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Biomedical subjects

W H Hall

Publications and source records attributed to W H Hall.

At least 19 recordsLinked to original sources

Treatment of Pseudomonas endophthalmitis associated with prosthetic intraocular lens implantation.

Eight patients were treated for Pseudomonas endophthalmitis associated with the implantation of contaminated intraocular lenses. All patients showed clinical signs of infection (loss of red reflex, diminished visual acuity, and intraocular lens coagulum) and P. aeruginosa was isolated from vitreous aspirates and unused lenses of the same lot. Antibiotic treatment was initiated with systemic penicillin G, cephalothin, and chloramphenicol as well as subtenon-injected gentamicin. After identification of the organism, treatment was continued with systemic carbenicillin and gentamicin and subtenon-injected gentamicin. The intraocular lens was left in place for the first 48 hours of treatment in all eight patients. Five patients were successfully treated without removal of the intraocular lens and attained visual acuity of 6/6 (20/20) to 6/15 (20/50). Three patients (the two most seriously infected and one in whom antibiotics were discontinued) eventually lost their infected eye. Vitreous concentrations of gentamicin were good in one patient (1.7 micrograms/ml) and undetectable in another. Carbenicillin concentrations in vitreous (96 and 140 micrograms/ml) were high in two patients sampled. Endophthalmitis in the presence of a prosthetic intraocular lens can be successfully treated in some patients without removal of the prosthesis.

Anti-Bacterial Agents

Comparative susceptibility of penicillinase-positive and -negative Neisseria gonorrhoeae to 30 antibiotics.

The minimal inhibitory concentrations of 30 antibiotics were determined by the agar dilution method for 17 penicillinase-positive and 50 penicillinase-negative strains of Neisseria gonorrhoeae. The latter included 42 strains that were penicillin susceptible (pen S) (minimal inhibitory concentration, <0.125 mug/ml) and 8 strains with intermediate resistance to penicillin (pen I; minimal inhibitory concentration, 0.125 to 0.5 mug/ml). Two penicillinase-resistant penicillins (methicillin and nafcillin) were inhibitory for penicillin-resistant (pen R) strains. Three new cephalosporins (cefuroxime, cefamandole, cefaclor) and a cephamycin (cefoxitin) were bacteriostatic (minimal inhibitory concentration </=0.8 mug/ml) for 90% of pen S, pen I, and pen R strains. Pen I strains were more resistant than pen R strains to 6 of 13 cephalosporins. Rifampin, erythromycin, spectinomycin, chloramphenicol, and the tetracyclines were inhibitory for both pen S and pen R strains. The minimal bactericidal concentrations of cefuroxime, cefamandole, cefaclor, and cefoxitin were measured for 17 pen R strains and eight pen I strains by serial dilution of the antibiotics in Trypticase soy broth supplemented with 1% Iso VitaleX and 1% hemoglobin. All tubes were subcultured after overnight incubation at 37 degrees C. Cefuroxime and cefoxitin were bactericidal at low concentrations (minimal bactericidal concentration, </=1.0 mug/ml) for 16 of 17 pen R strains and 6 of 8 pen I strains.

Anti-Bacterial Agents

Serious staphylococcal infections with strains tolerant to bactericidal antibiotics.

The clinical response in 20 cases of serious staphylococcal infection was compared with the in vitro resistance or "tolerance" of the infecting Staphylococcus to killing by antibiotics used in treatment. Cases were divided into two groups: (1) patients who initially received nonbactericidal antibiotics (ten cases), and (2) patients who initially received bactericidal antibiotics with or without nonbactericidal antibiotics. Mortality due to uncontrolled staphylococcal infection was 40% (4/10) in group 1 as compared with no mortality (1/10) in group0) in group 1 as compared with no mortality (0/10) in group 2. The duration of positive cultures after start of therapy in group 1 (mean, 6.1 days) was significantly longer than that in group 2 (mean, 1.3 days). The duration of fever after start of therapy in group 1 was not significantly different when compared with group 2.

