Medical comorbidities are independent preoperative risk factors for surgical infection after total joint arthroplasty.

BACKGROUND: Surgical site infection (SSI) after total joint arthroplasty (TJA) is a major cause of morbidity. Multiple patient comorbidities have been identified as SSI risk factors including obesity, tobacco use, diabetes, immunosuppression, malnutrition, and coagulopathy. However, the independent effect of multiple individual patient factors on risk of subsequent periprosthetic infection is unclear. QUESTIONS/PURPOSES: The purposes of this study are (1) to collect data on several preestablished infection risk factors in addition to SSI-related data on a large TJA cohort; and (2) to use multivariate modeling on previously established patient risk factors to determine independent preoperative predictors of SSI. METHODS: We reviewed records of patients undergoing TJA from January 1, 2010, to July 30, 2012. Confirmation of SSI followed published guidelines for superficial, deep, and periprosthetic. A total of 29 culture-positive SSIs (1.5% total) and 1846 controls were identified. The prevalence of known patient-specific infection risk factors was determined for both infected cases and healthy control subjects followed by multiple regression analysis to determine independent risk. RESULTS: Isolated organisms consisted of methicillin-resistant Staphylococcus aureus (MRSA; 34.5%) followed by gram-negative rods (31.0%). After adjusting for anatomic site, independent risk factors for infection include: revision surgery (odds ratio [OR], 2.28; confidence interval [CI], 1.26-3.98), super obesity (body mass index>50 kg/m2; OR, 5.28; CI, 1.38-17.1), diabetes mellitus (OR, 1.83; CI, 1.02-3.27), tobacco abuse (OR, 2.96; CI, 1.65-5.11), MRSA colonization or infection (OR, 4.17; CI, 1.63-9.66), and current or prior bone cancer (OR, 3.86; CI, 1.21-12.79). CONCLUSIONS: Multiple patient comorbidities independently contribute to infection risk after TJA. Preoperative TJA infection risk stratification may be feasible and should be investigated further. LEVEL OF EVIDENCE: Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Prevention of infections associated with combat-related extremity injuries.

During combat operations, extremities continue to be the most common sites of injury with associated high rates of infectious complications. Overall, ∼ 15% of patients with extremity injuries develop osteomyelitis, and ∼ 17% of those infections relapse or recur. The bacteria infecting these wounds have included multidrug-resistant bacteria such as Acinetobacter baumannii, Pseudomonas aeruginosa, extended-spectrum ß-lactamase-producing Klebsiella species and Escherichia coli, and methicillin-resistant Staphylococcus aureus. The goals of extremity injury care are to prevent infection, promote fracture healing, and restore function. In this review, we use a systematic assessment of military and civilian extremity trauma data to provide evidence-based recommendations for the varying management strategies to care for combat-related extremity injuries to decrease infection rates. We emphasize postinjury antimicrobial therapy, debridement and irrigation, and surgical wound management including addressing ongoing areas of controversy and needed research. In addition, we address adjuvants that are increasingly being examined, including local antimicrobial therapy, flap closure, oxygen therapy, negative pressure wound therapy, and wound effluent characterization. This evidence-based medicine review was produced to support the Guidelines for the Prevention of Infections Associated With Combat-Related Injuries: 2011 Update contained in this supplement of Journal of Trauma.

Executive summary: Guidelines for the prevention of infections associated with combat-related injuries: 2011 update: endorsed by the Infectious Diseases Society of America and the Surgical Infection Society.

Despite advances in resuscitation and surgical management of combat wounds, infection remains a concerning and potentially preventable complication of combat-related injuries. Interventions currently used to prevent these infections have not been either clearly defined or subjected to rigorous clinical trials. Current infection prevention measures and wound management practices are derived from retrospective review of wartime experiences, from civilian trauma data, and from in vitro and animal data. This update to the guidelines published in 2008 incorporates evidence that has become available since 2007. These guidelines focus on care provided within hours to days of injury, chiefly within the combat zone, to those combat-injured patients with open wounds or burns. New in this update are a consolidation of antimicrobial agent recommendations to a backbone of high-dose cefazolin with or without metronidazole for most postinjury indications and recommendations for redosing of antimicrobial agents, for use of negative pressure wound therapy, and for oxygen supplementation in flight.

