You are in: eMedicine Specialties > Infectious Diseases > MEDICAL TOPICS Diabetic Foot InfectionsArticle Last Updated: Jun 23, 2008AUTHOR AND EDITOR INFORMATIONAuthor: Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital Burke A Cunha is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America Editors: Charles S Levy, MD, Associate Professor, Department of Medicine, Section of Infectious Disease, George Washington University School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Richard B Brown, MD, FACP, Chief, Division of Infectious Diseases, Baystate Medical Center; Professor, Department of Internal Medicine, Tufts University School of Medicine; Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital; Michael Stuart Bronze, MD, Professor, Stewart G Wolf Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center Author and Editor Disclosure Synonyms and related keywords: diabetic foot infections, diabetic foot infection, diabetes-related foot infection, diabetes foot infection, fetid foot, diabetes, diabetes mellitus, foot infections, cellulitis, osteomyelitis, microvascular disease, group A streptococci, group B streptococci, Streptococcus, Staphylococcus aureus, S aureus, staph infection, chronic osteomyelitis INTRODUCTIONBackgroundFoot infections are the most common problems in persons with diabetes. These individuals are predisposed to foot infections because of a compromised vascular supply secondary to diabetes. Local trauma and/or pressure (often in association with lack of sensation because of neuropathy), in addition to microvascular disease, may result in various diabetic foot infections. For additional information, see Medscape’s Diabetic Microvascular Complications Resource Center. The spectrum of foot infections in diabetes ranges from simple superficial cellulitis to chronic osteomyelitis. Infections in patients with diabetes are difficult to treat because these patients have impaired microvascular circulation, which limits the access of phagocytic cells to the infected area and results in a poor concentration of antibiotics in the infected tissues. For this reason, cellulitis is the most easily treatable and reversible form of foot infections in patients with diabetes. Deep skin and soft tissue infections are also usually curable, but they can be life threatening and result in substantial long-term morbidity. In terms of the infecting microorganisms and the likelihood of successful treatment with antimicrobial therapy, acute osteomyelitis in people with diabetes is essentially the same as in those without diabetes. Chronic osteomyelitis in patients with diabetes mellitus is the most difficult infection to cure. Adequate surgical debridement, in addition to antimicrobial therapy, is necessary to cure chronic osteomyelitis. Patients with diabetes also can have a combined infection involving bone and soft tissue called fetid foot. This extensive, chronic soft tissue and bone infection causes a foul exudate and usually requires extensive surgical debridement and/or amputation. Individuals with diabetes may also have peripheral vascular disease that involves the large vessels, in addition to microvascular and capillary disease that results in peripheral vascular disease with gangrene. Dry gangrene is usually managed with expectant care, and gross infection is usually not present. Wet gangrene usually has an infectious component and requires surgical debridement and/or antimicrobial therapy to control the infection. Except for chronic osteomyelitis, infections in patients with diabetes are caused by the same microorganisms that can infect the extremities of those without diabetes. Gas gangrene is conspicuous because of its low incidence in patients with diabetes, but deep skin and soft tissue infections, which are due to gas-producing organisms, frequently occur in patients with diabetes. In general, people with diabetes have infections that are more severe and take longer to cure than equivalent infections in other people. PathophysiologyDiabetes mellitus is a disorder that primarily affects the microvascular circulation. In the extremities, microvascular disease due to "sugar-coated capillaries" limits the blood supply to the superficial and deep structures. Pressure due to ill-fitting shoes or trauma further compromises the local blood supply at the microvascular level, predisposing the patient to infection. The infection may involve the skin, soft tissues, bone, or all of these tissues. Diabetes also accelerates macrovascular disease, which is evident clinically as accelerating atherosclerosis and/or peripheral vascular disease. Most diabetic foot infections occur in the setting of good dorsalis pedis pulses; this finding indicates that the primary problem in diabetic foot infections is microvascular compromise. Impaired microvascular circulation hinders white cell migration into the area of infection and limits the ability of antibiotics to reach the site of infection in an effective concentration. Diabetic neuropathy may be encountered in conjunction with vasculopathy. This may allow for incidental trauma that goes unrecognized (eg, blistering, penetrating foreign body). In chronic osteomyelitis, a sequestrum and involucrum form; these represent islands of infected bone. Bone fragments that are isolated have no blood supply. Administered antibiotics do not penetrate the devascularized infected bone fragments; they can enter the area of osteomyelitis only via the remaining blood supply. Therefore, antibiotic therapy alone cannot cure patients with chronic osteomyelitis without surgical debridement to remove these isolated infected elements. Surgical debridement is essential to remove the infected bony fragments that the antibiotics cannot reach so that affected areas can be treated with antimicrobial therapy. FrequencyInternationalDiabetic foot infections range from cellulitis to chronic osteomyelitis, and, globally, they are the most common skeletal and soft tissue infections in patients with diabetes. Mortality/MorbidityMortality is not common, except in unusual circumstances. The mortality risk is highest in patients with chronic osteomyelitis and in those with acute necrotizing soft tissue infections. RaceThe incidence of diabetic foot infections is similar to that of diabetes in various ethnic groups. SexNo important sex differences exist. AgeDiabetic foot infections most frequently affect elderly patients. CLINICALHistoryPatients may or may not have a history of trauma or previous infection. PhysicalFindings after physical examination may include the following:
CausesThe microbiologic features of diabetic foot infections vary according to the tissue infected.
