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Prostatitis has remained a pathological entity that is difficult to treat. Part of the difficulty revolves about the putative offending pathogens. For acute prostatitis, members of the Enterobacteriaceae, particularly Escherichia coli, play a central role, while intracellular pathogens such as Chlamydia are more frequently seen in chronic prostatitis. Consequently, a drug needs to be able to penetrate to this specialized site in both the acute and chronic infection forms of the disease and also have potent activity against the most common causative pathogens, both intracellular and extracellular. Levofloxacin has such an activity profile. We wished to document its ability to penetrate to the site of infection. Patients undergoing prostatectomies were administered 500 mg of levofloxacin orally every 24 h for 2 days prior to surgery, and then on the day of surgery, 500 mg was administered as an hour-long, constant-rate intravenous (i.v.) infusion. A set of blood samples was obtained as guided by stochastic optimal design theory. Prostate biopsy times were determined by randomizing subjects into one of four groups, based on the interval after the i.v. dose. All plasma and prostate drug concentrations were comodeled by a population modeling program, BigNPEM, implemented on the Cray T3E Supercomputer housed at the Supercomputer Center at the University of California at San Diego. Penetration was determined as the ratio of the area under the concentration-time curve (AUC) of levofloxacin in the prostate to the plasma levofloxacin AUC. When calculated from the mean population parameters, this penetration ratio was 2.96. We also performed a 1,000-subject Monte Carlo simulation from the mean parameter vector and covariance matrix. The mean penetration ratio here was 4.14 with a 95% confidence interval of 0.20 to 19.6. Over 70% of the population had a penetration ratio in excess of 1.0. Levofloxacin adequately penetrates a noninflamed prostate and should be evaluated for the therapy of prostatitis.Prostatitis, particularly chronic prostatitis, is often difficult to treat. Part of the difficulty revolves around defining the infecting pathogen. Another aspect of the problem lies in the protected nature of the prostate with regard to antimicrobial penetration. The causative pathogen can be extracellular (e.g., as in acute or chronic prostatitis due to Escherichia coli) or intracellular (e.g., as in chronic prostatitis due to Chlamydia). Consequently, the agent chosen for therapy should have a spectrum that is appropriate for the suspected pathogen and should penetrate well into the protected space of the prostate.Levofloxacin is an agent that has good microbiological activity against the pathogens that cause the vast majority of infections of the prostate (9). Because it is a fluoroquinolone, one would, on first principles, believe that it would have excellent penetration properties into extracellular fluid as well as into cells. However, it is important to validate the penetration properties of an agent before testing the d...

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A mouse model of cerebral nocardiosis was used to determine relative antibiotic efficacy by reducing bacterial colony counts per gram of brain tissue. The antimicrobial agents employed were demonstrated in vitro to be inhibitory to most strains of Nocardia asteroides at very low concentrations. The agents used in this study were imipenem-cilastatin, amikacin, trimethoprim-sulfamethoxazole, and minocycline. Antibiotics were administered every 4 h for 72 h before animal sacrifice. Bacterial colony counts were assayed at various time points before the completion of therapy. Imipenem-cilastatin and amikacin were the most effective agents tested. Trimethoprim-sulfamethoxazole was less effective than imipenem and amikacin but more effective than minocycline. Minocycline did not eradicate intracerebral organisms and was similar to saline (control) in its effects.Nocardia asteroides is being increasingly recognized as a pathogen of normal and immunologically incompetent hosts (7,19). The most common sites of infection are the lungs, central nervous system, and skin (3). A central nervous system infection usually implies single or multiple brain abscesses, yet meningitis has been reported alone (14). Intracerebral nocardiosis, in contrast to other forms of nocardiosis in the immunologically incompetent patient, can be a rapidly progressive and fulminant infection and has been associated with mortality rates of up to 90% (15). Therapy for all forms of nocardiosis usually consists of a sulfonamide alone or in fixed combination with trimethoprim and these have been advocated by some authors as the drugs of choice (20,22). There are reports of cures with other antibiotics for those patients who have either failed on sulfonamides or experienced serious side effects which resulted in therapy being discontinued. These antibiotic regimens have included minocycline (23), amikacin, ampicillin (6), and erythromycin in combination with other agents (2). These alternative forms of therapy usually have been based on in vitro susceptibility testing of the specific strain of N. asteroides isolated from the patient and on previous anecdotal reports.Recent as this represents one of the more common forms of treatment and would provide a basis for comparison with other agents. MATERIALS AND METHODSAnimals. Female Swiss Webster mice weighing approximately 20 g were used in this study. The animals were received from Charles River Breeding Laboratories, Inc., Wilmington, Mass., at 6 weeks of age and were used several days thereafter. The mice were housed in standard cages and fed food and water ad libitum.Bacteria. A strain of N. asteroides isolated from a patient with cerebral nocardiosis at the Downstate Medical Center was used throughout this study. The isolate was maintained on Sabouraud agar slants and transfers to new agar slants were performed periodically. Inoculum preparation was performed by the method of Beaman and Maslan (5)

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