Clinical efficacy of monotherapy with stavudine compared with zidovudine in HIV-infected, zidovudine-experienced patients. A randomized, double-blind, controlled trial. Bristol-Myers Squibb Stavudine/019 Study Group.

BACKGROUND: Stavudine is a promising antiretroviral agent, but its clinical efficacy has not been determined. OBJECTIVE: To evaluate the clinical effect of stavudine (2',3'-didehydro-3'-deoxythymidine) monotherapy in patients with human immunodeficiency virus (HIV) infection. DESIGN: Randomized, controlled, double-blind trial. SETTING: 56 outpatient clinics in private practices, universities, and contract research organizations in the United States, France, and Italy. PATIENTS: 822 HIV-infected adults who had 50 to 500 CD4+ cells/mm3 and had previously received at least 6 months of zidovudine treatment. INTERVENTION: Monotherapy with peroral stavudine capsules or peroral zidovudine capsules. MEASUREMENTS: The primary end point was clinical progression, which was defined as all occurrences of acquired immunodeficiency syndrome (AIDS)-defining events or death. RESULTS: Patients receiving stavudine reached clinical end points at a rate of 26 per 100 person-years, compared with 32 per 100 person-years for patients receiving zidovudine (relative risk, 0.75 [95% CI, 0.58 to 0.98]; P = 0.03). The risk for death alone was 26% lower in the stavudine group than in the zidovudine group, but the comparison was not statistically significant (relative risk, 0.74 [CI, 0.53 to 1.02]; P = 0.066). The benefit of stavudine therapy was seen in all CD4+ cell strata (< or = 100 cells/mm3, 101 to 300 cells/mm3, and > 300 cells/mm3) and clinical stages of HIV disease (asymptomatic, symptomatic, and AIDS). Four weeks after treatment began, CD4+ cell counts were 30 cells/mm3 higher in the stavudine group than in the zidovudine group; this difference was sustained for 96 weeks (P < 0.001). Nausea and vomiting were more common in patients receiving zidovudine (P < 0.01), and neuropathy occurred more frequently in those receiving stavudine (12% in the stavudine group compared with 4% in the zidovudine group; P < 0.001). Neuropathy resolved completely in many patients (63%) after interruption of stavudine treatment; these patients could resume stavudine therapy at a lower dose. CONCLUSIONS: Stavudine was well tolerated and delayed progression of HIV disease in patients who had previously received 6 or more months of zidovudine treatment. Benefits were apparent in all CD4+ cell strata and clinical stages of HIV disease. Stavudine is an important agent to consider for trials of combination chemotherapy.

Ampicillin/Sulbactam vs. Cefoxitin for the treatment of pelvic inflammatory disease.

OBJECTIVE: The safety and efficacy of ampicillin plus sulbactam were compared with those of cefoxitin in the treatment of women with pelvic inflammatory disease (PID). METHODS: This single-site, randomized, prospective, third-party-blinded, comparative, parallel-treatment study enrolled 93 women with a diagnosis of PID. Patients were treated with either ampicillin/sulbactam (2 g/1 g, administered intravenously [IV], every 6 h) or cefoxitin (2 g, administered IV, every 6 h) for a minimum of 12 doses. Patients with cultures positive for Chlamydia trachomatis also received concurrent oral or IV doxycycline (100 mg twice daily). Patients with cultures negative for C. trachomatis received prophylactic oral doxycycline (100 mg twice daily) for 10-14 days after treatment with either ampicillin/sulbactam or cefoxitin was completed. RESULTS: Ninety-three patients were entered in the study: 47 in the ampicillin/sulbactam arm and 46 in the cefoxitin arm. All 93 patients were evaluable for safety; 61 (66%) were evaluable for efficacy. Demographic characteristics were similar for the groups. Of the 27 evaluable ampicillin/sulbactam-treated patients, 67% experienced clinical cure, 30% improved, and 4% failed treatment. Respective values for the 34 cefoxitin-treated patients were 68%, 24%, and 9% (P = 0.67). Pathogens were eradicated in 70% of the women given ampicillin/sulbactam vs. 56% of those who received cefoxitin (P = 0.64). CONCLUSIONS: Overall, ampicillin/sulbactam demonstrated clinical and bacteriologic efficacy at least equivalent to that of cefoxitin in the treatment of women with acute PID. The use of ampicillin/sulbactam for this indication may avoid the complex dosing regimens associated with other treatments.

Antibiotic prophylaxis during clean neurosurgery: a large, multicenter study using cefuroxime.

