IWGDF Infection Guideline PDF

IWGDF Infection Guideline Table 1. The classification system for defining the presence and severity of an infection of the foot in a person with diabetes Clinical classification of infection, with definitions IWGDF classification Uninfected No systemic or loc...

IWGDF Infection Guideline Table 1. The classification system for defining the presence and severity of an infection of the foot in a person with diabetes Clinical classification of infection, with definitions IWGDF classification Uninfected No systemic or local symptoms or signs of infection 1 (uninfected) Infected At least two of these items are present: § Local swelling or induration § Erythema >0.5 cm* around the wound § Local tenderness or pain § Local increased warmth § Purulent discharge And no other cause(s) of an inflammatory response of the skin (e.g. trauma, gout, acute Charcot neuro-osteoarthropathy, fracture, thrombosis or venous stasis) Infection with no systemic manifestations (see below) involving 2 (mild infection) § only the skin or subcutaneous tissue (not any deeper tissues), and § any erythema present does not extend >2 cm** around the wound Infection with no systemic manifestations, and involving: 3 (moderate infection) § erythema extending ≥2 cm* from the wound margin, and/or § tissue deeper than skin and subcutaneous tissues (e.g. tendon, muscle, joint, bone,) Any foot infection with associated systemic manifestations (of the 4 (severe infection) systemic inflammatory response syndrome [SIRS]), as manifested by ≥2 of the following: § Temperature >38 °C or 90 beats/minute § Respiratory rate >20 breaths/minute or PaCO2 12,000/mm3, or 10% immature (band) forms Infection involving bone (osteomyelitis) Add “(O)” after 3 or 4*** Note: * Infection refers to any part of the foot, not just of a wound or an ulcer; ** In any direction, from the rim of the wound. The presence of clinically significant foot ischemia makes both diagnosis and treatment of infection considerably more difficult; *** If osteomyelitis is demonstrated in the absence of ≥2 signs/symptoms of local or systemic inflammation, classify the foot as either grade 3(O) (if 2 cm), distant from ulceration or rapidly progressive (including lymphangitis) Local signs/symptoms Severe inflammation or induration, crepitus, bullae, discoloration, necrosis or gangrene, ecchymoses or petechiae and new anesthesia or localized pain General Presentation Acute onset/worsening or rapidly progressive Systemic signs Fever, chills, hypotension, confusion and volume depletion Laboratory tests Leukocytosis, highly elevated C-reactive protein or erythrocyte sedimentation rate, severe or worsening hyperglycemia, acidosis, new/worsening azotemia and electrolyte abnormalities Complicating features Presence of a foreign body (accidentally or surgically implanted), puncture wound, deep abscess, arterial or venous insufficiency, lymphedema, immunosuppressive illness or treatment, acute kidney injury Failing treatment Progression while on apparently appropriate antibiotic and supportive therapy B – Some Factors suggesting hospitalization may be necessary Severe infection (see findings suggesting a more serious diabetic foot infection above) Metabolic or hemodynamic instability Intravenous therapy needed (and not available/appropriate as an outpatient) Diagnostic tests needed that are not available as an outpatient Foot ischemia is present Surgical procedures (more than minor) required Failure of outpatient management Patient unable or unwilling to comply with outpatient-based treatment Need for more complex dressing changes than patient/caregivers can provide Need for careful, continuous observation PICO 2a: In a person with diabetes and a suspected foot infection, how well do the IWGDF/IDSA clinical criteria for diagnosing soft tissue infection correlate with other diagnostic tests? Recommendation 3: In a person with diabetes and a possible foot infection for whom the clinical examination is equivocal or uninterpretable, consider ordering an inflammatory serum biomarker, such as C-reactive protein, erythrocyte sedimentation rate and perhaps procalcitonin, as an adjunctive measure for establishing the diagnosis. (Weak; Low) Rationale: There are several diagnostic methods against which clinical examinations could be compared to evaluate their ability to assess the presence or severity of foot infection, or to differentiate soft tissue © 2019 The International Working Group on the Diabetic Foot IWGDF Guidelines IWGDF Infection Guideline Table 3. Features characteristic of diabetic foot osteomyelitis on plain X-rays 109-114 New or evolving radiographic features* on serial radiographs**, including: § Loss of bone cortex, with bony erosion or demineralization § Focal loss of trabecular pattern or marrow radiolucency (demineralization) § Periosteal reaction or elevation § Bone sclerosis, with or without erosion Abnormal soft tissue density in the subcutaneous fat, or gas density, extending from skin towards underlying bone, suggesting a deep ulcer or sinus tract. Presence of sequestrum: devitalized bone with radiodense appearance separated from normal bone Presence of involucrum*: layer of new bone growth outside previously existing bone resulting and originating from stripping off the periosteum. Presence of cloacae*: opening in the involucrum or cortex through which sequestrum or granulation tissue may discharge. Note: *Some features (e.g. sequestrum, involucrum and cloacae) are seen less frequently in diabetic foot osteomyelitis than in younger patients with osteomyelitis of larger bones. **Usually spaced several weeks apart. MICROBIOLOGY PICO 4: In a person with diabetes and a foot infection, do specimens of wound tissue (obtained by curettage or biopsy) provide more clinically useful information on growth of pathogens or avoidance of contaminants than wound swabs? Recommendation 8: a) Collect an appropriate specimen for culture for almost all clinically infected ulcers to determine the causative pathogens. (Strong; Low) b) For a soft tissue diabetic foot infection, obtain a sample for culture by aseptically collecting a tissue specimen (by curettage or biopsy) from the ulcer. (Strong; Moderate) Rationale: In the great majority of cases obtaining a specimen (after cleansing and debridement, avoiding contamination) for culture from a DFI provides useful information on the causative pathogen(s) and their antibiotic susceptibility, allowing appropriate selection of antibiotic therapy. In cases of an acute, non-severe DFI in a patient who has not recently received antibiotic therapy and has no other risk factors for unusual or antibiotic-resistant pathogens (e.g., based on specific exposures or previous culture results), selecting empiric therapy without culture may be reasonable. In most clinical situations it is easiest to collect a soft tissue specimen by superficial swab, but recent studies, including two systematic reviews115,116 (with low quality evidence), one small prospective study117 and one well- designed prospective study,118 have generally shown that the sensitivity and specificity of tissue specimens for culture results are higher than for swabs. Collecting a tissue specimen may require slightly more training and poses a slight risk of discomfort or bleeding, but we believe the benefits clearly outweigh these minimal risks. The evidence informing what method of specimen collection to use is limited by the absence of a definitive criterion standard for defining ulcer infection. Repeating cultures may be useful for a patient who is not responding to apparently appropriate therapy, but this may result © 2019 The International Working Group on the Diabetic Foot IWGDF Guidelines IWGDF Infection Guideline Similarly, laboratory personnel should offer clear information (when requested) on how to obtain optimal specimens and provide preliminary and final identifications as soon as practical. TREATMENT Figure 1. Suggested overview of a stepwise approach to managing a patient with diabetes and a suspected foot infection PICO 6: In a person with diabetes and a foot infection, is any particular antibiotic regimen (specific agent[s], route, duration) better than any other for treating soft tissue or bone infection? © 2019 The International Working Group on the Diabetic Foot IWGDF Guidelines IWGDF Infection Guideline SOFT TISSUE INFECTION Recommendation 10: Treat a person with a diabetic foot infection with an antibiotic agent that has been shown to be effective in a published randomized controlled trial and is appropriate for the individual patient. Some agents to consider include: penicillins, cephalosporins, carbapenems, metronidazole (in combination with other antibiotic[s]), clindamycin, linezolid, daptomycin, fluoroquinolones, or vancomycin, but not tigecycline. (Strong; High) Recommendation 11: Select