Antibiotics delivered by an implantable drug pump. A new application for treating osteomyelitis.

Osteomyelitis is usually treated with wide surgical debridement and prolonged intravenous antibiotics. The advent of the implantable drug pump has led us to evaluate this therapeutic modality for the treatment of osteomyelitis. We have previously shown that amikacin retains microbiologic activity in an implantable drug pump over a six-week period when incubated at 37 degrees C. We have also demonstrated in rabbits that high local levels and low systemic levels of antibiotic can be achieved using an implantable drug pump as a delivery system and that this method can be used to sterilize infected wounds. This method was applied in the treatment of osteomyelitis in 14 patients whose duration of symptoms ranged from one month to 22 years. In 13 patients, active drainage had been present for more than six months, and all patients had undergone one or more attempts at eradication of their infection. Prior therapy included surgical debridement alone (one patient), one or more attempts at debridement and extended intravenous antibiotic therapy (13 patients), debridement and local flap procedures (four patients), and extended oral antibiotic therapy (two patients). The bones involved were the tibia (six patients), femur (four patients), and elbow, shoulder, hip, and radius (one patient each). Intra-operative cultures indicated that the infecting organism was Staphylococcus aureus alone (seven patients), S. aureus in combination with gram-negative bacteria (five patients), or gram-negative organisms alone (two patients). Debridement and pump implantation were performed in one stage. On an outpatient basis, the pumps were filled with amikacin in a concentration determined by each patient's serum level. Duration of therapy was based upon cessation of drainage and erythrocyte sedimentation rate. During therapy, serum amikacin levels ranged from less than 2.5 micrograms/ml to 8.2 micrograms/ml. The amikacin concentration in the wound drainage was always greater than the upper limits of what could be measured (greater than 55 micrograms/ml to greater than 5,000 micrograms/ml). There were no cases of ototoxicity and one case of minimal renal toxicity (posttreatment creatinine clearance of 66 ml per minute; normal equal to 70 ml per minute). Length of therapy ranged from 32 to 140 days (mean equal to 63 days). Length of hospitalization ranged from five to 52 days (mean equal to 24 days). Drainage in all patients stopped during therapy, but resumed in three patients after pump removal--in two patients, for brief periods of time, and in one patient, it continues. Twelve patients have posttreatment erythrocyte sedimentation rates less than or equal to 20 mm per hour.(ABSTRACT TRUNCATED AT 400 WORDS)

Isolated avulsion of the tibial origin of the anterior tibiofibular ligament.

A case report of a patient with an isolated avulsion of the anterior tubercle of the tibia is presented. This is the origin of anterior tibiofibular ligament, and this injury is the first stage of a supination external rotation injury of the ankle. It can be easily missed and, if not treated properly, can result in an unstable ankle. The patient was not treated initially and the result was an unstable ankle.

Cefamandole levels in serum and necrotic bone.

Seven patients with chronic osteomyelitis were treated by surgical debridement. Cefamandole was administered intravenously before surgery. During the debridement, cefamandole concentrations were measured in serum and necrotic bone. Although adequate levels of antibiotic were achieved in the serum, minimal or no concentration of antibiotic was found in the necrotic bone. There was only minimal penetration of cefamandole into necrotic bone.

Local administration of antibiotics with an implantable osmotic pump.

A totally implantable drug pump was evaluated as a delivery system in the treatment of osteomyelitis. Gentamicin levels in rabbit serum and bone obtained by systemic administration are compared with levels in rabbit serum and bone obtained by local administration via an implantable drug pump. Systemic administration gave mean gentamicin bone levels ranging from less than 1 microgram/gm to 3.6 micrograms/gm, while drug pump administration gave bone levels ranging from 10.8 micrograms/gm to 64.0 micrograms/gm (micrograms = microgram, or 10(-6) gram). To evaluate the drug pump as a mode of therapy, acute staphylococcal osteomyelitis was induced in ten rabbits. Drug pumps filled with amikacin were inserted in five of the infected animals. Three of these were culture-negative at one week. One had a scant growth of Staphylococcus from the pump, and one had scant growth from the pump and the wound. Clinically, none of these five rabbits appeared infected at seven days. The remaining five rabbits were all culture-positive, with heavy growths of staphylococci from their wounds, and clinically, all appeared grossly infected at seven days. These data demonstrate that high local and low systemic levels of antibiotics can be achieved with an implantable drug pump and that this method can sterilize an infected musculoskeletal wound. Therefore, antibiotic administration via an implantable drug pump is an important potential mode of therapy in the treatment of osteomyelitis.