showed osteopenia with marginal erosion of cartilages. A 14-month-old boy presented with a 2-week history of painless swelling ankle. Radiographs showed decreased bone density of talocalcanear bones. Mantoux test and synovial biopsy confirmed TB in both patients; treatment with a three-drug regimen greatly reduced symptoms. A careful suspicion of the diagnosis of tuberculosis is paramount in children with chronic or subacute monoarticular arthritis, even in absence of a positive tuberculin test or abnormalities on chest radiograph. When negative early on, the tuberculin test should be repeated after 6 weeks of arthritis, and a needle biopsy of the synovium is required in those children with monoarticular arthritis and a positive tuberculin test. Careful therapy is necessary to avoid sequelae that may lead to severe osteoarticular damage.

Topics: Ankle Joint; Arthritis; Biopsy; Child; Drug Therapy, Combination; Female; Humans; Infant; Isoniazid; Male; Osteomyelitis; Pyrazinamide; Radiography; Rifampin; Tomography, Emission-Computed; Tuberculosis, Osteoarticular

Topics: Adult; Anti-Bacterial Agents; Antibiotics, Antitubercular; Arthrodesis; beta-Lactam Resistance; Hip Prosthesis; Humans; Joint Prosthesis; Knee Prosthesis; Osteomyelitis; Prognosis; Prospective Studies; Prosthesis-Related Infections; Reoperation; Rifampin; Risk Factors; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Teicoplanin; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

A 4-year-old child with probable multifocal BCG osteomyelitis is reported. The lesions in the skull, clavicula, humerus, ribs, fibula, calcaneus, metatarsus, and hard palate were mainly osteolytic and healed rapidly with antituberculotic therapy. This is the first time that involvement of the hard palate has been described.

Topics: Antibiotics, Antitubercular; Antitubercular Agents; BCG Vaccine; Child, Preschool; Humans; Isoniazid; Male; Mycobacterium tuberculosis; Osteomyelitis; Palate; Rifampin; Tuberculosis, Oral; Tuberculosis, Osteoarticular

The spinal form of brucellosis is still a disabling disease in many countries outside North America and northern and central Europe. Fifteen consecutive cases of spinal brucellosis diagnosed and treated over a 20-year period were reviewed retrospectively. Six patients were farmers, while 10 patients had a history of ingestion of unpasteurized milk or other dairy products. A high index of suspicion is necessary for the diagnosis, since there are no pathognomonic signs or symptoms. Radiological assessment of the disease was reviewed and highlights in the differential diagnoses were stressed. The diagnosis was based on actual culture of Brucella bacilli in seven patients. The principal treatment of brucellosis of the spine is conservative, namely, immobilization and antimicrobial therapy. We have found both a combination of ofloxacin and rifampin and ofloxacin monotherapy efficient as the early regimens used in this series. Three patients had to undergo surgery, since a diagnosis could not be made in any other way.

Topics: Adolescent; Adult; Aged; Brucella melitensis; Brucellosis; Combined Modality Therapy; Diagnosis, Differential; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Immobilization; Male; Middle Aged; Neurologic Examination; Ofloxacin; Osteomyelitis; Rifampin; Spine; Spondylitis; Tomography, X-Ray Computed

We examined the effect of azithromycin (CP-62,993), a new oral macrolide-like antibiotic, alone and in combination with rifampin, as treatment for experimental staphylococcal osteomyelitis. Clindamycin was used as a comparison drug. Rats (n = 10 to 15 per group) were infected by direct instillation of Staphylococcus aureus into the tibial medullary cavity. After 10 days, 21-day treatments with azithromycin (50 mg/kg of body weight, once daily, by the oral route), rifampin (20 mg/kg, once daily, subcutaneously), or clindamycin (90 mg/kg, three times daily, by the oral route) were started. The drugs were used singly or in combination (azithromycin plus rifampin or clindamycin plus rifampin). Peak azithromycin concentrations in bone were > 30 times higher than levels in serum, but the drug had little effect on final bacterial titers (5.13 +/- 0.46 log10 CFU/g of bone; for controls, 6.54 +/- 0.28 log10 CFU/g). Clindamycin was more active than azithromycin (3.26 +/- 2.14 log10 CFU/g of bone; 20% of sterilized bones), but rifampin was the most active single drug (1.5 +/- 1.92 log10 CFU/g; 53% of sterilized bones). Therapy with rifampin or clindamycin alone was associated with the emergence of resistance. Rifampin plus azithromycin (0.51 +/- 1.08 log10 CFU/g of bone; 80% of sterilized bones) and rifampin plus clindamycin (0.87 +/- 1.34 log10 CFU/g of bone; 66% of sterilized bones) were the most active regimens. Thus, azithromycin is ineffective as a single drug for the treatment of experimental staphylococcal osteomyelitis, despite high levels in bone that markedly exceeded the MIC, but it may be an attractive partner drug for rifampin.