an antibiotic agent for treating a diabetic foot infection based on: the likely or proven causative pathogen(s) and their antibiotic susceptibilities; the clinical severity of the infection; published evidence of efficacy of the agent for diabetic foot infections; risk of adverse events, including collateral damage to the commensal flora; likelihood of drug interactions; agent availability; and, financial costs. (Strong; Moderate) Recommendation 12: Administer antibiotic therapy initially by the parenteral route to any patient with a severe diabetic foot infection. Switch to oral therapy if the patient is clinically improving, has no contraindications to oral therapy and if there is an appropriate oral agent available. (Strong; Low) Recommendation 13: Treat patients with a mild diabetic foot infection, and most with a moderate diabetic foot infection, with oral antibiotic therapy, either at presentation or when clearly improving with initial intravenous therapy. (Weak; Low) Recommendation 14: We suggest not using any currently available topical antimicrobial agent for treating a mild diabetic foot infection. (Weak; Moderate) Rationale: Antibiotic therapy, administered by an appropriate route, is required in virtually all patients with a soft tissue DFI. For mild and most moderate infections treatment with well-absorbed oral antibiotic agents is generally effective. In patients with a more severe infection (some 3 and most 4), initial parenteral antibiotic therapy is preferable to achieve immediate high serum levels, but can usually be switched to oral therapy within a week. Based on many studies (most limited by methodological flaws) that compared various oral or parenteral antibiotic agents in patients with DFI, treatment with any appropriately selected agent of most classes of antibiotics is effective in the great majority of cases.125 Empiric therapy should be based on the clinician’s best guess at the likely causative pathogen(s) and their local antibiotic susceptibilities, along with a variety of other factors (e.g., history of drug allergies, recent hospitalization, patient co-morbidities [e.g., renal dialysis], likelihood of adverse events or potential drug interactions, availability and cost of various agents). In light of the complexity and often polymicrobial nature of DFI, definitive treatment should especially be based on principles of antibiotic stewardship (preferably selecting, when appropriate, a regimen with the narrowest spectrum, shortest duration, fewest adverse effects, safest and least expensive route). Wound culture results from a DFI are often polymicrobial; while virulent pathogens (e.g., Staphylococcus aureus or beta-hemolytic streptococci) that are isolated should be treated, some less virulent isolates (e.g., corynebacteria or coagulase-negative staphylococci) are often contaminants or colonizers that may not need targeted antibiotic treatment. © 2019 The International Working Group on the Diabetic Foot IWGDF Guidelines IWGDF Infection Guideline Some countries or institutions restrict the use of certain antibiotics (e.g., fluoroquinolones, rifampicin) for various reasons. In general, “first line” antibiotic choices are most often well-established agents while newer agents are often held in reserve for antibiotic-resistant pathogens. Clinicians should consider consulting an infectious diseases/microbiology expert about antibiotic therapy for difficult cases, such as those caused by unusual or highly resistant pathogens. Treatment with topical antimicrobial therapy has many theoretical advantages, particularly using a small dose only at the site of infection, thus potentially limiting issues of cost, adverse events and antibiotic resistance. Unfortunately, no published studies support treating either mild infections (with topical therapy alone) or moderate infections (with topical therapy adjunctive to systemic antibiotics).126 Specifically, recent large unpublished studies of topical therapy for a mild DFI with pexiganan (an antimicrobial peptide)127,128 or with the gentamicin-collagen sponge129 failed to demonstrate superiority to standard of care treatment alone. Similarly, a published trial of the gentamicin-collagen sponge for treating mild DFI130 or as adjunctive therapy (to systemic antibiotics) for moderate or severe DFI showed no benefit.131 No one antibiotic class or agent has been shown to be superior to others, but tigecycline was