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Much early experience with antibiotic therapy involved oral administration of sulfonamides, penicillins, tetracyclines, and chloramphenicol. Newer acid-labile, less-soluble agents created the need for intravenous (i.v.) administration, and i.v. technology (hyporeactive catheter polymers, infusion pumps, etc.) improved to where i.v. administration became normative for the treatment of serious infections. Recently, this preference is being reconsidered in light of agents that are highly effective orally, growing appreciation that i.v. treatment has serious complications, and economic pressures to provide the best care at the lowest cost. This article presents a brief history of administration routes and reviews the rationale for considering oral treatment for serious infections, including consideration of pharmacokinetics and minimum inhibitory concentrations. Published reports supporting the efficacy of orally administered antibiotics either as sole treatment or following an initial parenteral course are reviewed in detail, and examples of programs that educate physicians about the rationale, acceptibility, and benefits of oral administration are given.

Alterations of chemosensory function have been noted in human immunodeficiency virus (HIV)-infected patients, but their frequency, severity, and relationship to diet have not been adequately assessed. Odor and taste identification tests and a taste-intensity scaling task were administered to 25 men who were HIV-infected but otherwise healthy. Responses were compared to those of 49 comparably aged male control subjects. Dietary information was obtained by questionnaire. Although 72% of HIV-infected patients reported some chemosensory alteration, no significant differences in taste identification ability or intensity ratings were observed between patients and controls. Twelve percent of patients had poor odor identification scores, but the group mean was similar to that of controls. Neither measured nor self-reported sensory indices were significantly related to any variable of health (e.g., HIV helper cell (CD4) count, body weight, or body composition), treatment, or diet.

Objective : The hypothesis of the study is that cefotetan and cefoxitin will be equally efficacious and safe in the treatment of post-cesarean section endometritis. Study design : In a double-blind, randomized manner 140 patients with post-cesarean section endometritis were treated with cefotetan, 2 gm intravenously every 12 hours, or cefoxitin, 2 gm intravenously every 6 hours. They were followed prospectively for clinical response and side effects. Cure rates between the two groups were compared with the χ 2 test. Results : The cure rates were 83% for cefotetan and 79% for cefoxitin ( p = 0.56). No patient required a change in therapy due to adverse effects, and no abnormal bleeding occurred. Conclusions : In this study cefotetan and cefoxitin appeared equally effective in treating endometritis with no difference in side effects or complications.

This article presents an overview of the toxicities associated with the antibiotics more commonly used for the treatment of osteomyelitis. Included in each drug monograph are major and minor side effects, significant drug-drug and drug-food interactions, and the relative safety of the antimicrobial during pregnancy and in breast-feeding women.

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.

Foscarnet is an investigational antiviral agent that has been used effectively in the treatment of cytomegalovirus (CMV) retinitis in AIDS patients. However, it has not been readily available to AIDS patients with renal insufficiency because its major side effect is nephrotoxicity. In this report, the efficacy, safety, and dosing requirements of foscarnet in a hemodialysis-dependent patient with CMV retinitis are presented. Foscarnet was administered for 14 weeks, at an initial dosage of 60 mg/kg after each dialysis session. Plasma concentrations were monitored weekly, and the dosage was adjusted to maintain peak plasma levels in the range of 500-800 microM. Although some laboratory abnormalities occurred (a preexisting anemia continued, serum calcium and phosphorus decreased, and ionized calcium increased), they did not limit therapy. Foscarnet is a potentially useful alternative treatment for CMV retinitis in hemodialysis-dependent AIDS patients.

Ciprofloxacin is a new, oral, broad spectrum fluoroquinolone antibiotic which has a long serum half-life, a low incidence of significant adverse reactions, and is administered twice daily. Eighteen patients with osteomyelitis were treated with ciprofloxacin, 750 mg orally twice daily. The mean age of the patients was 43 years (range, 21 to 73 years); 12 were men. The duration of treatment ranged from 5 to 52 weeks (mean, 20.0±15.7 weeks). At follow up (mean, 18±8.5 months; range, 4 to 34.5 months), 11 patients (61.6%) achieved arrest of infection, 4 (22.2%) had improved with therapy, and 3 (16.6%) failed to improve. Ciprofloxacin was well tolerated. Four case histories are given.

