Jon T. Mader

Diagnosis and Treatment of Diabetic Foot Infections

EXECUTIVE SUMMARY: 1. Foot infections in patients with diabetes cause substantial morbidity and frequent visits to health care professionals and may lead to amputation of a lower extremity. 2. Diabetic foot infections require attention to local (foot) and systemic (metabolic) issues and coordinated management, preferably by a multidisciplinary foot-care team (A-II). The team managing these infections should include, or have ready access to, an infectious diseases specialist or a medical microbiologist (B-II). 3. The major predisposing factor to these infections is foot ulceration, which is usually related to peripheral neuropathy. Peripheral vascular disease and various immunological disturbances play a secondary role. 4. Aerobic Gram-positive cocci (especially Staphylococcus aureus) are the predominant pathogens in diabetic foot infections. Patients who have chronic wounds or who have recently received antibiotic therapy may also be infected with Gram-negative rods, and those with foot ischemia or gangrene may have obligate anaerobic pathogens. 5. Wound infections must be diagnosed clinically on the basis of local (and occasionally systemic) signs and symptoms of inflammation. Laboratory (including microbiological) investigations are of limited use for diagnosing infection, except in cases of osteomyelitis (B-II). 6. Send appropriately obtained specimens for culture before starting empirical antibiotic therapy in all cases of infection, except perhaps those that are mild and previously untreated (B-III). Tissue specimens obtained by biopsy, ulcer curettage, or aspiration are preferable to wound swab specimens (A-I). 7. Imaging studies may help diagnose or better define deep, soft-tissue purulent collections and are usually needed to detect pathological findings in bone. Plain radiography may be adequate in many cases, but MRI (in preference to isotope scanning) is more sensitive and specific, especially for detection of soft-tissue lesions (A-I). 8. Infections should be categorized by their severity on the basis of readily assessable clinical and laboratory features (B-II). Most important among these are the specific tissues involved, the adequacy of arterial perfusion, and the presence of systemic toxicity or metabolic instability. Categorization helps determine the degree of risk to the patient and the limb and, thus, the urgency and venue of management. 9. Available evidence does not support treating clinically uninfected ulcers with antibiotic therapy (D-III). Antibiotic therapy is necessary for virtually all infected wounds, but it is often insufficient without appropriate wound care. 10. Select an empirical antibiotic regimen on the basis of the severity of the infection and the likely etiologic agent(s) (B-II). Therapy aimed solely at aerobic Gram-positive cocci may be sufficient for mild-to-moderate infections in patients who have not recently received antibiotic therapy (A-II). Broad-spectrum empirical therapy is not routinely required but is indicated for severe infections, pending culture results and antibiotic susceptibility data (B-III). Take into consideration any recent antibiotic therapy and local antibiotic susceptibility data, especially the prevalence of methicillin-resistant S. aureus (MRSA) or other resistant organisms. Definitive therapy should be based on both the culture results and susceptibility data and the clinical response to the empirical regimen (C-III). 11. There is only limited evidence with which to make informed choices among the various topical, oral, and parenteral antibiotic agents. Virtually all severe and some moderate infections require parenteral therapy, at least initially (C-III). Highly bioavailable oral antibiotics can be used in most mild and in many moderate infections, including some cases of osteomyelitis (A-II). Topical therapy may be used for some mild superficial infections (B-I). 12. Continue antibiotic therapy until there is evidence that the infection has resolved but not necessarily until a wound has healed. Suggestions for the duration of antibiotic therapy are as follows: for mild infections, 12 weeks usually suffices, but some require an additional 12 weeks; for moderate and severe infections, usually 24 weeks is sufficient, depending on the structures involved, the adequacy of debridement, the type of soft-tissue wound cover, and wound vascularity (A-II); and for osteomyelitis, generally at least 46 weeks is required, but a shorter duration is sufficient if the entire infected bone is removed, and probably a longer duration is needed if infected bone remains (B-II). 13. If an infection in a clinically stable patient fails to respond to 1 antibiotic courses, consider discontinuing all antimicrobials and, after a few days, obtaining optimal culture specimens (C-III). 14. Seek surgical consultation and, when needed, intervention for infections accompanied by a deep abscess, extensive bone or joint involvement, crepitus, substantial necrosis or gangrene, or necrotizing fasciitis (A-II). Evaluating the limbs arterial supply and revascularizing when indicated are particularly important. Surgeons with experience and interest in the field should be recruited by the foot-care team, if possible. 15. Providing optimal wound care, in addition to appropriate antibiotic treatment of the infection, is crucial for healing (A-I). This includes proper wound cleansing, debridement of any callus and necrotic tissue, and, especially, off-loading of pressure. There is insufficient evidence to recommend use of a specific wound dressing or any type of wound healing agents or products for infected foot wounds. 16. Patients with infected wounds require early and careful follow-up observation to ensure that the selected medical and surgical treatment regimens have been appropriate and effective (B-III). 17. Studies have not adequately defined the role of most adjunctive therapies for diabetic foot infections, but systematic reviews suggest that granulocyte colony-stimulating factors and systemic hyperbaric oxygen therapy may help prevent amputations (B-I). These treatments may be useful for severe infections or for those that have not adequately responded to therapy, despite correcting for all amenable local and systemic adverse factors. 18. Spread of infection to bone (osteitis or osteomyelitis) may be difficult to distinguish from noninfectious osteoarthropathy. Clinical examination and imaging tests may suffice, but bone biopsy is valuable for establishing the diagnosis of osteomyelitis, for defining the pathogenic organism(s), and for determining the antibiotic susceptibilities of such organisms (B-II). 19. Although this field has matured, further research is much needed. The committee especially recommends that adequately powered prospective studies be undertaken to elucidate and validate systems for classifying infection, diagnosing osteomyelitis, defining optimal antibiotic regimens in various situations, and clarifying the role of surgery in treating osteomyelitis (A-III).