Guidelines for the prevention of infections associated with combat-related injuries: 2011 update: endorsed by the Infectious Diseases Society of America and the Surgical Infection Society.

Despite advances in resuscitation and surgical management of combat wounds, infection remains a concerning and potentially preventable complication of combat-related injuries. Interventions currently used to prevent these infections have not been either clearly defined or subjected to rigorous clinical trials. Current infection prevention measures and wound management practices are derived from retrospective review of wartime experiences, from civilian trauma data, and from in vitro and animal data. This update to the guidelines published in 2008 incorporates evidence that has become available since 2007. These guidelines focus on care provided within hours to days of injury, chiefly within the combat zone, to those combat-injured patients with open wounds or burns. New in this update are a consolidation of antimicrobial agent recommendations to a backbone of high-dose cefazolin with or without metronidazole for most postinjury indications, and recommendations for redosing of antimicrobial agents, for use of negative pressure wound therapy, and for oxygen supplementation in flight.

Biographical sketch: William S. Baer (1872-1931).

This biographical sketch on William S. Baer corresponds to the historic text, The Classic: The Treatment of Chronic Osteomyelitis With the Maggot (Larva of the Blow Fly), available at DOI 10.1007/s11999-010-1416-3.

Biographical sketch: Fuller Albright, MD 1900-1969.

This biographical sketch on Fuller Albright corresponds to the historic text, The Classic: The Metabolic Effects of Steroid Hormones in Osteoporosis, available at DOI 10.1007/s11999-011-1832-z .

Biographical sketch: royal whitman, 1857-1946.

This biographical sketch of Royal Whitman corresponds to the historic text, The Classic: A Study of the Weak Foot, with Reference to its Causes, its Diagnosis, and its Cure; with an Analysis of a Thousand Cases of So-Called Flat-Foot, available at DOI 10.1007/s11999-009-1130-1 .

Biographical sketch: Ruth Jackson, MD, FACS 1902-1994.

This biographical sketch on Ruth Jackson corresponds to the historic text, The Classic: The Cervical Syndrome, available at DOI 10.1007/s11999-010-1278-8 .

Efficacy of telavancin in the treatment of methicillin-resistant Staphylococcus aureus osteomyelitis: studies with a rabbit model.

OBJECTIVES: Staphylococcus aureus is the most common pathogen isolated in osteomyelitis. This study evaluated the efficacies of telavancin (an investigational, rapidly bactericidal lipoglycopeptide with a multifunctional mechanism of action against Gram-positive bacteria), vancomycin and linezolid in a rabbit methicillin-resistant S. aureus (MRSA) osteomyelitis model. METHODS: Localized osteomyelitis was induced in New Zealand White rabbits by percutaneous injection of 10(6) cfu of MRSA clinical isolate 168-1 into the intramedullary cavity. Two weeks post-infection, rabbits with radiographically confirmed, localized proximal tibial osteomyelitis were randomized into four groups (n = 15 per group): untreated controls; vancomycin 30 mg/kg subcutaneously every 12 h; linezolid 60 mg/kg orally every 8 h; and telavancin 30 mg/kg subcutaneously every 12 h. After 4 weeks of antibiotic treatment, animals were left untreated for 2 weeks. Rabbits were then euthanized and the tibias harvested. Bone matrix and marrow from each tibia were cultured and bacterial counts determined. RESULTS: For MRSA isolate 168-1, the MIC was 0.25 mg/L for telavancin, 0.5 mg/L for vancomycin and 0.5 mg/L for linezolid. Tibial cultures were positive for MRSA in 9 of 15 (60%) untreated controls, and 3 of 15 (20%) telavancin-treated, 3 of 15 (20%) vancomycin-treated and 4 of 14 (29%) linezolid-treated rabbits. CONCLUSIONS: Telavancin has comparable efficacy to vancomycin and linezolid in a rabbit model of MRSA osteomyelitis.

