Randomized study of cefotaxime versus ceftriaxone for uncomplicated gonorrhea.

Cefotaxime is a third-generation cephalosporin with excellent in vitro antimicrobial activity against Neisseria gonorrhoeae, including beta-lactamase-producing strains. A single 1-g intramuscular dose is suitable for the treatment of uncomplicated gonorrhea. We conducted an open, randomized study to evaluate the efficacy, safety, and cost impact of a lower dose (500 mg) of cefotaxime versus 250 mg ceftriaxone, an often recommended treatment for uncomplicated gonorrhea. Of the 222 patients enrolled, the cases of 151 were fully assessable. Bacteriologic elimination rates were 99% in the cefotaxime group and 100% in the ceftriaxone group. Clinical response rates were 78% and 83% in the two groups, respectively. Adverse clinical events occurred in 4% and 9% of patients in the two groups, respectively. The average wholesale price of 500 mg cefotaxime is 31% lower than that of 250 mg ceftriaxone. A 500-mg dose of cefotaxime appears to be a safe and cost-effective alternative to 250 mg ceftriaxone for the treatment of uncomplicated gonorrhea.

Multicenter, comparative study of cefotaxime and ceftriaxone for treatment of uncomplicated gonorrhea.

BACKGROUND AND OBJECTIVES: Cefotaxime is a third-generation cephalosporin that has in vitro activity against Neisseria gonorrhoeae, including beta-lactamase-producing strains. A single 1-g intramuscular dose is effective and is recommended by the Centers for Disease Control and Prevention as an alternative treatment for uncomplicated gonorrhea. GOAL OF THIS STUDY: This study was conducted to evaluate the efficacy and safety of a lower 500-mg dose of cefotaxime in the treatment of uncomplicated gonococcal infections. STUDY DESIGN: In a randomized multicenter study, patients who had uncomplicated gonorrhea were treated with 500 mg of cefotaxime or 250 mg of ceftriaxone. Both antibiotics were given intramuscularly. Efficacy and safety were assessed four to seven days following treatment. RESULTS: Six hundred thirteen patients were enrolled. Bacteriologic eradication rates for anogenital infection were 97.7% of the patients (213/218) in the cefotaxime group and 99.1% of the patients (221/223) in the ceftriaxone group (P = 0.243). Adverse events occurred in 4.2% and 7.5% of patients in the two groups, respectively. CONCLUSION: Cefotaxime 500 mg appears to be a safe and cost-effective alternative to ceftriaxone 250 mg for the treatment of uncomplicated gonorrhea.

Multicenter trial of fleroxacin versus ceftriaxone in the treatment of uncomplicated gonorrhea.

In a multicenter, randomized, open, comparative trial, patients with uncomplicated gonorrhea were treated with 400 mg of oral fleroxacin or 250 mg of intramuscular ceftriaxone. A total of 458 men and 447 women were enrolled. Of these, 312 men (68%) and 245 women (55%) were evaluable for efficacy. The treatment groups were demographically similar. Among evaluable men, fleroxacin eradicated 154 of 155 (99%; 95% confidence interval [CI]: 98.1-100%) urethral and 2 of 2 pharyngeal infections, while ceftriaxone eradicated 156 of 156 (95% CI: 99.4-100%) urethral and 5 of 5 pharyngeal infections. Among evaluable women, fleroxacin eradicated 127 of 128 (99%; 95% CI: 97.7-100%) cervical, 20 of 20 anorectal, 16 of 16 urethral, and 7 of 7 pharyngeal infections, while ceftriaxone eradicated 108 of 108 (95% CI: 99.1-100%) cervical, 24 of 24 anorectal, 25 of 25 urethral, and 9 of 9 pharyngeal infections. Adverse events were reported by 68 (16%) of 426 subjects in the fleroxacin group and 20 (5%) of 380 in the ceftriaxone group (p < 0.0001). The most common adverse events reported by the patients who received fleroxacin were nausea (5%), headache (3%), and vaginitis (3%). One patient had severe vomiting, 19 participants had adverse reactions classified as moderate, and 48 patients had mild adverse reactions. Fleroxacin was highly effective in the treatment of uncomplicated gonorrhea and represents an oral alternative to ceftriaxone. Adverse events were more common with fleroxacin than with ceftriaxone.