To determine the frequency and significance of cytomegalovirus (CMV) viremia and viruria in HIV-positive subjects with low CD4+ lymphocyte counts but with no clinical indications for culture, we studied 100 consecutive clinically stable subjects with CD4+ cells 100/microliters; CMV antibody was present in 96% of the remainder. Isolation of CMV from blood was uncommon (2 of 93 seropositive subjects) whereas viruria occurred in 51.6%; likelihood of having a positive urine culture was significantly related to the subject's absolute CD4+ lymphocyte count: 60% for those with CD4+ < or = 50/microliters, vs. 26.1% for those with CD4+ 51-100/microliters. Neither serum p24 antigen nor neopterin was predictive of CMV in urine or blood. No subjects submitting to ophthalmologic exam had unsuspected CMV retinitis. Subsequent development of retinitis correlated with CMV viruria on entry: 13.5% if urine-positive, 1.9% if negative (p = 0.029; Fisher exact test).

Imipenem-cilastatin concentrations in bile were measured in 12 cholecystectomy patients (group 1) and 12 patients with common duct drainage (group 2). Six patients in each group received 0.5 g, and six received 1.0 g intravenously over 30 to 60 min. In group 1, bile was collected a mean of 85 min postinfusion. The mean concentrations of imipenem in bile were 1.3 microgram/ml after the 0.5-g dose and 3.5 micrograms/ml after the 1.0-g dose. The mean concentrations of cilastatin in bile were 9.0 micrograms/ml after the 0.5-g dose and 38.0 micrograms/ml after the 1.0-g dose. In patients with common duct drainage, bile was collected predose and 0 to 2, 2 to 3, 3 to 4, and 4 to 6 h postinfusion. Peak imipenem concentrations in bile were 4.4 micrograms/ml after the 0.5-g dose and 8.6 micrograms/ml after the 1.0-g dose. Peak cilastatin concentrations in bile were 4.6 micrograms/ml for the 0.5-g dose and 10.9 micrograms/ml for the 1.0-g dose. Peak imipenem concentrations in bile occurred a mean of 2.3 h after administration of the drug; cilastatin peak concentrations occurred at a mean of 2.4 h. Less than 0.3% of each drug was recovered in the bile. Our results suggest that imipenem enters bile by simple diffusion and in most patients attains concentrations sufficient to inhibit susceptible organisms. In contrast, cilastatin had a bimodal entry into bile. Some patients had very high concentrations in bile, whereas others had very low or undetectable concentrations, suggesting that cilastatin may be actively secreted into the bile.

Concentrations of vancomycin in bones of 14 patients undergoing total hip arthroplasty (group 1) and 5 patients with osteomyelitis (group 2) were studied. Group 1 received vancomycin, 15 mg/kg intravenously, 1 h prior to anesthesia. Group 2 received doses adjusted to achieve peak levels in serum of 20 to 30 micrograms/ml and trough levels of less than 12 micrograms/ml; bone specimens were collected during surgical debridement. The specimens were pulverized and eluted into phosphate buffer, and the supernatants were analyzed for vancomycin content by fluorescence polarization immunoassay. In group 1, vancomycin was detectable in all cancellous specimens with a mean concentration of 2.3 +/- 4.0 micrograms/g (range, 0.5 to 16 micrograms/g); 10 of 14 cortical specimens had detectable vancomycin; the mean cortical concentration was 1.1 +/- 0.8 micrograms/g (range, not detectable to 2.6 micrograms/g). In group 2, vancomycin was detectable in only two of five cortical bone specimens (mean concentration, 5.9 +/- 3.5 micrograms/g). Cancellous bone was obtained in one patient; the vancomycin concentration was 3.6 micrograms/g. In most patients the vancomycin levels in bones were higher than the MIC for susceptible staphylococci following single prophylactic doses. In the few infected patients studied, penetration was variable and deserves further study.