Treatment of war wounds: a historical review.

The treatment of war wounds is an ancient art, constantly refined to reflect improvements in weapons technology, transportation, antiseptic practices, and surgical techniques. Throughout most of the history of warfare, more soldiers died from disease than combat wounds, and misconceptions regarding the best timing and mode of treatment for injuries often resulted in more harm than good. Since the 19th century, mortality from war wounds steadily decreased as surgeons on all sides of conflicts developed systems for rapidly moving the wounded from the battlefield to frontline hospitals where surgical care is delivered. We review the most important trends in US and Western military trauma management over two centuries, including the shift from primary to delayed closure in wound management, refinement of amputation techniques, advances in evacuation philosophy and technology, the development of antiseptic practices, and the use of antibiotics. We also discuss how the lessons of history are reflected in contemporary US practices in Iraq and Afghanistan.

Efficacies of ceftobiprole medocaril and comparators in a rabbit model of osteomyelitis due to methicillin-resistant Staphylococcus aureus.

The pharmacokinetics and distribution into bone tissue of ceftobiprole in uninfected New Zealand White rabbits were determined after subcutaneous administration of the prodrug ceftobiprole medocaril. Serum exposure (maximum concentration of the drug in serum, trough concentration, area under the concentration-time curve) to ceftobiprole at 20 and 80 mg/kg was dose proportional, and there was no accumulation of ceftobiprole following repeated (every 6 h [q6h]) injections of the antibiotic. Ceftobiprole titers in the tibial matrix and marrow were 3.2 +/- 1.3 microg/g and 11.2 +/- 6.5 microg/g, respectively, in uninfected animals treated with 20 mg/kg of the antibiotic and 13.4 +/- 7.3 microg/g and 66.3 +/- 43.2 microg/g, respectively, in uninfected animals treated with 80 mg/kg of the antibiotic. No differences in ceftobiprole titers were observed between right and left tibiae for either bone matrix or marrow. The efficacies of 4 weeks of treatment with ceftobiprole (40 mg/kg administered subcutaneously [s.c.] q6h), vancomycin (30 mg/kg administered s.c. q12h), or linezolid (60 mg/kg administered orally q8h) were compared, using a rabbit model of methicillin-resistant Staphylococcus aureus tibial osteomyelitis. After treatment with ceftobiprole, the bacterial titers in all infected left tibiae from evaluable rabbits were below the level of detection, whereas only 73% of infected left tibiae from vancomycin- or linezolid-treated animals had bacterial titers below the level of detection; the mean titers of ceftobiprole were 3 to 5 times higher in infected left tibiae than in uninfected right tibiae. These results indicate that ceftobiprole provided effective parenteral treatment of osteomyelitis in this rabbit model.

Osteomyelitis and the role of biofilms in chronic infection.

Understanding the mechanisms implicated in the initial attachment, development, and maturation of a biofilm phenotype are of tremendous importance for their effect on the medical, industrial, and public health arenas. This review explores the current understanding of the nature of biofilms and the impact that molecular interactions between the bacteria themselves, as well as between bacteria and the host, may have on biofilm development and phenotype using the nonmotile Gram-positive coccus, Staphylococcus aureus, as an example.

Prevention and management of infections associated with combat-related extremity injuries.

