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Biomedical subjects

P T Frame

Publications and source records attributed to P T Frame.

32 records · Page 2Linked to original sources

Clinical evaluation of efficacy, pharmacokinetics, and safety of teicoplanin for serious gram-positive infections.

Nineteen patients hospitalized for serious gram-positive infections were treated with teicoplanin, a new glycopeptide antibiotic. A variety of infections were treated, including endocarditis, septic thrombophlebitis, osteomyelitis, pyogenic arthritis, and soft tissue infection. Of 13 infections that could be evaluated in 12 patients, there were 8 clinical cures, 2 improvements, 1 recurrence, and 2 failures. Of the eight patients with Staphylococcus aureus bacteremia, seven were clinically cured or improved with teicoplanin therapy. Of the nine patients in whom the bacteriological response to treatment could be fully evaluated, six were cured; there was recurrence of infection in one, and treatment failed in two patients. In vitro testing showed the 13 bacterial isolates (9 S. aureus, 3 S. epidermidis, and 1 group B streptococcus) to be uniformly susceptible to teicoplanin, with MICs ranging from 0.12 to 0.5 microgram/ml. Every isolate was more susceptible in vitro to teicoplanin than to vancomycin. Three of the staphylococcal isolates were resistant to methicillin. Pharmacokinetic studies demonstrated that after an initial drug-accumulation period, a single daily dose adequately maintained the teicoplanin concentrations in serum within therapeutic ranges. Teicoplanin also penetrated well into synovial fluid. The drug was well tolerated by either intravenous or intramuscular administration. The most significant adverse reaction was an urticarial rash which required discontinuation of therapy in one patient; a second patient experienced a modest decrease in high-frequency auditory threshold. Asymptomatic eosinophilia and mild elevation of serum transaminases were noted as well. The results of this study suggest that teicoplanin is a safe and effective new agent for treatment of serious infections caused by gram-positive organisms.

Adult↗

Use of the protected specimen brush in patients with endotracheal or tracheostomy tubes.

Twenty-one patients on mechanical ventilators for greater than 48 hours who had new localized infiltrates were evaluated using a quantitative culture technique of the involved lung compared to the non-involved lung. Based on the clinical course, response to antibiotics, or subsequent analysis of pathologic specimens, eight patients were felt to have acute bacterial pneumonia, while the remaining 13 were felt to have an alternative cause of their infiltrate. Cultures of the protected brush specimen of the involved lung in all eight cases of bacterial pneumonia had one or more organisms grown at a greater than 100 colony forming units (cfu) per ml while only one of the 13 cases of non-pneumonia had a culture from the involved area having greater than 100 cfu per ml (p less than 0.001). The non-involved area always grew fewer organisms than the involved area, and in 16 cases, there was no growth from the specimen obtained from the non-involved area.

Bacterial Infections↗

Treatment of CSF shunt infections with intrashunt plus oral antibiotic therapy.

Infections of 12 cerebrospinal fluid (CSF) shunts in 11 children were treated with oral systemic antibiotic therapy plus daily intrashunt injections of antibiotics. Eight patients were infected with Staphylococcus epidermidis (four patients) or Staphylococcus aureus (four patients), and were treated with intrashunt vancomycin, plus oral trimethoprim/sulfamethoxazole (T/S), plus oral rifampin. One of these eight patients was later changed to a course of intrashunt cephapirin and oral cephalexin plus oral rifampin. One patient with Micrococcus varians infection was treated with oral T/S and rifampin, without intrashunt therapy, another patient with Pseudomonas cepacia infection was treated with intrashunt kanamycin plus oral T/S, and a third with Corynebacterium sp. infection was treated with intrashunt vancomycin plus oral T/S. Eight of the 11 patients required some form of shunt surgery, the most common being temporary externalization of the peritoneal end of the catheter. Only two shunts were completely replaced (both were ventriculojugular shunts which were changed to ventriculoperitoneal shunts). Nine of 10 evaluable cases were considered cured of their infections. The patient treated with cephalosporins had an uncorrected shunt malfunction and relapsed 1 month after completing therapy. The authors have shown that CSF shunts infected with Staphylococci can be effectively cleared with daily intrashunt vancomycin plus systemic therapy with oral T/S and rifampin. Less common infections may also be amenable to this form of therapy. Revision surgery, if necessary, should be carried out during the antibiotic therapy.