found to be clinically inferior to ertapenem (with or without added vancomycin) for treating soft tissue (and, in a small subset, bone) infections in a well-designed clinical trial of over 1000 patients.132 This study also showed that rates of adverse events were significantly higher in the tigecycline treated patients. A prospective observational study of 105 patients treated with tigecycline for DFI reported clinical success in only ~57% of patients with a moderate or severe infection, significantly lower cure rates in those with peripheral artery disease, and adverse treatment effects in 44%.133 Other studies have shown high failure rates with long-term treatment with tigecycline and it is associated with a high rate of nausea.134 Recent studies suggest that many (perhaps most) DFIs are caused by bacteria in a biofilm mode, although biofilm infection is difficult to diagnose clinically.135,136 Pathogens in biofilm, compared to planktonic, infections are more difficult to treat but some antibiotics (e.g., rifampicin, daptomycin, fosfomycin) appear to be more effective for biofilm infection than others.137,138 With appropriately selected antibiotic therapy (combined with any necessary surgery and proper metabolic control and wound care), most DFIs can treated be successfully with limited harms. Recommendation 15: a) Administer antibiotic therapy to a patient with a skin or soft tissue diabetic foot infection for a duration of 1 to 2 weeks. (Strong; High) b) Consider continuing treatment, perhaps for up to 3-4 weeks, if the infection is improving but is extensive, is resolving slower than expected, or if the patient has severe peripheral artery disease. (Weak; Low) c) If evidence of infection has not resolved after 4 weeks of apparently appropriate therapy, re-evaluate the patient and reconsider the need for further diagnostic studies or alternative treatments. (Strong; Low) Rationale: Principles of antimicrobial stewardship include limiting the duration of antibiotic therapy for treating wounds to the minimum number of days needed for good results.139,140 More prolonged antibiotic therapy is associated with increased risks of adverse events, greater disruption of host microbiomes, higher costs and more patient inconvenience. In published studies of DFIs, duration of © 2019 The International Working Group on the Diabetic Foot IWGDF Guidelines IWGDF Infection Guideline antibiotic therapy ranged from 5 to 28 days, but they do not provide any data upon which to recommend an optimal duration nor criteria for when stopping antibiotic therapy is appropriate.18 In most of these studies patients underwent any needed superficial or deep debridement of necrotic or purulent tissue and patients with severe peripheral artery disease were excluded.51,132,141,142 Based on expert opinion, minor soft tissue infections that resolve quickly can be treated with less than one week of antibiotic therapy, while extending antibiotic therapy to 2—4 weeks may be appropriate for some patients with extensive infection or when limb ischemia limits antibiotic delivery and ulcer healing. When apparently appropriate treatment for a DFI appears to be failing, rather than extending the course of antibiotic therapy the clinician should re-consider what therapy might be more appropriate. Key questions to ask (see Figure 1) include: were all likely pathogens covered by the selected antibiotic agent; are there new pathogens (perhaps related to intercurrent antibiotic treatment); was the antibiotic agent being administered/taken as prescribed (whether in hospital or ambulatory setting); could intestinal absorption be impaired; was the possibility of insufficient perfusion due to peripheral artery disease not addressed; could there be an undiagnosed abscess, foreign body, osteomyelitis or other complication that may require surgery? While the evidence for most of these suggestions is either low or limited, decades of clinical experience support our making these strong recommendations. Recommendation 16: For patients who have not recently received antibiotic therapy and who reside in a temperate climate area, target empiric antibiotic therapy at just aerobic gram-positive pathogens (beta- hemolytic streptococci and Staphylococcus aureus) in cases of a mild diabetic foot infection. (Strong; Low) Recommendation 17: For patients residing in a tropical/subtropical climate, or who have been treated with antibiotic