Guidelines for total parenteral nutrition.
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Biomedical subjects
Publications and source records attributed to M Barza.
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Marked differences were noted among 14 antibiotics in their filterability through collodion (nitrated cellulose) membranes. The findings could not be attributed to differences in molecular weight or degree of serum protein binding, although the latter factor imposed an additional restraint on the passage of certain agents. Poorly filtered antibiotics appeared to be absorbed by the collodion. Some of these observations might be accounted for by the known ability of nitrated cellulose to interact with anions. However, the extreme differences in filterability among the various penicillins and the very restricted passage of certain cationic antibiotics appeared to be better explained by intrinsic differences in the diffusibility of these agents through water. Although differential filtration offers a means of assaying samples containing certain mixtures of antibiotics, the degree of separation exhibited by collodion membranes is not sufficient to make them useful for clinical purposes.
The in vitro bactericidal activity of cefazolin was found to be similar to that of cephaloridine and cephalothin but slightly greater than that of cephalexin against a majority of 233 strains of gram-positive and gram-negative organisms. Cefazolin, however, was two- to eightfold more active than the other two drugs against Escherichia coli and klebsiella. The mean peak concentrations in the serum in 10 normal subjects 1 h after intramuscular injections of 1,000, 500, and 250 mg of cefazolin were 38.8, 18.6, and 12.2 mug/ml, respectively. The antibiotic could still be detected at 8 h. Peak values for a given dose of cephaloridine were comparable. However, blood levels of cefazolin were regularly higher than those of cephaloridine over the first 8 h. The mean half-life of cefazolin in the serum was 2 h, whereas that of cephaloridine was 1.4 h. The degree of serum protein-binding was strikingly higher for cefazolin (81%) than for cephaloridine (24%), suggesting that the antibacterial activity of the former in serum might be less than that of cephaloridine after equal doses. This proved to be the case when the bacterial activity of blood drawn 1, 4, and 8 h after injection of the two drugs was examined.
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Sulfonamide concentrations were studied in 210 serum samples from 10 volunteers after ingestion of sulfacytine, sulfisoxazole, and sulfadiazine. Results obtained by chemical assay were compared with bioassay values determined by two techniques: twofold broth dilution and agar diffusion. Although the correlation for individual samples was rather poor for the twofold broth-dilution method, the agar-diffusion bioassay correlated well with chemical determinations. The agar-diffusion assay tended to "underread" the chemical assay by an amount characteristic of each drug.
Clinical isolates of gentamicin-resistant organisms were found to be resistant to tobramycin, a new aminoglycoside antibiotic.
The reversibility of human serum protein binding of oxacillin, nafcillin, and cephalothin was investigated by using a diafiltration technique. While the temperature, pH, and protein concentration were kept constant, 20% of the serum volume was exchanged every 4 to 5 min. The binding of all three drugs was rapidly reversible, and the percentage of protein binding remained the same throughout the experiment.
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Five years ago, we established the Viewpoints section on the premise that written constructive expression of differences of opinion about ophthalmic problems would increase the level of understanding in the profession. Since we thought that neither eloquence of expression nor vigor of debate would resolve the questions, we avoided a response-rebuttal format and simply asked each author to express his or her point of view along with the evidence supporting it, without seeing the other's manuscript. Rather than rigidly cementing opinions, we hoped this approach would maintain maleable minds in the search for solutions to perplexing problems. In the inaugural Viewpoints section, Baum and Peyman discussed periocular versus intravitreal administration of antibiotics in the treatment of bacterial endophthalmitis (Antibiotic administration in the treatment of bacterial endophthalmitis. I. Baum JL: Periocular injections. II. Peyman GA: Intravitreal injections. Surv Ophthalmol 21:332-346, 1977). Now, in a novel format, the authors reappraise the subject and come to a consensus that minimizes the therapeutic quandary engendered by the original articles. While acknowledging that intravitreal administration of antibiotic is the preferred route for the treatment of bacterial endophthalmitis, the authors emphasize the lack of controlled and randomized clinical trials in this area. Their practical recommendations will assist the ophthalmologist who tries to forestall the devastation of bacterial endophthalmitis.