Orthopedic injuries suffered by casualties during combat constitute approximately 65% of the total percentage of injuries and are evenly distributed between upper and lower extremities. The high-energy explosive injuries, environmental contamination, varying evacuation procedures, and progressive levels of medical care make managing combat-related injuries challenging. The goals of orthopedic injury management are to prevent infection, promote fracture healing, and restore function. It appears that 2% to 15% of combat-related extremity injuries develop osteomyelitis, although lower extremity injuries are at higher risk of infections than upper extremity. Management strategies of combat-related injuries primarily focus on early surgical debridement and stabilization, antibiotic administration, and delayed primary closure. Herein, we provide evidence-based recommendations from military and civilian data to the management of combat-related injuries of the extremity. Areas of emphasis include the utility of bacterial cultures, antimicrobial therapy, irrigation fluids and techniques, timing of surgical care, fixation, antibiotic impregnated beads, wound closure, and wound coverage with negative pressure wound therapy. Most of the recommendations are not supported by randomized controlled trials or adequate cohorts studies in a military population and further efforts are needed to answer best treatment strategies.

Guidelines for the prevention of infection after combat-related injuries.

Management of combat-related trauma is derived from skills and data collected in past conflicts and civilian trauma, and from information and experience obtained during ongoing conflicts. The best methods to prevent infections associated with injuries observed in military combat are not fully established. Current methods to prevent infections in these types of injuries are derived primarily from controlled trials of elective surgery and civilian trauma as well as retrospective studies of civilian and military trauma interventions. The following guidelines integrate available evidence and expert opinion, from within and outside of the US military medical community, to provide guidance to US military health care providers (deployed and in permanent medical treatment facilities) in the diagnosis, treatment, and prevention of infections in those individuals wounded in combat. These guidelines may be applicable to noncombat traumatic injuries under certain circumstances. Early wound cleansing and surgical debridement, antibiotics, bony stabilization, and maintenance of infection control measures are the essential components to diminish or prevent these infections. Future research should be directed at ideal treatment strategies for prevention of combat-related injury infections, including investigation of unique infection control techniques, more rapid diagnostic strategies for infection, and better defining the role of antimicrobial agents, including the appropriate spectrum of activity and duration.

Multidrug-resistant organisms in military wounds from Iraq and Afghanistan.

Mortality from battlefield wounds has historically declined, thanks to better surgical management, faster transport of casualties, and improved antibiotics. Today, one of the major challenges facing U.S. military caregivers is the presence of multidrug-resistant organisms in orthopaedic extremity wounds. The most frequently identified resistant strains of bacteria are Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter calcoaceticus-baumannii complex. Overuse of broad-spectrum antibiotics may be an important factor in building resistant strains. Acinetobacter infections appear to hospital-acquired and not from an initial colonization of the injury. More research is required to give military physicians the tools they require to reduce the infection rate and defeat multidrug-resistant organisms.

Orthopaedic war injuries: from combat casualty care to definitive treatment: a current review of clinical advances, basic science, and research opportunities.

Musculoskeletal war wounds often involve massive injury to bone and soft tissue that differ markedly in character and extent compared with most injuries seen in civilian practice. These complex injuries have challenged orthopaedic surgeons to the limits of their treatment abilities on the battlefield, during medical evacuation, and in subsequent definitive or reconstructive treatment. Newer methodologies are being used in the treatment of these wounds to prevent so-called second hit complications, decrease complications associated with prolonged medical evacuation, reduce the incidence of infection, and restore optimal function. Basic science advances hold the promise of providing foundations for future treatment options that may improve both bone and soft-tissue healing. Research on the treatment of these often devastating wounds also will have broad applicability to trauma resulting from acts of terrorism or from natural disasters.

Targeting intracellular Staphylococcus aureus to lower recurrence of orthopaedic infection.

