The Lower-Extremity Physician's Prescription for Effectively Treating Infection
The discovery of antibiotic drugs was one of the most significant medical achievements of the 20th century. The improper use of antibiotic drugs to prevent and treat infections has resulted in the emergence of resistance. Antimicrobic stewardship programs are becoming a mainstay in the fight against multidrug-resistant organisms. Individual clinicians should be encouraged to adopt the principles of antibiotic stewardship when treating lower-extremity infections in their scope of practice. First, a review of the available literature outlining the concept and practice of antibiotic stewardship is offered. Second, a discussion describing how to adopt and apply these principles to the individual clinician's practice as it applies to lower-extremity infections is offered. Finally, specific antimicrobial pharmacologic spectra and antibiogram information are offered.
Antibiotic Tissue Penetration in Diabetic Foot Infections
A Review of the Microdialysis Literature and Needs for Future Research
Although many antimicrobial agents display good in vitro activity against the pathogens frequently implicated in diabetic foot infections, effective treatment can be complicated by reduced tissue penetration in this population secondary to peripheral arterial disease and emerging antimicrobial resistance, which can result in clinical failure. Improved characterization of antibiotic tissue pharmacokinetics and penetration ratios in diabetic foot infections is needed. Microdialysis offers advantages over the skin blister and tissue homogenate studies historically used to define antibiotic penetration in skin and soft-tissue infections by defining antibiotic penetration into the interstitial fluid over the entire concentration versus time profile. However, only a select number of agents currently recommended for treating diabetic foot infections have been evaluated using these methods, which are described herein. Better characterization of the tissue penetration of antibiotic agents is needed for the development of methods for maximizing the pharmacodynamic profile of these agents to ultimately improve treatment outcomes for patients with diabetic foot infections.
Adverse reactions to antibiotics comprise a number of classes of reactions, including toxicity, side effects, and allergy. Each one of these differs in its implication for treatment of the patient. The authors discuss some of the more common and unusual reactions to antibiotics frequently used in the practice of podiatric medicine.
Lower-Extremity Osteomyelitis Treatment Using Calcium Sulfate/Hydroxyapatite Bone Void Filler with Antibiotics
Seven-Year Retrospective Study
Over a 74-month period (∼6 years), 143 lower-extremity osteomyelitis locations in 125 patients were treated with a calcium sulfate/hydroxyapatite liquid bone void filler with antibiotic(s).
The osteomyelitis locations were treated with a percutaneous antibiotic delivery technique delivering intraosseous antibiotic followed by either oral or intravenous antibiotics for 4 weeks.
There was no recurrence of osteomyelitis in 96.15% of the treatable patients. Outcomes classified by the Cierny-Mader clinical classification are discussed as well.
A bone void filler with antibiotic(s) using the percutaneous antibiotic delivery technique is a safe, reliable, and effective means to treat lower-extremity osteomyelitis with either oral or intravenous antibiotics for 4 weeks.
This study investigated the resistance of bacteria isolated from diabetic foot ulcers (DFUs) to antibiotics frequently used in the management of the diabetic foot infections, at a range of pH values (pH 6.5, 7.5, and 8.5) known to exist in DFU wound fluid. This study aimed to determine whether changes (or atypical stasis) in wound fluid pH modulate the antibiotic resistance of DFU isolates, with potential implications in relation to the suppression/eradication of bacterial infections in DFUs.
Thirty bacterial isolates were recovered from DFU wound fluid, including Staphylococcus spp, Staphylococcus aureus, Escherichia coli, Streptococcus spp, Pseudomonas spp, and Pseudomonas aeruginosa. The resistances of these isolates to a panel of antibiotics currently used in the treatment of infected or potentially infected DFUs, ie, ciprofloxacin, amoxicillin-clavulanate, doxycycline, and piperacillin-tazobactam, at the previously mentioned pH values were determined by a modification of the Kirby-Bauer assay.
The resistance of DFU isolates to clinically relevant antibiotics was significantly affected by the pH levels in DFU wound fluid.
These findings highlight the importance of a more comprehensive understanding of the conditions in DFUs to inform clinical decision making in the selection and application of antibiotics in treating these difficult-to-heal wounds. The scale of the differences in the efficacies of antibiotics at the different pH values examined is likely to be sufficient to suggest reconsideration of the antibiotics of choice in the treatment of DFU infection.
Stenotrophomonas maltophilia is an uncommon gram-negative bacterium often found in individuals with long-standing broad-spectrum antibiotic use or catheter use; individuals undergoing hemodialysis; and individuals with prolonged respiratory disease, specifically, cystic fibrosis. To our knowledge, there are few reported cases of S maltophilia being the causative pathogen of infection in a diabetic foot wound.
Following multiple surgical procedures and deep tissue cultures, S maltophilia was determined to be a secondary opportunistic colonizer of the wound, necessitating a change in antibiotic therapy.
The cultured pathogen was sensitive to ceftazidime, levofloxacin, and trimethoprim-sulfamethoxazole. The treatment team chose to use ceftazidime, as it also provided antibiotic coverage for the initial wound and blood cultures. Change in antibiotic therapy was initiated following multiple surgical procedures and angioplasty of the lower limb. The patient was discharged with a peripheral intravenous central catheter for outpatient antibiotic therapy.