Hematogenous Pyogenic Spinal Infections and Their Surgical Management

STUDY DESIGN Mainly a retrospective study of 101 cases of pyogenic spinal infection, excluding postoperative infections. Data were obtained through medical record review, imaging examination, and patient follow-up evaluation. SUMMARY OF BACKGROUND DATA Hematogenous pyogenic spinal infection has been described variously as spondylodiscitis, discitis, vertebral osteomyelitis, and epidural abscess. Recommended treatment options have included conservative methods (antibiotics and bracing) and surgical intervention. However, a comprehensive classification that would aid in diagnosis, treatment planning, and prognosis has not yet been devised. OBJECTIVES To analyze the bacteriology, pathologic entities, complications, and results of treatment options for pyogenic spinal infection. METHOD All patients received plain radiographs, gadolinium-enhanced magnetic resonance imaging scans, and bone/gallium radionuclide studies. All patients had tissue biopsies. Bacteriology, hematology, and predisposing factors were analyzed. All patients received intravenous and oral antibiotics. A total of 58 patients underwent surgery. Patient outcomes were correlated with clinical status, with treatment method and, where applicable, with location and nature of epidural compression. Statistical analyses were performed. RESULTS Spondylodiscitis occurred most commonly with primary epidural abscess, spondylitis, discitis, and pyogenic facet arthropathy, all occurring rarely. Staphylococcus aureus was the main organism. Infection elsewhere was the most common predisposing factor. Leukocyte counts were elevated in 42.6% of spondylodiscitis cases. The erythrocyte sedimentation rate was elevated in all cases of epidural abscess. There were 35 cases of epidural abscess (frank abscess, 29; granulation tissue, 6). Epidural abscess complicating spondylodiscitis occurred most often in the cervical spine, followed by thoracic and lumbar areas. The rate of paraplegia or paraparesis also was highest in cervical and thoracic regions. There were no cases of quadriplegia. All patients with either epidural granulation tissue or paraparesis recovered completely after surgical decompression. Only 18% of patients with frank epidural abscess and 23% of patients with paralysis recovered completely after surgical decompression. Patients with spondylodiscitis who were treated nonsurgically reported residual back pain more often (64%) than patients treated surgically (26.3%). CONCLUSIONS Pyogenic spinal infection can be thought of as a spectrum of disease comprising spondylitis, discitis, spondylodiscitis, pyogenic facet arthropathy, and epidural abscess. Spondylodiscitis is more prone to develop epidural abscesses in the cervical spine (90%) than the thoracic (33.3%) or lumbar (23.6%) areas. Thecal sac neurocompression has a greater chance of causing neurologic deficit in the thoracic spine (81.8%). Treatment of neurologic deficit caused by epidural abscess is prompt surgical decompression, with or without fusion. Patients with frank abscess had less favorable outcomes than those with granulation tissue, and paraplegia responded to treatment more poorly than paraparesis. Surgery was preferable to nonsurgical treatment for improving back pain.