Topics: Animals; Azithromycin; Bone and Bones; Clindamycin; Drug Resistance, Microbial; Drug Therapy, Combination; Erythromycin; Male; Osteomyelitis; Rats; Rifampin; Staphylococcal Infections

An unusual case of Mycobacterium marinum cutaneous infection is described. As a result of marked delay in the diagnosis, extensive local inflammation and destructive osteomyelitis occurred together with cutaneous dissemination in an immunocompetent host. Pathologic fractures in the infected bone necessitated amputation of the involved digit. The most striking feature of this case was the development of multiple widespread cutaneous lesions for several months following amputation of the infected digit and initiation of appropriate antimicrobial therapy. These new cutaneous lesions may reflect local immune and inflammatory reactions to previously disseminated microorganisms.

Topics: Amputation, Surgical; Ethambutol; Female; Finger Injuries; Fractures, Bone; Humans; Middle Aged; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Osteomyelitis; Rifampin; Skin Diseases, Bacterial; Water Microbiology; Wounds, Penetrating

Topics: Amphotericin B; Aspergillosis; Child; Femur; Flucytosine; Humans; Male; Osteomyelitis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Rifampin

The efficacies of the quinolones ciprofloxacin and pefloxacin alone and in combination with rifampin were compared with those of vancomycin alone and in combination with rifampin in a rat model of chronic osteomyelitis caused by methicillin-resistant Staphylococcus aureus. Neither the quinolones nor vancomycin alone was effective in reducing titers of organisms in bone after therapy, while rifampin alone was effective. All combination regimens with rifampin were more effective than the regimen with rifampin alone was, although these differences did not achieve statistical significance. Rifampin-resistant isolates were detected rarely. Quinolone-rifampin combination regimens may offer a nonparenteral option for the treatment of chronic osteomyelitis caused by methicillin-resistant S. aureus.

Topics: Animals; Chronic Disease; Ciprofloxacin; Disease Models, Animal; Drug Therapy, Combination; Male; Methicillin; Osteomyelitis; Pefloxacin; Penicillin Resistance; Rats; Rats, Inbred Strains; Rifampin; Staphylococcal Infections; Vancomycin

Clinical efficacy of rifampicin, a semisynthetic broad spectrum antibiotic was estimated in 247 patients with purulent inflammations. It was shown advisable to use rifampicin intravenously in treatment of severe bronchopulmonary pathology, disorders of the bile excretion system, osteomyelitis, severe wound infections and in prophylaxis of postoperative purulent complications in cardiovascular surgery and other cases. High rifampicin sensitivity of staphylococci and streptococci belonging to various species was revealed. Rifampicin was found to be less active against gramnegative pathogens. The isolation frequency of rifampicin sensitive strains of E. coli, Proteus spp., Klebsiella spp. and P. aeruginosa amounted to 88.4, 52.1, 58.8 and 49.3 per cent respectively.

