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Biomedical subjects

S E Berning

Publications and source records attributed to S E Berning.

27 records · Page 2Linked to original sources

Failure of drug penetration and acquisition of drug resistance in chronic tuberculous empyema.

We describe a patient with drug-resistant chronic tuberculous empyema in whom substantial differences between achievable pleural fluid and serum drug concentrations were displayed. The ratio of maximum concentration in pleural fluid to serum was especially low for rifampin (4%) but was also low for streptomycin (34%) and ofloxacin (48%). Subtherapeutic drug concentrations in the pleural fluid may have contributed to acquisition of drug resistance in this case.

Aged↗

Long-term safety of ofloxacin and ciprofloxacin in the treatment of mycobacterial infections.

Ofloxacin and ciprofloxacin are potentially useful agents for treating mycobacterial infections. We retrospectively reviewed 7 years' experience with these agents in 103 patients. Ofloxacin was used primarily to treat tuberculosis (TB), dosed to achieve 2-hour postdose serum concentrations of 8-12 micrograms/ml. Ciprofloxacin was used primarily to treat Mycobacterium avium complex (MAC) infection, dosed to achieve 2-hour post-dose serum concentrations of 4-6 micrograms/ml. Despite differences in patient characteristics, underlying disease, and concurrent medications, ofloxacin and ciprofloxacin were associated with a similar spectrum and incidence of adverse reactions. Both drugs were generally well tolerated. Adverse effects led to an ofloxacin dosage change in 1 patient (3%) and discontinuation of ofloxacin in 2 patients (6%). Adverse effects led to a ciprofloxacin dosage change in 2 patients (3%) and discontinuation of ciprofloxacin in 5 patients (7%). Ofloxacin and ciprofloxacin appear to be tolerated as well as or better than other "second-line" antimycobacterial drugs.

Antitubercular Agents↗

Infection caused by Mycobacterium tuberculosis.

OBJECTIVE: To update readers on the clinical management of infections caused by Mycobacterium tuberculosis, to provide a general description of the organism, culture and susceptibility testing, and clinical manifestations of the disease, and to provide several aspects of the treatment of the disease, including historical perspective, current approaches, and research opportunities for the future. DATA SOURCES: The current medical literature, including abstracts presented at recent international meetings, is reviewed. References were identified through MEDLINE, MEDLARS II, Current Contents, and published meeting abstracts. STUDY SELECTION: Data regarding the epidemiology, clinical manifestations, culture and susceptibility testing, and treatment of tuberculosis are cited. Specific attention has been focused on the clinical management of patients with noncontagious infection and potentially contagious active disease (TB) caused by M. tuberculosis. DATA EXTRACTION: Information contributing to the discussion of the topics selected by the authors is reviewed. Data supporting and disputing specific conclusions are presented. DATA SYNTHESIS: The incidence of TB is increasing in the US, despite the fact that available technologies are capable of controlling the vast majority of existing cases. Fueling the fire is the problem of coinfection with HIV and M. tuberculosis. Very few drugs are available for the treatment of TB, and few of these approach the potency of isoniazid and rifampin. Preventive therapy of patients exposed to multiple-drug-resistant M. tuberculosis (MDR-TB) is controversial and of unknown efficacy. Treatment of active disease caused by MDR-TB requires up to four times longer, is associated with increased toxicity, and is far less successful than the treatment of drug-susceptible TB. Strategies for the management of such cases are presented. The rising incidence of TB in the US reflects a breakdown in the healthcare systems responsible for controlling the disease, which reflects the past budgetary reductions. Although TB control is one of the most cost-effective public health strategies, funding has been cut repeatedly despite the fact that TB was never eliminated. This has helped to produce the current crisis, including the spread of MDR-TB in many urban areas. The elimination of TB will now take decades longer, cost hundreds of millions of dollars more, and result in vastly higher morbidity and mortality rates than would have occurred with timely, adequate measures. CONCLUSIONS: Tremendous effort and far more funding will be required to eliminate TB in the US. The selection of drug therapy must be based on the susceptibility data for each isolate. Multiple-drug therapy must be continued for 6 to > or = 24 months, and patient adherence to prescribed regimens must be verified in all cases of TB. Significant antimycobacterial drug malabsorption has been documented in AIDS patients with TB, and may result in treatment failure. New agents are needed to improve the clinical outcome in patients with MDR-TB.