Cefuroxime is a second-generation cephalosporin with in vitro activity against the organisms that are commonly associated with neurosurgical wound infections. Other properties of cefuroxime are an elimination half-life of 1.3 hours, which yields prolonged serum concentrations, and its ability to penetrate the blood-brain barrier in proportion to the degree of inflammation. A prospective, multicenter, open-label study was conducted to evaluate the efficacy and safety of cefuroxime for antibiotic prophylaxis in patients undergoing clean neurosurgery. Cefuroxime 1.5 g was given intravenously 25 to 60 minutes before surgery; for procedures lasting more than 3 hours, cefuroxime 750 mg was given intravenously 8 hours after the initial dose. Patients were examined before surgery, daily during hospitalization, and at 8 weeks after surgery. A total of 956 adults were enrolled in the study. The most common procedures in study patients were laminectomy (41.8% of patients) or craniotomy (24.3%), and the mean duration of surgery was 3.2 hours. Infection occurred in 2 (0.3%) of 592 assessable patients by the time of discharge and in 1 additional patient by the 8-week follow-up evaluation for a total of 3 (0.5%) of 560 assessable patients. Drug-related adverse events occurred in 5 (0.5%) of 956 patients. These results indicate that antibiotic prophylaxis with cefuroxime is associated with a low incidence of postoperative wound infection and is well tolerated in patients undergoing clean neurosurgery.

Cephalosporin therapy in intraabdominal infections. A multicenter randomized, comparative study of cefotetan, moxalactam, and cefoxitin.

Three broad-spectrum cephalosporins (cefotetan, moxalactam, and cefoxitin) proved effective in this randomized, prospective trial for treatment of 303 surgical patients with moderately severe regional peritonitis.

A multicenter comparative study of cefotetan once daily and cefoxitin thrice daily for the treatment of infections of the skin and superficial soft tissue.

To compare the effectiveness of cefotetan administered at 2 g once a day with cefoxitin at 1 or 2 g three times a day in the treatment of hospitalized patients with skin and superficial soft tissue infections, 194 patients from eight centers were enrolled in an open, randomized trial. Most of the 104 evaluable patients in the cefotetan group and 50 in the cefoxitin group were young men with community-acquired, moderate or severe cellulitis, or abscesses of the upper and lower extremities caused by Staphylococcus aureus, Streptococcus species, Escherichia coli, Proteus mirabilis, Bacteroides fragilis and other species of bacteroides, peptococcus species, and peptostreptococcus species. The mean duration of treatment was 7.5 days for cefotetan and 7.1 days for cefoxitin. A successful clinical response was achieved in 97 percent of the cefotetan patients and in 94 percent of the cefoxitin patients. Of the 88 and 39 bacteriologically evaluable patients in the cefotetan and cefoxitin groups, respectively, a satisfactory bacteriologic response occurred in 96 percent and 87 percent of the patients. No clinically significant changes in clinical laboratory determinations were noted. The incidence of adverse reactions in the cefotetan group (17 percent) was significantly different from that for the cefoxitin group (6 percent) (p less than 0.05); however, the incidence of treatment-related reactions was not significant and the events were mild. Discontinuation of therapy was necessary only in two patients in whom allergic-type reactions developed. A once-daily regimen of cefotetan was as effective as thrice-daily cefoxitin in this study in the treatment of primarily polymicrobial, moderate, or severe infections of the skin and superficial soft tissue.

Comparative study of cefotetan and cefoxitin in the treatment of intra-abdominal infections.

One hundred eighty-eight patients were enrolled in a multicenter, randomized clinical trial to compare the safety and effectiveness of 1 to 2 gm cefotetan every 12 hours with those of 1 to 2 gm cefoxitin every 6 hours in patients with intra-abdominal infections. Most of the infections were community acquired, were associated with gastrointestinal tract perforation, and were caused by both anaerobic and aerobic bacteria. The median duration of therapy was 6 days for each group. The clinical response rate for the 95 evaluable patients in the cefotetan group was 98%, and that for the 43 evaluable patients in the cefoxitin group was 95%. Bacteriologically, 97% of the 58 evaluable patients in the cefotetan group and 89% of the 27 evaluable patients in the cefoxitin group had a satisfactory or presumed satisfactory response; two patients in the cefotetan group and three in the cefoxitin group were considered bacteriologic failures. Cefotetan was as effective as cefoxitin in eradicating Bacteroides fragilis and other species of Bacteroides, Clostridium sp., and gram-negative bacilli. The incidence of treatment-related adverse reactions for cefotetan (27%) was not statistically different from that for cefoxitin (17%). No clinically significant differences were detected between the treatment groups in changes in the results of clinical laboratory tests performed before and after treatment; a decrease in hematocrit among the cefotetan group was statistically greater (p = 0.04) than that for the cefoxitin group, and a decrease in serum creatinine level for the cefoxitin group was greater than that for the cefotetan group (p = 0.02). Cefotetan may represent an effective, safe, and cost-saving alternative to cefoxitin for the prompt treatment of community-acquired intra-abdominal infections.

Effects of sodium piperacillin on platelet function in normal volunteers.