Topics: Bacteria; Bacterial Infections; Cholangitis; Drug Resistance, Microbial; Hepatitis; Humans; Osteomyelitis; Respiratory Tract Infections; Rifampin; Wound Infection

Therapy with vancomycin alone or ciprofloxacin alone did not significantly reduce the number of methicillin-resistant Staphylococcus aureus (MRSA) in bone in rats with experimental osteomyelitis, compared with the number in control rats. Treatment with rifampin significantly (p less than 0.01) decreased the number of MRSA per gram of bone compared with the number in control animals. There was no significant difference in the results of therapy with rifampin compared with the results obtained with the combination of vancomycin plus rifampin. The combination of ciprofloxacin plus rifampin was the most effective regimen for the treatment of MRSA experimental osteomyelitis and the results of therapy were significantly (p less than 0.01) superior to those following treatment with rifampin alone or the combination of vancomycin and rifampin. Following cessation of antimicrobial therapy, significant (p less than 0.01) regrowth of MRSA in bone occurred in animals treated with rifampin alone or ciprofloxacin plus rifampin. The emergence of resistance of MRSA during treatment occurred in two rats treated with rifampin alone and in one treated with rifampin plus vancomycin.

Topics: Animals; Anti-Bacterial Agents; Ciprofloxacin; Drug Therapy, Combination; Osteomyelitis; Rats; Rats, Inbred Strains; Rifampin; Staphylococcal Infections; Vancomycin

Osteomyelitis of the left tibia of a two year old boy secondary to neonatal BCG immunisation is described. He made a good recovery following surgical debridement and anti-tuberculosis chemotherapy.

Topics: BCG Vaccine; Child, Preschool; Drug Therapy, Combination; Fibula; Humans; In Vitro Techniques; Isoniazid; Male; New Zealand; Osteomyelitis; Rifampin; Tibia; Vaccination

Combination of rifampicin with trimethoprim, erythromycin, tetracycline or fusidic acid have some desirable features in the treatment of difficult infections. They are active against a very wide range of possible pathogens. Resistance to rifampicin is rare. Such combinations may be bactericidal and may be usefully synergistic. They may prevent or delay the emergence of bacterial resistant seen when some single agents are used. They can be used in patients with penicillin hypersensitivity. A series of life-threatening infections has been treated with rifampicin-containing combinations. The infections included endocarditis, meningitis, pneumonia, Legionnaire's disease, and head and neck sepsis. A major reason for the choice of drug was often penicillin hypersensitivity. A second reason was the presumption (mostly subsequently confirmed) that streptococci and/or staphylococci were implicated. The clinical outcome of these infections was generally satisfactory, with few side effects and little evidence of the emergence of antibiotic resistance.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Drug Therapy, Combination; Erythromycin; Female; Fusidic Acid; Humans; Infant; Legionnaires' Disease; Male; Meningitis; Middle Aged; Osteomyelitis; Rifampin; Sepsis; Skin Diseases, Infectious; Staphylococcal Infections; Tetracycline; Trimethoprim

This study in 32 patients was undertaken to determine the penetration of rifampicin into bone tissue using the recently developed intravenous formulation of this antibiotic. 300 mg rifampicin given as an intravenous injection over 5 min followed by 300 mg slow intravenous drip infusion over 1 h give a plasma level of rifampicin of more than 2 micrograms/ml for 6 h. In patients with osteomyelitis, bone rifampicin concentrations ranged from 1.4 to 8.8 micrograms/g at 2.5-3.5 h after the start of treatment. Osteomyelitis due to gram-positive organisms and to Haemophilus can be treated with rifampicin in combination with a second antibiotic, depending on the minimum inhibitory concentration of the infecting organism(s).

Topics: Adult; Aged; Bone and Bones; Haemophilus Infections; Humans; Infusions, Parenteral; Kinetics; Middle Aged; Osteomyelitis; Rifampin

The author has tested the action of antibiotic-loaded plaster of Paris loaded pellets in 15 patients with success in 13. Previous studies using plaster of Paris for filling bone defects are noted, plaster being well tolerated and absorbable. Gentamycin, Fucidin and Cefazolin were tested first. In a second series, Netilmicin, Amikacin, Rifamycin and Rifampicin were also used. The preparation of the pellets is fully described. In most instances they can be sterilized by gamma rays except for Fucidin and Cefazolin. Several hundred pellets can be used simultaneously. A study of the elimination of antibiotic in the urine was made. It was concluded that the concentrations obtained by this method in the tissues were highly satisfactory.

