Antibiotic cycling and marketing into the 21st century: a perspective from the pharmaceutical industry.

Before the development of the first antimicrobial agents, bacteria already had demonstrated an ability to adapt to stress in the environment, resulting in the development of resistance that often makes the prevailing antibiotic treatment ineffective. The response to antimicrobial resistance in the medical community has been to use new or alternative antibiotics not previously used against the resistant bacteria. The pharmaceutical industry has responded to the resistance problem by producing newer antibiotics, either as modifications of currently existing compounds or as combinations of compounds that may inhibit or bypass the bacterial resistance mechanisms. The development of new antibiotics is a lengthy and costly process. To be successful, the pharmaceutical industry must anticipate the changing needs of the medical community, as well as the dynamic process of antimicrobial resistance. The marketing of new antimicrobial agents must be adaptable to the potential environmental pressures that induce bacterial resistance in order to ensure the longevity of the agents.

Syphilis and neurosyphilis in a human immunodeficiency virus type-1 seropositive population: evidence for frequent serologic relapse after therapy.

OBJECTIVE: To describe clinical and treatment aspects of syphilis infection among patients seropositive for the human immunodeficiency virus (HIV). PATIENTS AND METHODS: Results of serologic tests for syphilis, CD4+ T-lymphocyte counts, and clinical response to therapy were retrospectively monitored in 100 HIV-infected adults with syphilis from a tertiary-care military HIV program. RESULTS: Of the 1,206 HIV-infected patients, 100 (8.3%) in the cohort had syphilis; 61 patients were treated for active syphilis. Serologic or clinical relapse eventually occurred in 10 of the 56 treated patients (17.9%) with follow-up available; 7 of the 10 who relapsed had previously received high-dose intravenous or procaine penicillin therapy. Relapse occurred more than 12 months after initial therapy in 6 of 10 patients (60%) who experienced relapse; 5 patients experienced multiple relapses. The mean CD4+ T-lymphocyte count was not predictive of relapse. Patients with reactive cerebrospinal fluid (CSF) Venereal Disease Research Laboratory (VDRL) test titers (4 of 7 patients [57%]) or the rash of secondary syphilis (4 of 14 patients [29%]) were at highest risk of subsequent relapse or treatment failure when monitored for an average of 2 years. CONCLUSION: Standard penicillin regimens, including high-dose intravenous penicillin, transiently lowered serum VDRL titers in nearly all cases, but were sometimes inadequate in preventing serologic and clinical relapse in patients infected with HIV type-1, especially among those with secondary syphilis and reactive CSF VDRL titers. Careful long-term follow-up is essential, and repeated courses of therapy may be needed for patients infected with HIV type-1 who have syphilis.

Evaluation of the standardized disk diffusion and agar dilution antibiotic susceptibility test methods by using strains of Neisseria gonorrhoeae from the United States and Southeast Asia.

Presently, most Neisseria gonorrhoeae testing is based on beta-lactamase tests and agar dilution with common therapeutic agents. The National Committee for Clinical Laboratory Standards (NCCLS) recently described a disk diffusion test that produced results similar to the reference agar dilution method for the antibiotic susceptibility of N. gonorrhoeae. We obtained 71 gonococcal isolates from active-duty males aboard a United States Navy vessel while deployed in the Western Pacific during 1989. In addition, 47 isolates of N. gonorrhoeae were obtained from sexually transmitted disease clinics within the branch clinic operations of the Naval Hospital, San Diego (SD), and tested. Antibiotic susceptibility tests by using the NCCLS agar dilution and disk diffusion techniques were compared. Among the Southeast Asia (SEA) isolates, 47% were beta-lactamase producers compared with 10.5% of the SD isolates. The mean MICs (SEA/SD) in micrograms per milliliter for both groups were as follows: penicillin, 88/15; tetracycline, 2.2/0.95; erythromycin, 1.2/0.49; ceftriaxone, 0.016/0.012; cefotaxime, 0.034/0.03; cefuroxime, 0.44/0.17; cefoxitin, 1.3/0.97; spectinomycin, 150/131; ciprofloxacin, 0.07/0.034; norfloxacin, 0.77/0.29; lomefloxacin, 0.15/0.0.056; and ofloxacin, 0.07/0.036. The established NCCLS interpretive criteria for both susceptibility methods appear applicable to domestic gonococcal strains. However, modifications may be necessary for the more antimicrobial agent-resistant SEA isolates on the basis of the clinical success and cure rates following the indicated single-dose regimens for the geographic region.

Gastrointestinal side effects of intravenous erythromycin: incidence and reduction with prolonged infusion time and glycopyrrolate pretreatment.

OBJECTIVE: To determine the frequency of gastrointestinal toxicity due to intravenous (IV) erythromycin and to attempt to decrease this toxicity by prolonging the infusion time of erythromycin and/or pretreating with the peripheral anticholinergic, glycopyrrolate 0.1 mg IV. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: General medical wards of a tertiary medical center. PATIENTS: A total of 51 hospitalized patients 18 years of age or older who were prescribed IV erythromycin lactobionate (EMLB) 500 mg every 6 hours by their attending physicians. INTERVENTIONS: Each of eight consecutive infusions of EMLB was randomly assigned to one of four groups: control--30-minute infusion/placebo pretreatment; 60/P--60-minute infusion/placebo pretreatment; 30/G--30-minute infusion/glycopyrrolate pretreatment; and 60/G--60-minute infusion/glycopyrrolate pretreatment. MAIN OUTCOME MEASURES: Each infusion was accompanied by a questionnaire in which patients rated the magnitude of nausea and vomiting on a scale of 1 (no toxicity) to 9 (severe toxicity). Scores for both nausea and vomiting were added together for a total toxicity score ranging from 2 to 18. A total score of greater than 8 was defined as clinically important. RESULTS: The 51 patients received a total of 356 infusions with gastrointestinal toxicity occurring in 27 of 51 (53%) patients. Among patients under the age of 40, 22 of 33 (67%) experienced toxicity compared with only five of 18 patients (28%) over the age of 40 (p = 0.018). Clinically important toxicity was seen in 19 of 51 patients (37%), including five who withdrew during the study because of severe nausea and vomiting. In this group, the combination of a 60-minute erythromycin infusion and glycopyrrolate pretreatment decreased clinically important toxicity by 79% from 47% to 10%, a statistically and clinically significant 37% (95% CI, 14% to 60%) difference (p = 0.007). CONCLUSIONS: Gastrointestinal toxicity associated with the IV infusion of erythromycin is common and is more likely to occur in younger patients. A 1-hour infusion of erythromycin combined with pretreatment with glycopyrrolate, 0.1 mg IV, is effective in reducing this toxicity.