Ciprofloxacin versus ampicillin and probenecid in the treatment of uncomplicated gonorrhoea in men

Eighty-six men with uncomplicated gonorrhoea were entered into a study comparing the efficacy of a single oral dose of 250 mg of ciprofloxacin with a single oral dose of ampicillin 2 g and probenecid 1 g for urethral gonorrhoea and a course of ampicillin, 500 mg four times per day for five days in rectal and pharyngeal infection. Two patients were excluded. Of the remaining 84, 45 were treated with ampicillin and 39 with ciprofloxacin. In the ampicillin group there were two treatment failures out of 40 urethral infections. Three patients with rectal infection were cured. Only one patient out of three pharyngeal infections was cured. Ciprofloxacin cured all of 34 urethral and three rectal infections including one penicillinase producing strain of Neisseria gonorrhoeae (PPNG). Four of five pharyngeal infections were cured but there was one treatment failure. There were no major side effects in either treatment group. In conclusion, a single oral dose of 250 mg of ciprofloxacin is an effective treatment for uncomplicated gonorrhoea in men.     

Comparison of piperacillin and penicillin in the treatment of uncomplicated gonorrhea.

A total of 120 men with uncomplicated infections caused by beta-lactamase-negative, highly penicillin-susceptible strains of Neisseria gonorrhoeae were included in this study. They were randomly assigned to regimens of either piperacillin (2.0 g) or procaine penicillin G (4.8 X 10(6) U) intramuscularly, both delivered concomitantly with an oral dose of 1.0 g probenecid. A total of 103 patients completed the study, providing data from 112 infected sites: for the penicillin regimen--urethra, 46; pharynx, 5; and rectum, 4; for the piperacillin regimen--urethra, 53; pharynx, 3; and rectum, 1. In the penicillin group, there were no failures at any of the infected sites. In the piperacillin group, all except one pharyngeal infection were cured. Also, in the piperacillin group, four men visit, whereas no cases of this type occurred in the penicillin group. No major side effects were noted in either group. Clinically, piperacillin was as effective as procaine penicillin G in the treatment of gonococcal urethritis in men. Pharyngeal infection may be refractory to piperacillin therapy.     

Multicenter randomized study of single-dose ofloxacin versus amoxicillin-probenecid for treatment of uncomplicated gonococcal infection.

The safety and efficacy of ofloxacin, 400 mg orally, were compared with those of amoxicillin, 3.0 g, plus probenecid, 1.0 g orally, as single-dose therapy in 201 heterosexual patients (101 men and 100 women) with uncomplicated gonococcal infection. Treatment groups were comparable in age, duration of symptoms, number of sexual partners within the previous month, and number of previous episodes of sexually transmitted diseases. The cure rate for men treated with ofloxacin was 98% (47 of 48), and that for women was 100% (52 of 52). Cure rates for both men and women treated with amoxicillin-probenecid were 96% (51 of 53 men; 46 of 48 women). All 13 patients with positive rectal cultures and 7 of 8 patients with positive pharyngeal cultures treated with ofloxacin were cured. Neither regimen reliably eradicated coexistent infection with Chlamydia trachomatis. The MIC of ofloxacin for all but two of 198 pretreatment isolates was 0.3 microgram/ml or less. The MIC of amoxicillin for 90% of isolates tested was 1.0 microgram/ml. Single oral doses of ofloxacin and of amoxicillin plus probenecid were equally effective for treatment of urethral and cervical gonorrhea. Ofloxacin appears promising as treatment for rectal and pharyngeal infection, but studies with larger numbers of patients with rectal or pharyngeal infection or both are required for confirmation. Relative contraindications in children and possibly pregnant women plus the potential for single-step, high-level resistance may limit the usefulness of quinolone therapy for gonorrhea.     