Topics: Amikacin; Anti-Bacterial Agents; Bone and Bones; Calcium Sulfate; Drug Implants; Humans; Kinetics; Netilmicin; Osteomyelitis; Rifampin; Rifamycins

10 patients with serious infections caused by Staphylococcus epidermidis (8 cases of endocarditis in non-prosthetic valves, 1 was complicated by osteomyelitis, 1 case of osteomyelitis, and 1 case of septicemia) are described. Clinical and microbiologic features were evaluated including antibiotic sensitivity and synergy studies, phage typing and biotyping. Endocarditis tended to affect the elderly population and the clinical manifestations were quite similar to those caused by Streptococcus viridans. Both patients with osteomyelitis had involvement of the cervical spine with excellent response to antibiotic therapy. The only patient with septicemia acquired via hyperalimentation had delayed clearance of the bacteremia but ultimately responded to intravenous antibiotics. Rifampicin was the most effective of all antibiotics tested. All isolates were sensitive to penicillinase-resistant penicillins and cephalosporins and over half were sensitive to penicillin. Full synergistic activity was demonstrated with cephalothin and nafcillin in combination with rifampicin, and rifampicin-vancomycin was partially synergistic against the majority of the strains. Five of 8 available isolates were non-phage typeable and no definite pattern was established for various types of infections. Four of the 8 isolates were classified as biotype SIIa, 2 biotype SIIc and 2 biotype SVh.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteriological Techniques; Endocarditis, Bacterial; Female; Humans; Male; Middle Aged; Osteomyelitis; Rifampin; Sepsis; Staphylococcal Infections; Staphylococcus epidermidis

The right tibias of sixty-six rabbits were injected with a suspension of Staphylococcus aureus and sodium morrhuate. After four weeks, 43 rabbits developed osteomyelitis and were started on a course of antibiotics. During treatment a gallium-67 scintigram was obtained every two weeks, for up to 10 weeks. During the treatment weeks, 25 rabbits developed negative gallium-67 scintigrams and were killed. All 25 had negative bacteriologic cultures of the right tibia. At the end of 10 wk after start of treatment, the 18 rabbits with persistently positive scintigrams were killed. Eleven of these had positive bacteriologic cultures of the tibia, and seven were negative. The findings suggest that sequential gallium-67 scintigrams may be useful in predicting the cure of osteomyelitis during treatment.

Topics: Animals; False Positive Reactions; Gallium Radioisotopes; Gentamicins; Osteomyelitis; Rabbits; Radionuclide Imaging; Rifampin; Staphylococcus aureus; Tibia

Vancomycin was used alone and in combination with rifampin in the treatment of experimental osteomyelitis due to Staphylococcus aureus in rabbits. Treatment with 60 mg of vancomycin/kg of body weight twice a day for 28 days was ineffective in sterilizing infected rabbit bones. Rifampin (40 mg/kg) injected once a day for 28 days sterilized 57% of infected rabbit bones. Treatment with a combination of vancomycin and rifampin for either 14 or 28 days was significantly more effective than either drug used alone, sterilizing 84% and 90%, respectively, of the infected bones of treated animals. A possible explanation for the failure of vancomycin when used alone may be that its in vitro activity against the infecting strain of S. aureus (as measured by minimal inhibitory concentrations or minimal bactericidal concentrations) was substantially less under anaerobic conditions (that is, at partial pressures of oxygen analogous to those in osteomyelitic bones) than under aerobic conditions.

Topics: Animals; Chronic Disease; Drug Therapy, Combination; Female; Microbial Sensitivity Tests; Osteomyelitis; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

Topics: Acute Disease; Cephalosporins; Child; Clindamycin; Cloxacillin; Diabetes Complications; Humans; Osteomyelitis; Rifampin

Rifampin and trimethoprim were used alone and in combination in the treatment of chronic osteomyelitis due to Staphylococcus aureus in rabbits. Rifampicin levels in infected bone were well above the minimum inhibitory concentration of the infecting strain of S. aureus for at least 4 h after injection. In contrast, trimethoprim levels in diseased bone were below the minimum inhibitory concentration as early as 1 h after injection. Trimethoprim or rifampin, administered alone for 14 days, were ineffective in sterilizing infected rabbit bones. The combination of rifampin plus trimethoprim was significantly more effective (P less than 0.005) than either agents given alone for a comparable duration of time. Staphylococci isolated from the bones of rabbits treated with rifampin alone or rifampin plus trimethoprim were uniformly resistant to rifampin, but retained their susceptibility to trimethoprim.

