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Biomedical subjects

L D Sarff

Publications and source records attributed to L D Sarff.

17 recordsLinked to original sources

Fortified antibiotic ointment in bacterial keratitis.

We conducted experiments to determine the effectiveness of fortified antibiotic ointment in the treatment of Pseudomonas keratitis in rabbits. We evaluated gentamicin ointment (3, 10, 20, and 40 mg/g), gentamicin solution (3 and 10 mg/ml), and placebo, each given every 30 minutes. We also examined the effectiveness of fortified ointment given in extended treatment intervals. In short-term trials, commercial-strength gentamicin solution (3 mg/ml) was therapeutically superior (P less than .001) to commercial-strength gentamicin ointment (3 mg/g) in reducing corneal bacterial colony counts. No significant difference in antimicrobial effect was noted between fortified gentamicin ointment and fortified gentamicin solution at 30-minute treatment intervals. Fortified gentamicin ointment reduced colony counts even at extended treatment intervals of up to four hours in a severe keratitis model.

Animals

Cryotherapy for experimental Pseudomonas keratitis.

The effectiveness of cryotherapy alone and in combination with topical tobramycin sulfate therapy for experimental Pseudomonas keratitis was determined in guinea pigs and rabbits. Results were evaluated quantitatively by determining numbers of viable bacteria surviving in corneas. A brass probe cooled to--79 degrees C and applied directly to infected corneas for six seconds resulted in an immediate 99.9% reduction in bacteria. One freeze-thaw cycle followed by topical tobramycin therapy was significantly more effective than tobramycin therapy alone in five of six strains tested. None of the corneas treated with tobramycin alone demonstrated no growth, whereas 24 of 42 of these infected corneas showed no growth after the combination treatment. We conclude that cryotherapy alone had a rapid bactericdal effect on experimental Pseudomonas keratitis and that it significantly potentiated topical antibiotic therapy for most strains.

Animals

Comparison of therapeutic routes in experimental Pseudomonas keratitis.

We determined the efficacy of tobramycin administered by topical, intramuscular, and subconjunctival routes in guinea pigs and rabbits with experimental Pseudomonas keratitis. The topical route of administration was consistently more effective than either subconjunctival or intramuscular routes. Subconjunctival injection of antibiotic did not enhance the effectiveness of topical therapy in either guinea pigs or rabbits. Intramuscular tobramycin was more effective than saline in guinea pigs with keratitis but not in rabbits with keratitis.

Administration, Topical

Experimental Pseudomonas keratitis in guinea-pigs: therapy of moderately severe infections.

We have previously shown that antibiotic therapy of experimental Pseudomonas keratitis was more effective in early moderate infections than in late severe infections. The purpose of this study was to determine the relative efficacies of various drugs, routes, and vehicles in the treatment of moderately severe infection. As in the late severe infections, the most consistently effective regimen was an aminoglycoside applied topically in solution. No synergistic or additive effect was observed with a combination of aminoglycoside given topically and a penicillin given intramuscularly. Topical therapy with antibiotic in ointment was less effective than topical therapy with antibiotic in solution.

Administration, Topical

Topical tobramycin therapy of experimental Pseudomonas keratitis: an evaluation of some factors that potentially enhance efficacy.

We evaluated several therapeutic modifications in an attempt to improve efficacy of topical therapy with tobramycin of experimental Pseudomonas keratitis in guinea pigs. Removal of corneal epithelium enhanced efficacy of topical therapy with 0.3 mg/ml and 3 mg/ml tobramycin sulfate but did not influence therapy with 40 mg/ml or 400 mg/ml tobramycin. The highest concentration of antibiotic was the most effective; 7 of 12 infected corneas treated with 400 mg/ml tobramycin were sterile in 48 hours. Therapy begun soon after the infection was established, when there were relatively few organisms present, was more effective than therapy begun later, when there were many more bacteria in the cornea. Our results are consistent with a basic therapeutic concept. The most effective regimen is one that achieves the highest safe concentration of antibiotic at the site of infection as early in the course of infection as possible.

Administration, Topical

Corticosteroid in experimentally induced Pseudomonas keratitis: failure of prednisolone to impair the efficacy of tobramycin and carbenicillin therapy.