A clinical staging system for adult osteomyelitis.

INTRODUCTIONJon Terry Mader (Fig 1) was born on March 21, 1944 in Madison, WI. He earned his BA and MD degrees at Wabash College at Indiana University in 1966 and 1970, respectively. He trained in Internal Medicine at the University of Texas Medical Branch in Galveston, TX and made his career there

Acute Septic Arthritis

SUMMARY Acute septic arthritis may develop as a result of hematogenous seeding, direct introduction, or extension from a contiguous focus of infection. The pathogenesis of acute septic arthritis is multifactorial and depends on the interaction of the host immune response and the adherence factors, toxins, and immunoavoidance strategies of the invading pathogen. Neisseria gonorrhoeae and Staphylococcus aureus are used in discussing the host-pathogen interaction in the pathogenesis of acute septic arthritis. While diagnosis rests on isolation of the bacterial species from synovial fluid samples, patient history, clinical presentation, laboratory findings, and imaging studies are also important. Acute nongonococcal septic arthritis is a medical emergency that can lead to significant morbidity and mortality. Therefore, prompt recognition, rapid and aggressive antimicrobial therapy, and surgical treatment are critical to ensuring a good prognosis. Even with prompt diagnosis and treatment, high mortality and morbidity rates still occur. In contrast, gonococcal arthritis is often successfully treated with antimicrobial therapy alone and demonstrates a very low rate of complications and an excellent prognosis for full return of normal joint function. In the case of prosthetic joint infections, the hardware must be eventually removed by a two-stage revision in order to cure the infection.

Osteomyelitis in Long Bones

Osteomyelitis in long bones remains challenging and expensive to treat, despite advances in antibiotics and new operative techniques. Plain radiographs still provide the best screening for acute and chronic osteomyelitis. Other imaging techniques may be used to determine diagnosis and aid in treatment decisions. The decision to use oral or parenteral antibiotics should be based on results regarding microorganism sensitivity, patient compliance, infectious disease consultation, and the surgeons experience. A suppressive antibiotic regimen should be directed by the results of cultures. Standard operative treatment is not feasible for all patients because of the functional impairment caused by the disease, the reconstructive operations, and the metabolic consequences of an aggressive therapy regimen. Operative treatment includes debridement, obliteration of dead space, restoration of blood supply, adequate soft-tissue coverage, stabilization, and reconstruction.

In vitro and in vivo evaluation of antibiotic diffusion from antibiotic-impregnated polymethylmethacrylate beads

The elution of antibiotics from antibiotic-impregnated polymethylmethacrylate (PMMA) beads was measured in mongrel dogs. The antibiotics, used in mixture with Simplex cement, included cefazolin (Ancef; 4.5 g/40 g cement powder), ciprofloxacin (Cipro; 6 g/40 g powder), clindamycin (Cleocin; 6 g/40 g powder), ticarcillin (Ticar; 12 g/40 g powder), tobramycin (Nebcin; 9.8 g/40 g powder), and vancomycin (Vancocin; 4 g/40 g powder). After a pneumatic drill was used to dredge a trough in the tibia, five beads were implanted. During the next 28 days, seroma samples and serum samples were taken for antibiotic measurements. On Day 28, the dogs were killed, beads removed, and the seroma, serum, bone, and granulation tissue sampled. The results of the study showed that clindamycin, vancomycin, and tobramycin exhibited good elution characteristics and had consistently high levels in bone and granulation tissue.

