How To Choose Appropriate Antibiotics For Diabetic Foot Infections

By Guy Pupp, DPM, FACFAS, and Chad Westphal, DPM

   Diabetes is clearly an epidemic in this country. According to the most recent statistics from the Centers for Disease Control and Prevention, 18.2 million people in the United States have the disease and 1.3 million new cases are diagnosed each year. Foot infection is the most common reason for lower extremity amputation and leads to billions of dollars a year in hospitalization costs in this country alone.    Despite becoming almost commonplace, diabetic foot infections are often mismanaged, particularly with regard to antibiotics. The solution to this problem requires a strong knowledge of diagnostic essentials, culture techniques, common pathogenic isolates, and appropriate antibiotic selection and usage.1    Infection typically arises in patients with diabetes secondary to a neuropathic ulceration. Neuropathy causes disturbances in sensory, motor and autonomic function, leading to tissue breakdown from underlying foot pathology or trauma. Once the protective epidermal layer is violated, normal skin flora and environmental microorganisms are free to colonize in the underlying tissues. Depending on the patient’s vascular status, the proliferation and extension of bacteria into deeper tissues can be rapid and life threatening.2-5    Proper clinical evaluation of the diabetic foot is paramount. Upon the initial presentation of the patient with a diabetic ulceration, one must first examine the wound for local signs of infection including edema, warmth, surrounding erythema, ascending cellulitis, purulence, malodor, sinus tract formation, crepitation, depth of probe and pain. Clinicians should also check for systemic signs of infection including nausea, vomiting, fever, chills, tachycardia and malaise. However, keep in mind that systemic signs of infection rarely accompany diabetic foot infections.6    Following the initial clinical evaluation, assess the wound and infection severity. The initial visual inspection of the limb, the presence of local and systemic signs, and radiographic evaluation often provide all the information necessary to formulate a treatment regimen. The severity of the infection will dictate whether the patient needs oral or parenteral antibiotics, hospitalization or surgical intervention.

When Should You Culture A Wound?

   One of the greatest controversies in treating diabetic foot infections is when and how to culture a wound appropriately. Culturing a clinically uninfected wound is a mistake that many inexperienced physicians make and doing so can be worse than taking no culture at all. This mistake can lead to the prescribing of an unnecessary, often broad spectrum antibiotic for organisms that are simply contaminants or colonizers. Poor clinical judgment such as this is helping to fuel the rising prevalence of antibiotic resistant organisms such as methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococci (VRE).7    A culture will identify the underlying pathogens but only if one collects the specimens properly. A common mistake that clinicians make is swabbing the surface of a superficial ulceration without prior wound cleansing or debridement. This results in a mixed flora that significantly lowers the culture’s sensitivity. A deep tissue culture from the base of a cleansed and thoroughly debrided ulceration provides the most accurate results. A bone biopsy can diagnose osteomyelitis if there is clinically exposed bone. Clinicians can send collected specimens to a lab for aerobic, anaerobic, acid fast and fungal culture, and sensitivity evaluation.8    Culture and sensitivity results will provide valuable information for treating the diabetic foot infection but one must target the isolates appropriately. For example, if Staphylococcus aureus is the predominant organism cultured along with a few obligate Gram-negative aerobes, then one can treat the Staph alone with predictably good results. One can also effectively use a broad spectrum antibiotic to treat this type of infection. However, this is often overkill and can lead to resistant strains. However, if one is treating the infection effectively with a broad spectrum empiric antibiotic with noted improvement in local and systemic symptoms, continue this therapy regardless of what the sensitivity results show.8-10

Differentiating Between Organisms That Cause Acute And Chronic Infections

   The most common microorganisms that colonize and cause acute wound infection are aerobic gram-positive cocci, particularly Staphylococcus aureus and group B Streptococcus. Wounds that have only been infected for a short period of time also tend to be monomicrobial.11-15 Chronically infected wounds, on the other hand, often result from aerobic gram-negative rods and anaerobes. They also tend to be polymicrobial with an average of three to five isolates. However, organisms such as Enterococci, coagulase-negative Staphylococci and Corynebacteria are less virulent isolates and one can ignore them and target antibiotics toward more virulent pathogens.9,10,16,17    Note that extended hospital stays and prolonged or broad spectrum antibiotic usage are the leading causes of infections with antibiotic-resistant organisms such as MRSA and VRE.7    The clinician must also be knowledgeable of the most common pathogens in his or her particular geographic area. Having an insight into what pathogens one is most likely to encounter will greatly enhance empiric therapy. For example, in our particular area, the Detroit Medical Center Update recently published the fact that three-quarters of inpatients with diabetic staphylococcal infections turned out to have MRSA. Therefore, when a complex diabetic foot infection occurs in a patient with a long-standing history of similar infections, we automatically assume MRSA and treat it accordingly.    Published clinical trials and research studies also provide great insight into the treatment of diabetic foot infections. The SIDESTEP study, which was published last year, was the study of ertapenem (Invanz, Merck) versus pipercillin/tazobactam in almost 600 patients with diabetic foot infections. This randomized, double-blinded, multicenter trial provided very valuable insight into bacterial isolates and antibiotic therapy in diabetic foot infections.18    Diabetic foot infections are typically described as being polymicrobial consisting of aerobic gram positive, aerobic gram negative and anaerobic organisms. The SIDESTEP study showed that MRSA was isolated in about 8 percent of patients, Pseudomonas in 6 percent and Enterococcus accounted for about 2 percent of isolated organisms. This study also showed that ertapenem was as successful an antibiotic for treating diabetic foot infections as one of the most widely used agents on the market.18