The effect of prednisolone on tobramycin and carbenicillin therapy for experimentally induced Pseudomonas keratitis was evaluated. Results were assessed quantitatively by determining the number of bacteria that survived in the cornea. Simultaneous administration of prednisolone did not adversely alter results of treatment with carbenicillin or tobramycin. In another trial, pretreatment with prednisolone for 48 hours before antibiotic therapy was begun did not change significantly the results of therapy with intramuscular tobramycin or carbenicillin. We conclude that corticosteroid therapy does not affect adversely results of antibiotic therapy with tobramycin or carbenicillin in this experimental model.

Administration, Topical

Staphylococcal keratitis. Experimental model in guinea pigs.

An experimental model of staphylococcal keratitis in guinea pigs was devised that is suitable for quantitative evaluation of therapy. The growth curve in the cornea of a virulent strain of Staphylococcus aureus was determined. The organism multiplied rapidly, reached a peak in about 12 hours, and began to decline in numbers after three days. Infections were relatively resistant to therapy begun 24 hours after infection was established. Treatment started earlier when fewer bacteria were present was more effective than treatment begun later. Treatment begun at the time of infection, which might be considered prophylaxis, was highly effective. When treatment was begun eight hours after infection, tobramycin sulfate and gentamicin sulfate solutions administered topically in doses of 20 mg/ml were more effective than topical bacitracin, erythromycin, clindamycin phosphate, or a solution containing polymyxin B sulfate, neomycin sulfate, and gramicidin. Bacitracin and erythromycin ointments were ineffective.

Administration, Topical

Bacteriologic cure of experimental Pseudomonas keratitis.

Two long-term therapy trials with high concentrations of antibiotic were carried out to determine the duration of therapy required to achieve bacteriologic cure of experimental Pseudomonas keratitis in guinea pigs. In the first study, corneas still contained Pseudomonas after 4 days of continual topical therapy with either tobramycin 400 mg/ml, amikacin 250 mg/ml, ticarcillin 400 mg/ml, or carbenicillin 400 mg/ml. In an 11-day trial of topical therapy with tobramycin 20 mg/ml, 34 of 36 corneas grew no Pseudomonas after 6 or more days of therapy. The bacteriologic response to therapy in this model occurred in two phases. About 99.9% or more of the organisms in the cornea were killed in the first 24 hr of therapy. The numbers of bacteria remaining in the cornea declined gradually over the next several days until the corneas were sterile. Optimal antibiotic therapy may include two stages: initial intensive therapy with high concentrations of antibiotic applied frequently to achieve a large rapid decrease in numbers of organisms in the cornea, followed by prolonged, less intensive therapy to eradicate organisms and prevent relapse.

Administration, Topical

Therapeutic effect of topical antibiotic on untreated eye in experimental keratitis.

We studied the systemic absorption ot topical tobramycin and amikacin in experimental Pseudomonas keratitis in guinea pigs. After giving two drops of tobramycin 40 mg/ml every 30 minutes for 24 hours to both infected eyes (the corneal epithelium having removed) the mean serum concentration was 1.5 mcg/ml. Treatment of one of the infected eyes with the same strength of tobramycin or amikacin drops did not alter the number of viable bacteria in contralateral eyes treated with saline. Tobramycin 400 mg/ml or amikacin 250 mg/ml however, decreased the number of viable bacteria in the contralateral eyes. We conclude that the therapeutic effect on the contralateral eye was the result of systemic absorption.

Absorption

Antibiotic therapy of experimental Pseudomonas keratitis in guinea pigs.

Antibiotic therapy of experimental Pseudomonas keratitis was evaluated quantitatively by determining numbers of viable bacteria in the cornea of guinea pigs. Topically applied carbenicillin disodium, gentamicin sulfate, and tobramycin sulfate were often significantly more effective than topically applied polymyxin B sulfate. Intramuscular therapy with tobramycin was as effective as topical therapy, and the results exhibited less variability. Topical tobramycin every 30 minutes was significantly more effective than topical therapy every 60 minutes. No combination of antibiotics was significantly better than a single effective drug. The concentration of tobramycin in the aqueous correlated more closely to therapeutic efficacy than did the concentration in the cornea. Although all antibiotics reduced numbers of bacteria in the cornea by more than 99% in the first 24 hours of therapy, none was able to sterilize the cornea in four additional days of continuous therapy. Persistence of organisms despite apparently adequate topical therapy may explain some reported cases of relapse in humans.

