Ceftriaxone in treatment of serious infections. Sexually transmitted diseases.

The most recent CDC guidelines for treatment of STDs list a number of syndromes for which ceftriaxone is the recommended therapy, including those caused by N. gonorrhoeae and H. ducreyi. The drug has successfully eradicated incubating syphilis. Its use in primary, secondary, and latent syphilis is promising, although adequate data regarding optimal dose and duration of therapy are not yet available. It remains to be seen whether ceftriaxone represents the sun rising on a new era of successful STD treatment or the sun setting on the old penicillin era.

Treatment of gonorrhea with first- and second-generation cephalosporins and other new beta-lactam antibiotics.

Aqueous procaine penicillin, ampicillin, and amoxicillin have been used successfully in treatment of gonococcal infections for many years. Many of the new beta-lactam antimicrobial agents subsequently have proved effective for treating these infections as well. First-generation cephalosporins are less active (by weight) than second-generation cephalosporins, which, in turn, are less active than third-generation drugs. Single-dose therapy of uncomplicated mucosal gonococcal infections with first-generation cephalosporins has resulted in generally unacceptably low cure rates of less than 90% in most studies, whereas parenterally and orally administered second-generation cephalosporins show good clinical efficacy. Both second- and third-generation cephalosporins are active against beta-lactamase-producing Neisseria gonorrhoeae. The extended-spectrum and ureido-penicillins are active in vitro against non-beta-lactamase-producing N. gonorrhoeae and have parallel activity in vivo. Single doses of aztreonam, the first monobactam studied in humans, have also shown excellent clinical efficacy.

Cytotoxic lymphocytes generated in vivo with acute measles virus infection.

We studied the generation of cytotoxic lymphocytes in adults during an outbreak of acute measles virus infection. Nine patients were studied determining in particular whether virus-specific cytotoxic T lymphocytes could be directly detected in peripheral blood during this acute infection. The cytotoxicity of PBL was assayed against measles virus-infected and uninfected phytohemagglutinin-induced blast cells of matched and mismatched HLA, A, B, and C types, in a standard 4-h 51Cr release assay. There was greater cytotoxicity against measles virus-infected than uninfected target cells in at least one sample from every patient. In 4 patients this preferential lysis of virus infected cells was greater (a difference of more than 10% virus-specific lysis) against HLA-matched than mismatched targets. This preference for HLA A and B matched infected target cells was also clearly seen when the effector PBL were depleted of FC receptor bearing cells. The other 5 subjects exhibited no evidence of preferential lysis of HLA-matched measles virus-infected cells. All 9 patients limited the spread of measles virus infection and recovered equally from the acute infection. These studies provide some evidence to suggest that MHC-restricted virus-specific CTL are detectable in human peripheral blood during acute measles virus infection, albeit only with low frequency, but are not necessarily associated with recovery from disease.

A comparison of penicillin G plus a beta-lactamase inhibitor (sulbactam) with spectinomycin for treatment of urethritis caused by penicillinase-producing Neisseria gonorrhoeae.

When combined with penicillin, sulbactam, a beta-lactamase inhibitor with weak intrinsic antibacterial activity, produces a marked synergistic effect in vitro against penicillinase-producing Neisseria gonorrhoeae. We compared a regimen of aqueous procaine penicillin G, sulbactam, and probenecid with spectinomycin for the treatment of uncomplicated gonococcal urethritis. Of 101 patients receiving the penicillin-sulbactam regimen, 97 (97%) were cured of their infection, as were 87 (95%) of 92 patients who received spectinomycin. Fifty per cent of patients were infected with penicillinase-producing N. gonorrhoeae; 43 (94%) of 46 treated with the penicillin-sulbactam regimen were cured as compared with 47 (92%) of 51 treated with spectinomycin. Neither regimen was associated with serious adverse effects. The results show that aqueous procaine penicillin G given with sulbactam and probenecid is an effective alternative for single-session therapy of urethritis caused by penicillinase-producing N. gonorrhoeae.

Treatment of penicillin-resistant Neisseria gonorrhoeae with oral norfloxacin.

