The aim of the study was to lower the immunosuppressory, prooxidant and hepatotoxic effects of rifampicin and cephalexin by their immobilization in erythrocyte vehicles. The experiments were performed on Wistar rats with the use of rifampicin, cephalexin and lysozyme (ZAO Ferane) and hemodes (6% aqueous saline solution of low molecular polyvinylpyrrolidone, mol. wt. 12600+/-2700). Rifampicin- and cephalexin-entrapped erythrocytes were prepared. Spectrophotometric procedures for quantitative assay of the immobilized antibiotics were developed. The impact of the solution concentration and incubation time on the level of the antibiotic entrapping was studied. The erythrocyte vehicles were shown to be able to entrap the antibiotics for 9 days and to preserve their stability for 24 hours. It was observed that the increase of the immunosuppressory, prooxidant and hepatotoxic effects of the antibiotics administered without the vehicles to the laboratory animals infected by staphylococci was dose-dependent. The use of the antibiotics entrapped in the erythrocyte vehicles stimulated the immune reactivity of the animals and normalized the indices of lipid peroxidation, the antioxidant system, cytolysis and cholestasis.

Most diabetic foot infections are believed to be caused by both aerobic and anaerobic bacteria and to require hospitalization and parenteral antimicrobial therapy. We prospectively evaluated diabetic patients with non-limb-threatening lower-extremity infections not yet treated with antibiotics. The patients were randomized to outpatient treatment with oral clindamycin hydrochloride or cephalexin for 2 weeks and evaluated every 3 to 7 days. In 56 assessable patients, curettage yielded a mean of 2.1 microorganisms. Aerobic gram-positive cocci were isolated in 50 cases (89%), and were the sole pathogen in 21 (42%) of these. Aerobic gram-negative bacilli and anaerobes were isolated in 20 (36%) and 7 (13%) cases, respectively, and almost always in polymicrobial infections. Fifty-one infections (91%) were eradicated, 42 (75%) after 2 weeks of treatment; only 5 (9%) were initially treatment failures, and 3 (5%) were subsequently cured with further outpatient oral antibiotic treatment. After a mean follow-up of 15 months, no further treatment was required in 43 (84%) of the cured patients. Previously untreated lower-extremity infections in diabetic patients are usually caused by aerobic gram-positive cocci, and generally respond well to outpatient management with oral antibiotic therapy.

The cost-effectiveness of quality assurance programs is often poorly documented, especially for innovative approaches. The authors analyzed the economic effects of an experimental educational outreach program designed to reduce inappropriate drug prescribing, based on a four-state randomized controlled trial (N = 435 physicians). Primary care physicians randomized into the face-to-face group were offered two individualized educational sessions with clinical pharmacists, lasting an average of 18 minutes each, concerning optimal use of three drug groups that are often used inappropriately. After the program, expenditures for target drugs prescribed by these physicians to Medicaid patients decreased by 13%, compared with controls (P = 0.002); this effect was stable over three quarters. Implementation of this program for 10,000 physicians would lead to projected drug savings (to Medicaid only) of $2,050,000, compared with resource costs of $940,000. Net savings remain high, even after adjustment for use of substitution medications. Although there was a ninefold difference in average preintervention prescribing levels between the highest and lowest thirds of the sample, all groups reduced target drug expenditures at the same rate. Targeting of higher-volume prescribers would thus further raise the observed benefit-to-cost ratio from approximately 1.8 to at least 3.0. Net benefits would also increase further if non-Medicaid savings were added, or if the analysis included quality-of-care considerations. Although print materials alone may be marginally cost-effective, print plus face-to-face approaches offer greater net benefits. The authors conclude that a program of brief, face-to-face "detailing" visits conducted by academic rather than commercial sources can be a highly cost-effective method for improving drug therapy decisions. Such an approach makes possible the enhancement of physicians' clinical expertise without relying on restriction of drug choices.

Cellulitis occurring in the limbs of patients who have previously undergone saphenous venectomy and coronary bypass surgery has been the subject of several recent reports. Although isolation of pathogenic microorganisms from these lesions has been uncommon, this report describes three patients who had undergone venectomy previously and in whom non-group A beta-hemolytic streptococci were recovered either during acute episodes of cellulitis or during quiescent intervals. There are to date only four other reported cases of post-venectomy cellulitis from which beta-hemolytic streptococci were isolated: one was non-group A and the others were not serologically characterized. Moreover, studies in patients without bypass who have experienced cellulitis in extremities with compromised venous and/or lymphatic circulation have also yielded a substantial number of non-group A streptococci. The data thus far implicate non-group A beta-hemolytic streptococci as a major cause of cellulitis, especially in the setting of circulatory compromise.

