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Biomedical subjects

M Barza

Publications and source records attributed to M Barza.

At least 109 records · Page 6Linked to original sources
PubMed1982

Ocular penetration of subconjunctival oxacillin, methicillin, and cefazolin in rabbits with staphylococcal endophthalmitis.

The concentrations of oxacillin, methicillin, and cefazolin were examined in the infected eyes of pigmented rabbits with Staphylococcus aureus endophthalmitis after a subconjunctival dose of 100 mg. The three drugs had fairly similar ocular pharmacokinetics. The tissue concentration usually peaked within 30 min. Levels in the aqueous humor rose more slowly; the respective maximal concentrations of methicillin, oxacillin, and cefazolin were 72, 1,180, and 111 micrograms/ml. Oxacillin also produced the highest levels in the cornea. Penetration of the vitreous humor was poor with all three drugs, apparently owing to a diffusional barrier in the choroid-retina tissue complex. The respective median vitreous levels of methicillin, oxacillin, and cefazolin were 0.7, 0.6, and less than 0.8 micrograms/ml. These values are close to the concentrations usually required to inhibit S. aureus in vitro. Our results suggest that subconjunctival oxacillin achieves higher concentrations in anterior ocular tissues than do the other two drugs, but more aggressive approaches are necessary in treating endophthalmitis.

Animals↗
PubMed1982

Clinical experience with Moxalactam in the treatment of pseudomonal and nonpseudomonal infections.

A total of 38 patients with 39 infections involving a variety of organ systems were treated with moxalactam. The overall cure rate was 79.5%. Most of the failures occurred in patients with severe underlying disease such as peripheral vascular disease. The cure rate for infections with Pseudomonas aeruginosa was 62.5% (10 of 16) and for nonpseudomonal infections was 91% (21 of 23). However, excluding the six infections involving organisms which were initially resistant to moxalactam, the cure rate for pseudomonal infections was 77% (10 of 13) compared with 90% (18 of 20) for nonpseudomonal infections. Two patients with gram-negative bacillary meningitis were cured, as were seven of eight with mixed aerobic-anaerobic infections. There were no serious adverse drug effects. Three patients became colonized with the enterococcus and two became colonized with Candida albicans; one other patient developed candida vaginitis. These results suggest that moxalactam will be a valuable drug in therapy of gram-negative bacillary and anaerobic infections.

Adult↗
PubMed1982

In vitro activity of azthreonam, a monobactam antibiotic.

We studied the activity of azthreonam (SQ 26,776), a novel monocyclic beta-lactam compound, against a variety of clinical isolates. It was more potent than moxalactam, cefoperazone, cefamandole, cefoxitin, ticarcillin, tobramycin, or amikacin against strains of Klebsiella spp., Serratia spp., and the Proteus group. It was highly effective against Escherichia coli and strains of Salmonella spp. The median minimal inhibitory concentration for all species of Enterobacteriaceae was less than or equal to 2 micrograms/ml. Azthreonam was moderately active against Pseudomonas aeruginosa, including tobramycin-resistant strains, and against Pseudomonas cepacia (median minimal inhibitory concentration, 16 to 32 micrograms/ml), but was weakly active against Pseudomonas maltophilia and strains of Acinetobacter spp. and Achromobacter spp. The drug showed little activity against Staphylococcus aureus, enterococci, and anaerobic bacteria, including Bacteroides fragilis, Clostridium spp., and gram-positive cocci. Like moxalactam and cefoperazone, azthreonam exhibited a considerable inoculum effect with strains of Enterobacter spp. and Pseudomonas spp. Combination with clavulanic acid did not increase the activity of azthreonam against S. aureus but was synergistic for 5 of 15 strains of B. fragilis. Azthreonam is about 50% bound to human serum protein. The selective range of activity of this compound could be of clinical benefit.

Anti-Bacterial Agents↗
PubMed1982

The effects of infection and probenecid on the transport of carbenicillin from the rabbit vitreous humor.

We examined the effects of inflammation (S. aureus endophthalmitis) and of probenecid on the kinetics of intravitreally injected carbenicillin in rabbits. The half-life of antibiotic in the vitreous of animals with normal eyes was only 5 hr and levels in anterior ocular sites (cornea, aqueous, iris) were low. There findings are consistent with an active retinal transport pump for organic anions. Concomitant intraperitoneal administration of probenecid caused a marked prolongation of the ocular half-life of carbenicillin to 13 hr and augmentation of the levels in anterior sites, as might be anticipated from inhibition of the retinal transport pump. Inflammation produced an intermediate effect that is most readily explained by postulating two opposing consequences: partial inhibition of the transport pump and simultaneous "leakiness" of the normal retinal barrier. There findings suggest that the intraocular kinetics of antibiotics in inflamed eyes are markedly different from those in normal ones and that systemic probenecid significantly augments the intraocular levels of carbenicillin.