Oral cefixime versus intramuscular ceftriaxone in patients with uncomplicated gonococcal infections.

A randomized trial was conducted to compare cefixime (400 mg or 800 mg single oral dose) with ceftriaxone (250 mg single intramuscular dose) in terms of efficacy and safety for the treatment of uncomplicated Neisseria gonorrhoeae urethritis or cervicitis. Of 75 men and 150 women screened, 187 had positive culture results for N. gonorrhoeae. The course of treatment was evaluable in 155 cases (59 men, 96 women). Bacteriologic eradication was evident in 97% (105 out of 108) of the patients treated with cefixime and in 100% (47 out of 47) of the patients treated with ceftriaxone. N. gonorrhoeae was eliminated at 98% (143 out of 146) and 100% (72 out of 72) of the infection sites in the respective treatment groups. Of the 187 isolates, 8 were penicillinase-producing (PPNG) and 20 had high-level tetracycline resistance (TRNG). The cefixime and ceftriaxone MIC90 for all 187 study isolates was 0.008 micrograms/ml. The adverse clinical experiences reported by the patients treated with cefixime (10%) were self-limiting; no adverse experiences occurred in the patients treated with ceftriaxone. Cefixime was as well tolerated and efficacious as ceftriaxone in the treatment of the patients with uncomplicated N. gonorrhoeae urethritis or cervicitis reported here.

Recent developments in the treatment of sexually transmitted diseases.

Recent changes in the treatment of sexually transmitted diseases include recognition of penicillin-resistant Neisseria gonorrhoeae, identification of Chlamydia trachomatis as the leading cause of bacterial genital infection in the United States, and the realization that the urethritis syndrome is often associated with multiple pathogens. There is currently no monotherapy that eradicates all STD pathogens. The role of fluoroquinolones in the treatment of STDs is still evolving. The investigational agent, temafloxacin, has good activity against gonococci, nongonococcal organisms, and, unlike other quinolones, against Bacteroides fragilis and other anaerobes. Norfloxacin, ciprofloxacin, enoxacin, ofloxacin, and temafloxacin single-dose therapy have demonstrated clinical efficacy for gonococcal infections in non-comparative and comparative trials, including bacterial eradication of isolates resistant to other agents.

Single-dose oral temafloxacin versus parenteral ceftriaxone in the treatment of gonococcal urethritis/cervicitis.

Temafloxacin is an oral fluoroquinolone with potent in vitro activity against Neisseria gonorrhoeae. The efficacy and safety of a single dose of temafloxacin were compared with ceftriaxone, the current treatment of choice for gonorrhea, in a randomized, multicenter study. A total of 421 patients with uncomplicated gonococcal urethritis or cervicitis were randomly assigned to receive a single oral dose of temafloxacin 200 mg (n = 63) or 400 mg (n = 175), or a single intramuscular injection of ceftriaxone 250 mg (n = 183). In evaluable patients, bacteriologic cure rates were greater than 99% for both temafloxacin and ceftriaxone recipients. Corresponding clinical cure rates were 93.6% and 94.6%, respectively. Both regimens were well tolerated. A single oral dose of temafloxacin appears to be as safe and effective as injectable ceftriaxone in the treatment of uncomplicated gonococcal urethritis or cervicitis.

Randomized comparison of cefotaxime and ceftriaxone in patients with uncomplicated gonorrhea.

Cefotaxime is a third-generation cephalosporin with excellent in vitro antimicrobial activity against Neisseria gonorrhoeae, including beta-lactamase-producing strains. A single, 1-gm, intramuscular dose has previously been shown to be effective in the treatment of uncomplicated gonorrhea. A randomized, multicenter study was conducted to evaluate the efficacy and safety of a lower, 500-mg dose of cefotaxime in comparison with ceftriaxone 250 mg, the standard treatment for uncomplicated gonorrhea. One hundred forty-two patients were enrolled and 115 were evaluable. Bacteriologic eradication rates were 95% in the cefotaxime group and 100% in the ceftriaxone group (P = 0.119). Adverse events that were possibly related to the study drug occurred in 3% and 8% of patients in the cefotaxime and ceftriaxone groups, respectively. Cefotaxime 500 mg appears to be a safe and cost-effective alternative to ceftriaxone 250 mg for the treatment of uncomplicated gonorrhea.