Norfloxacin, an orally administered quinoline carboxylic acid that is structurally related to nalidixic acid, has been shown to be highly active in vitro against penicillinase-producing Neisseria gonorrhoeae. Ninety-two men with culture-proved gonococcal urethritis, 46 per cent with penicillinase-producing N. gonorrhoeae, and 27 per cent with non-penicillinase-producing N. gonorrhoeae that was resistant to penicillin were given either 1200 mg of norfloxacin divided into two equal oral doses four hours apart (59 patients) or 2 g of spectinomycin intramuscularly (33 patients). All patients in both treatment groups were cured. No adverse reactions were reported in either group. We conclude that a two-dose, single-day regimen of orally administered norfloxacin is effective therapy for uncomplicated urethritis caused by penicillin-resistant strains of N. gonorrhoeae.

Gonococcal urethritis.

Gonorrhea continues to maintain its position as the most common reportable infectious disease in the United States. Penicillin is still the antibiotic of choice for the treatment of uncomplicated gonococcal urethritis in most of the United States, but the increasing incidence of penicillinase-producing Neisseria gonorrhoeae (PPNG) in many areas of the world necessitates a reconsideration of standard therapy. In addition to penicillin resistance, the gonococcus is also developing resistance to spectinomycin and tetracycline, which further complicates the choice of therapy.

Cefonicid as therapy for uncomplicated gonococcal urethritis caused by penicillinase-producing Neisseria gonorrhoeae.

Young men with uncomplicated gonococcal urethritis were treated with 1 gram of cefonicid given intramuscularly plus 1 gram of probenecid by mouth. Of 53 evaluable patients, 33 (62%) had penicillinase-producing Neisseria gonorrhoeae. All but one of these patients were cured. All men who had penicillin-sensitive infections were cured. Cefonicid was highly effective in the treatment of both penicillin-sensitive and penicillin-resistant N gonorrhoeae. Other than moderate pain at the site of injection, there were no adverse side effects. Cefonicid can be added to the group of newer cephalosporins that are effective in the treatment of gonococcal urethritis caused by either penicillin-sensitive or penicillin-resistant strains.

Laboratory-acquired gonococcal conjunctivitis: successful treatment with single-dose ceftriaxone.

Gonococcal conjunctivitis can be a severe disease with sequelae of corneal ulceration, hypopyon, and global perforation. Current recommended therapy is hospitalization and repeated courses of parenteral antibiotics. The authors report a case successfully managed with a single injection of the new third-generation cephalosporin, ceftriaxone.

Ceftizoxime (FK-749) is effective therapy for urethritis caused by penicillinase-producing Neisseria gonorrhoeae.

Fifty-five men with culture-proved gonococcal urethritis caused by either penicillin-sensitive or penicillinase-producing Neisseria gonorrhoeae were treated with 1 g of ceftizoxime given intramuscularly. All patients were cured, including 26 (47%) with penicillinase-producing strains. Patients experienced no local or systemic side effects and tolerated the injection of ceftizoxime well. These results show that ceftizoxime is an effective alternative to either spectinomycin or cefoxitin in treatment of uncomplicated gonococcal urethritis caused by penicillin-resistant bacteria.

Effectiveness of aztreonam, a new monobactam antibiotic, against penicillin-resistant gonococci.

Since the recognition of penicillinase-producing strains of N gonorrhoeae (PPNG) in 1976, these organisms have attained a worldwide distribution. The treatment of choice for infection due to PPNG has generally been spectinomycin administered im. In 1981, however, an infection from California was reported to be due to a strain of PPNG that was also resistant to spectinomycin (MIC, greater than 2,048 micrograms/ml) [1]. Throughout 1982, seven such isolates were reported worldwide [2], and in January 1983 an epidemiologically linked series of 27 cases of infection due to spectinomycin-resistant PPNG occurred in Korea. Because of the apparent declining utility of spectinomycin, we studied the efficacy and safety of aztreonam, a synthetic monobactam antibiotic from the Squibb Institute for Medical Research (Princeton, NJ) [3], in the treatment of acute uncomplicated gonococcal urethritis in men. Men with gonococcal urethritis were randomly treated with either 1 g of aztreonam or 2 g of spectinomycin im. Of the 112 men so treated, 93 could ultimately be evaluated: 51 who received aztreonam and 42 who received spectinomycin. Both drugs were 100% effective in the treatment of urethritis produced by both penicillin-sensitive and penicillin-resistant strains of gonococci. Furthermore, there were no reported side effects in either group and no laboratory abnormalities attributable to the aztreonam, with the exception of one patient with a minimally elevated level of serum glutamic oxaloacetic transaminase (serum glutamic pyruvic transaminase and alkaline phosphatase levels were normal).(ABSTRACT TRUNCATED AT 250 WORDS)

One gram of cefoxitin cures uncomplicated gonococcal urethritis caused by penicillinase-producing Neisseria gonorrhoeae (PPNG).

