cilastatin--imipenem-drug-combination and Osteomyelitis

We conducted a prospective, randomized, open-label trial, comparing oral ofloxacin with intravenous imipenem-cilastatin for the treatment of chronic osteomyelitis in order to evaluate the efficacy and tolerance. Hospitalized patients with diagnosis of chronic osteomyelitis and isolation of susceptible organisms to ofloxacin and imipenem/cilastatin were eligible for enrollment. Ofloxacin was administered orally (400 mg every 12 hours), and imipenem-cilastatin was given intravenously (500 mg every 6 hours). Organisms were considered susceptible to ofloxacin when the minimal inhibitory concentration (MIC) was <2 micrograms/ml, and to imipenem-cilastatin when the MIC was <4 micrograms/ml. Thirty-two patients were enrolled, 16 in each group. In the intent to treat analysis 11 (69%) patients in the ofloxacin group and eight (50%) in the imipenem-cilastatin group were cured (p = 0.473; 95% confidence interval of the difference from -14.7% to 52.2%). In the per protocol analysis 10 (91%) patients in the ofloxacin group and seven (70%) in the imipenem/cilastatin group were cured (p = 0.311; 95% confidence interval of the difference from -12.2% to 54%). Our trial suggests that oral ofloxacin is as effective as parenteral therapy with betalactam antibiotics in the treatment of osteomyelitis, which could allow a reduction of the period of hospitalization and economic costs.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Chronic Disease; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Injections, Intravenous; Male; Middle Aged; Ofloxacin; Osteomyelitis; Prospective Studies

Twenty-five infants and children with acute osteomyelitis (n = 7), suppurative arthritis (n = 11), or both (n = 7) were treated with imipenem and cilastatin sodium. Patients ranged in age from 5 months to 11.3 years. Needle aspiration of infected sites was performed in all patients, and 11 (44%) required further surgical drainage. Imipenem and cilastatin sodium in a dosage of 100 mg/kg/d was used for children 3 years of age or younger, while older ones received 60 mg/kg/d intravenously, divided in four equal doses. Bacterial pathogens were identified in 15 patients (60%): Staphylococcus aureus in five, Haemophilus influenzae b in four, Pseudomonas aeruginosa in two, Streptococcus pneumoniae in one, group A Streptococcus in one, Kingella kingae in one, and Citrobacter amalonaticus in one. All isolates were susceptible to imipenem in vitro. Imipenem and cilastatin therapy was continued for a median of six days followed by treatment with appropriate orally administered antibiotics. Median peak serum bactericidal titers after imipenem and cilastatin infusions were 1:512 for S aureus, 1:32 for H influenzae b, 1:512 for streptococci, and 1:16 for gram-negative rods. All but one patient with P aeruginosa osteomyelitis responded favorably to imipenem and cilastatin. The median duration until resolution of symptoms was six days. Imipenem and cilastatin infusions were well tolerated, and side effects included maculopapular rash in one patient, watery diarrhea in one, and mild transient elevation of alanine aminotransferase levels in three. Because of imipenem and cilastatin's unusually broad spectrum of activity and its relative safety, this drug combination can be used for the initial, empiric therapy of acute bone and joint infections in pediatric patients.

Topics: Acute Disease; Administration, Oral; Anti-Bacterial Agents; Arthritis, Infectious; Bacterial Infections; Child; Child, Preschool; Cilastatin; Cilastatin, Imipenem Drug Combination; Clinical Trials as Topic; Cyclopropanes; Drainage; Drug Combinations; Female; Follow-Up Studies; Humans; Imipenem; Infant; Infusions, Intravenous; Male; Osteomyelitis; Random Allocation; Suppuration; Thienamycins

Topics: Adult; Anti-Bacterial Agents; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Neutropenia; Osteomyelitis