Multicenter study of a single 500-mg dose of cefotaxime for treatment of uncomplicated gonorrhea.

One hundred thirty-seven evaluable patients with uncomplicated gonorrhea were treated with a single 500-mg intramuscular dose of cefotaxime. All isolates were susceptible to concentrations of cefotaxime less than or equal to 0.1 microgram/ml. The minimum concentration of cefotaxime needed to inhibit 90% of isolates was less than 0.04 microgram/ml. At follow-up, infection was eradicated in 181 of 187 (97%) infection sites. Bacteriologic cures of 100 of 101 (99%), 55 of 56 (98%), 23 of 25 (92%), and 3 of 5 (60%) were attained at the urethral, endocervical, rectal, and oropharyngeal sites, respectively. Side effects were minor, and 90% of patients rated the injection-site pain as absent or mild. A single 500-mg dose of cefotaxime is an effective, economic treatment for uncomplicated gonorrhea.

Cefotetan therapy for gonococcal urethritis and cervicitis.

The authors compared the safety and efficacy of 0.5 and 1.0 g of cefotetan with that of 0.25 g of ceftriaxone in a 3:3:2 randomized distribution. Of 172 patients (96 men, 76 women) aged 18-43 years who were being treated at the Delgado Venereal Disease Clinic, New Orleans Health Department, for acute gonococcal urethritis or cervicitis, 123 were evaluable (81 men, 42 women). All men and 16 women were initially symptomatic. All were culture positive for Neisseria gonorrhoeae. At the 4-8 day follow-up, cultures were negative for N. gonorrhoeae in all except one man and one woman, each of whom received cefotetan 0.5 g. Symptoms were eliminated 12-72 hr after therapy in all groups. Cefotetan was well tolerated, and there were few adverse experiences reported. Thus, the authors consider cefotetan safe and effective for the treatment of uncomplicated gonorrhea.

Randomized comparison of ofloxacin and doxycycline for chlamydia and ureaplasma urethritis and cervicitis.

Fifty-eight males and 34 females with nongonococcal urethritis and/or cervicitis were treated to compare the efficacy and safety of 7-day regimens of oral ofloxacin 300 mg twice daily and doxycycline hyclate 100 mg twice daily. Forty-seven patients were randomized to receive ofloxacin and 45 patients to receive doxycycline. The microbiologic response rate was 97% (32/33) for both ofloxacin and doxycycline; the combined microbiologic and clinical cure rates were 98% for both treatment groups (ofloxacin 46/47, doxycycline 44/45). Ofloxacin was as effective as doxycycline in the treatment of chlamydial infections (96% vs. 100%). In patients with Ureaplasma urealyticum, the initial response was complete with either drug, but recurrence of infection was observed with both treatment groups (1 of 4 patients in the ofloxacin group and 2 of 11 patients in the doxycycline group). In the treatment of mixed Chlamydia trachomatis and U. urealyticum infections, all 5 patients treated with ofloxacin and 3 of 4 patients treated with doxycycline were cured. In symptomatic patients whose initial cultures were negative, clinical cures were complete with both drugs, but Ureaplasma was isolated at 3 or more weeks post-treatment in 2 patients treated with ofloxacin. In a study of single-dose ofloxacin treatment of uncomplicated gonorrhea, Neisseria gonorrhoeae was eradicated in all subjects, but C. trachomatis was not reliably eradicated. Both drugs were well tolerated with only minimal adverse effects reported in either treatment group. A multiple-dose regimen of ofloxacin appears to be a highly effective and well-tolerated alternative to doxycycline in nongonococcal sexually transmitted disease.

A collaborative report: rhinoviruses--extension of the numbering system from 89 to 100.