Comparison of Antimicrobial Susceptibilities of Pharyngeal,Rectal, and Urethral Neisseria gonorrhoeae Isolates among Men Who Have Sex with Men

U.S. surveillance for Neisseria gonorrhoeae antimicrobial susceptibilities is based exclusively on male urethral isolates. These data inform gonorrhea treatment guidelines, including recommendations for the treatment of extragenital infections, but data on the susceptibilities of extragenital isolates are limited. We compared the antimicrobial susceptibilities of pharyngeal, rectal, and urethral gonococcal isolates collected from men who have sex with men (MSM), at five sentinel sites throughout the United States. MICs were determined by the agar dilution method. Generalized linear models were used to compare (i) the proportions of isolates with elevated MICs and (ii) geometric mean MICs according to anatomic site, adjusted for city. In December 2011 to September 2013, totals of 205 pharyngeal, 261 rectal, and 976 urethral isolates were obtained. The proportions of isolates with elevated ceftriaxone MICs (≥0.125 μg/ml) did not differ according to anatomic site (0.5% of pharyngeal isolates, 1.5% of rectal isolates, and 1.7% of urethral isolates, with a city-adjusted odds ratio [aOR] of 0.4 [95% confidence interval {CI}, 0.0 to 3.9] for pharyngeal versus urethral isolates and an aOR of 0.9 [95% CI, 0.2 to 4.2] for rectal versus urethral isolates). The city-adjusted geometric mean ceftriaxone MICs of pharyngeal (0.0153 μg/ml) and rectal (0.0157 μg/ml) isolates did not differ from that of urethral isolates (0.0150 μg/ml) (ratios of geometric mean MICs of 1.02 [95% CI, 0.90 to 1.17] and 1.05 [95% CI, 0.93 to 1.19], respectively). Similar results were observed for other antimicrobials, including cefixime and azithromycin. These findings suggest that, at the population level, gonococcal antimicrobial susceptibility surveillance based on urethral isolates from MSM adequately reflects the susceptibilities of N. gonorrhoeae strains circulating among MSM.     

Effectiveness of aztreonam for the treatment of gonorrhea.

Aztreonam, 1 g intramuscularly, was compared with spectinomycin, 2 g intramuscularly, for uncomplicated gonorrhea. There were no failures with either drug. For aztreonam, there were 26 urethral, 3 rectal, and 3 endocervical sites that were infected. Aztreonam in a single dose of 1 g intramuscularly is satisfactory therapy for uncomplicated urethral gonorrhea in men and may be effective for rectal and endocervical infection as well.     

Therapeutic trial and pharmacokinetics of sulbactam for uncomplicated gonorrhea in men.

The efficacy of intramuscular sulbactam for uncomplicated gonorrhea was assessed in 20 men infected with beta-lactamase-negative Neisseria gonorrhoeae. Ten subjects received 2.0 g of sulbactam given in a single intramuscular dose with 1.0 g of probenecid orally; 4 of 10 urethral infections persisted, as did one rectal infection. Ten subjects were treated with 0.5 g of intramuscular sulbactam given twice, 4 h apart; 3 of 10 urethral infections and 2 of 2 rectal infections persisted. The geometric mean MIC of sulbactam for 20 pretreatment isolates of N. gonorrhoeae was 1.37 microgram/ml (range, 0.25 to 8.0 micrograms/ml). Serum levels of sulbactam, determined for nine subjects in the two treatment groups, fell below the MIC of some gonococci after less than 6 h with both regimens. In the regimens studied, sulbactam alone is not suitable as therapy for uncomplicated gonorrhea. determined for nine subjects in the two treatment groups, fell below the MIC of some gonococci after less than 6 h with both regimens. In the regimens studied, sulbactam alone is not suitable as therapy for uncomplicated gonorrhea.     

Dose ranging study of cefpimizole (U-63196E) for treatment of uncomplicated gonorrhea in men.

We conducted a two-center dose ranging study to evaluate the efficacy, tolerance, and toxicity of cefpimizole, a new cephalosporin, in the treatment of uncomplicated gonorrhea in 96 males. Twelve patients at each center were treated intramuscularly with single doses of 1.0, 0.5, 0.25, and 0.125 g of cefpimizole. All urethral infections were cured at the highest dose, but lower doses produced progressively decreasing cure rates of 90% (0.5 g), 83% (0.25 g), and 71% (0.125 g). Treatment failures of rectal and pharyngeal infections occurred at the highest dose level. Geometric mean MICs for cefpimizole for successfully and unsuccessfully treated volunteers were 0.088 and 0.282 micrograms/ml, respectively. A prominent adverse effect was clinically significant pain at the injection site, which occurred in 57 (59%) of 96 patients. Results of the study demonstrate that cefpimizole offers no advantage over currently available antibiotics in the treatment of uncomplicated gonorrhea in men.     

