Endocarditis in mice infected with Coxsackie virus B4.

Endocarditis has not been generally considered to be a complication of viral infection. We show that mural and valvular endocarditis can be produced in mice infected with Coxsackie virus B(4). Because this virus commonly infects man and is highly cardiotropic, it is important to know whether it produces valvular lesions in man similar to those we describe in mice.

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.

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.

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.

Cefoperazone therapy of serious infections.

Cefoperazone was evaluated as the therapeutic agent in 64 adults with serious infections. Included were pneumonias, urinary tract infections, septicemia, osteomyelitis, joint infections, and superficial infections. A total of 84 organisms, including many multiantibiotic-resistant strains, were designated as the etiological agents. In most patients therapy was initiated before information on cefoperazone sensitivity of the infecting organism was available. This proved suitable in most instances. Clinical response to therapy was excellent in these individuals. Bacteriological responses coincided with the problems of the patient but did not reflect inadequacy of the antibacterial effect of cefoperazone. Adverse effects on renal function, including already impaired function, were not observed.

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.

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.

Third-generation beta-lactam antibiotics for treatment of orthopedic infections.

Third-generation beta-lactam antibiotics are effective against a wider range of microorganisms than are older antibiotics. Cefotaxime, moxalactam, cefoperazone, ceftizoxime, ceftazidime, cefsulodin, and ceftriaxone were used to treat 102 patients hospitalized with orthopedic infections. Sensitivity of the pathogens to the antibiotic used was established in all cases. Patients allergic to penicillin were given either moxalactam or ceftazidime. Pathogens were eradicated in all but six instances, five of which were Pseudomonas aeruginosa. Four of these developed resistance during therapy. Only three patients had clinical responses that were less than satisfactory. No serious adverse reaction occurred, and no allergic reactions developed. This new class of antibiotics is thus safe and effective as the sole therapeutic agent for many orthopedic infections, including those that require long periods of treatment.

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.

Comparison of the efficacy and safety of ceftibuten and cefaclor in the treatment of pneumonia and bronchiectasis.

In a multicentre, international study of 187 adult patients with bacterial pneumonia or bronchiectasis, the safety and efficacy of a regimen of 200 mg ceftibuten administered twice-daily was compared with cefaclor given in a dosage of 500 mg three times a day. Of the 94 evaluable patients, 66 received ceftibuten and 28 received cefaclor. The overall bacteriological response was similar in the two treatment groups with elimination of the original pathogen in 91% and 89% of the patients receiving ceftibuten and cefaclor, respectively. The overall clinical response mirrored the bacteriological results with a successful clinical outcome in 92% of ceftibuten-treated patients compared with 93% in patients receiving cefaclor. Adverse experiences were, in general, few and mild, being reported in 8% and 17% of patients receiving ceftibuten and cefaclor, respectively.

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.

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.