Animals↗
PubMed1981

Past and current roles for cephalosporin antibiotics in treatment of meningitis. Emphasis on use in gram-negative bacillary meningitis.

The therapy of gram-negative bacillary meningitis is less than adequate to date; the agents recommended do not achieve bactericidal levels in purulent cerebrospinal fluid. Because optimal antibiotic therapy of meningitis occurs when the cerebrospinal fluid level of an antibiotic is above the concentration needed to kill the offending pathogen, another group of agents needs to be considered. The newer cephalosporins or cehalosporin-type antibiotics (cefotaxime, moxalactam), by virtue of their marked activity against gram-negative bacilli and their ability to achieve significant CSF levels, merit serious consideration as therapy for gram-negative bacillary meningitis. Investigators in Europe and the United States have developed preliminary data demonstrating the efficacy of these agents in a growing number of cases. In the group presented herein, of the 35 cases in which gram-negative bacillary meningitis was treated with the newer cephalosporins, there were only four failures.

Adolescent↗
PubMed1981

Penetration of ocular tissues and fluids by moxalactam in rabbits with staphylococcal endophthalmitis.

Moxalactam was administered subconjunctivally in 100-mg doses to rabbits with infected eyes (Staphylococcus aureus endophthalmitis). High concentrations of drug were detected in the sclera, cornea, and choroid; much lower levels were found in the retina, whereas peak concentrations in the vitreous were about 6 microgram/ml. Repeated intramuscular injections of 50 mg/kg every 4 h produced peak serum levels of about 100 microgram/ml. A gradient between the choroid and the retina was again evident, and peak vitreous levels were about 6 microgram/ml after six injections. These data are consistent with the concept of a blood-retina barrier analogous to the blood-brain barrier. Moxalactam appears to penetrate the eye somewhat better than do other beta-lactams; however, the peak levels produced in the vitreous humor in this animal model were below the level required to inhibit most strains of Pseudomonas aeruginosa.

Animals↗
PubMed1981

Penicillin-binding proteins in Clostridium perfringens.

The penicillin-binding proteins (PBPs) of Clostridium perfringens were studied. Six PBPs ranging in molecular weight from approximately 42,000 to 100,000 were detected in the cytoplasmic membrane. The relative affinities of the PBPs for 16 beta-lactam antibiotics were determined. Most of the drug saturated PBP 3 and 4 at concentrations equal to their minimal inhibitory concentrations, suggesting that these PBPs are the killing targets for beta-lactams. Mecillinam showed unique properties; it had a higher affinity for PBP 5 than for other PBPs, and it was the only agent tested which caused inhibition of growth without saturating PBP 4. Interestingly, all beta-lactam antibiotics tested induced filament formation despite having different binding patterns to the PBPs of C. perfringens.

Azlocillin↗
PubMed1981

Intravitreal injection of gentamicin in rabbits. Effect of inflammation and pigmentation on half-life and ocular distribution.

Most regimens for intravitreal injection of antibiotics are based on studies in normal albino rabbits. We examined the effect of two variables, infection and pigmentation, on the ocular distribution of an intravitreal injection of 50 micrograms of gentamicin in rabbit eyes. The half-life of gentamicin in the vitreous of normal pigmented rabbits after intravitreal administration was 24 hr. Antibiotic levels in cornea and aqueous reached a peak 18 hr after injection; terminal half-lives in these sites were similar to those in vitreous. With inflammation, the half-life in the vitreous was decreased to 10 hr, and there was no accumulation of drug in anterior sites. To the extent that these data are applicable to humans, they suggest that the treatment of bacterial endophthalmitis by the intravitreal route may require more frequent injections than had been recommended on the basis of studies in normal eyes. Normal pigmented and albino rabbits showed similar levels of gentamicin in the cornea, aqueous, and vitreous; however, the drug was barely detectable in iris, choroid-retina, and sclera of pigmented animals, presumably on account of an interaction with melanin-containing tissues. This effect of pigment may explain the differences in the reported thresholds for toxicity of gentamicin with intravitreal injection.

Animals↗
PubMed1981

The difficulty of determining the route of intraocular penetration of gentamicin after subconjunctival injection in the rabbit.