Administration, Oral↗

Penetration of nafcillin, methicillin, and cefazolin into human brain tissue.

To determine the penetration of the antistaphylococcal antibiotics, nafcillin, methicillin, and cefazolin, into brain tissue, we gave to each of 27 patients undergoing craniotomy and brain biopsy one of the antibiotics in a 2-g intravenous infusion just before operation. At the time of brain tissue removal (30 to 225 minutes after the start of the infusion), a serum specimen was obtained, and tissue and serum were assayed for antibiotic concentration. Eleven of 13 brain specimens contained detectable nafcillin concentrations between 0.36 and 11 micrograms/g of tissue (mean, 2.7 micrograms/g for all 13 specimens). Fourteen of 18 brain tissue specimens contained detectable methicillin concentrations between 0.56 and 5.0 micrograms/g of tissue (mean, 2.0 micrograms/g for all 18 specimens). Ten of 11 brain tissue specimens contained detectable cefazolin concentrations between 2.0 and 40 micrograms/g of tissue (mean, 10.6 micrograms/g for all 11 specimens). Each antibiotic penetrated "abnormal" brain tissue better than "relatively normal" brain tissue. Because nafcillin is more active against Staphylococcus aureus, we conclude that nafcillin is preferable to methicillin for the therapy of central nervous system staphylococcal infections. Cefazolin achieves higher brain tissue concentrations than the penicillins, but has not been clinically evaluated for the therapy of central nervous system infections.

Brain Chemistry↗

Infection of bone by Mycobacterium fortuitum masquerading as Nocardia asteroides.

A case of traumatic osteomyelitis of the leg yielded on culture a branching partially acid-fast organism that failed to respond to therapy directed at Nocardia asteroides. Subsequent laboratory investigation revealed the organism to be Mycobacterium fortuitum. N. asteroides and M. fortuitum can demonstrate similar staining and morphologic patterns microscopically, as well as common colonial and cultural characteristics. Separation can be aided by careful examination of the branching pattern, and can be established by thin-layer chromatography of lipid extracts of the organism. Correct identification of these species in the laboratory is important because of some overlap in their clinical syndromes and because of differences in their susceptibilities to antibiotics.

Aged↗

Invasive fungal infections in patients with chronic mucocutaneous candidiasis.

Patients with chronic mucocutaneous candidiasis have persistent Candida infection of nails, skin, and mucous membranes, but rarely, if ever, does an invasive fungal infection develop. We describe two patients with chronic mucocutaneous candidiasis who died of fungal infection; one had C albicans meningitis and the second had Cryptococcus neoformans meningitis. The cases of four other patients with chronic mucocutaneous candidiasis and invasive fungal infection, three with crytococcosis and one with histoplasmosis, have been reported previously. Immunological profiles on these six patients revealed no differences from those of other patients with chronic mucocutaneous candidiasis without invasive fungal infection. Three of the four patients who received amphotericin B were cured of their infection; three patients died, including one patient with overwhelming cryptococcosis who had received intensive antifungal therapy and transfer factor.

Adolescent↗

Pharmacologic factors associated with gentamicin nephrotoxicity in rabbits.

Nine rabbits were given subcutaneous doses of 7.5 mg of gentamicin/kg every 24 hr, and nine were given 2.5 mg of gentamicin/kg every 8 hr for three weeks or longer. Renal function was evaluated by monitoring of the concentration of creatinine in serum and the rate of clearance of gentamicin from serum. In the animals receiving the 8-hr divided dosage, a deterioration of renal function as early as day 7 was demonstrated by the rate of clearance of gentamicin, and deterioration by day 21 was evidenced by the concentration of creatinine in serum; the renal function of the animals receiving the single daily dose was unchanged. There was no relationship between peak or trough concentrations of gentamicin in serum and the development of nephrotoxicity. The animals receiving the 8-hr dosages had a significantly longer daily duration of exposure to concentrations of greater than or equal to 0.1, greater than or equal to 1.0, greater than or equal to 2.0, and greater than or equal to 3.0 microng of gentamicin/ml in serum than did animals receiving the daily dosage.

Animals↗

Bone marrow toxicity associated with 5-fluorocytosine therapy.