Administration, Topical

Clinical pharmacology of methicillin in neonates.

The pharmacokinetic properties of methicillin were investigated in 59 newborn infants. Concentrations of methicillin in serum were approximately 58 and 80 microng/ml at one hour after 25 and 50 mg/kg doses, respectively. The average serum half-life values ranged from one to three hours and were inversely correlated with birth weight and chronologic age. The half-life values, volumes of distribution, and plasma clearances of methicillin are shown in relationship to gestational age and chronologic age. A dosage of 25 mg/kg is recommended for therapy of most neonatal staphylococcal diseases; the frequency of administration is altered on the basis of birth weight and chronologic age.

Birth Weight

Cerebrospinal fluid evaluation in neonates: comparison of high-risk infants with and without meningitis.

Results of CSF examinations from 117 high-risk neonates were reviewed. The mean CSF cell count was 8.4 cells/mm3 and the range was 0 to 32 cells/mm.3 Approximately 60% of the CSF WBC were polymorphonuclear leukocytes. Average CSF protein concentrations were 90 mg/dl (range, 20-170 mg/dl) in term and 115 mg/dl (range, 65-150 mg/dl) in preterm infants. The average CSF glucose was 81% of the blood glucose value in term and 74% in preterm infants. Comparison of these CSF findings with those from 119 infants with bacterial meningitis revealed that there was considerable overlapping of values, but only one of the 119 infants with meningitis had a completely normal initial CSF examination. The decision to initiate antimicrobial therapy in neonates with suspected meningitis must be based on total evaluation of the patient.

Cerebrospinal Fluid

Epidemiology of Escherichia coli K1 in healthy and diseased newborns.

Although at least 100 different Escherichia coli capsular antigens have been recognised, strains possessing the K1 antigen are responsible for 77% of neonatal E. coli meningitis cases. K1 strains were found in 20-40% of rectal swab cultures from healthy infants, children, and adult women. Vertical transmission from mother to infant was the most common means of aquiring K1 organisms in term infants. Premature babies in a nursery with little maternal contact aquired K1 strains later then did term infants, and this aquisition may have been related to carriage by nursery staff. Capsular content and fermentation reactions of cerebrospinal-fluid K1 organisms were comparable to those found in rectal strains from healthy individuals. E. coli K1 with identical O and H antigens were found in maternal and infantile cultures of babies with E. coli meningitis. It seems very likely that host immune mechanisms play a significant role in the pathogenesis of neonatal E. coli K1 meningitis.

Adolescent

Hemolytic uremic syndrome associated with Corynebacterium diphtheria infection.

Although hemolytic uremic syndrome (HUS) is usually idiopathic, it follows a number of infections. The pathogenesis of post-infectious HUS is endothelial cell damage by either circulating endotoxin or exotoxin. Diphtheria exotoxin has never been implicated in HUS. We report HUS following diphtheria infection in a 9 yr old un-immunized white female admitted with a short history of sorethroat and thrombocytopenia. There were hemorrhages in sclera, gums and left tonsillar area and a grayish exudate on right tonsil. Laboratory values revealed Hgb 14.4 g/dl, decreasing to 7.6 g/dl, WBC/26,900 mm3, platelet count 7,000/mm3. Bone marrow examination revealed normal megakaryocytes. She was oliguric with BUN 214 mg/dl, serum creatinine 12.4 mg/dl and serum uric acid 19.2 mg/dl. Despite peritoneal dialysis, red cell and platelet transfusions and exchange transfusion she expired. A postmortem examination was refused. A throat culture done on admission grew corynebacterium species which was later confirmed to be toxigenic C. diphtheriae. Diphtheria exotoxin inactivates an enzyme in cytoplasm which is necessary for peptide chain elongation. This may have interfered with prostacyclin synthesis thereby allowing the development of HUS.

Blood Transfusion