Adult

Prediction of the concentration of penicillins in ascitic fluid from serum kinetics and protein binding of the antibiotics in serum and ascitic fluid of dogs.

Ascites was induced in dogs by partial ligation of the inferior vena cava. Concentrations of ampicillin, penicillin G, oxacillin, cloxacillin, dicloxacillin, nafcillin, and methicillin in ascitic fluid and serum were each determined in three animals. All antibiotics were administered intramuscularly in a dose of 15 mg/kg (dry weight) for both single-dose and multiple-dose (eight doses at 4-hr intervals) studies. Binding of antibiotics to serum and ascitic fluid proteins was measured by ultracentrifugation. After single doses the highly protein-bound drugs (oxacillin, cloxacillin, dicloxacillin, and nafcillin) had lower percentages of penetration (ratio of peak in ascitic fluid to that in serum, multipled by 100) than did methicillin, ampicillin, and penicillin G, which have a lower degree of protein binding. The effect was partially overcome by repetitive doses, but five to six doses were usually required to reach equilibrium. In addition to protein binding, serum kinetics (particularly the log mean total concentration of drug in serum after multiple doses) were important determinants of antibiotic concentrations in ascitic fluid. The total antibiotic concentration in ascitic fluid at equilibrium can be accurately calculated from the log mean serum concnetration and the percentages of protein binding in serum and ascitic fluid.

Ampicillin

Medium-dependent variation in bactericidal activity of antibiotics against susceptible Staphylococcus aureus.

Staphylococcus aureus resistant to bactericidal activity of antibiotics caused sepsis in three patients. Bacteriological and clinical responses were not achieved until serum and tissue fluid levels of administered antibiotics exceeded the minimum bactericidal concentration (MBC) of the infecting organism. Fifteen clinical isolates of S. aureus were tested in brain heart infusion broth and Mueller-Hinton broth for the MBC of gentamicin, vancomycin, clindamycin, oxacillin, cefazolin, and cephalothin. Results showed significant eightfold or greater broth-dependent differences in the MBC of at least one antibiotic against 87% (13/15) of strains tested. The MBC was unpredictable and varied with the strain, antibiotic, and medium used. No controlled studies are available to indicate the clinical significance of the MBC demonstrated in different media. The necessity for treating serious infection with bactericidal drugs has not yet been established; however, in septicemia such as that caused by bacterial endocarditis, bacteriostatic antibiotics have generally failed to eradicate the infection, whereas bactericidal agents have often been curative. Therefore, in patients unresponsive to usual antistaphylococcal therapy, we suggest that MBC testing be performed in at least two media and that treatment be instituted with antibiotics demonstrating the lowest MBC in all media used.

Anti-Bacterial Agents

Ascitic fluid cephalosporin concentrations: influence of protein binding and serum pharmacokinetics.

Mongrel dogs with ascites created by inferior vena cava ligation were given cephalothin, cephaloridine, cefazolin, and cefamandole to evaluate the effect of protein binding and serum pharmacokinetics on the distribution of cephalosporins into ascitic fluid. Antibiotics were given intramuscularly (15 mg/kg) every 4 h for a total of eight doses. Antibiotic binding to dog serum and ascitic fluid was measured by ultracentrifugation. Binding of the cephalosporins to dog serum ranged from 31% for cephaloridine to 46% for cephalothin, considerably lower than human serum binding for cefazolin, cephalothin, and cefamandole. Antibiotic binding to ascitic fluid was only slightly lower than that to serum. Ascitic fluid antibiotic concentrations, which approached equilibrium at 16 to 28 h, were significantly higher for cefazolin and cephaloridine than for cephalothin and cefamandole. However, serum concentrations were also higher for cefazolin and cephaloridine, and percent penetration (ratio of serum peak to ascites peak x 100) was not statistically different among the four drugs. Binding of these cephalosporins to extravascular fluid protein was an important factor that determined the total ascitic fluid antibiotic level achieved. A formula utilizing the log mean serum level and binding to serum and extravascular fluid protein was used to accurately predict ascitic fluid drug levels at equilibrium.

Animals

Therapy of Candida peritonitis: penetration of amphotericin B into peritoneal fluid.

