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Biomedical subjects

M Barza

Publications and source records attributed to M Barza.

At least 127 records · Page 7Linked to original sources
PubMed1979

Radioactive and bioassay of intraocular antibiotics: double-assay technique to compare penicillin G, cefamandole, and gentamicin in ocular tissues in vivo.

We examined the correlation between radioactive assay and trephine-discbioassay of penicillin G sodium, cefamandole nafate, and gentamicin sulfate in ocular tissues of pigmented rabbits after subconjuctival administration of antibiotic. We devised a technique whereby a single sample of tissue could be assayed by both methods. This was achieved by performing the bioassay first, then measuring the resudual radioactivity in the agar and specimens. The results of both methods were generally within 13%. An exception was gentamicin in iris and choroidretina, for which the bioassay result was strikingly less than the radioassay value. No such discrepancy was evident when similar studies were carried out with gentamicin in albino rabbits. This suggests that the phenomenon is due to tight binding of gentamicin by melanin-containing tissues. The trephine-disc bioassay provides an accurate measure of diffusible bioactive antibiotic in ocular tissues.

Animals↗
PubMed1979

Marked differences between pigmented and albino rabbits in the concentration of clindamycin in iris and choroid-retina.

The concentrations of clindamycin were significantly higher in iris and choroid-retina or pigmented rabbits than in those of albino rabbits after subconjunctival injection. Equilibrium dialysis experiments showed no affinity of clindamycin for synthetic melanin or for collagenase digests of pigmented tissues. In contrast, strips of iris and choroid-retina took up clindamycin rapidly from solution, achieving concentrations substantially higher than those in the medium. Uptake by tissue strips was not influenced by temperature (4 C vs. 37 C), cyanide, or ouabain. However, N-ethylmaleimide, which reacts with sulfhydryl groups, decreased the tissue-to-medium ratios by about 50% for both albino and pigmented choroid-retina. Even in the presence of this inhibitor, the ratio for pigmented tissues remained higher than that for albino specimens. These findings suggest the existence of one, or possibly two, mechanisms of energy-independent accumulation of clindamycin by pigmented ocular tissues: one may relate to protein sulfhydryl bonds that are present in both breeds; the other may involve the pigmentation apparatus.

Animals↗
PubMed1979

Netilmicin in gram-negative bacterial infections.

Netilmicin, a new semisynthetic aminoglycoside, was used in the treatment of 42 patients with serious gram-negative bacterial infections. Of the 40 evaluable patients, 24 (60%) were cured, and 8 (20%) had a favorable clinical response, for a total clinical response rate of 80%. Eight patients failed to respond; of these, three had undrained abscesses and two had severe granulocytopenia. Three of the patients who failed had organisms in which resistance to netilmicin developed during therapy, and in two of these three netilmicin was the only aminoglycoside to which resistance developed. Of the 37 patients evaluable for toxicity, 8 (22%) developed renal insufficiency. Two patients had mild but persistant elevation in serum creatinine. Three patients had nephrotoxicity while on gentamicin in the past. Pre- and posttherapy audiograms were done on 26 patients; none had hearing loss. Four patients had mild, transient asymptomatic elevations in alkaline phosphatase. The pretreatment clinical isolates were tested for in vitro susceptibility. The median minimal inhibitory concentration of netilmicin, gentamicin, and tobramycin ranged between 0.5 and 2 mug/ml. The median minimal inhibitory concentration of amikacin was approximately twofold higher. No clear in vitro superiority of one aminoglycoside over another was observed.

Bacterial Infections↗
PubMed1979

In vitro activity of LY127935.

The activity of LY127935, a beta-lactam antibiotic of novel structure, was studied in vitro against facultative gram-negative bacilli, Staphylococcus aureus, and Bacteroides fragilis. The strains were recent clinical isolates, many of which were relatively resistant to other antibiotics. LY127935 exhibited striking activity against Escherichia coli, Klebsiella pneumoniae, Enterobacter sp., Proteus sp., Serratia marcescens, and B. fragilis with median minimum inhibitory concentrations of less than or equal to 1.0 micrograms/ml. It was somewhat less active against Pseudomonas aeruginosa and S. aureus. Cefotaxime (HR 756) showed very similar activity except that it was substantially weaker against B. fragilis. LY127935 was more active than cefamandole, cefoxitin, or piperacillin; it was also as potent as tobramycin or amikacin against all species except for P. aeruginosa.

