Newer oral antimicrobials for resistant respiratory tract pathogens. Which show the most promise?

As antimicrobial resistance to tried-and-true drugs continues to build, an arsenal of new drugs aimed at resistant respiratory tract pathogens is needed. Penicillin is now ineffective against several common pathogens, including many pneumococcal organisms. Newer antimicrobials, including macrolides, cephalosporins, and fluoroquinolones, have been developed to take its place. The authors of this article present a progress report of the fight against respiratory tract infection and an assessment of the most promising newer agents for use against multidrug-resistant pathogens.

Sparfloxacin: potential clinical and economic impact in the treatment of respiratory infections.

Sparfloxacin is a new oral fluoroquinolone antimicrobial that is highly active against common respiratory pathogens, including multiresistant strains. It is well absorbed and has excellent penetration into upper and lower respiratory tissues. Sparfloxacin is administered once a day and does not interfere with the metabolism of other drugs. The agent is highly effective and safe in the treatment of acute sinusitis, exacerbations of chronic bronchitis, and community-acquired pneumonia. Due to its activity against multidrug-resistant respiratory pathogens, it has the potential to prevent hospitalization as well as decrease parenteral antibiotic therapy. Consequently, it may generate significant pharmacoeconomic benefits to patients and payers of medical care.

A preliminary study of clarithromycin versus doxycycline in the treatment of nongonococcal urethritis and mucopurulent cervicitis.

In a comparison of drug safety and efficacy, 40 adult outpatients with clinical signs and symptoms of nongonococcal urethritis or mucopurulent cervicitis were treated with either clarithromycin 250 mg or doxycycline 100 mg twice/day for 7 days. Clinical and laboratory evaluations were repeated during, at the end, and 3 weeks after the completion of therapy. Isolation and susceptibility tests of Chlamydia and Mycoplasma isolates were performed at each visit. All but one patient who received doxycycline were clinically cured or improved at the end of treatment. Two (10%) patients who received clarithromycin and three (15%) who received doxycycline had clinical relapses of the infection. All isolates of Chlamydia trachomatis were eradicated and did not recur in both groups. Doxycycline was more effective than clarithromycin in eradicating Ureaplasma urealyticum (p < 0.01). Both groups reported a high frequency of minor adverse effects, but no patient discontinued therapy. Overall, clarithromycin was clinically safe and effective treatment in patients with nongonococcal urethritis and mucopurulent cervicitis.

Legionella lansingensis sp. nov. isolated from a patient with pneumonia and underlying chronic lymphocytic leukemia.

A Legionella-like organism, strain 1677-MI-H, was isolated from the bronchoscopy washings of a patient with pneumonia who had a 2-year history of progressive, chronic lymphocytic leukemia. The growth characteristics, cellular fatty acids, and ubiquinone content of the isolate were consistent with those for Legionella spp. The isolate was serologically distinct in the slide agglutination test with absorbed antisera. DNA hybridization studies showed that strain 1677-MI-H (ATCC 49751) represents a new Legionella species which is named Legionella lansingensis.

The new macrolide antibiotics. Azithromycin and clarithromycin.

Azithromycin (Zithromax) and clarithromycin (Biaxin Filmtabs) are new macrolide antibiotics with several advantages over erythromycin. Azithromycin has an expanded spectrum against gram-negative bacilli. Clarithromycin is more active than erythromycin against gram-positive cocci; combination with its 14-hydroxy metabolite enhances its antimicrobial activity. These new agents penetrate well into tissues and concentrate in macrophages and polymorphonuclear leukocytes. They offer improved bioavailability and an extended half-life. The high tissue-to-serum level and extended elimination half-life of azithromycin allow for once-daily dosing and short-course therapy. Clarithromycin and 14-hydroxyclarithromycin maintain high serum levels and tissue-to-serum concentrations. Both of these new agents have been effective in streptococcal pharyngitis, acute sinusitis, acute lower respiratory tract infections, skin and soft-tissue infections, and sexually transmitted diseases. A single dose of azithromycin is effective for genital chlamydial infections. Adverse reactions to these agents have usually been mild and have not included serious organ toxicity. In clinical trials, the rate of premature discontinuation of therapy has been less than observed with erythromycin. Azithromycin and clarithromycin should be used according to the current guidelines of the Food and Drug Administration; their future role will be determined by ongoing laboratory and clinical evaluations.

High prevalence of historical risk factors for blood-borne infections among inpatients at three community hospitals.

To determine the prevalence of risk factors for blood-borne infections in a city with a low prevalence of human immunodeficiency virus (HIV), we confidentially surveyed 397 adult inpatients in three community hospitals. Twenty-one percent of inpatients reported one or more risk factors, 56% denied risks, 15% were unable to respond, and 8% declined to respond. Inpatients reporting a blood-borne infection risk factor, those declining response, and those denying risk were of comparable age, sex, race, and marital status. On medical floors, 28% of patients reported risk; on surgical floors, 23%; in intensive care units, 11%; and on obstetric floors, 5%. A recent blood transfusion (59%) and history of hepatitis (40%) were reported most often. Only 2.4% of persons with risks reported being positive for HIV antibody; however, 24% of reported risks were those frequently associated with HIV infection. By using history alone to determine isolation categories and by classifying patients unable to respond and those declining response as potentially infectious, more than 40% of our community's inpatients would require blood and body fluid precautions. This high historical risk supports use of a type of body substance isolation for all patients.

Comparison of chlamydial culture with Chlamydiazyme assay during erythromycin PCE treatment of Chlamydia genital infections.

We compared chlamydial culture with the chlamydial antigen detection enzyme immunoassay system (Chlamydiazyme, Abbott Diagnostic Products; Abbott Park, IL) during treatment of Chlamydia genital infections. Participants received 333 mg of erythromycin PCE (Abbott Laboratories; Abbott Park, IL) 3 times per day for 7 days. On days 0, 3, 7, and 14, chlamydial cultures were positive in 30/30 (100%), 5/29 (17.2%), 0/27, and 0/25 participants, respectively. Concurrent Chlamydiazyme assays were positive in 30/30 (100%), 11/30 (37%), 1/28 (4%), and 0/25 participants. Twenty-eight of 28 persons who received erythromycin PCE for at least 3 days had negative test results for both chlamydial culture and Chlamydiazyme at their last clinic visit. Chlamydiazyme assay tended to remain positive longer than chlamydial culture during treatment, but 7 days after therapy was completed, no Chlamydia trachomatis antigens were detectable by this assay. Erythromycin PCE was well tolerated and rapidly eliminated Chlamydia genital infections in 83% of persons showing negative cultures by the third day of therapy.