Diagnosis and treatment of diabetic foot infections

Executive Summary: 1. Foot infections in patients with diabetes cause substantial morbidity and frequent visits to health care professionals and may lead to amputation of a lower extremity. 2. Diabetic foot infections require attention to local (foot) and systemic (metabolic) issues and coordinated management, preferably by a multidisciplinary foot-care team (A-II) (Table 1). The team managing these infections should include, or have ready access to, an infectious diseases specialist or a medical microbiologist (B-II). 3. The major predisposing factor to these infections is foot ulceration, which is usually related to peripheral neuropathy. Peripheral vascular disease and various immunological disturbances play a secondary role. 4. Aerobic Gram-positive cocci (especially Staphylococcus aureus) are the predominant pathogens in diabetic foot infections. Patients who have chronic wounds or who have recently received antibiotic therapy may also be infected with Gram-negative rods, and those with foot ischemia or gangrene may have obligate anaerobic pathogens. 5. Wound infections must be diagnosed clinically on the basis of local (and occasionally systemic) signs and symptoms of inflammation. Laboratory (including microbiological) investigations are of limited use for diagnosing infection, except in cases of osteomyelitis (B-II). 6. Send appropriately obtained specimens for culture before starting empirical antibiotic therapy in all cases of infection, except perhaps those that are mild and previously untreated (B-III). Tissue specimens obtained by biopsy, ulcer curettage, or aspiration are preferable to wound swab specimens (A-I). 7. Imaging studies may help diagnose or better define deep, soft-tissue purulent collections and are usually needed to detect pathological findings in bone. Plain radiography may be adequate in many cases, but MRI (in preference to isotope scanning) is more sensitive and specific, especially for detection of soft-tissue lesions (A-I). 8. Infections should be categorized by their severity on the basis of readily assessable clinical and laboratory features (B-II). Most important among these are the specific tissues involved, the adequacy of arterial perfusion, and the presence of systemic toxicity or metabolic instability. Categorization helps determine the degree of risk to the patient and the limb and, thus, the urgency and venue of management. 9. Available evidence does not support treating clinically uninfected ulcers with antibiotic therapy (D-III). Antibiotic therapy is necessary for virtually all infected wounds, but it is often insufficient without appropriate wound care. 10. Select an empirical antibiotic regimen on the basis of the severity of the infection and the likely etiologic agent(s) (B-II). Therapy aimed solely at aerobic Gram-positive cocci may be sufficient for mild-to-moderate infections in patients who have not recently received antibiotic therapy (A-II). Broad-spectrum empirical therapy is not routinely required but is indicated for severe infections, pending culture results and antibiotic susceptibility data (B-III). Take into consideration any recent antibiotic therapy and local antibiotic susceptibility data, especially the prevalence of methicillin-resistant S. aureus (MRSA) or other resistant organisms. Definitive therapy should be based on both the culture results and susceptibility data and the clinical response to the empirical regimen (C-III). 11. There is only limited evidence with which to make informed choices among the various topical, oral, and parenteral antibiotic agents. Virtually all severe and some moderate infections require parenteral therapy, at least initially (C-III). Highly bioavailable oral antibiotics can be used in most mild and in many moderate infections, including some cases of osteomyelitis (A-II). Topical therapy may be used for some mild superficial infections (B-I). 12. Continue antibiotic therapy until there is evidence that the infection has resolved but not necessarily until a wound has healed. Suggestions for the duration of antibiotic therapy are as follows: for mild infections, 12 weeks usually suffices, but some require an additional 12 weeks; for moderate and severe infections, usually 24 weeks is sufficient, depending on the structures involved, the adequacy of debridement, the type of soft-tissue wound cover, and wound vascularity (A-II); and for osteomyelitis, generally at least 46 weeks is required, but a shorter duration is sufficient if the entire infected bone is removed, and probably a longer duration is needed if infected bone remains (B-II). 13. If an infection in a clinically stable patient fails to respond to 1 antibiotic courses, consider discontinuing all antimicrobials and, after a few days, obtaining optimal culture specimens (C-III). 14. Seek surgical consultation and, when needed, intervention for infections accompanied by a deep abscess, extensive bone or joint involvement, crepitus, substantial necrosis or gangrene, or necrotizing fasciitis (A-II). Evaluating the limb’s arterial supply and revascularizing when indicated are particularly important. Surgeons with experience and interest in the field should be recruited by the foot-care team, if possible. 15. Providing optimal wound care, in addition to appropriate antibiotic treatment of the infection, is crucial for healing (A-I). This includes proper wound cleansing, debridement of any callus and necrotic tissue, and, especially, off-loading of pressure. There is insufficient evidence to recommend use of a specific wound dressing or any type of wound healing agents or products for infected foot wounds. 16. Patients with infected wounds require early and careful follow-up observation to ensure that the selected medical and surgical treatment regimens have been appropriate and effective (B-III). 17. Studies have not adequately defined the role of most adjunctive therapies for diabetic foot infections, but systematic reviews suggest that granulocyte colony-stimulating factors and systemic hyperbaric oxygen therapy may help prevent amputations (B-I). These treatments may be useful for severe infections or for those that have not adequately responded to therapy, despite correcting for all amenable local and systemic adverse factors. 18. Spread of infection to bone (osteitis or osteomyelitis) may be difficult to distinguish from noninfectious osteoarthropathy. Clinical examination and imaging tests may suffice, but bone biopsy is valuable for establishing the diagnosis of osteomyelitis, for defining the pathogenic organism(s), and for determining the antibiotic susceptibilities of such organisms (B-II). 19. Although this field has matured, further research is much needed. The committee especially recommends that adequately powered prospective studies be undertaken to elucidate and validate systems for classifying infection, diagnosing osteomyelitis, defining optimal antibiotic regimens in various situations, and clarifying the role of surgery in treating osteomyelitis (A-III). Table 1. Infectious Diseases Society of America–United States Public Health Service Grading System for Ranking Recommendations in Clinical Guidelines