Comparative trial of single-dose ciprofloxacin and ampicillin plus probenecid for treatment of gonococcal urethritis in men.

In a double-blind comparative trial, 100 men with uncomplicated gonorrhea caused by beta-lactamase-negative Neisseria gonorrhoeae were treated with a single 0.25-g dose of ciprofloxacin administered orally or with 3.5 g of ampicillin plus 1.0 g of probenecid administered orally. Urethral infection was eradicated in all 49 men treated with ciprofloxacin and in 47 (92%) of 51 men treated with ampicillin-probenecid (P = 0.12). The geometric mean MICs for pretreatment isolates were 0.008 microgram of ciprofloxacin per ml, 0.09 microgram of penicillin G per ml, 0.52 microgram of tetracycline per ml, and 23.5 micrograms of spectinomycin per ml. Chlamydia trachomatis infection persisted in 10 of 11 men treated with ciprofloxacin and in 11 of 14 men treated with ampicillin-probenecid. A single 0.25-g dose of ciprofloxacin was effective for treatment of uncomplicated urethral gonorrhea in men, but it did not eradicate coinfection with C. trachomatis.     

Efficacy of cefmenoxime in experimental group B streptococcal bacteraemia and meningitis

Cefmenoxime, a new semisynthetic cephalosporin, was evaluated in vitro and in vivo in comparison with penicillin G against a type III group B streptococcal strain. In vitro, the minimal inhibitory and minimal bactericidal concentrations of the two drugs were very close (less than or equal to 2 dilutions). In-vivo studies using experimental bacteraemia and meningitis in newborn rats revealed that despite similar drug levels, cefmenoxime had significantly greater bactericidal titres in blood at 6-7 h after administration and bacterial clearance from blood was significantly faster with cefmenoxime than with penicillin G at the end of one day of treatment. In addition, all animals with cefmenoxime therapy had bactericidal titres in cerebrospinal fluid greater than or equal to 1:8 at 1-2 h after administration, whereas most (67%) animals receiving penicillin G had titres less than 1:8. However, overall efficacy of cefmenoxime was similar to that of penicillin G. These findings suggest that cefmenoxime may be an effective alternative against group B streptococcal infection.     

Cefuroxime axetil for treatment of uncomplicated gonorrhea.

Oral cefuroxime axetil (1 g) plus probenecid cured 29 of 30 urethral and 6 of 6 rectal gonococcal infections in men; alone the drug cured 22 of 23 urethral and 4 of 6 rectal infections. No toxicity was observed. Cefuroxime axetil alone is effective for urethral gonorrhea in males; rectal gonorrhea probably requires additional probenecid.     

Comparison of cefuroxime and penicillin in the treatment of uncomplicated gonorrhea.

In a randomized double-blind trial, 216 men and 142 women infected with uncomplicated gonorrhea were treated with either 1.5 g of cefuroxime or 4.8 x 10(6) U of aqueous procaine penicillin G intramuscularly and 1.0 g of probenecid. The cure rates in the treatment groups were 96 and 95%, respectively. Intramuscularly administered cefuroxime was better tolerated than was procaine penicillin. Comparative antibiotic susceptibility studies revealed that cefuroxime and penicillin were about equally active and that both were more active than cefamandole or cefoxitin. Because cefuroxime is not degraded by the action of beta-lactamase enzymes, it has promise as an alternative to spectinomycin in the treatment of penicillinase-producing Neisseria gonorrhoeae infections.     