Key Factors To Consider When Prescribing Antibiotics

   Appropriate antibiotic therapy involves decisions about mode of administration, organisms that need to be covered, the drug to be used and its duration. Initial antibiotic therapy is empirical and one should base this on the severity of the infection and the most likely organisms to be involved.    Clinicians can usually treat minor infections effectively with a narrow-spectrum antibiotic focusing on Staphylococcus aureus and group B Streptococcus.8 With more severe infections, one should initially treat them with a broad spectrum antibiotic, ensuring coverage of aerobic gram positive cocci (including MRSA), aerobic gram negatives and anaerobes.10-17 There is very little clinical data to suggest that clinicians can effectively treat diabetic foot infections with any form of topical antibiotic.19    Antibiotics vary greatly in the serum and tissue levels they achieve in diabetic foot infections.20-23 These levels depend on the pharmacokinetics and dynamics of the particular drug and, more importantly, the pedal arterial perfusion.24,25 Peripheral arterial disease (PAD) is often overlooked not only as a major component in non-healing diabetic ulcerations but also in the inability to effectively achieve adequate tissue levels of antibiotic to decrease the bioburden of bacteria to less than 100,000 organisms per gram of tissue.26    It is our opinion that tissue penetration levels of antibiotics in PAD patients with palpable pulses are often significantly reduced due to a lack of direct arterial flow and secondary collateral runoff. Our clinic has a PAD screening and assessment program that screens every new and existing patient. We assess all possible risk factors including: smoking history, diabetes, coronary artery disease, high cholesterol, previous stroke, hypertension, age >50 and BMI >30.    When patients have significant risk factors and clinical findings suggestive of PAD, they receive arterial Dopplers and ankle brachial indexes (ABI). If these exams are positive for PAD, proximal arterial runoff and atherectomy are warranted. Since implementing our PAD screening program, we have seen a significant decrease in wound healing time and suspect increased tissue penetration levels of antibiotics.    One must also address patient compliance with the selected antibiotic therapy. Prior to initiating a treatment regimen, one must consider insurance coverage of the selected antibiotic, the long-term cost to the patient, route of administration and the number of times per day it will need to be taken. Considering these issues can help ensure patient compliance and efficacy of treatment.

Case Study: When A Patient With Diabetes Has MRSA

   A 52-year-old woman presented to our clinic and was referred by another DPM. She had a full thickness ulceration on her right plantar medial foot. She had been receiving podiatric care for more than two years and was not responding to traditional wound care. The patient had a chronic, gradual onset of a bilateral foot deformity with a subsequent non-healing ulcer on the midfoot.    The patient’s past medical history revealed morbid obesity, non-insulin dependent diabetes and bilateral Charcot neuroarthropathy. She denied tobacco use. She was taking penicillin, erythromycin, tetracycline, vancomycin, Allegra, Benadryl, Vicodin and aspirin.    The midfoot ulceration measured 7 cm x 4 cm x 0.2 cm, did not probe to bone and featured no drainage or malodor. Periwound erythema was localized to 2 cm around the wound margin. She had no ascending cellulitis. She had palpable pedal pulses and biphasic Doppler waveforms. The patient’s protective sensation, measured by a Semmes Weinstein 5.07 monofilament, was absent.    The physical exam revealed the patient had decreased range of motion in her ankle and subtalar joint. She had undergone amputation of the left fourth pedal digit and had midfoot collapse with a medial talar prominence. She had a pantalar Charcot deformity with complete medial talar dislocation and questionable osteomyelitis.    For her first surgery, the woman underwent a talectomy and ulcer excision with secondary healing. She received vancomycin-impregnated polymethyl-methacrylate (PMMA) beads and a below-knee, non-weightbearing cast. Postoperatively, she was negative for osteomyelitis but intraoperative deep tissue cultures revealed MRSA.    For the second surgery, we removed the PMMA beads. We performed an Achilles tenotomy, a tibial-calcaneal fusion and a tibial-navicular fusion with application of an Ilizarov circular ring frame.    For the third surgery, we removed external fixation and provided four applications of Dermagraft (Advanced BioHealing). The patient received a below-knee non-weightbearing cast and a bone stimulator. We transitioned her to a weightbearing cast. She now bears weight in an AFO.

In Summary

   Diabetic foot infections typically arise secondary to neuropathic ulceration. Recognizing the signs and symptoms of diabetic foot infection is of key importance.    There is no need to culture clinically uninfected wounds. Deep tissue cultures from a cleansed, debrided wound provide the most accurate results. Culture and sensitivity results will help guide antibiotic therapy. Knowledge and predictability of microorganisms will assist in empiric therapy. Peripheral arterial disease plays a major role in wound healing and infection.    One should treat minor infections with narrow spectrum antibiotics while treating severe infections with the broad spectrum antibiotics. It is important to stay current with clinical trial and research results regarding diabetic foot infections. One should always tailor treatment for such infections to the individual patient. Dr. Pupp is a Fellow of the American College of Foot and Ankle Surgeons. He is the Clinical Director of the Foot and Ankle Clinic at Southeast Michigan Surgical Hospital in Warren, Mich. Dr. Westphal is a third-year and chief surgical resident at Southeast Michigan Surgical Hospital in Warren, Mich.



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