Oral Is the New IV. Challenging Decades of Blood and Bone Infection Dogma: A Systematic Review.

BACKGROUND: We sought to determine if controlled, prospective clinical data validate the long-standing belief that intravenous (IV) antibiotic therapy is required for the full duration of treatment for 3 invasive bacterial infections: osteomyelitis, bacteremia, and infective endocarditis. METHODS: We performed a systematic review of published, prospective, controlled trials that compared IV-only to oral stepdown regimens in the treatment of these diseases. Using the PubMed database, we identified 7 relevant randomized controlled trials (RCTs) of osteomyelitis, 9 of bacteremia, 1 including both osteomyelitis and bacteremia, and 3 of endocarditis, as well as one quasi-experimental endocarditis study. Study results were synthesized via forest plots and funnel charts (for risk of study bias), using RevMan 5.4.1 and Meta-Essentials freeware, respectively. RESULTS: The 21 studies demonstrated either no difference in clinical efficacy, or superiority of oral versus IV-only antimicrobial therapy, including for mortality; in no study was IV-only treatment superior in efficacy. The frequency of catheter-related adverse events and duration of inpatient hospitalization were both greater in IV-only groups. DISCUSSION: Numerous prospective, controlled investigations demonstrate that oral antibiotics are at least as effective, safer, and lead to shorter hospitalizations than IV-only therapy; no contrary data were identified. Treatment guidelines should be modified to indicate that oral therapy is appropriate for reasonably selected patients with osteomyelitis, bacteremia, and endocarditis.

Executive Summary: 2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults.

These guidelines are intended for use by infectious disease specialists, orthopedic surgeons, neurosurgeons, radiologists, and other healthcare professionals who care for patients with native vertebral osteomyelitis (NVO). They include evidence and opinion-based recommendations for the diagnosis and management of patients with NVO treated with antimicrobial therapy, with or without surgical intervention.

2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults.

These guidelines are intended for use by infectious disease specialists, orthopedic surgeons, neurosurgeons, radiologists, and other healthcare professionals who care for patients with native vertebral osteomyelitis (NVO). They include evidence and opinion-based recommendations for the diagnosis and management of patients with NVO treated with antimicrobial therapy, with or without surgical intervention.

Microbiology of bone and joint infections in injecting drug abusers.

BACKGROUND: The literature contains variable reports on the causative organisms of osteomyelitis and septic arthritis in patients with injecting drug abuse and on the rate of oxacillin-resistant S aureus. It is important to have a clear notion of the organisms to initiate empiric antimicrobial therapy. QUESTIONS/PURPOSES: We therefore determined the spectrum of organisms in bone and joint infections in patients who were injecting drug users. METHODS: We retrospectively reviewed the medical records of 215 patients (154 male, 61 female) with a history of injecting drug abuse and concurrent bone and/or joint infection from 1998 to 2005. The mean age was 43 years (range, 23-83 years). Osteomyelitis was present in 127 of the 215 patients (59%), septic arthritis in 53 (25%), and both in 35 (16%). The lower extremity was most commonly involved (141 cases, 66%), with osteomyelitis of the tibia present in 70 patients (33%) and septic knee arthritis in 30 patients (14%). RESULTS: Cultures yielded predominately Gram-positive bacteria: Staphylococcus aureus in 52% and coagulase-negative Staphylococcus in 20%. The proportion of oxacillin-resistant S aureus among S aureus infections increased from 21% in 1998 to 73% in 2005. Gram-negative organisms were present in 19% of infections and anaerobes in 13%. Patients with osteomyelitis had a higher prevalence of polymicrobial infections (46% versus 15%), infections due to Gram-negative organisms (24% versus 9%), and anaerobic infections (19% versus 6%) compared to patients with septic arthritis. CONCLUSIONS: These findings suggest broad-spectrum empiric antibiotic therapy, including vancomycin, should be considered for bone and joint infections in patients with injecting drug abuse. LEVEL OF EVIDENCE: Level IV, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

Hematogenous septic ankle arthritis.

UNLABELLED: Ankle infection is a serious problem with limited published information on microbiology and associated morbidities. We describe the laboratory findings, microbiology, and occurrence of adjacent osteomyelitis in patients with hematogenous septic ankle arthritis. We retrospectively reviewed 30 patients with hematogenous septic arthritis of the ankle admitted over a 10-year period. Twenty-two patients were male and eight female. The mean age was 46 years (range, 23-67 years). C-reactive protein and erythrocyte sedimentation rate were elevated in all patients, but the peripheral white blood cell count was elevated in only 47% of patients. Staphylococcus aureus (S. aureus) was the most common pathogen, isolated in 13 (54%) of the 24 patients with positive cultures; four of these isolates (four of 24; 17% of positive cultures) were oxacillin-resistant. Four (17%) of the 24 patients with positive cultures had a mycobacterial infection. We identified adjacent osteomyelitis in 30% of patients, which was considerably associated with the presence of patient comorbidities. S. aureus is the most common pathogen in septic ankle arthritis and empiric antibiotic therapy is recommended. Adjacent osteomyelitis may be present and a high index of suspicion is necessary in patients with comorbidities. LEVEL OF EVIDENCE: Level III, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Clinical experience with daptomycin treatment of foot or ankle osteomyelitis: a preliminary study.