The predictive value of transcutaneous oxygen tension measurement in diabetic lower extremity ulcers treated with hyperbaric oxygen therapy: a retrospective analysis of 1144 patients

The objective of this retrospective analysis was to determine the reliability of transcutaneous oxygen tension measurement (TcPO2) in predicting outcomes of diabetics who underwent hyperbaric oxygen therapy for lower extremity wounds. Six hyperbaric facilities provided TcPO2 data under several possible conditions: breathing air, breathing oxygen at sea level, and breathing oxygen in the chamber. Overall, 75.6% of the patients improved after hyperbaric oxygen therapy. Baseline sea‐level air TcPO2 identified the degree of tissue hypoxia but had little statistical relationship with outcome prediction because some patients healed after hyperbaric oxygen therapy despite very low prehyperbaric TcPO2 values. Breathing oxygen at sea level was unreliable for predicting failure, but 68% reliable for predicting success after hyperbaric oxygen therapy. TcPO2 measured in chamber provides the best single discriminator between success and failure of hyperbaric oxygen therapy using a cutoff score of 200 mmHg. The reliability of in‐chamber TcPO2 as an isolated measure was 74% with a positive predictive value of 58%. Better results can be obtained by combining information about sea‐level air and in‐chamber oxygen. A sea‐level air TcPO2 < 15 mmHg combined with an in‐chamber TcPO2 < 400 mmHg predicts failure of hyperbaric oxygen therapy with a reliability of 75.8% and a positive predictive value of 73.3%. (WOUND REP REG 2002;10:198–207)

Molecular interactions in biofilms.

A biofilm may be defined as a microbially derived, sessile community characterized by cells that attach to an interface, embed in a matrix of exopolysaccharide, and demonstrate an altered phenotype. This review covers the current understanding of the nature of biofilms and the impact that molecular interactions may have on biofilm development and phenotype using the motile gram-negative rod Pseudomonas aeruginosa and the nonmotile gram-positive cocci Staphylococcus aureus as examples.

Treatment of osteomyelitis with a biodegradable antibiotic implant

A biodegradable antibiotic implant was developed and evaluated in a localized osteomyelitic rabbit model. The biodegradable antibiotic implant was made of polylactic acid and poly(DL-lactide):co-glycolide combined with vancomycin. Localized rabbit tibial osteomyelitis was developed with Staphylococcus aureus. Infected rabbits were divided into eight groups, depending on treatment with or without debridement, systemic antibiotics, or biodegradable beads. After 4 weeks of therapy, the radiographs were obtained of the involved bones, which also were cultured for concentrations of Staphylococcus aureus per gram of bone. Treatment with antibiotic containing polylactic acid and poly(DL-lactide):co-glycolide beads, with and without systemic vancomycin, resulted in bone colony forming unit levels of 102.93 and 102.84 colony forming units per gram bone, respectively. These bacterial concentrations were approximately 100 times lower than those observed for all other treatment groups. A biodegradable antibiotic bead may provide extended bactericidal concentrations of antibiotics for the time needed to completely treat the particular orthopaedic infection and does not require the surgery needed to remove the polymethylmethacrylate beads.