cilastatin--imipenem-drug-combination and Skin-Diseases--Infectious

Meropenem is a new carbapenem antibiotic shown to resist degradation by renal dehydropeptidase I. In a multicenter, open-label, prospective trial, we compared the efficacy and safety of meropenem with imipenem/cilastatin in patients with skin and soft tissue infections. Patients received either 500 mg of meropenem every 8 hours (n = 184) or 500 mg of imipenem/cilastatin every 6 hours (n = 193), by intravenous infusion for an average of 6 to 7 days. Satisfactory clinical responses were achieved in 120 (98%) of 123 assessable meropenem-treated patients and in 120 (95%) of 126 assessable imipenem/cilastatin-treated patients. Satisfactory bacteriologic responses were achieved in 120 (98%) of 123 assessable meropenem-treated patients and in 120 (95%) of 126 assessable imipenem/cilastatin-treated patients. Satisfactory bacteriologic response rates were high as well: 94% with meropenem and 91% with imipenem/cilastatin. Between-group differences in satisfactory response rates were not significant (95% confidence interval, -2.29 to 6.93 [clinical]; -2.73 to 10.39 [bacteriologic]). Overall pathogen eradication rates (for aerobes and anaerobes) were slightly higher for meropenem. Elevated liver enzymes were the most frequent adverse events in each treatment group. Meropenem was well tolerated and as effective as imipenem/cilastatin in treatment of hospitalized patients with skin and soft tissue infections.

Topics: Abscess; Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Cellulitis; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Hospitalization; Humans; Imipenem; Infusions, Intravenous; Male; Meropenem; Middle Aged; Prospective Studies; Skin Diseases, Infectious; Soft Tissue Infections; Thienamycins; Ulcer

One hundred and two patients were enrolled in an open-label evaluation of intramuscular imipenem/cilastatin using doses of either 500 or 750 mg every 12 h in the treatment of mild to moderately severe skin and soft tissue infections. Seventy-four of 102 patients were clinically evaluable. Thirty-one patients had abscesses, 20 had cellulitis and 23 had wound infections. One hundred seventy-eight isolates were recovered from these 74 patients (average 2.4 isolates/patient). Sixty of 74 evaluable patients (82%) were cured; 12 of 74 (16%) were improved. Two patients failed to improve. Therapy was well tolerated. Adverse effects occurred in 8 patients. All of these effects were minor, and none required discontinuation of therapy. Eighty-two percent of patients reported no pain with injections. Therapy did not need to be interrupted or discontinued in the remaining 18% of patients reporting moderate local pain with injections. Peak and trough serum imipenem levels were measured in 15 patients receiving a 500-mg intramuscular dose of imipenem/cilastatin. The mean peak imipenem concentration in 15 patients was 10.7 micrograms/ml (range 3.3-17.8); the mean trough concentration was 2.1 micrograms/ml (range 0.8-4.9). The trough levels were higher than those found in healthy volunteers and may reflect the age and mild renal dysfunction in this group of treated patients. Imipenem/cilastatin used for mild or moderate skin and soft tissue infections was both efficacious and well tolerated. Intramuscular therapy with this agent offers advantages over intravenous therapy because of its long apparent half-life and pharmacokinetics.

Topics: Abscess; Bacterial Infections; Cellulitis; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Humans; Imipenem; Injections, Intramuscular; Skin Diseases, Infectious; Wound Infection

Multicenter noncomparative trials of intramuscular administration of imipenem/cilastatin for the treatment of a variety of infections requiring multiple-dose therapy are reviewed. Fourteen centers in the United States and 18 centers elsewhere participated in these studies. A total of 686 patients (461 evaluable) were treated worldwide. The severity of the infection was rated as moderate in 58.9%, mild in 37.2% and severe in 0.6%. The most common sites of infection were the skin and soft tissue (36.2%) and intra-abdominal (17.6%). Polymicrobial infections were relatively common (27%). Dosing regimens in evaluable patients were 500 mg every 12 h (45.1%), 750 mg every 12 h (36.2%) and 500 mg every 8 h (18.6%). The overall clinical outcome was favorable (clinical cure or improvement) for 95% or more of the evaluable patients with the various body system infections, except in gynecologic infections where 89% of the evaluable patients had a favorable outcome and for sepsis where the favorable outcome was 76%. Where data were available for analysis (skin and soft tissue infections) there was no difference in favorable clinical outcome among patients with moderate infection treated with 1.0 g/day (95% favorable) compared with 1.5 g/day (94% favorable). The overall bacteriologic eradication rate was 91%. Clinical adverse effects were similar in type but less common in frequency than those noted in other studies with the intravenous formulation, with nausea, vomiting and diarrhea being most common; no instances of seizures or confusion were observed. The laboratory adverse effects were similar to those seen in other studies with the intravenous formulation, with increased liver enzyme values the most common. The intramuscular injection was well tolerated in 87% of the patients and moderately well tolerated in 6.6%. The efficacy and low incidence of side effects of the intramuscular formulation of imipenem/cilastatin are significant advantages in the cost-effective treatment of infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Injections, Intramuscular; Male; Middle Aged; Pelvic Inflammatory Disease; Respiratory Tract Infections; Skin Diseases, Infectious; United States; Urinary Tract Infections

The efficacy and safety profile of imipenem/cilastatin was investigated in 94 patients with diabetes mellitus with infections of the lower extremity. Ninety-eight percent of the pathogens were susceptible to imipenem; this was higher than to other antibiotics tested. Ninety-two percent of the patients were cured (47%) or improved (45%). Bacterial eradication was achieved for 79% of the pathogens. Adverse experiences were similar to those reported previously. Imipenem-cilastatin proved to be a very effective antibiotic with a good safety profile for use in diabetic patients with lower extremity infections.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Cyclopropanes; Diabetes Complications; Drug Combinations; Drug Evaluation; Female; Foot Diseases; Humans; Imipenem; Leg; Male; Middle Aged; Skin Diseases, Infectious; Thienamycins