We retrospectively reviewed 25 patients with foot or ankle osteomyelitis reported to a registry who were treated with daptomycin. The patients' clinical experience was analyzed and described at a median dose of 6 mg/kg (range, 4-6.2 mg/kg) and a median duration of 38 days (range, 6-59 days). Twenty-three patients received daptomycin as secondary or tertiary therapy, primarily for not responding to their prior antibiotic therapy (n = 15). Concomitant antibiotics were given to 11 patients, mostly for Gram-negative and/or anaerobic coverage. Methicillin-resistant Staphylococcus aureus was the most common pathogen overall (15 of 25 patients). The median followup interval was 9 weeks (range, 0.5-77 weeks). Outcomes at the end of therapy were 16 patients' symptoms resolved, eight patients improved, and one patient did not respond to therapy; at followup, 19 patients' symptoms resolved, three patients improved, and three patients did not respond to therapy. Ongoing antibiotics were given to 52% of patients for a minimum of 8 days (median, 30 days; range, 8-232 days). Four patients with an implant (all removed) were successfully treated. Daptomycin appears promising for foot and ankle osteomyelitis caused by Gram-positive bacteria. Prospective, controlled clinical trials of daptomycin for osteomyelitis are warranted.

Antibiotic prophylaxis: current recommendations.

Antibiotic prophylaxis consists of a brief course of antibiotics initiated preoperatively in order to decrease the risk of postoperative wound infection in the patient with a clean wound. The antibiotic should be started within 60 minutes before skin incision and continued for not more than 24 hours. Antibiotic therapy is indicated for the contaminated or dirty wound. In open fractures, antibiotics should be started as soon as possible after injury and continued for 3 days (type I and II fractures) or 5 days (type III). This treatment should be combined with local therapy consisting of antibiotic-impregnated polymethylmethacrylate beads. Although the utility of antibiotics in low-velocity gunshot wounds is controversial, high-velocity gunshot wounds should be treated with 48 to 72 hours of antibiotic therapy.

Septic arthritis in patients with human immunodeficiency virus.

The literature contains few descriptions of the infective organisms and diagnostic issues associated with musculoskeletal infections in patients with HIV. We retrospectively reviewed 19 patients with HIV treated at our musculoskeletal infection ward for septic arthritis. The mean CD4 count was 154/mm (range, 7-482/mm), and 11 patients had a CD4 count < 200/mm and were diagnosed with AIDS. The most common pathogen (six patients) was oxacillin-resistant Staphylococcus aureus. Mycobacterial infections occurred in three patients but no fungal pathogens were identified. Septic arthritis was monoarticular in 14 patients and involved the knee in eight patients, the hip in three patients, and the wrist in three patients. Five patients presented with polyarticular septic arthritis. All mycobacterial infections and four of the five polyarticular infections occurred in patients with a CD4 count < 200/mm. Patients with CD4 count < 200/mm had a lower joint fluid WBC count compared to patients with a CD4 count > 200/mm (40,500 vs 69,000/mm). Oxacillin-resistant Staphylococcus aureus was the most common pathogen. A high index of suspicion for Mycobacterium. tuberculosis arthritis and polyarticular septic arthritis is necessary in patients with HIV and a CD4 count < 200/mm.

Recalcitrant septic knee arthritis due to adjacent osteomyelitis in adults.

We asked whether adjacent osteomyelitis with acute septic knee arthritis explained a lack of response to initial management, and whether patient comorbidities predisposed to the nonresponsiveness. From 147 adult patients (151 knees) with septic arthritis, we identified 29 patients (33 knees) who had persistence or recurrence of symptoms after surgical drainage. Adjacent osteomyelitis was present in 31 (94%) of the 33 knees (27 of 29 patients) with poor response to treatment. Patients with adjacent osteomyelitis had more comorbid conditions (23 of 27 patients, 85%) than patients without osteomyelitis (64 of 120, 53%). The most common comorbid conditions in patients with adjacent osteomyelitis were diabetes mellitus (10 patients, 37%) and intravenous drug use (eight patients, 30%). We identified Staphylococcus aureus in 19 of 31 knees (61%) with osteomyelitis, eight (26% of total cases) of which were methicillin-resistant. Persistence of clinical signs of infection after surgical management of septic knee arthritis in adults should raise the suspicion of adjacent osteomyelitis, especially in patients with comorbid conditions. Additional imaging studies may be necessary to evaluate the distal femur and proximal tibia.