Therapy of disease caused by penicillinase-producing Neisseria gonorrhoeae with lower-than-standard doses of cefoxitin was evaluated. A pilot study showed that doses of greater than or equal to 1 g were adequate, whereas 500-mg doses consistently failed. After the pilot study, 89 men with gonorrhea were treated with 1 g of cefoxitin given intramuscularly plus 1 g of probenecid given orally. Of the 89 men, 86 were cured. Sixty per cent were infected with penicillin-resistant strains of N. gonorrhoeae. The three men who were culture-positive on follow-up had been sexually reexposed, whereas none of those with negative cultures had had reexposure. These clinical results indicate that a treatment regimen of 1 g of parenteral cefoxitin plus 1 g of oral probenecid appears to be as effective as the standard 2-g dose. Regimens using doses lower than 1 g are ineffective.

Comparison of ceftriaxone with cefoxitin in the treatment of penicillin-resistant gonococcal urethritis.

Since cefoxitin has been shown to be an effective alternative to spectinomycin for the treatment of infections due to penicillinase-producing strains of Neisseria gonorrhoeae (PPNG) its efficacy was compared with that of a new cephalosporin, ceftriaxone (R013-9904). One hundred and twenty eight men with culture-confirmed gonococcal urethritis were treated with either 250 mg of ceftriaxone intramuscularly or 2 g of cefoxitin intramuscularly with oral probenecid 1 g. The incidence of penicillin-resistant strains in each group was about 60%. Ceftriaxone was completely effective in treating both penicillin-sensitive and penicillin-resistant gonococcal urethritis. No side effects were noted. Ceftriaxone thus seems to be an effective and safe alternative to either spectinomycin or cefoxitin in the treatment of penicillin-resistant gonococcal urethritis.

In vitro antimicrobial activity of eight new beta-lactam antibiotics against penicillin-resistant Neisseria gonorrhoeae.

Increasing numbers of cases of penicillin-resistant gonorrhea necessitate the evaluation of new antibiotics for treatment of this disease. We tested the susceptibility of 92 penicillinase-producing (PP) Neisseria gonorrhoeae isolates and 88 penicillin-susceptible (PS) isolates to eight new beta-lactam antibiotics. The minimal inhibitory concentrations of these antibiotics were determined by the agar plate method. PP and PS N. gonorrhoeae isolates were susceptible to clinically achievable levels of all antibiotics tested. There were, however, marked differences among the drugs with regard to the concentration required to inhibit growth. The PP N. gonorrhoeae isolates were extremely susceptible to ceftriaxone, ceftizoxime, and cefotaxime, highly susceptible to moxalactam and cefoperazone, and less susceptible to cefoxitin, ceforanide, and cefonicid (geometric mean minimal inhibitory concentrations were 0.002, 0.003, 0.007, 0.03, 0.07, 0.6, 2.4, and 3.1 micrograms/ml, respectively). Although this in vitro study showed PP N. gonorrhoeae isolates to be comparatively more susceptible to ceftriaxone, ceftizoxime, and cefotaxime than to the other antibiotics, these results may not correlate with clinical efficacy.

Brief prophylaxis with doxycycline for the prevention of traveler's diarrhea.

A prospective, randomized double-blind trial of doxycycline prophylaxis for traveler's diarrhea was conducted on 145 volunteers during a 2.5-day visit to Mexico. Traveler's diarrhea occurred in 15 (21%) of the placebo group and in 3 (4%) of the doxycycline group (p = 0.002). There was no rebound increase in the incidence of acute diarrhea after departure from the high risk area in the doxycycline-treated group. A variety of bacterial pathogens were isolated from individuals symptomatic with traveler's diarrhea. Nausea alone (8%) or nausea with vomiting (4%) occurred in the doxycycline-treated group only and were the only side effects observed (p = 0.003). We conclude that doxycycline is safe and efficacious for the prophylaxis of traveler's diarrhea for short-term exposure in a high risk area.