Candida albicans peritonitis developed in a 48-year-old man with a perforated gastric ulcer who subsequently was treated with intravenous amphotericin B. The drug penetrated well into the inflamed peritoneal cavity and eradicated the organism from the peritoneal fluid. Nevertheless, at post-mortem, Candida organisms were demonstrated in a gall-bladder empyema and within the gall-bladder wall. Because intra-abdominal organs may be involved in Candida peritonitis, the use of high dose amphotericin B administered either intravenously, intraperitoneally, or both intravenously and intraperitoneally is recommended.

Amphotericin B

Cavitary pneumonia associated with tularemia.

A wide range of microorganisms has been associated with cavitary pneumonia and pulmonary abscess. We present a case of serologically documented tularemia in an animal-hide handler who demonstrated multiple pulmonary infiltrates with cavitation. Inclusion of tularemia in the differential diagnosis of cavitary pneumonia in patients with exposure to animals is emphasized.

Adult

Hemostatic defect in endoscoped upper gut bleeding.

In an effort to assess the role of salicylate ingestion in upper gastrointestinal bleeding, one observer obtained a blood specimen for salicylate determination, performed a Duke bleeding time, and obtained a detailed drug history at the time of diagnostic endoscopy. Although a salicylate ingestion history was common, other variables did not correlate with it. Prolonged bleeding time occurred in 21 of the 81 patients, versus 1 of 22 controls. It was strongly associated with liver disease, with the alcohol habit by history, and with endoscopically severe gastritis, but was not correlated with plasma salicylate levels or evidence of salicylate ingestion by history, or with thrombocytopenia. Additional relationships linked liver disease and gastritis with prolonged bleeding time. There was no direct evidence from this study that salicylate ingestion occurred more frequently among gastrointestinal bleeders than among controls, and there was no evidence that the hemostatic defect increased the magnitude of bleeding.

Alcoholism

Gastric emptying of lactose and milk in subjects with lactose malabsorption.

Six lactose absorbers (LA) and 5 lactose malabsorbers (LM) had tests of gastric emptying with 750-ml meals of glucose in water, lactose in water, plain milk, and chocolate milk. The glucose and lactose meals emptied in a similar fashion in LA and LM subjects with a significant decrease in gastric emptying as the osmolarity of the meals was doubled. If the data are normalized by dividing lactose emptying by the emptying of glucose meals of twice the osmolality in each individual, the lactose malabsorbers empty significantly more lactose. Both LA and LM subjects emptied comparable amounts of milk meals having similar osmolarity. Chocolate milk, which had a higher osmolality than plain milk, emptied more slowly than plain milk in both groups, and this difference was significant in the LM group.

Adult

Effect of cholestyramine on digoxin absorption and excretion in man.

Six subjects receiving digoxin therapy for heart disease were studied on two occasions with a single oral dose of 0.5 mg of tritiated digoxin. In every study, all stools and urine were saved for 1 week. Before the second study, treatment with cholestyramine, 4 g every 6 hours, was begun and continued throughout. In three patients, a third study was performed after cholestyramine treatment had been continued for 1 month. Results showed that after cholestyramine administration serum levels, stool output and urinary output of tritiated digoxin varied over a wider range, but cholestyramine had no net short-term effect of any of these variables. After 1 month of cholestyramine administration, there was a small statistically significant increase in stool output of tritiated digoxin and metabolites. In vitro studies suggested that cholestyramine is likely to be a weak digoxin binder in the gut and that changes induced by this resin in digoxin metabolism are not likely to be due to drug binding.

Administration, Oral

Penetration of tobramycin into infected extravascular fluids and its therapeutic effectiveness.