Management of open fractures.

Open fractures are high-energy injuries that require a principle-based approach, starting with detailed evaluation of patient status and injury severity. Early, systemic, wide-spectrum antibiotic therapy should cover gram-positive and gram-negative organisms, and a common regimen is a 3-day administration of a first-generation cephalosporin and an aminoglycoside, supplemented with ampicillin or penicillin to cover anaerobes in farm or vascular injuries. Local antibiotic delivery with the bead pouch technique increases the local concentration of antibiotics, minimizes systemic toxicity, and prevents secondary wound contamination. Thorough irrigation and surgical debridement is critical for prevention of infection. Primary wound closure remains controversial because of concerns for gas gangrene. Partial wound closure is an alternative, with delayed wound closure within 3 to 7 days. In the presence of extensive soft tissue damage, local or free muscle flaps should be transferred to achieve coverage. Stable fracture fixation should be achieved with a method suitable for the bone and soft tissue characteristics. Early bone grafting is indicated for bone defects, unstable fractures treated with external fixation, and delayed union. A management plan guided by the above principles will achieve the goals of prevention of infection, fracture healing, and restoration of function in most of these challenging injuries.

Spinal epidural abscess: early clinical outcome in patients treated medically.

Treatment of spinal epidural abscess has been based on surgical debridement. Medical treatment with antibiotics has been proposed as an alternative, but data on its efficacy are limited. The purpose of this study was to determine the early clinical outcome of medical treatment. This is a retrospective review of 52 patients with a spinal epidural abscess who were treated at our institution. Medical treatment was selected if no systemic sepsis was present and the neurologic examination was normal or stable (radiculopathy or signs of partial cord compression present for more than 72 hours before admission without deterioration). Twenty-nine patients had medical treatment and 23 patients were treated surgically. Medical treatment resulted in good or excellent early neurologic outcome in 24 of 29 patients (83%) at a median followup of 2 months. Three patients (11%) had failed medical treatment and required surgery and one patient (3%) who had severe comorbidities died. Staphylococcus aureus was the most common infectious pathogen, isolated in 28 of 36 positive cultures (78%). Medical treatment is a viable alternative to surgery for selected patients with a spinal epidural abscess. However, close clinical followup is essential and surgical decompression should be done when neurologic deterioration or development of systemic sepsis is observed.

Microbiology of osteomyelitis in patients infected with the human immunodeficiency virus.

Osteomyelitis rarely develops in patients infected with the human immunodeficiency virus despite their immunosuppressed state. In the limited literature available on this subset of patients, the role of opportunistic micro-organisms is controversial. Our purpose is to describe the microbiologic features of osteomyelitis. This is a retrospective review of 20 patients infected with the human immunodeficiency virus who were admitted to our musculoskeletal infection ward with the diagnosis of osteomyelitis. Eleven patients (55%) were intravenous drug users. Medical comorbidities were present in 14 of 20 patients (70%), including tuberculosis in five patients and hepatitis C in three patients. The mean CD4 count was 269/mm (range, 20-539/mm). Osteomyelitis was monomicrobial in 10 patients (50%) and polymicrobial in seven patients (35%) whereas in three patients no organism was cultured. The most common pathogen was Staphylococcus aureus, present in 10 patients (50%). No mycobacterial or fungal pathogens were identified. Infection recurred in 3 of 14 patients (21%) that were available for followup. Despite their immunocompromised status, patients infected with the human immunodeficiency virus did not develop osseous infections with opportunistic pathogens. Staphylococcus aureus was the most common pathogen found; however, a considerable proportion of infections were polymicrobial.

Porcine small intestine submucosa does not show antimicrobial properties.

The goal of this study is to examine whether porcine small intestine submucosa (SIS) exhibits antimicrobial properties in a standard in vitro system, without pretreatment with acetic acid or extraction of soluble proteins. Previous animal studies suggest that porcine SIS may have inherent antibiotic properties. Using the guidelines for disk diffusion susceptibility testing by Bauer, 17/64-inch diameter disks made of porcine small intestine submucosa and of gortex were compared with standard antibiotic-impregnated disks against six organisms. The zone of inhibition was measured after 24 hours and minimum bacterial concentrations were determined by serial dilutions of a solution in which porcine small intestine submucosa was allowed to elute for 24 hours. Neither porcine SIS or gortex discs caused inhibition of the growth of any organism. The porcine small intestine submucosa discs showed bacterial growth on top of the discs whereas the gortex did not. Neither the dilutional concentrations of the porcine small intestine submucosa eluent nor the gortex eluent inhibited the growth of any organism. These findings suggest that the porcine small intestine submucosa does not have intrinsic antimicrobial properties. The growth of bacteria on top of the porcine small intestine submucosa suggests that porcine small intestine submucosa itself may provide a favorable environment for the growth of bacteria. More research is necessary to decide what role porcine small intestine submucosa plays in the treatment of infected surgical sites.