To define the number of rhinovirus serotypes, cross neutralization tests and characterization studies were completed on 25 candidate prototype rhinoviruses submitted to a third phase of a collaborative program. Based on the results, 11 distinct prototype strains were designated and the numbering system was extended to include 100 rhinoviruses. In addition, recent evidence indicates that over 90% of rhinoviruses isolated in three areas of the country could be typed with antisera for rhinovirus types 1-89.

Cephalosporins in cutaneous infections. A prospective comparison of two dosage regimens of ceftazidime for therapy of skin and skin structure infections.

The safety and efficacy of ceftazidime administered as 0.5 g every 8 hours (q8h) or 1.0 g q8h for at least 5 days were compared in 197 patients and found to be effective in the treatment of cellulitis, abscesses, skin ulcers, and wound infections. Staphylococcus aureus was the predominant pathogen in both treatment groups with approximately half of the isolates from each treatment group being gram-positive. Pseudomonas aeruginosa was the most common gram-negative isolate. P. aeruginosa, Proteus mirabilis, and Escherichia coli each comprised 5-12% of the isolates from each treatment group. Clinical cure or improvement was achieved in 98.7% of the patients in each treatment group. Concurrently with clinically successful treatment, a high rate of bacteriologic eradication without superinfection was achieved with the 0.5-g regimen (84% of all isolates) and the 1.0-g regimen (92%).

Cefsulodin treatment for serious Pseudomonas aeruginosa infections.

Cefsulodin, a narrow-spectrum cephalosporin with excellent antipseudomonal activity was used to treat 48 patients with 51 Pseudomonas aeruginosa infections. These included osteomyelitis, infected prostheses, post-operative and post-traumatic superficial wounds, decubitus and stasis ulcers, lower respiratory tract infections and infections of the urinary tract. Many of the patients were compromised by underlying debilitating conditions such as severe trauma, diabetes mellitus, vascular impairment, and abuse of alcohol and drugs. In cases of polymicrobial infections, a concomitant non-antipseudomonal antibiotic was sometimes administered. Cefsulodin was administered intravenously to 47 patients and by intramuscular injections to one individual. The dosage ranged from 0.5 to 2.0 g every six hr and duration of therapy was from 4 to 70 days. A satisfactory clinical response was observed in 88% of the patients. P. aeruginosa was eradicated from 76% of the infection sites. Failures, which included relapse within one year, were generally associated with prior severe trauma or vascular impairment in cases of osteomyelitis. Reinfections and superinfections developed in 12 individuals. Adverse reactions reported for two patients were nausea and vomiting. A third patient had transient increases in alkaline phosphatase and SGOT. These data indicate that cefsulodin is an effective and safe antibiotic in various types of P. aeruginosa infections.

Aztreonam in the treatment of serious orthopedic infections.

Aztreozam was evaluated in the treatment of a variety of orthopedic infections. Included were 17 patients with osteomyelitis, three with purulent arthropathy with prostheses, and 16 with superficial infections secondary to trauma or surgical procedure. Pathogens were gram-negative bacilli sensitive to aztreonam. Concomitant antibiotics were administered for gram-positive cocci that were present initially or by superinfection. Infecting organisms included Pseudomonas aeruginosa (minimal inhibitory concentration 4 to 16 micrograms/ml), Serratia marcescens, Enterobacter cloacae, Enterobacter sakazakii, Morganella morganii, Citrobacter freundii, Proteus vulgaris, Proteus rettgeri, Acinetobacter calcoaceticus and others (all with minimal inhibitory concentrations less than 1.0 microgram/ml). Dosage of aztreonam was 2 to 8 g per day administered intravenously or intramuscularly for five to 52 days. Clinical and bacteriologic responses were adequate in all instances. Recurrences were observed in two individuals with osteomyelitis and one with purulent arthropathy. Adverse clinical or laboratory observations were infrequent and inconsequential.

Treatment of skin and soft-tissue infections with cefsulodin.