Bone marrow toxicity occurred in 4 of 15 patients treated with 5-fluorocytosine (5-FC) for serious fungal infections. The development of marrow toxicity appeared to be related to serum 5-FC levels of 125 mug/ml or greater. In three patients, accumulation of toxic levels of 5-FC was related to diminished renal function. One patient with acute renal failure and prolonged high levels of 5-FC developed marrow aplasia and died of bacterial sepsis. Three patients experienced leukopenia, which was readily reversed when the dosage of 5-FC was decreased and the serum concentration was lowered. With careful monitoring of serum 5-FC concentration and renal function, the dose-related toxic effects of 5-FC on the marrow can be avoided.

Adult↗

Simple assay for 5-fluorocytosine in the presence of amphotericin B.

A simple method for the measurement of 5-fluorocytosine in the presence of amphotericin B is described. The antifungal activity of amphotericin B is abolished by heating serum at 100 C for 45 min. 5-Fluorocytosine is unaffected by this treatment, and serum levels can be subsequently assayed by either tube dilution or disk diffusion methods.

Amphotericin B↗

Treatment of infections of cerebrospinal fluid shunts.

There is no unanimity at present concerning the best method of treatment of cerebrospinal fluid shunt-related infections. The most frequently used method includes removal of the shunt followed by antibiotic therapy and later replacement of the shunt. The experience at the University of Cincinnati during the past 15 years indicates that many shunt infections can be effectively treated without shunt removal. This report summarizes experiences with 11 consecutive ventriculoperitoneal shunt infections. These were treated by externalization of the peritoneal catheter followed by intraventricular and systemic antimicrobial therapy and by later replacement of the peritoneal catheter. The advantages of this method include the avoidance of two major operative procedures and the elimination of a period in which the intracranial pressure is not controlled. The need for externalization of the peritoneal catheter relates to the occurrence of localized peritoneal infection and pseudocyst formation, which prevents cure of the infection in many instances if the catheter is left in place. After follow-up periods of four months to five years, 10 of the 11 patients have apparently been cured of their infection.

Adolescent↗

Generalized immune response to Pneumocystis carinii infection in the lung.

We studied inflammatory cells retrieved by bronchoalveolar lavage (BAL) from immunocompromised patients with or without Pneumocystis carinii pneumonia (PCP). Twenty-four patients with PCP, and 20 patients without PCP underwent lavages of both an uninvolved lobe and the lobe involved in pulmonary infection. Patients without P. carinii, had a significant increase (p less than 0.02) in the percentages of neutrophils (22 +/- 7.1%, mean +/- SEM) and lymphocytes (16 +/- 3.8%) in the involved lobe compared to those in the uninvolved area (neutrophils: 9 +/- 4.8%; lymphocytes: 10 +/- 2.4%). Patients with PCP, had no differences between the % neutrophils or % lymphocytes in the involved vs. uninvolved lobes. Patients with PCP had more (p less than 0.01) P. carinii in the upper lobe (23 +/- 4.6 P. carinii clusters/500 cells) than the middle lobe (11 +/- 3.6). In PCP, despite regional infections, there was a diffuse inflammatory response.

Bronchoalveolar Lavage Fluid↗

Open-label efficacy and safety trial of 42 days of 566C80 for Pneumocystis carinii pneumonia in AIDS patients.

Pneumocystis carinii pneumonia continues to be a cause of morbidity and mortality in AIDS patients. Current therapies have a high rate of toxicity and failure. Compound 566C80 is a 1-4,hydroxynaphthoquinone with potent antiprotozoal activity which shows good efficacy and safety in 21-day treatment trials of P. carinii pneumonia (PCP) in AIDS patients. Because there is a generally high recurrence rate after treatment of PCP and there may be a possible advantage in decreasing the P. carinii burden in the lung with extended anti-Pneumocystis therapy, we performed an open label-trial of the safety and efficacy of 42-day therapy with 566C80 for PCP in AIDS patients. Ten patients were enrolled and one was lost to follow-up. Eight of the remaining nine patients successfully completed 42 days of therapy with minimal toxicity. This trial suggests that 566C80 for 42 days can be an effective, safe, and well-tolerated oral therapy for PCP in AIDS patients.

Acquired Immunodeficiency Syndrome↗