Prolonged exposure to broad-spectrum antibiotics in individuals with multiple comorbidities including diabetes mellitus provides an advantageous environment for growth of uncommon multidrug-resistant organisms. Stenotrophomonas maltophilia may complicate the treatment of diabetic foot infections as an opportunistic pathogen. Understanding the implication of long-term broad-spectrum antibiotic treatment in the diabetic patient is important in managing postoperative complications and determining the correct course of treatment. The emergence of atypical pathogens in diabetic wounds must be managed appropriately.
A percutaneous antibiotic delivery technique (PAD-T) used for the adjunctive management of osteomyelitis is presented.
This surgical technique incorporates a calcium sulfate and hydroxyapatite (calcium phosphate) bone void filler acting as a carrier vehicle with either an antibiotic or an antifungal medicine, delivering this combination directly into the area of osteomyelitis.
The benefit of the PAD-T is reviewed with a case presentation of a successfully treated calcaneal osteomyelitis.
No previously reported PAD-T using a simple bone cortex incision in the adjunctive treatment of osteomyelitis has been reported. The PAD-T safely and effectively uses a calcium sulfate and hydroxyapatite bone void filler carrier vehicle to deliver either an antibiotic or an antifungal medicine directly into the area of osteomyelitis.
Background: Several absorbable and nonabsorbable antibiotic carrier systems are available in the adjunctive surgical management of osteomyelitis of the foot, ankle, and lower leg. These carrier systems have significant limitations regarding which antibiotics can be successfully incorporated into the carrier vehicle. The calcium sulfate and hydroxyapatite Cerament Bone Void Filler is a biocompatible, absorbable ceramic bone void filler that can successfully deliver multiple heat-stable and heat-unstable antibiotics that have not been generally used before with antibiotic beads in treating musculoskeletal infections.
Methods: Cerament Bone Void Filler discs with the antibiotics rifampin, vancomycin, tobramycin, cefazolin, cefepime hydrochloride, vancomycin-tobramycin, piperacillin-tazobactam, ceftazidime, and ticarcillin-clavulanate were tested in vitro against methicillin-resistant Staphylococcus aureus.
Results: The zones of inhibition for the Cerament Bone Void Filler antibiotic discs plated against Staphylococcus aureus obtained were 33% to 222% greater than the minimum zones of inhibition breakpoints for bacteria susceptibility as defined by the standard set by the Clinical and Laboratory Standards Institute. Cerament Bone Void Filler discs with the antibiotics plated against Pseudomonas aeruginosa produced zones of inhibition of 93% to 200% greater than the minimum zones of inhibition breakpoints for bacteria susceptibility as defined by the standard set by the Clinical and Laboratory Standards Institute.
Conclusions: The calcium sulfate and hydroxyapatite Cerament Bone Void Filler was an excellent carrier vehicle for multiple antibiotics creating in vitro significant zones of inhibition, thus demonstrating susceptibility against Staphylococcus aureus and Pseudomonas aeruginosa, which holds tremendous promise in treating osteomyeilits. (J Am Podiatr Med Assoc 101(2): 146–152, 2011)
The authors presented an overview of the development of antibiotic-loaded bone cement beads and their indications for usage, method of application, advantages, disadvantages, and causes of failure. This method of treatment for bone and soft tissue infections of the foot is not a panacea and should be used only in selected cases. The vascular status and the physiologic ability of the patient to heal a peripheral wound or infection are the basis for the success of this method of therapy. European literature makes little mention of adjunctive systemic antibiotic therapy with local antibiotic-loaded bone cement bead use. It is the authors' opinion that clinical judgment should be used to determine the necessity for such therapy.
Topical Application of a Gentamicin-Collagen Sponge Combined with Systemic Antibiotic Therapy for the Treatment of Diabetic Foot Infections of Moderate Severity
A Randomized, Controlled, Multicenter Clinical Trial
The aim of this pilot study was to determine the safety and potential benefit of adding a topical gentamicin-collagen sponge to standard of care (systemic antibiotic therapy plus standard diabetic wound management) for treating diabetic foot infections of moderate severity.
We randomized 56 patients with moderately infected diabetic foot ulcers in a 2:1 ratio to receive standard of care plus the gentamicin-collagen sponge (treatment group, n = 38) or standard of care only (control group, n = 18) for up to 28 days of treatment. Investigators performed clinical, microbiological, and safety assessments at regularly scheduled intervals and collected pharmacokinetic samples from patients treated with the gentamicin-collagen sponge. Test of cure was clinically assessed 14 days after all antibiotic therapy was stopped.
On treatment day 7, we noted clinical cure in no treatment patients and three control patients (P = .017). However, for evaluable patients at the test-of-cure visit, the treatment group had a significantly higher proportion of patients with clinical cure than did the control group (22 of 22 [100.0%] versus 7 of 10 [70.0%]; P =.024). Patients in the treatment group also had a higher rate of eradication of baseline pathogens at all visits (P ≤ .038) and a reduced time to pathogen eradication (P < .001). Safety data were similar for both groups.
Topical application of the gentamicin-collagen sponge seems safe and may improve clinical and microbiological outcomes of diabetic foot infections of moderate severity when combined with standard of care. These pilot data suggest that a larger trial of this treatment is warranted. (J Am Podiatr Med Assoc 102(3): 223-232, 2012)