The in vitro activities of cephalothin and cefoxitin against Bacteroides fragilis were studied by time-kill curves and measurement of residual drugs in culture supernatants. Cefoxitin was bactericidal, causing a decrease of 10(7) in viable counts over 24 hr. Cephalothin caused an initial decrease of 10(2) B. fragilis at 2 hr; this change was followed by growth of the organism within 24 hr back to the number present before addition of cephalothin. The concentration of cephalothin in broth decreased rapidly within 2 hr and was undetectable within 24 hr, whereas the level of cefoxitin decreased only 25% over the 24-hr period. Penetration of these drugs into perforated ping pong balls implanted intraperitoneally in rabbits was studied. Three weeks after implantation the reservoirs were infected with B. fragilis. After intramuscular administration of five doses of antibiotic, the penetration of cephalothin, as measured by bioassay, in uninfected and infected capsules was 16% and 2%, respectively, of the peak serum concentration; similar findings were noted with cefoxitin. For determination of the rate of breakdown within the infected site, radiolabeled antibiotic was injected into the capsule, and the concentrations of bioactive and radioactive drug were determined. With radiolabeled cephalothin there was a rapid decrease in bioactivity during the initial 60 min, and no active drug was measurable after 2 hr. In contrast, only 40% of cefoxitin was inactivated at the end of 6 hr. The results indicate that levels of cephalothin and cefoxitin are reduced significantly in sites infected with B. fragilis. The decrease appears to be mediated by both a decrease in penetration and inactivation at the site of infection.
A review of published data indicates that the new quinolones readily penetrate the tissues and secretions of the upper respiratory tract. The concentrations of ciprofloxacin and ofloxacin in tonsillar tissue and the concentrations of ofloxacin in the mucosa of the paranasal sinuses generally exceeded the peak concentrations of these agents in serum after oral administration of the drugs. Good penetration was noted for ciprofloxacin into nasal secretions, ofloxacin into tears, and various quinolones into saliva. Penetration into ocular humors appears to be moderate. Reports in English concerning clinical trials of the new fluoroquinolones in the treatment of infections of the eyes, ears, nose, and throat are sparse, but a number of studies of ofloxacin have been published in Japanese. The data suggest that the new quinolones may be useful for the treatment of acute sinusitis and chronic suppurative otitis media. However, studies comparing these agents with more established drugs and using carefully defined criteria for diagnosis and for evaluation of the response to treatment are needed.
Forty-eight case report forms for patients with cultures positive for intraabdominal infection treated with moxalactam were reviewed. The infections included abscess or peritonitis due to appendicitis (26); intraabdominal abscess of other causes (7); peritonitis due to bowel perforation (6), bowel infarction (5), or salpingitis (3); and gangrenous cholecystitis (1). Cultures of peritoneal fluid or abscess contents were performed for all patients. Seventy-eight aerobes and 118 anaerobes were isolated from the 48 patients. Thirty-eight patients (79.2%) were cured, therapy failed in nine (18.8%), and one (2%) developed fatal superinfection with Candida. The nine patients for whom treatment failed had a higher frequency of resistant anaerobes in their initial cultures (59%) than did the patients who were cured (29%; P = 0.036). An enterococcal isolate appeared to play a role in at least one treatment failure. There were no serious adverse reactions; eosinophilia (greater than 500 eosinophils/mm3) occurred in 17.4% of the patients, and phlebitis at the intravenous administration site occurred in one patient. Thus moxalactam shows promise as a single agent for the treatment of intraabdominal infections.
Flucloxacillin, a recent addition to the group of isoxazolyl penicillins, was studied in vitro and in normal volunteers. The bactericidal activity of the drug against most strains of gram-positive bacteria including penicillin-resistant Staphylococcus aureus was similar to that of oxacillin and approximately fourfold greater than that of cloxacillin. Each of the three penicillins was administered orally to a group of ten volunteers for eight days in a dose of 500 mg four times a day. The mean concentrations of flucloxacillin in the serum were two- to sixfold higher than those of the other two agents on the first, fourth and eighth days of therapy. The percentage of flucloxacillin bound by serum protein was 94.6 per cent; for cloxacillin and oxacillin the values were 93.5 and 91.5 per cent, respectively. Using these data, the concentrations of free flucloxacillin in serum were found to be twice as high as those of cloxacillin and oxacillin. These findings suggest that, when administered orally, this new agent may offer some therapeutic advantage over oxacillin and cloxacillin.
Although it is widely recommended that serum levels of aminoglycoside antibiotics be monitored by assay, the justification for this approach has not been clearly presented. A number of studies indicate that serum levels of these agents cannot be predicted reliably on the basis of simple dosage formulae; the major confounding factors being abnormalities of renal function and of extracellular fluid volume in addition to less well defined variables such as fever and anaemia. The influence of haemodialysis and concomitant administration of carbenicillin further complicate dosage estimations in patients with renal insufficiency. On the basis of currently available data, it is reasonable to suggest an optimum range of 5 to 8 microgram/ml for peak serum levels of gentamicin. There are no reliable studies from which to derive a comparable value for trough (pre-dose) concentrations. The relative importance of peak and trough values for nephrotoxicity and ototoxicity is an unresolved subject of controversy. However, it seems possible that neither of these individual values, but rather the 'area under the time-concentration curve' is the major risk factor for toxicity. In view of the unpredictability of serum levels, especially in seriously ill patients in a fluctuating physiological state, periodical serum gentamicin assays should be performed. The main objective of these assays is to ensure that the peak serum levels attained are adequate, but not unnecessarily high.