therapy within a few weeks, have a severely ischemic affected limb, or a moderate or severe infection, we suggest selecting an empiric antibiotic regimen that covers gram-positive pathogens, commonly isolated gram-negative pathogens, and possibly obligate anaerobes in cases of moderate to severe diabetic foot infections. Then, reconsider the antibiotic regimen based on both the clinical response and culture and sensitivity results. (Weak; Low) Recommendation 18: Empiric treatment aimed at Pseudomonas aeruginosa is not usually necessary in temperate climates, but consider it if P. aeruginosa has been isolated from cultures of the affected site within the previous few weeks or in tropical/subtropical climates (at least for moderate or severe infection). (Weak; Low) Rationale: Initial antibiotic therapy for most patients with a DFI will be empiric; the goal is to cover the likely pathogens without prescribing an unnecessarily broad-spectrum regimen. Definitive therapy should then be tailored to the clinical response to empiric therapy and the results of properly collected specimens. For decades, studies (almost exclusively from temperate climates in North America and Europe) consistently demonstrated that the most common pathogens in DFIs are aerobic gram-positive cocci, especially S. aureus, and to a lesser extent streptococci and coagulase-negative staphylococci. More recent studies of DFIs from patients in tropical/subtropical climates (mainly Asia and northern Africa) have shown that aerobic gram-negative bacilli are often isolated, either alone or in combination with gram-positive cocci. These considerations, along with whether or not the patient has recently © 2019 The International Working Group on the Diabetic Foot IWGDF Guidelines IWGDF Infection Guideline received antibiotic therapy, has had gram-negative bacilli isolated from a recent previous culture, has had frequent exposure to water (a source for P. aeruginosa) or comes from an environment in which pathogens are often resistant to commonly used antibiotics, are key in selecting an empiric antibiotic regimen. Empiric treatment aimed at P. aeruginosa, which usually requires either an additional or broader-spectrum agent, is generally unnecessary in temperate climates. It should, however, be considered in tropical/subtropical climates or if P. aeruginosa has been isolated from previous cultures of the affected patient. Of course, clinicians should reassess the regimen based on the clinical response and culture and sensitivity results and consider changing to more appropriate, safer, more convenient, or less expensive agent(s). Obligate anaerobes can play a role in DFI, especially in ischemic limbs and in case of abscesses, 121,143 Empiric treatment of these pathogens, e.g. with an imidazole (metronidazole), or beta-lactam with beta lactamase inhibitor, should be considered for DFI associated with ischemia or a foul-smelling discharge. Some newer cephalosporins (combined with enzyme inhibitors) and fluoroquinolones have activity against most obligate anaerobes, which might preclude the need for combining them with anti-anaerobic agents. There are, however, insufficient published data recommend use of these agents to target anaerobes in diabetic foot infections. Table 4. Selecting an empiric antibiotic regimen for diabetic foot infections* Infection Additional factors Usual Potential empirical regimens b severity pathogen(s) a Mild No complicating GPC S-S pen; 1st gen ceph features ß-lactam allergy or GPC Clindamycin; FQ; T/S; macrolide; doxy intolerance Recent antibiotic GPC+GNR ß-L-ase-1; T/S; FQ exposure High risk for MRSA MRSA Linezolid; T/S; doxy; macrolide Moderate or No complicating GPC±GNR ß-L-ase 1; second/third gen ceph Severe c features Recent antibiotics GPC±GNR ß-L-ase 2; 3rd gen ceph; group 1 carbapenem (depends on prior therapy; seek advice) Macerated ulcer or GNR, including ß-L-ase 2; S-S pen + ceftazidime; S-S pen warm climate Pseudomonas + cipro; group 2 carbapenem Ischemic GPC±GNR± ß-L-ase 1 or 2; group 1 or 2 carbapenem; limb/necrosis/gas Anaerobes 2nd/3rd gen ceph + clindamycin or forming metronidazole MRSA risk factors MRSA Consider adding, or substituting with, glycopeptides; linezolid; daptomycin; fusidic acid T/S (±rif)**; doxycycline Risk factors for ESBL Carbapenems; FQ; aminoglycoside and resistant GNR colistin © 2019 The International Working Group on the Diabetic Foot IWGDF Guidelines