Negative pressure dressings as an alternative technique for the treatment of infected wounds.

Coverage of wounds caused by infection and subsequent treatment often are variable because of the location of the wound and wound size. Although much research has been done to expand the indications of negative pressure wound treatment systems, little investigation has been done to quantify the reduction of wound size for vacuum-assisted closure treatment in the presence of infection. In this series, 14 patients who had wounds caused by infections were treated with the vacuum-assisted wound closure system. All wounds were greater than 20 cm2. The duration of treatment averaged 10 days (range, 2-27 days), and the initial wound size averaged 70 cm2 (range, 22.5-288 cm2). After the course of treatment, the final wound size averaged 39 cm2 (range, 10-147 cm2). The average wound size reduction was 43%. This method seems to enhance the rapidity of wound reduction, and because it is a closed system of treatment, it has the added benefit of minimizing exposure of staff and other patients to communicable diseases. Vacuum-assisted wound closure systems add another option in the care of musculoskeletal infections.

Newer methods of antimicrobial delivery for bone and joint infections.

The advantages of systemic therapy include the ability to deliver antibiotics to areas that cannot be reached with topical therapy, the choice of a large selection of agents directed against the pathogens encountered in orthopaedic infections, and arrest or eradication of infection in most cases (in conjunction with adequate débridement). Disadvantages include the potential for toxicity from systemic agents, difficulty in achieving high concentrations of antimicrobial agents at the site of infection, and problems with compliance. To combat these disadvantages, newer methods for the delivery of antimicrobial agents have been investigated. Some of these newer methods include new formulations of antimicrobial agents to decrease systemic toxicity and improved methods for delivering local antimicrobial therapy.

Laboratory monitoring in pediatric acute osteomyelitis and septic arthritis.

The purpose of the current study was to determine the usefulness of erythrocyte sedimentation rate and C-reactive protein in pediatric bone and joint infections treated with and without surgery. The medical records of 50 patients admitted for acute osteomyelitis, septic arthritis, or both were reviewed retrospectively. There were 22 patients with septic arthritis, 20 with osteomyelitis, and eight with osteomyelitis with adjacent septic arthritis. There were 25 patients each in the surgical and nonsurgical groups. There was a statistically significant difference between the two groups regarding mean days to peak and normalization of erythrocyte sedimentation rate values and normalization of C-reactive protein values. Statistically significant differences were revealed for the mean days to normalization of erythrocyte sedimentation rate and C-reactive protein values among the patients with a diagnosis of osteomyelitis, septic arthritis, or both. The mean days to peak and normalization for erythrocyte sedimentation rate and C-reactive protein were twice as long in the surgical group as compared with the nonsurgical group. Complete recovery was achieved by all patients. This information should help the clinician in the diagnosis and treatment of children having surgery for acute osteomyelitis and septic arthritis.

Osteomyelitis attributable to vancomycin-resistant enterococci.

Vancomycin-resistant enterococcus first was described in 1988, and has become a major problem in nosocomial infections. This is a retrospective review of 10 patients, seen at the authors' hospital during a 2-year period, with confirmed vancomycin-resistant enterococcal osteomyelitis: four patients had total joint arthroplasty infections, one patient had an infected tibial nail, three patients had infections associated with external fixators, and two patients had osteomyelitis of the femur. Four of the 10 patients had underlying medical illnesses (diabetes mellitus, systemic lupus erythematosus, human immunodeficiency virus infection); four of the 10 patients were intravenous drug users. Two patients had vancomycin-resistant enterococci on admission, and the other eight patients were admitted to the hospital for a mean of 21.3 days (range, 3-73 days) before vancomycin-resistant enterococci were identified in the bone. Eight of the 10 patients had monomicrobial infections with vancomycin-resistant enterococci. Patients were treated by surgical debridement, removal of hardware, and antibiotics (chloramphenicol in eight patients, quinupristin and dalfopristin (Synercid) in two patients). All patients initially improved with therapy, but one patient had a recurrence of vancomycin-resistant enterococcal osteomyelitis and died of bacteremia. Bone infections with vancomycin-resistant enterococcus still may be uncommon, but with time and selective antibiotic pressures, vancomycin-resistant enterococci may become a more prominent entity in orthopaedic infections.