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C A Peloquin

Publications and source records attributed to C A Peloquin.

At least 73 records · Page 4Linked to original sources
PubMed1993

Pharmacology of the antimycobacterial drugs.

The management of MDR-TB requires that the clinician become familiar with the "second-line" antimycobacterial agents. These drugs are generally less potent and frequently more toxic than isoniazid and rifampin. Because they are less active, innovative dosing schedules may allow us to take advantage of the few strengths that they possess. This approach will require further research into the dose-response relationships for each agent. Based on our current knowledge of these drugs, practical guidelines for their use have been described. These guidelines include the gradual escalation of the oral doses of PAS, cycloserine, and ethionamide over several days, and the intravenous administration of streptomycin and capreomycin. Both ciprofloxacin and ofloxacin may be used for the treatment of MDR-TB, but data from clinical trials are currently lacking. Finally, because patients with AIDS appear to develop antimycobacterial drug malabsorption over the course of their HIV infection, therapeutic drug monitoring can be used to verify drug absorption in the individual patient. This approach may improve therapy for that patient and prevent the selection of additional drug resistance.

Antitubercular Agents↗
PubMed1993

Low serum levels of oral antimycobacterial agents in patients with disseminated Mycobacterium avium complex disease.

Twenty-seven human immunodeficiency virus-infected patients with disseminated Mycobacterium avium complex disease who were treated with oral antimycobacterial agents (clofazimine, ciprofloxacin, ethambutol, and rifampin) were studied to evaluate the usefulness of monitoring serum drug concentrations and testing in vitro susceptibility of M. avium complex (MAC) isolates. Twenty patients tolerated treatment with three or four antimycobacterial agents for at least 8 weeks; mycobacteremia was eradicated in 7 (35%). The in vitro susceptibilities of MAC isolates to antimycobacterial agents were similar for these 7 and for the 13 who did not respond to antimycobacterial treatment. Serum drug levels were below the expected range in 6 of the 7 whose mycobacteremia was cleared and in 9 of the 13 nonresponders (P = .41). These low serum concentrations of antimycobacterial drugs may be due to impaired drug absorption in patients with AIDS and disseminated MAC disease.

AIDS-Related Opportunistic Infections↗
PubMed1991

Improved high-performance liquid chromatographic assay for the determination of ethionamide in serum.

A solid-phase extraction (SPE) method was developed to simplify the preparation of human serum prior to high-performance liquid chromatography of ethionamide (ETA). Octadecyl SPE columns were used. Serum constituents were removed from the column with water, and ETA was eluted with methanol. Samples were evaporated to dryness, reconstituted in mobile phase, and assayed. The method is reproducible, with a recovery of ETA of 64%, comparable to the more tedious liquid-liquid extraction method for ETA.

Chromatography, High Pressure Liquid↗
PubMed1991

Kinetics and dynamics of tobramycin action in patients with bacteriuria given single doses.

We studied the effect of a single intravenous dose of tobramycin on the rate of bacterial eradication from urine in 10 patients with bladder catheters. The catheter was replaced 4 to 6 h after the tobramycin dose. Pseudomonas aeruginosa was found in 7 of the 10 patients, while members of the family Enterobacteriaceae accounted for the remaining pathogens. The MIC for each bacterium was determined in both broth and urine. Tobramycin eradicated the bacteria from eight patients. Bacteriuria resolved in 21.8 +/- 18.0 h, and urine bactericidal activity persisted for 43.4 +/- 20.3 h after the dose of tobramycin. Most patients were recolonized by another bacterial species if use of Foley catheters was resumed on a continuous basis. Two patients required additional doses of tobramycin to eradicate the original pathogen. There were significant temporal relationships between the pharmacokinetics of tobramycin and the change in colony count of bacteria in urine.

Aged↗
PubMed1991

Pharmacokinetic evaluation of ethionamide suppositories.

The absorption and elimination of ethionamide (ETA) after oral tablets and rectal suppositories were determined in 12 healthy, adult male volunteers. A randomized, double-blind, double-dummy, crossover design was used. Treatments compared 250-mg ETA tablets and a placebo suppository to a 500-mg ETA suppository and two placebo tablets, given 7 days apart. Blood samples were collected at predetermined intervals for 12 hours after the dose. Serum concentrations of ETA were determined using high-performance liquid chromatography. The area under the serum concentration-time curve was used to compare the relative bioavailability of ETA from the two preparations. Relative bioavailability after rectal administration was 57.3% of that after oral administration. The maximum serum concentration after rectal administration was 33% of that after oral administration. Higher doses of ETA and serum concentration monitoring are recommended whenever the suppositories are used.

Administration, Oral↗
PubMed1989

Evaluation of intravenous ciprofloxacin in patients with nosocomial lower respiratory tract infections. Impact of plasma concentrations, organism, minimum inhibitory concentration, and clinical condition on bacterial eradication.