Comparative study of ceftriaxone and aqueous procaine penicillin G in the treatment of uncomplicated gonorrhea in women

Uncomplicated gonorrhea of 122 mucosal sites in 51 women was successfully treated with either a single intramuscular dose of 250 mg of ceftriaxone (23 patients) or two intramuscular doses of 4.8 X 10(6) U of aqueous procaine penicillin G (28 patients). Women treated with ceftriaxone had 22 cervical, 12 urethral, 10 anal canal, and 5 pharyngeal infections. All 122 pretreatment isolates were inhibited by 0.0125 microgram or less of ceftriaxone per ml. The minimal concentration needed to inhibit 90% of isolates was 0.006 microgram/ml for ceftriaxone and 0.2 microgram/ml for penicillin G. Ceftriaxone was very well tolerated and caused no toxicity.     

Comparative study of mezlocillin and ticarcillin in the treatment of urinary tract infections

Mezlocillin (1.5 gm) or ticarcillin (2 gm) was administered intramuscularly every six hours for seven days in this prospective, randomized study of 60 men with complicated urinary tract infections. The two patient groups were comparable as to age, weight, and infecting microorganisms. The underlying urologic disorders, which were comparable in the two groups, included hypertrophy of the prostate, carcinoma of the prostate, bladder tumors, and urethral strictures. No patient had an indwelling catheter for more than three days. Both drugs were well tolerated except for mild pain on injection. A cure of the urinary tract infection, defined as a negative urine culture one week after treatment, was obtained in 64% of the mezlocillin group and in 47% of the ticarcillin group. There was no statistical difference between these results. This study demonstrated that mezlocillin and ticarcillin, administered intramuscularly, were safe and effective in the treatment of complicated urinary tract infections.     

A double-blinded comparative study of sultamicillin and potassium penicillin V in the treatment of childhood streptococcal pharyngitis

Fifty-two children with positive pharyngeal cultures for group A streptococci were randomized to receive phenoxymethyl penicillin or sultamicillin, an ester of ampicillin and sulbactam. By serological and bacteriological criteria, sultamicillin was effective in 100% of the 20 evaluable cases of infection and carriage while penicillin was effective in six out of eight (75%) and three out of eight (93%) respectively. Of the eight children with infections treated with sultamicillin, three (37.5%) became recolonized with the organism compared to none of the children in the penicillin group. These differences were not statistically significant.     

Controversies in the treatment of streptococcal pharyngitis

An increasing number of cases of sore throat caused by group A beta-hemolytic streptococci occur with concomitant colonization by organisms that may "protect" the streptococci through beta-lactamase inactivation of penicillin at the site of infection. The failure of penicillin to eradicate many of these bacteria, which include Staphylococcus aureus, Haemophilus influenzae, Moraxella (Branhamella) catarrhalis and a multitude of pharyngeal anaerobes, may help to explain why penicillin is sometimes ineffective for acute and recurrent group A streptococcal infections. Therapeutic alternatives currently include cephalosporins, erythromycin, rifampin combined with penicillin, amoxicillin/clavulanate potassium and others.     

Study of the diffusion of cefmenoxime into the bronchial secretions

The wide spectrum of antibacterial activity of cefmenoxime as well as its resistance to beta-lactamase degradation, confers upon this drug a probable efficacy in the treatment of common respiratory infections. The objective of this study was to evaluate the penetration of cefmenoxime into bronchial secretions taken in patients, mostly with chronically superinfected bronchial pathology. Bronchial samples were collected by means of fiber-optic bronchoscopy; simultaneous serum samples were also taken after bolus intravenous injection of 1 g of cefmenoxime, after a single dose in 12 patients (group I); after multiple doses in 12 patients (group II). Concentrations of cefmenoxime were determined by means of microbiological procedure. The results showed: bronchial kinetics of cefmenoxime similar to those of other cephalosporins studied previously; after multiple doses a bronchial steady state with a slow decrease of bronchial levels as a function of time; no difference between levels measured after single or multiple doses; a ratio between bronchial levels (B) and simultaneous serum (S) levels (B/S, %) of about 10% at the 2nd hour, 20% at the 4th hour. Due to the extremely low MICs for most bacteria responsible for respiratory infections, cefmenoxime might be expected as the drug of choice in the treatment of bronchopulmonary infections.     