Anti-Bacterial Agents↗
PubMed1979

Intraocular levels of cefamandole compared with cefazolin after subconjunctival injection in rabbits.

We compared the intraocular pharmacokinetics of cefazolin with those of cefamandole, a recently marketed cephalosporin with enhanced activity against gram-negative bacilli. Following subconjunctival injection of 12.5 mg into infected eyes (S. aureus endophthalmitis) of pigmented rabbits, both drugs reached peak concentrations greater than 100 microgram/gm in cornea, sclera, and choroid-retina. The half-life was markedly shorter in sclera and choroid-retina than in cornea. Levels in the aqueous humor rose and fell more slowly than those in ocular tissues, reaching a maximum of only 5 to 10 microgram/ml. The pharmacokinetics of the two drugs were virtually identical in most intraocular sites. When cefazolin, which was less irritating than cefamandole by the subconjunctival route, was given in a dosage of 100 mg, levels in ocular tissues were increased by twofold to fourfold and in aqueous humor by 15-fold, compared to the concentrations produced by the 12.5 mg dosage. Levels in the vitreous humor were exceedingly low with both drugs; mean peak concentrations were 0.24 microgram/ml after the 12.5 mg dosage of cefamandole and less than 1.6 microgram/ml after the 100 mg dose of cefazolin.

Animals↗
PubMed1978

Efficacy of penicillin G, cefazolin, and gentamicin in M-K medium at 4 degrees C.

Corneal-scleral shells are routinely stored in McCarey-Kaufman (M-K) medium at 4 degrees C. Antibiotics are added to the medium to suppress bacterial growth. We examined the antibacterial activity of penicillin G potassium, 100 microgram/ml, cefazolin sodium, 100 microgram/ml, and gentamicin sulfate, 20 microgram/ml against test organisms in M-K medium at 4 degrees, 23 degrees, and 37 degrees C for periods up to 18 hours. Within the limits of the experimental conditions, none of the antibiotics used could be relied on to sterilize an inoculum of sensitive bacteria in M-K medium at 4 degrees C, the recommended storage temperature.

Anti-Bacterial Agents↗
PubMed1978

Penetration of clindamycin into the human appendix.

Clindamycin penetrated extremely well into inflamed (19) and normal (one) appendices. Average levels in appendiceal tissue taken 26 to 300 minutes after a single intravenous dose were 154% of the simultaneous serum concentration.

Adolescent↗
PubMed1978

Intraocular penetration of gentamicin after subconjunctibal and retrobulbar injection .

We compared the ocular penetration of labeled with radioactive carbon gentamicin in squirrel monkeys after subconjunctival and retrobulbar administration. In both normal and infected (Staphylococcus aureus endophthalmitis) eyes, high concentrations of drug were achieved in the sclera and choroid-retina by both routes, while corneal levels were markedly higher after subconjunctival injection than after retrobulbar injection. Regional variations in concentration were evident in these tissues; the highest levels were clustered about the site of injection. Aqueous humor concentrations were lowest in the group with normal eyes treated by the retrobulbar route; vitreous humor levels were extremely low in normal eyes injected subconjunctivally. These data differ from those in rabbits, especially with regard to penetration of the vitreous humor of normal eyes. Interspecies differences were less marked in inflamed eyes. The two species were similar in demonstrating maximum access to the cornea and aqueous humor with subconjunctival injection, and equivalence of the two routes in penetrating the vitreous humor of the inflamed eyes.

Animals↗
PubMed1978

Excretion of gentamicin in rabbit tears after subconjunctival injection.

We subconjunctivally, injected gentamicin, in a dose of 10 mg, into normal and inflamed (Staphylococcus aureus endophthalmitis) rabbit eyes in which the nasolarcrimal ducts had been blocked. We retrieved approximately 10% of the dose of drug in the tears, the majority in the first 30 minutes. The difference in lacrimal excretion of the drug between normal and inflamed eyes was not significant. Higher concentrations of gentamicin found in the ocular tissues of normal eyes than inflamed eyes cannot be attributed to loss in the tears.

Animals↗
PubMed1978

Inactivation of penicillin G during experimental infection with Bacteroides fragilis.