Fifty patients with gram-negative lower respiratory tract infections were treated with intravenous ciprofloxacin to evaluate efficacy and safety. Relationships between individual pharmacokinetics and clinical and bacteriologic outcome were studied. Ciprofloxacin concentrations in plasma were determined by high-performance liquid chromatography. Respiratory secretion cultures were obtained daily to determine the eradication day of the infecting organism. Susceptibility (minimum inhibitory concentration) to ciprofloxacin and other antimicrobials was determined using standard microdilution techniques. The mean age of the patients was 70 years. They had multiple underlying diseases, and two thirds of them were ventilator dependent at entry. Approximately 50% of the patients had failed previous treatment for the same infections. Patients infected with Enterobacteriaceae or Haemophilus influenzae with minimum inhibitory concentrations of less than 0.25 mg/L responded well to intravenous ciprofloxacin therapy (200 mg every 12 hours). The organisms were eradicated from sputum cultures usually within 1 day after ciprofloxacin therapy was started. Most clinical failures occurred in patients who were infected with Pseudomonas aeruginosa and had multiple underlying diseases. Pseudomonas aeruginosa was isolated from 10 patients with pneumonia, 2 patients with lung abscess, and 1 patient with bronchiectasis. The Pseudomonas isolate acquired resistance during ciprofloxacin treatment in 7 patients with pneumonia and in all of the remaining 3 patients. We conclude that ciprofloxacin is safe and effective at a dosage of 200 mg administered intravenously every 12 hours for nosocomial lower respiratory tract infections caused by Enterobacteriaceae or Haemophilus species. Many patients who had failed previous antibiotic treatment for Enterobacteriaceae infections had good clinical response to ciprofloxacin therapy. Studies using either higher dosages of ciprofloxacin or combination therapy should be conducted to determine if acquired resistance can be avoided in Pseudomonas infections.

Aged↗
PubMed1987

Dual individualization of intravenous ciprofloxacin in patients with nosocomial lower respiratory tract infections.

Dual individualization is the integration of patient-specific pharmacokinetic parameters with the pharmacodynamics (concentration versus response) of the infecting pathogen. This technique allows description of the time of in vivo bacterial eradication, and allows estimation of optimal dosages using small numbers of seriously ill patients. In an ongoing study, 11 patients with nosocomial lower respiratory tract infections were given 200 mg of intravenous ciprofloxacin every 12 hours. Ten blood samples were taken after the first dose, with additional peaks and troughs measured on Day 4 and at the end of treatment. Bacterial isolates had minimal inhibitory concentrations (MICs) determined by standard microdilution techniques. In the 11 patients, there were 14 bacterial isolates, of which seven were Pseudomonas aeruginosa and the remainder were other pathogens. Ciprofloxacin MICs ranged from 0.008 to 1.0 microgram/ml. The pharmacokinetics of ciprofloxacin in these patients varied with renal function, and average peak serum concentrations ranged from 1.7 to 4.9 micrograms/ml. Eradication of bacteria from tracheal aspirates occurred between Days 1 and 7, except in four patients in whom the organism persisted. Correlations were observed between the day of eradication and the length of time ciprofloxacin concentrations remained above the minimal inhibitory concentration (MIC). Essentially all bacteria with MICs of less than 0.25 were eradicated. Of the non-eradicated bacteria, most had either MICs of more than 0.25, or less than 100 percent time above the MIC. The clinical response was satisfactory. It is concluded that 200 mg of intravenous ciprofloxacin every 12 hours is highly effective for bacteria with MICs less than 0.25 microgram/ml, but higher dosages may be required to eradicate organisms with higher MICs.

Aged↗
PubMedDate not supplied

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↗
PubMedDate not supplied

Controversies in the management of Mycobacterium avium complex infection in AIDS patients.

OBJECTIVE: To update readers on the clinical management of infections secondary to Mycobacterium avium complex (MAC) in patients with AIDS. A general description of the organism, culture and susceptibility testing, and clinical manifestations of the disease is provided. Several aspects of the treatment of the disease, including an historical perspective, current approaches, and future research opportunities, are described. DATA SOURCES: Current medical literature, including abstracts presented at international meetings, is reviewed. References were identified through MEDLINE, Current Contents, and published meeting abstracts. STUDY SELECTION: Data regarding the epidemiology, clinical manifestations, culture and susceptibility testing, and treatment of MAC are cited. Specific attention is given to the management of patients with MAC infection. DATA EXTRACTION: Information contributing to the discussion of the topics selected by the author is reviewed. Data supporting and disputing specific conclusions are presented. DATA SYNTHESIS: Disseminated MAC infection is diagnosed antemortem in approximately 30 percent of patients with AIDS; postmortem rates of isolation exceed 50 percent. The incidence of MAC may increase as attempts at isolating the organism become more aggressive. The traditional approach to the isolation, susceptibility testing, and treatment of MAC has been derived from the management of Mycobacterium tuberculosis, with disappointing results. Newer radiometric in vitro methods of susceptibility testing appear to show more promise. Current mouse models of MAC are not true AIDS models; new CD4-deficient mouse models are being developed. Clinical mycobacteriologic and pharmacokinetic laboratory support have been underused, with treatment generally proceeding empirically. New agents that may contribute to the management of disseminated MAC infection include the macrolide derivatives clarithromycin and azithromycin. Research also continues with new rifamycins (including rifabutin) and fluoroquinolones (ciprofloxacin, sparfloxacin). Preliminary results suggest a central role for macrolides in the treatment of disseminated MAC; effective companion drugs are needed to prevent the rapid emergence of macrolide-resistant MAC. CONCLUSIONS: Treatment results for disseminated MAC infection remain poor. Therapy may be improved by selecting drugs on the basis of susceptibility data for each isolate, rather than by using empiric regimens based on susceptibility trends. Significant antimycobacterial drug malabsorption has been documented, and may contribute to poor outcomes. More-potent agents are needed to improve the clinical outcome in AIDS patients with MAC.

Acquired Immunodeficiency Syndrome↗