OBJECTIVES: To evaluate whether antistaphylococcal prophylaxis in infants and young children with cystic fibrosis (CF) would suppress the acquisition of Staphylococcus aureus and delay the onset of the manifestations of bronchopulmonary disease. STUDY DESIGN: A 7-year, multicenter, double-blind, placebo-controlled study of continuous antistaphylococcal therapy. Otherwise healthy children <2 years of age with CF were randomly assigned to be treated with daily cephalexin (80-100 mg/kg/day) or placebo. Clinical, microbiologic, laboratory, radiographic, and anthropometric outcomes were evaluated. RESULTS: Of 209 children enrolled, 119 completed a 5- to 7-year course of therapy. Mean age at enrollment was 15.6 and 14.1 months in the cephalexin and placebo groups, respectively. Respiratory cultures from children treated with cephalexin were significantly less likely to be positive for S aureus (6.0% vs 30.4%; P <.001). They were, however, much more likely to be positive for Pseudomonas aeruginosa (25.6% vs 13.5%; P <.009). These differences became apparent in the first year after enrollment and persisted over the duration of the study. In contrast to these microbiologic differences, there were no differences in clinical outcome measures, including radiographic (Brasfield score, 23.4 vs 23.2) or anthropometric scores or pulmonary function. CONCLUSIONS: Although long-term prophylaxis with cephalexin successfully delayed the acquisition of S aureus, it enhanced colonization with P aeruginosa and did not lead to clinically significant improvement in major health outcomes. These data do not support routine antistaphylococcal prophylaxisin otherwise healthy infants and young children with CF.

Parenteral therapy with gentamicin, cloxacillin, ampicillin and cephalothin was surveyed on a surgical, a gynecologic and medical ward of a teaching hospital. During a 3-month period 219 patients (12.9% of the total number admitted to the three wards) received at least one of the four antibiotics parenterally. Ampicillin and gentamicin were used most frequently on the three wards when the indication for therapy was either infection or empirical use. Cephalothin was used most frequently for prophylaxis in the gynecologic and surgical patients; no medical patient received this drug. Overall, therapy was assessed to be irrational in 42.0, 50.0 and 12.0% of the surgical, gynecologic and medical patients, respectively. Prophylaxis was the indication for therapy in 76.9 and 86.8% of the surgical and gynecologic patients, respectively, for whom the therapy was assessed to be irrational.

Fourteen patients with chronic or multiple recurrences of infection of the urinary tract have self-administered a single oral dose of one of five antibiotics after sexual intercourse for periods of 19 to 111 months for a total of 761 months. Infections did not occur among 15 of 22 treatment periods. A total of 19 infections occurred while the patients were taking prophylactic medication, significantly less than the total of 90 infections recorded during the 705 months when these patients did not take prophylactic doses of antibiotics. Patients taking nitrofurantoin, a cephalosporin, or nalidixic acid had a significant reduction in the proportion of specimens of urine containing any Gram-negative bacteria. Serious toxic effects were not encountered.

The efficacy and safety of oral moxifloxacin (400 mg once daily, 7 days) versus cephalexin (500 mg three times daily, 7 days) were compared in a prospective, multicentre, randomised, double-blind trial in 401 adults with uncomplicated skin infections. Clinical outcome was evaluated in 351 patients. Moxifloxacin proved to be as effective as cephalexin both clinically (90% versus 91%, respectively) and bacteriologically in eradicating the most frequently isolated pathogen Staphylococcus aureus (92% and 93%, respectively). Moxifloxacin was more effective than cephalexin in eliminating Streptococcus spp.(90% and 82%, respectively). Drug-related adverse events were comparable in both treatment groups with the most frequently reported being nausea in the moxifloxacin-treated patients and headache in the cephalexin-treated patients. Medication was discontinued due to unwanted reactions in 3% of the moxifloxacin- and 4% of the cephalexin-treated patients. Moxifloxacin, 400 mg once daily for 7 days, is as safe and effective as cephalexin 500 mg three times daily for 7 days in the treatment of uncomplicated skin infections.