Adult↗

Pharmacokinetic evaluation of para-aminosalicylic acid granules.

STUDY OBJECTIVE: To determine the bioavailability and renal elimination of para-aminosalicylic acid (PAS) and its inactive metabolite acetyl-para-aminosalicylic acid (AcPAS) from a new PAS formulation. DESIGN: (a) Single-dose pharmacokinetic study in healthy volunteers; (b) Day-1 and day-8 pharmacokinetic comparison in patients with multidrug-resistant tuberculosis (MDR-TB). SETTING: Referral hospital that specializes in the treatment of mycobacterial infections. PATIENTS: (a) Twelve healthy male and female volunteers recruited by the investigators. Eleven subjects (92%) completed the study; one subject could not maintain venous access and was removed from the study. (b) Six sequential male and female patients receiving multidrug treatment for advanced MDR-TB. All patients completed the study. INTERVENTIONS: (a) Volunteers received a single 4-g dose of enteric-coated PAS granules administered with food. Blood and urine samples were collected over 24 hours after the dose. (b) Patients received 4-g doses of enteric-coated PAS granules every 8 hours for 7 days as part of their treatment regimen. Blood samples were obtained at approximately 2, 4, and 8 hours after the first dose on day 1 and the twenty-second dose on day 8. MEASUREMENTS AND MAIN RESULTS: Concentrations of PAS and AcPAS were determined using high-performance liquid chromatography. The serum concentration-time curves from volunteers and patients showed sustained PAS concentrations, in contrast to immediate-release sodium PAS tablets. In the six patients with tuberculosis, day 8 concentrations were considerably higher than those on day 1, and all were sustained well above the PAS minimal inhibitory concentration for Mycobacterium tuberculosis. CONCLUSIONS: Para-aminosalicylic acid granules produce adequate serum concentrations and appear to be safe.

Absorption↗

Tuberculosis and multi-drug resistant tuberculosis in children.

Infection and disease caused by Mycobacterium tuberculosis remain a hugh global problem, and are not well controlled in several areas within the United States. Co-infection with the human immunodeficiency virus (HIV) and immigration from areas with high rates of tuberculosis contribute to the problem in the United States. Organisms resistant to the two main drugs, isoniazid and rifampin, known as multidrug-resistant M. tuberculosis or MDR-TB, present serious therapeutic challenges. Strategies for the management of such cases are presented.

Antitubercular Agents↗

Pharmacokinetic evaluation of thiacetazone.

STUDY OBJECTIVE: To investigate the steady-state pharmacokinetics of thiacetazone (TB-1), which is active in vitro against Mycobacterium avium complex (MAC). DESIGN: Open-label phase I study. SETTING: Specialized referral hospital. PATIENTS: Twelve healthy men and women. INTERVENTIONS: Oral TB-1 150 mg/day was administered for 7 days, followed by blood and urine collection over 48 hours. MEASUREMENTS AND MAIN RESULTS: The serum concentration versus time curves of TB-1 showed sustained concentrations, with maximum values of 1.59 +/- 0.47 micrograms/ml, time to maximum 3.30 +/- 1.18 hours, and serum half-life of 15-16 hours. Less than 25% of TB-1 was recovered unchanged in the urine over 48 hours. Rashes occurred in two subjects at the end of the 7-day dosing period and resolved without progression or sequelae. CONCLUSIONS: Based on these data, we initiated a phase II study of TB-I in patients with pulmonary MAC infection who do not have the acquired immunodeficiency syndrome.

Adult↗