Skin and soft-tissue infections due to Pseudomonas aeruginosa were treated with intravenous infusions or intramuscular injections of cefsulodin sodium in an open, multicenter study. A total of 40 patients were evaluated to determine the safety and clinical and bacteriologic efficacy of cefsulodin. Cefsulodin was administered alone (31 patients) or in combination with a nonantipseudomonal antibiotic (nine patients) when additional infecting organisms were present. The duration of cefsulodin therapy ranged from two to 46 days (2-12 g/day). Twenty-five patients were treated at New Orleans hospitals for postoperative wound, traumatic wound, and skin ulcer infections with cefsulodin alone or in combination with nonantipseudomonal antibiotic. Therapy with cefsulodin (2-8 g/day) ranged from four to 37 days. P. aeruginosa was eradicated in all the patients, and all clinical responses were considered satisfactory. Fifteen patients were treated at the collaborative centers for postsurgical wound, traumatic wound, skin ulcer, cellulitis, and subcutaneous abscess infections. Therapy with cefsulodin (4-12 g/day) ranged from five to 45 days. The bacteriologic cure rate for assessable patients was 87% (13 of 15 patients), and a satisfactory clinical response was observed in 93% (14 of 15).

Treatment of serious Pseudomonas infections with azlocillin.

Azlocillin is a semisynthetic acylureidopenicillin with increased activity against most strains of Pseudomonas aeruginosa. It was given as the sole antibacterial agent in the treatment of 21 patients with serious pulmonary, wound, bone or joint, or urinary tract infections, endocarditis, or malignant external otitis caused by Pseudomonas sp. In preliminary in vitro tests, azlocillin inhibited 90% of 36 clinical isolates, while carbenicillin and ticarcillin inhibited only 60% and 73%, respectively. Mean MIC of azlocillin against Ps. aeruginosa isolated from the 21 study patients was 9.8 mg/l; more than 50% of the strains were inhibited by a concentration of 6.25 mg/l. Intravenous administration of the antibiotic at a mean dosage of 17 g/day for 6 to 59 days resulted in an excellent or good clinical response in 90% (19) of the patients treated. Pseudomonas sp. was eliminated from the site of infection in 67% (14) of the patients. Azlocillin therapy was well tolerated; in only two patients, both of whom had penicillin-type rashes, was it necessary to discontinue therapy. Azlocillin was a safe and effective antimicrobial agent for the treatment of serious infections caused by strains of Pseudomonas sp., primarily Ps. aeruginosa.

A single injection of moxalactam for acute gonorrhea.

This study evaluated the efficacy of and tolerance to moxalactam in the treatment of uncomplicated gonorrhea, including two infections with penicillin-resistant strains. After appropriate cultures, 87 women and 64 men each received 1 gm of moxalactam intramuscularly as a single injection. Penicillinase-producing Neisseria gonorrhoeae was isolated from one man who had persistent urethritis after therapy with ampicillin. Another isolate showed high relative resistance to penicillin. At follow-up in three to seven days, moxalactam eradicated N gonorrhoeae from all 120 evaluable patients including the two with penicillin resistance and five women with rectal gonorrhea. Moxalactam administered intramuscularly was well tolerated and the few adverse effects were usually mild. In this study, 1 gm of moxalactam appeared to be virtually 100% effective and safe for therapy of adults with uncomplicated anogenital gonorrhea.

Moxalactam therapy of difficult infections in patients with serious underlying conditions.

Moxalactam was the single therapeutic agent used to treat a variety of infections in sixty-three patients, most of whom had serious concomitant illnesses. Fifty-three patient case reports qualified for evaluation, including those with pneumonia (8), urinary tract infections (18), superficial infections (6), orthopaedic infections (7), osteomyelitis (8), septicaemia (4), pansinusitis (1), and meningitis (1). Preliminary in vitro studies had indicated that most organisms, including those resistant to other antibacterial agents, would respond to moxalactam. Infecting bacteria from the fifty-three evaluable patients included a wide variety of Gram-positive and Gram-negative organisms. Doses of moxalactam ranged from 1 to 16 g/day administered intravenously or intramuscularly for 5 to 41 days. With few explainable exceptions, clinical and bacteriologic responses were adequate and satisfactory. Adverse effects were inconsequential. Allergic reactions were not observed, even in patients with a past history of reactions to penicillin.