The aminoglycoside antibiotic tobramycin was given intramuscularly to 15 patients with infected body fluids (empyema in five patients, peritonitis in five, peritonitis and empyema in one, tracheobronchitis in three, and infection of the pacemaker pocket in one). The infecting bacteria included Pseudomonas aeruginosa, Klebsiella, Enterobacter, Serratia, Escherichia coli, Proteus species, and Staphylococcus aureus. The mean dose of tobramycin was 1.7 mg/kg given intramuscularly every 8 hr for nine to 10 days. Levels of tobramycin in specimens of serum and infected body fluid obtained simultaneously were measured at various intervals after a dose of the antibiotic. Comparison was made between levels of tobramycin and minimal inhibitory concentrations (MICs) of the infecting bacteria. Bacteriological and clinical failures were common if the level in body fluid did not exceed the MIC. In patients with levels of tobramycin in body fluid that were higher than the MIC, cures were frequent. Drainage of infected body fluids is a necessary part of successful therapy of these infections.

Anti-Bacterial Agents

Standardization of a preparative ultracentrifuge method for quantitative determination or protein binding of seven antibiotics.

A preparative ultracentrifuge method was standardized for determination of quantitative binding of cephalothin, cefamandole, cefazolin, cefaclor, erythromycin, gentamicin, and chloramphenicol to human serum proteins. At achievable in vivo concentrations, serum binding was 78.5% for cephalothin, 79.9% for cefamandole, 88.5% for cefazolin, 23.5% for cefaclor, 41.9% for erythromycin, 22.7% for gentamicin, and 59.5% for chloramphenicol. Techniques that use semipermeable cellophane or diaflow membranes, cross-linked dextran, inhibition of bacterial growth, protein precipitation, or liquid partitioning all have inherent problems with either the ligand or the antibiotic adversely interacting with the experimental apparatus. Ultracentrifugation provides a rapid, reproducible technique for protein-binding determinations of the classes of antibiotics described.

Anti-Bacterial Agents

Gentamicin intravenous infusion rate: effect on interstitial fluid concentration.

To assess the possible role of intravenous (i.v.) infusion rate as a determinant of degree and rate of interstitial fluid penetration, six rabbits, each with four intraperitoneal implanted capsules, were studied by crossover design after a single dose of 1.7 mg of gentamicin per kg by either slow 2.5-min i.v. bolus or 30 min i.v. infusion. The mean serum peak antibiotic level after slow bolus was 17.4 mug/ml. After 30 min of infusion, mean serum peak was 8.3 mug/ml (P < 0.025). Mean capsule fluid antibiotic levels at 30 min, 1, and 2 h were 0.9 mug/ml, 1.6 mug/ml, and 1.8 mug/ml, respectively, after slow bolus and 0.6 mug/ml, 0.9 mug/ml, and 1.3 mug/ml after 30-min infusion (P < 0.05 at 30 min, P < 0.001 at 1 h, and P < 0.05 at 2 h). Comparison of capsule levels beyond 2 h revealed no significant differences, and peak capsular concentrations achieved by the two methods were similar. Slow 2.5-min i.v. bolus administration of gentamicin established higher interstitial fluid levels during the first 2 h of therapy and may be the preferred mode of delivery when rapid extravascular penetration is desired.

Animals

Antibiotic concentrations in ascitic fluid of patients with ascites and bacterial peritonitis.

Thirty-six paired specimens of serum and ascitic fluid from 21 patients with peritonitis and ascites, most with sponetaneous bacterial peritonitis and alcoholic cirrhosis, were assayed for antibiotic content. Antibiotics assayed and number of determinations were gentamicin, 14; tobramycin, 7; ampicillin, 5; clindamycin, 3; penicillin G, 2; cephalothin, 2; chloramphenico, 2; and cefazolin, 1. In 31 pared specimens the ascitic fluid antibiotic concentration was about one half or more of the simultaneous serum level and in 17 assays exceeded 90% of the serum level. All antibiotics studied penetrated ascitic fluid equally well. Clinical response to antibiotic therapy was good in 12 of 16 patients with culture-proven bacterial peritonitis. Antibiotic levels in ascitic fluid exceeded the minimal inhibitory concentration of the infecting organisms in all but one patient who responded. Direct intraperitoneal instillation of antibiotics does not appear to be necessary routinely; however, there may be an initial lag of several hours before antibiotic concentrations is ascites achieve therapeutic levels.

Adult