DIFFERENTIALS
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| Drug Name | Meropenem (Merrem) |
|---|---|
| Description | Bactericidal broad-spectrum carbapenem antibiotic that inhibits cell-wall synthesis. Effective against most gram-positive and gram-negative bacteria. Has slightly increased activity against gram-negative species and slightly decreased activity against staphylococci and streptococci compared with imipenem. Structurally similar to beta-lactam antibiotics, but not related to beta-lactam drugs in terms of hypersensitivity. Carbapenems and monobactams do not cross-react in patients who are allergic to penicillin, even those who have an anaphylactic reaction to penicillin. |
| Adult Dose | 1 g IV q8h |
| Pediatric Dose | 40 mg/kg IV q8h |
| Contraindications | Documented hypersensitivity |
| Interactions | Probenecid may inhibit renal excretion, increasing levels |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | Pseudomembranous colitis and thrombocytopenia (immediately discontinue) |
| Drug Name | Ampicillin and sulbactam (Unasyn) |
|---|---|
| Description | Drug combination of a beta-lactamase inhibitor with ampicillin. Covers skin, enteric flora, and anaerobes. Not ideal for nosocomial pathogens. |
| Adult Dose | 1.5-3 g (1 g ampicillin and 0.5 g sulbactam to 2 g ampicillin and 1 g sulbactam) IV q6h; not to exceed 4 g/d sulbactam or 8 g/d ampicillin |
| Pediatric Dose | <3 months: Not established 3 months to 12 years: 100-200 mg ampicillin/kg/d (150-300 mg Unasyn) IV divided q6h >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Probenecid and disulfiram elevate ampicillin levels; allopurinol decreases ampicillin effects and has additive effect on ampicillin rash; may decrease effect of oral contraceptives |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | Adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction |
| Drug Name | Piperacillin and tazobactam (Zosyn) |
|---|---|
| Description | Antipseudomonal penicillin plus a beta-lactamase inhibitor. Inhibits biosynthesis of cell wall mucopeptide and is effective during the active multiplication stage. |
| Adult Dose | 4 g IV q8h |
| Pediatric Dose | 75 mg/kg IV q6h |
| Contraindications | Documented hypersensitivity; do not use oral penicillin in severe pneumonia, bacteremia, pericarditis, emphysema, meningitis, and purulent or septic arthritis during the acute stage |
| Interactions | Tetracyclines may decrease piperacillin effects; high concentrations of piperacillin may physically inactivate aminoglycosides if administered in the same IV line; synergistic effects with concurrent aminoglycosides; probenecid may increase penicillin levels; high-dose parenteral penicillins may increase risk of bleeding |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | Assess CBC count before therapy and at least weekly during therapy; during therapy, monitor AST and ALT for liver function abnormality; caution in hepatic insufficiency; perform urinalysis and determine BUN and creatinine levels during therapy (adjust dose if elevated); monitor blood levels (possible neurotoxic reaction) |
| Drug Name | Cefazolin (Kefzol, Ancef, Zolicef) |
|---|---|
| Description | First-generation semisynthetic cephalosporin that arrests bacterial cell-wall synthesis, inhibiting bacterial growth. Primarily active against skin flora, including S aureus. Typically used alone for skin and skin-structure coverage. IV/IM dosing regimens are similar |
| Adult Dose | 1 g IV q8h |
| Pediatric Dose | 25-100 mg/kg/d IV/IM divided q6-8h depending on severity of infection; not to exceed 6 g/d |
| Contraindications | Documented hypersensitivity |
| Interactions | Probenecid prolongs effect; coadministration with aminoglycosides may increase renal toxicity; may yield false-positive urine-dip results for glucose |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | Adjust dose in severe renal insufficiency (high doses may cause CNS toxicity); superinfections and promotion of nonsusceptible organisms may occur with prolonged or repeated therapy |
| Drug Name | Clindamycin (Cleocin) |
|---|---|
| Description | Lincosamide for the treatment of serious skin and soft tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci, except enterococci. Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, arresting RNA-dependent protein synthesis. |
| Adult Dose | 150-300 mg/dose PO q8h; not to exceed 1.8 g/d Up to 900 mg IV q8h depending on degree of infection |
| Pediatric Dose | 8-20 mg/kg/d PO as hydrochloride or 8-25 mg/kg/d as palmitate divided tid/qid 20-40 mg/kg/d IV/IM divided tid/qid |