Staphylococcus aureus is often found in orthopaedic infections and may be protected from commonly prescribed antibiotics by forming biofilms or growing intracellularly within osteoblasts. To investigate the effect of non-antibiotic compounds in conjunction with antibiotics to clear intracellular and biofilm forming S. aureus causing osteomyelitis. SAOS-2 osteoblast-like cell lines were infected with S. aureus BB1279. Antibiotics (vancomycin, VAN; and dicloxacillin, DICLOX), bacterial efflux pump inhibitors (piperine, PIP; carbonyl cyanide m-chlorophenyl hydrazone, CCCP), and bone morphogenetic protein (BMP-2) were evaluated individually and in combination to kill intracellular bacteria. We present direct evidence that after gentamicin killed extracellular planktonic bacteria and antibiotics had been stopped, seeding from the infected osteoblasts grew as biofilms. VAN was ineffective in treating the intracellular bacteria even at 10× MIC; however in presence of PIP or CCCP the intracellular S. aureus was significantly reduced. Bacterial efflux pump inhibitors (PIP and CCCP) were effective in enhancing permeability of antibiotics within the osteoblasts and facilitated killing of intracellular S. aureus. Confocal laser scanning microscopy (CLSM) showed increased uptake of propidium iodide within osteoblasts in presence of PIP and CCCP. BMP-2 had no effect on growth of S. aureus either alone or in combination with antibiotics. Combined application of antibiotics and natural agents could help in the treatment of osteoblast infected intracellular bacteria and biofilms associated with osteomyelitis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1086-1092, 2018.

Effects of loading concentration, blood and synovial fluid on antibiotic release and anti-biofilm activity of bone cement beads.

Antibiotic loaded cement beads are commonly used for the treatment of biofilm related orthopaedic periprosthetic infections; however the effects of antibiotic loading and exposure of beads to body fluids on release kinetics are unclear. The purpose of this study was to determine the effects of (i) antibiotic loading density (ii) loading amount (iii) material type and (iv) exposure to body fluids (blood or synovial fluid) on release kinetics and efficacy of antibiotics against planktonic and lawn biofilm bacteria. Short-term release into an agar gel was evaluated using a fluorescent tracer (fluorescein) incorporated in the carrier materials calcium sulfate (CaSO4) and poly methyl methacrylate (PMMA). Different fluorescein concentrations in CaSO4 beads were evaluated. Mechanical properties of fluorescein-incorporated beads were analyzed. Efficacy of the antibiotics vancomycin (VAN) or tobramycin (TOB) alone and in combination was evaluated against lawn biofilms of bioluminescent strains of Staphylococcus aureus and Pseudomonas aeruginosa. Zones of inhibition of cultures (ZOI) were measured visually and using an in-vivo imaging system (IVIS). The influence of body fluids on release was assessed using CaSO4 beads that contained fluorescein or antibiotics and were pre-coated with human blood or synovial fluid. The spread from the beads followed a square root of time relationship in all cases. The loading concentration had no influence on short-term fluorescein release and pre-coating of beads with body fluids did not affect short-term release or antibacterial activity. Compared to PMMA, CaSO4 had a more rapid short term rate of elution and activity against planktonic and lawn biofilms. This study highlights the importance of considering antibiotic loading and packing density when investigating the clinical application of bone cements for infection management.

Adult osteomyelitis.

Adult osteomyelitis remains difficult to treat, with considerable morbidity and costs to the health care system. Bacteria reach bone through the bloodstream, from a contiguous focus of infection, from penetrating trauma, or from operative intervention. Bone necrosis begins early, limiting the possibility of eradicating the pathogens, and leading to a chronic condition. Appropriate treatment includes culture-directed antibiotic therapy and operative debridement of all necrotic bone and soft tissue. Treatment often involves a combination of antibiotics. Operative treatment is often staged and includes debridement, dead space management, soft tissue coverage, restoration of blood supply, and stabilization. Clinicians and patients must share a clear understanding of the goals of treatment and the difficulties that may persist after the initial course of therapy or surgical intervention. Chronic pain and recurrence of infection still remain possible even when the acute symptoms of adult osteomyelitis have resolved.