Treatment of Gonorrhea with Spectinomycin Hydrochloride: Comparison with Standard Penicillin Schedules

Spectinomycin hydrochloride, a new parenteral antibiotic prepared from Streptomyces spectabilis, was compared with standard U.S. Public Health Service-recommended dosages of aqueous procaine penicillin G in the treatment of uncomplicated gonorrhea in 353 men and 314 women. Of the 314 women, 130 had a pretreatment positive rectal culture. All diagnoses were proven by culture on Thayer-Martin selective medium. Minimal inhibitory concentrations of both drugs were determined. Single doses of 2 and 4 g of spectinomycin were compared with 2.4 million units of procaine penicillin in males and with both 2.4 and 4.8 million units of procaine penicillin in females. Both spectinomycin schedules, 2.4 million units of penicillin in males and 4.8 million units of penicillin in females, resulted in cure rates in excess of 90%. There were no failures at the rectal site only in those women with positive rectal cultures. There was no advantage to using the larger amount of spectinomycin in either sex.     

Comparison of ciprofloxacin and ceftriaxone as single-dose therapy for uncomplicated gonorrhea in women.

Although women bear the brunt of gonococcal infection-related morbidity, few large studies of gonorrhea treatment in women have been conducted. In a multicenter, double-blind, placebo-controlled trial, 181 evaluable women with uncomplicated gonorrhea were treated with ciprofloxacin (250 mg orally; 94 women) or ceftriaxone (250 mg intramuscularly; 87 women). Twenty-four percent of the participants were infected with antibiotic-resistant Neisseria gonorrhoeae. Cervical gonorrhea was cured in 100% (93 of 93) of the women treated with ciprofloxacin and 99% (83 of 84) receiving ceftriaxone. All pharyngeal (n = 5) or rectal (n = 20) infections treated with ciprofloxacin were cured, as were ceftriaxone-treated patients with pharyngeal (n = 6) or rectal (n = 21) infection. Geometric mean MICs (range) for 248 pretreatment isolates were: penicillin, 0.28 (0.015 to 8.0); tetracycline, 0.46 (0.06 to 4); ciprofloxacin, 0.003 (0.002 to 0.015); and ceftriaxone, 0.004 (0.001 to 0.125) microgram/ml. Both drugs were well tolerated. Despite the high prevalence of antibiotic-resistant gonococci in these populations, 250 mg of oral ciprofloxacin was as effective as an injection of ceftriaxone.     

Penicillin Therapy of Experimental Endocarditis Induced by Tolerant Streptococcus sanguis and Nontolerant Streptococcus mitis

The response of tolerant Streptococcus sanguis and nontolerant Streptococcus mitis infections to penicillin therapy was compared in the rabbit model of endocarditis. The minimal inhibitory and bactericidal concentrations of penicillin were 0.1 and 0.1 μg/ml, respectively, for S. mitis and 0.05 and 6.2 μg/ml, respectively, for S. sanguis. Time-kill studies done in vitro with penicillin concentrations of 2 and 20 μg/ml demonstrated minimal killing of the tolerant strain, with a 3 log difference in survival between the two strains after 24 and 48 h. Both strains produced endocarditis with comparable bacterial densities on the valvular vegetations. Rabbits were treated with procaine penicillin G in two dosage regimens, 80,000 or 5,000 U/kg given every 8 h. There was no difference between bacterial densities in valvular vegetations removed from rabbits infected with either strain after 2, 4, or 6 days of treatment with the high-dose regimen (serum penicillin concentration at 0.5 h, 9.4 μg/ml), despite the fact that serum bactericidal activity against the tolerant strain at 0.5 h was minimal. With the low-dose penicillin regimen (serum concentration at 0.5 h, 2.5 μg/ml), therapy was significantly less effective in the tolerant group only after 6 days of treatment. Similar results were obtained when penicillin was administered in low and high doses to prevent infection. In this animal model of infection, penicillin tolerance was associated with a diminished response to penicillin therapy only when the dose was severely restricted. In the high-dose regimen, there was no difference in the response to penicillin therapy between animals infected with either strain, despite the presence of only minimal serum bactericidal activity in the rabbits infected with the tolerant strain.     

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.