| Contraindications | Documented hypersensitivity; regional enteritis, ulcerative colitis, hepatic impairment, and antibiotic-associated colitis |
| Interactions | Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects; antidiarrheals may delay absorption |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis by allowing overgrowth of Clostridium difficile |
| Drug Name | Levofloxacin (Levaquin) |
|---|---|
| Description | Used to treat complicated and uncomplicated skin and skin structure infections. Fluoroquinolones should be used empirically in patients likely to develop exacerbation due to resistant organisms to other antibiotics. This is the L stereoisomer of the D/L parent compound ofloxacin, the D form being inactive. Good monotherapy with extended coverage against Pseudomonas species, as well as excellent activity against pneumococci. Agent acts by inhibition of DNA gyrase activity. PO form has bioavailability that reportedly is 99%. |
| Adult Dose | 500 mg PO/IV q24h |
| Pediatric Dose | <18 years: Not recommended >18 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after fluoroquinolone use; cimetidine may interfere with metabolism of fluoroquinolones; reduces therapeutic effects of phenytoin; probenecid may increase serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT) |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus |
| Precautions | Periodically evaluate organ (eg, renal, hepatic, hematopoietic) function in prolonged therapy; adjust dose in renal impairment; superinfections may occur with prolonged or repeated antibiotic therapy |
| Drug Name | Metronidazole (Flagyl, Protostat) |
|---|---|
| Description | Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. Used in combination with other antimicrobial agents. Not used for C difficile enterocolitis. |
| Adult Dose | 1 g IV q24h or 250-500 mg PO q6-8h |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | May increase toxicity of anticoagulants, lithium, and phenytoin; cimetidine may increase toxicity; disulfiram reaction possible with alcohol ingestion |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | Adjust dose in hepatic disease; monitor for seizures and peripheral neuropathy |
| Drug Name | Nafcillin (Unipen, Nafcil, Nallpen) |
|---|---|
| Description | Initial therapy for suspected penicillin G–resistant streptococcal or staphylococcal infections. Initially, use parenteral therapy in severe infections; change to PO therapy as condition warrants. Because of thrombophlebitis, particularly in elderly patients, use parenteral administration only for a short term (1-2 d); change to PO route as clinically indicated. |
| Adult Dose | 1-2 g IV q4h |
| Pediatric Dose | <4 kg (neonates): 10 mg/kg IM bid 4-40 kg: 25 mg/kg IM bid, 100-200 mg/kg/d IV/IM in 4-6 divided doses, or 50 mg/kg/d PO divided qid >40 kg: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Associated with warfarin resistance when administered concurrently; effects may decrease with bacteriostatic action of tetracycline derivatives |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | To optimize therapy, determine causative organisms and susceptibility; treatment is >10 d to eliminate infection and prevent sequelae (eg, endocarditis, rheumatic fever); obtain cultures after treatment to confirm that infection is eradicated |
| Drug Name | Moxifloxacin (Avelox) |
|---|---|
| Description | Inhibits A subunits of DNA gyrase, inhibiting bacterial DNA replication and transcription. |
| Adult Dose | 400 mg IV/PO qd |
| Pediatric Dose | <18 years: Not recommended >18 years: Administer as in adults |
| Contraindications | Documented hypersensitivity; Q-T prolongation or concurrent administration of drugs that cause Q-T prolongation |
| Interactions | Antacids and electrolyte supplements reduce absorption; loop diuretics, probenecid, and cimetidine increase serum levels; NSAIDs enhance CNS-stimulating effect; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT) |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus |
| Precautions | Periodically evaluate organ (eg, renal, hepatic, hematopoietic) function in prolonged therapy; adjust dose in renal impairment; superinfections may occur with prolonged or repeated antibiotic therapy; may induce seizures in CNS disorder |
| Drug Name | Tigecycline (Tygacil) |
|---|---|
| Description | A glycylcycline antibiotic that is structurally similar to tetracycline antibiotics. Inhibits bacterial protein translation by binding to 30S ribosomal subunit and blocks entry of amino-acyl tRNA molecules in ribosome A site. Indicated for complicated skin and skin structure infections caused by E coli, E faecalis (vancomycin-susceptible isolates only), S aureus (methicillin-susceptible and -resistant isolates), S agalactiae, S anginosus grp (includes S anginosus, S intermedius, S constellatus), S pyogenes, and B fragilis. |