Piperacillin is a new semisynthetic penicillin which is similar in structure to carbenicillin and ticarcillin. Since the latter antibiotics have been shown to cause abnormalities in hemostasis, we studied the effects of piperacillin on blood coagulation and platelet function. Fifteen healthy volunteers received the drug in doses of either 100, 200, or 300 mg/kg per day for a period of 7 days. Serial studies showed no abnormalities in blood coagulation in any subject. Decreased platelet aggregation responses to adenosine diphosphate, epinephrine, collagen, and achidonic acid were commonly noted, but prolongation of the bleeding time occurred in only 3 of 15 subjects after 7 days of piperacillin administration. These results suggest that although piperacillin also induces platelet dysfunction, these effects may be less than those caused by ticarcillin or carbenicillin at an equivalent dosage.

Antimicrobial susceptibility testing of Haemophilus parainfluenzae by a kinetic killing-curve method.

A kinetic killing-curve method, designed to mimic several aspects of clinical therapy in endocarditis, was used to test 10 strains of Haemophilus parainfluenzae against 28 antibiotic regimens. In an effort to simulate changing in vivo levels of antibiotic in serum, concentrations of three penicillins, three cephalosporins, gentamicin, and chloramphenicol were sequentially adjusted over a 12-hr period. Against six beta-lactamase-negative strains, gentamicin in combination with penicillin or cephalosporin invariably resulted in an additive or synergistic effect. Chloramphenicol and a penicillin or cephalosporin usually displayed an indifferent effect, but chloramphenicol was often antagonistic when combined with gentamicin. With four beta-lactamase-positive strains, variable responses were noted to penicillin-aminoglycoside combinations; cephalosporin-aminoglycoside combinations were usually synergistic. This dynamic approach to killing-curve studies may be more appropriate than a static system for in vitro examination of the effect of antimicrobial combinations against selected organisms.

Malignant group B streptococcal endocarditis associated with saline-induced abortion.

A 20-year-old woman developed acute group B streptococcal endocarditis following saline-induced abortion. In the pre-antibiotic era, most cases of group B streptococcal endocarditis occurred in parturient or postabortal women. Currently, this disease is rarely described in obstetrical patients, and no previous cases following saline-induced abortion have been reported. Purulent pericarditis and a perivalvular abscess were present in our patient and represent only the second instance in which these findings have been documented in this disease.

PIP: This case report describes a 20-year-old woman who developed acute group B streptococcal endocarditis after a saline-induced abortion. She was admitted 2 weeks after an uncomplicated saline-induced abortion for a 16-week pregnancy with a 1-week history of fever, headaches, dizziness, and shortness of breath. The patient showed poor response to antibiotic therapies (initially to nafcillin and gentamicin and then to aqueous penicillin G). 6 to 6 blood cultures after hospital admission showed group B streptococcus which was penicillin sensitive by tetracycline resistant. On Day 3 of admission, a pericardial friction rub was noted and repeat chest x-rays showed marked enlargement of the cardiac shadow. Surgery was performed, and the mitral valve posterior leaflet was necrotic, and a mitral valve prosthesis was placed and an aortic embolectomy was performed. Postoperatively, she was treated with an additional 6-week course of intravenous penicillin, and subsequently, she has remained asymptomatic after 6 months. An addendum to this report, which was only the 2nd such report of endocarditis after saline abortion, describes another case of group B streptococcal endocarditis in a drug abuser after a saline-induced abortion. She required tricuspid valvulectomy and is slowly improving postoperatively.

Quantitative nasal cultures from carriers of Staphylococcus aureus: effects of oral therapy with erythromycin, rosamicin, and placebo.

Serial quantitative nasal cultures were performed on 87 healthy nasal carriers of Staphylococcus aureus, who were randomly assigned to 7 days of oral therapy with erythromycin, rosamicin (an investigational macrolide antibiotic), or placebo. Staphylococcal carrier rates decreased during therapy with both antibiotics; however, erythromycin was significantly more effective in lowering carrier rates than was rosamicin. The anti-staphylococcal effects of both antibiotics were similar when the mean numbers of S. aureus isolated from positive cultures during therapy were compared. Side effects to each regimen were minimal.

Treatment of acute bacterial bronchitis and pneumonia with cefaclor.

Sixty patients with pneumonia and/or bronchitis were treated with cefaclor, a new orally administered cephalosporin. Of those 60, 27 adults were treated with 500 mg every 8 hours, 26 adults with 250 mg every 6 hours, and 7 children with 50 mg/kg/day. In the adults, pneumonia was caused most frequently by Streptococcus pneumoniae and Haemophilus influenzae. The 7 children had pneumococcal pneumonia. All but 2 adults, both elderly patients with chronic obstructive pulmonary disease, were successfully treated. One instance of drug hypersensitivity occurred. All 7 children responded rapidly, with no side effects, to cefaclor therapy.