An animal model implanted with intraperitoneal plastic reservoirs was used for study of the penetration of penicillin G into sites infected with Bacteroides fragilis. Penicillin G was given to rabbits, and its concentration in uninfected reservoirs and in those infected with B. fragilis was determined. The mean percentage penetration ([concentration in capsule divided by peak concentration in serum] X 100) of penicillin into uninfected capsules was 19.9%, whereas that into heavily infected capsules was 1.5%. The percentage penetration of radiolabeled penicillin into infected capsules was 12.5%, whereas the proportion of bioactive drug in the same capsules was again very low (1%). These results show that there is a modest reduction in penetration of penicillin into infected sites and a striking inactivation of the drug by B. fragilis in this experimental model.

Animals↗
PubMed1978

The nephrotoxicity of cephalosporins: an overview.

The cephalosporin antibiotics cephaloridine and cephalothin are known to cause renal damage. Experience with newer congeners is not yet sufficient to predict their potential nephrotoxocity. The renal lesion produced by cephaloridine is primarily due to the intrinsic toxicity of this drug for the cells of the proximal renal tubule and depends upon its peculiar transport characteristics. In contrast, renal injury due to cephalothin resembles that seen with the penicillins. Thus, some instances of cephalothin nephropathy appear to be toxic in nature with a histologic picture of acute tubular necrosis, whereas others exhibit signs of hypersensitivity including rash, eosinophilia, and interstitial nephritis. Among the factors alleged to contribute to the nephrotoxicity of cephalosporins is their administration with aminoglycosides. Although the physician should be aware of the possibility of a potential adverse interaction between these groups of antibiotics, the evidence is not sufficiently conclusive to warrant avoidance of the combination when it appears to be therapeutically useful.

Aminoglycosides↗
PubMed1978

Penetration of clindamycin into decubitus ulcers.

Forty tissue samples, primarily of skin and bone, were obtained from 29 patients undergoing excision of decubitus ulcers after intravenous injection of 600 mg of clindamycin. Antibiotic concentrations exceeded 2.5 mug/g in 80% of the samples. In 50% of the instances, tissue levels were greater than those simultaneously present in the serum.

Adolescent↗
PubMed1978

Factors affecting the intraocular penetration of antibiotics. The influence of route, inflammation, animal species and tissue pigmentation.

Antibiotics which are sparingly lipid-soluble, such as the penicillins, cephalosporins and aminoglycosides, penetrate the eye with great difficulty, achieving intravitreal concentrations which are only a small percentage of the peak serum level. As a result, it is common practice to administer these agents by periocular injection. We have compared the penetration of gentamicin in albino rabbits with that in squirrel monkeys, in normal and infected eyes, after retrobulbar and subconjunctival administration. Generally speaking, the subconjunctival route produced levels equal to or higher than those resulting from retrobulbar injection in both species; it was distinctly superior with regard to cornea and aqueous humor. Inflammation had a neutral or enhancing influence upon intraocular penetration in the monkey, but had a more variable effect in the rabbit; this may be related to the balance between diminution of the blood-ocular barrier and increased dissipation of antibiotic into the systemic circulation. Interspecies differences were much more striking in normal than in infected eyes. This underlines the necessity for the investigator to study inflamed eyes if the results are to be relevant to the clinical situation. Iris and choroid-retina from pigmented rabbits contained significantly more clindamycin and less gentamycin and less gentamicin, in terms of diffusible drug, than tissues from albino animals. These discrepancies reflect opposite interactions between melanin and the two antibiotics in vivo.

Albinism↗
PubMed1978

A critique of animal models in antibiotic research.

The interactions between microbes and antimicrobial agents in vitro are often markedly different from those in vivo, presumably because of pharmacological factors and host defenses. Although animal models have long been used to evaluate the efficacy of chemotherapeutic agents, there are few guidelines for the conduct of these studies. Therefore, the results of these investigations must be assessed critically in terms of the balance between the infectious challenge and the therapeutic response, and in terms of their relevance to human disease. It has been clearly demonstrated that the "freshness" of the infecting organism, the interval between infection and therapy, the order of administration of drug combinations, and the presence of foreign bodies, may have a crucial impact upon the outcome of animal trials. Less well studied have been the influence of the quantity and growth phase of the infecting inoculum, the use of single- as opposed to multiple-dose therapy, and the anatomical and pharmacological attributes of the particular animal species. Greater understanding of these factors would resolve some of the apparently contradictory results of various investigations, and would permit more rational design of these studies in the future.

Animals↗