| Adult Dose | Infuse each dose over 30-60 min 100 mg IV once, then 50 mg IV q12h Severe hepatic impairment (ie, Child Pugh class C): 100 mg IV once, then 25 mg IV q12h |
| Pediatric Dose | <18 years: Not established >18 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Coadministration decreases warfarin clearance and increases warfarin Cmax and AUC (monitor aPTT and INR); coadministration of antibiotics with oral contraceptives may decrease contraceptive effect |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Caution in severe hepatic impairment (reduce dose); may adversely effect tooth development; may permit clostridia overgrowth, resulting in antibiotic-associated colitis; may have adverse effects similar to tetracyclines (eg, photosensitivity, pseudotumor cerebri, pancreatitis, antianabolic action) |
| Drug Name | Ertapenem (Invanz) |
|---|---|
| Description | Bactericidal activity results from inhibition of cell wall synthesis and is mediated through ertapenem binding to penicillin binding proteins. Stable against hydrolysis by various beta-lactamases, including penicillinases, cephalosporinases, and extended spectrum beta-lactamases. Hydrolyzed by metallo-beta-lactamases. |
| Adult Dose | 1 g qd for 14 d if IV and 7 d if IM; infuse over 30 min if IV CrCl 30 mL/min/1.73 m2: 500 mg IV qd |
| Pediatric Dose | <3 months: Not established 3 months to 12 years: 15 mg/kg IV q12h; not to exceed 1 g/d >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity to drug or amide type anesthetics |
| Interactions | Probenecid may reduce renal clearance of ertapenem and increase half-life but benefit is minimum and does not justify coadministration |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | Pseudomembranous colitis may occur; seizures and CNS adverse reactions may occur; when using with lidocaine to administer intramuscularly, avoid inadvertent injection into blood vessel; decrease dose in renal failure; serious and occasionally fatal hypersensitivity reactions may occur with beta lactams, caution with previous hypersensitivity reactions to penicillin, cephalosporins, other beta lactams, or other allergens; do not mix or coinfuse in same IV line as other medications; do not mix with dextrose-containing diluents |
| Drug Name | Minocycline (Dynacin, Minocin) |
|---|---|
| Description | Treats infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible Chlamydia, Rickettsia, and Mycoplasma. |
| Adult Dose | 100 mg PO bid for 5-7 d |
| Pediatric Dose | <8 years: Not recommended >8 years: 4 mg/kg PO initially, followed with 2 mg/kg q12h |
| Contraindications | Documented hypersensitivity; severe hepatic dysfunction |
| Interactions | Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy; tetracyclines can increase hypoprothrombinemic effects of anticoagulants |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one-half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines; hepatitis or lupuslike syndromes may occur |
| Drug Name | Daptomycin (Cubicin) |
|---|---|
| Description | First of new antibiotic class called cyclic lipopeptides. Binds to bacterial membranes and causes rapid membrane potential depolarization, thereby inhibiting protein, DNA, and RNA synthesis, and ultimately causing cell death. Indicated to treat complicated skin and skin structure infections caused by S aureus (including methicillin-resistant strains), S pyogenes, S agalactiae, S dysgalactiae, and E faecalis (vancomycin-susceptible strains only). |
| Adult Dose | CrCl >30 mL/min: 4 mg/kg IV q24h infused over 30 min CrCl <30 mL/min: 4 mg/kg IV q48h (including hemodialysis or CAPD) |
| Pediatric Dose | <18 years: Not established >18 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Coadministration with tobramycin slightly increase daptomycin Cmax and AUC and decreases tobramycin Cmax and AUC; may experience additive effects with other drugs causing myopathy (eg, HMG CoA reductase inhibitors) |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | Decrease dose with renal function <30 mL/min; pseudomembranous colitis may occur; may cause muscle pain or weakness, monitor CPK levels and discontinue daptomycin with elevated CPK and unexplained myopathy, or marked CPK elevation (10-times upper limits of normal); not indicated for pneumonia (higher death rate in daptomycin-treated patients during phase III trials); not compatible with dextrose-containing solutions |
Diabetic Foot Infections excerpt
Article Last Updated: Jun 23, 2008