Topics: Administration, Oral; Animals; Bone and Bones; Drug Therapy, Combination; Microbial Sensitivity Tests; Osteomyelitis; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus; Trimethoprim

Topics: Amphotericin B; Aspergillosis; Child, Preschool; Drug Therapy, Combination; Granulomatous Disease, Chronic; Humans; Male; Osteomyelitis; Rifampin

A 2-month-old infant with Enterobacter osteomyelitis complicating total parenteral nutrition was successfully treated with rifampicin and chloramphenicol. No untoward side effects attributed to rifampicin has been noted despite prolonged administration of rifampicin.

Topics: Chloramphenicol; Drug Therapy, Combination; Enterobacter; Enterobacteriaceae Infections; Humans; Infant; Male; Osteomyelitis; Parenteral Nutrition; Parenteral Nutrition, Total; Rifampin

Topics: Animals; Anti-Bacterial Agents; Gentamicins; Osteomyelitis; Rabbits; Rifampin; Sisomicin

Levels of rifampin, gentamicin, sisomicin, and cephalothin in normal and osteomyelitic rabbit bones were measured, and the efficacy of these drugs in the treatment of osteomyelitis was evaluated. Single drug regimens, including rifampin for 14 days and gentamicin, sisomicin, and cephalothin each for 28 days, were relatively ineffective (5%-33% sterile bone cultures). Rifampin, administered for 28 days, sterilized the bones of 55% of treated animals. The combination of gentamicin and rifampin, given for either 14 or 28 days, sterilized the bones of 67% of treated animals. The combinations of rifampin plus sisomicin and of rifampin plus cephalothin, given for 28 days, were significantly more effective than these agents alone, sterilizing 90%-95% of bones. The combination of rifampin, sisomicin, and cephalothin, given for only 14 days, sterilized the bones of all treated rabbits. Staphylococci isolated from the bones of therapeutic failures that had received rifampin alone or in combination with other antibiotics were highly resistant to rifampin (minimal inhibitory concentration, greater than 250 mug/ml), whereas the organisms recovered from animals not receiving rifampin remained sensitive. Results of in vitro studies of synergy and/or bactericidal activity of antibiotic combinations correlated with in vivo results in some, but not all, instances.

Topics: Animals; Anti-Bacterial Agents; Cephalothin; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Gentamicins; Osteomyelitis; Rabbits; Rifampin; Sisomicin; Staphylococcus aureus

Topics: Adolescent; Adult; Amputation, Surgical; Debridement; Diagnosis, Differential; Ethambutol; Female; Fingers; Hand; Humans; Male; Middle Aged; Mycobacterium; Mycobacterium Infections; Osteomyelitis; Rifampin; Skin Diseases, Infectious; Skin Ulcer; Synovitis; Tuberculosis

Topics: Animals; Bone and Bones; Fracture Fixation; Humans; Infection Control; Osteomyelitis; Rats; Rifampin; Tooth

Topics: Adult; Aged; Bronchiectasis; Bronchitis; Chronic Disease; Endocarditis, Bacterial; Female; Humans; Male; Middle Aged; Osteomyelitis; Rifampin

Topics: Cervical Vertebrae; Humans; Intervertebral Disc Displacement; Osteomyelitis; Rifampin

Topics: Acetylcholine; Adult; Aged; Arteriosclerosis; Chronic Disease; Humans; Injections, Intra-Arterial; Middle Aged; Osteomyelitis; Rifampin

Topics: Adolescent; Child; Child, Preschool; Female; Humans; Infant; Male; Osteomyelitis; Rifampin

Topics: Child; Female; Humans; Lung Diseases; Osteomyelitis; Penicillins; Rifampin; Staphylococcal Infections