In small animals such as the rabbit the ratio of eye size to body size is much larger than it is in humans. Accordingly, periocular injection of antibodies in this animal model results in significantly higher serum concentrations than does a comparable does in a human. To assess the effect of the systemic drug component on ocular penetration, we compared the levels of gentamicin in ocular tissues and fluids of the rabbit following injection of 20 mg by subconjunctival or intramuscular routes. Blood levels of gentamicin were similar with the two routes of administration. In normal rabbit eyes, no antibiotic was detectable in the vitreous humor for the first 3 hr after either subconjunctival or intramuscular injection. By 6 hr, low vitreous levels of drug were detectable after subconjunctival, but not after intramuscular, injection. Because these concentrations were so close to the threshold of sensitivity of the assay, it was not clear that the difference between the routes was significant in normal eyes. In infected eyes, the concentrations of gentamicin in the vitreous were similar after subconjunctival and intramuscular injection. These data indicate that the penetration of gentamicin in to the infected vitreous humor of rabbits after subconjunctival injection could be attributed as well to hematogenous carriage as to direct penetration. The problem in distinguishing systemic from direct transport with periocular injections may be inherent in any small animal model in which the ratio of eye size to body size is high.

Adult↗
PubMed1980

Uptake of gentamicin by separated, viable renal tubules from rabbits.

The proximal renal tubules have a marked affinity for gentamicin; they also are the major site of nephrotoxicity caused by this drug. The uptake of radiolabeled gentamicin in separated, viable renal tubules prepared by enzymatic digestion of rabbit kidneys was studied. The preparations showed rapid initial uptake of gentamicin followed by continued slower uptake. Accumulation was not affected by pH, but was significantly inhibited by ouabain, dinitrophenol, anoxia, and hypothermia in the absence of evident cellular damage. At gentamicin concentrations of greater than 50 microgram/ml in the medium, there was competition for drug uptake. Gentamicin efflux in tubules that were taken from a medium containing antibiotic and placed into antibiotic-free fluid was slow and incomplete. From these data it appears that gentamicin uptake by separated renal tubules occurs by a process that requires metabolic energy; thereafter, the drug resides in a poorly exchangeable cellular pool.

Aminoglycosides↗
PubMed1980

Prospective, randomized trial of netilmicin and amikacin, with emphasis on eighth-nerve toxicity.

The toxicity of netilmicin was compared with that of amikacin in a randomized, prospective trial in 90 adults with a variety of serious gram-negative infections. There was no instance of antibiotic-related nephrotoxicity in the group given amikacin and only one instance in the group given netilmicin. Cochlear toxicity, as measured by a change in audiogram, occurred in 4/14 (28.5%) of the amikacin recipients and 3/19 (15.8%) of the netilmicin recipients. Vestibular toxicity, as determined by a change in ice-water calorics, was noted in 3/16 (19%) of the amikacin-treated patients and 0/15 of the netilmicin-treated individuals. Despite the trend toward lesser ototoxicity with netilmicin, the differences between the drugs were not statistically significant. There was, however, a significant association between male sex and the development of ototoxicity. Although many patients could not be evaluated for efficacy, there did not appear to be any difference in the therapeutic activity of the two drugs.

Aged↗
PubMed1980

The decision to biopsy, treat, or wait in suspected herpes encephalitis.

The availability of vidarabine for the therapy of suspected herpes simplex encephalitis presents a difficult decision for a physician as to whether to do brain biopsy, to treat blindly, or to withhold specific therapy in a patient. The choice is made more difficult because the physician must weigh four likelihoods simultaneously: namely, of the disease, of a life-threatening complication from biopsy, of a beneificial effect from vidarabine, and of a serious adverse effect from the drug. Using decision analysis, we have derived a series of threshold probabilities whereby the physician can select his own estimates of these likelihoods to arrive at a rational approach to management. When reasonable assessments are made of the risks of biopsy and of vidarabine therapy, brain biopsy is likely to be the optimal approach in the majority of patients suspected of having herpes simplex encephalitis.

Biopsy↗
PubMed1980

Susceptibility of anaerobic bacteria to cefoperazone and other beta-lactam antibiotics.

The in vitro activity of cefoperazone was tested against 155 clinical isolates of anaerobic bacteria and compared to that of cefoxitin, LY127935 (moxalactam), cefotaxime, cefamandole, and cephalothin. Against the Bacteroides fragilis group, the compound was as active as LY127935, but less active than cefoxitin. Cefotaxime was less active than cefoperazone, cefoxitin, and LY127935. Cefoperazone, as well as cefoxitin, LY127935, and cefotaxime, exhibited excellent activity against all other anaerobic organisms tested. Cefamandole and cephalothin showed inferior activity when compared to the other four drugs.

Bacteroides↗
PubMed1980

Oxacillin for bacterial endophthalmitis: subconjunctival, intravenous, both, or neither?

We compared the intraocular concentrations of oxacillin given by continuous intravenous infusion, subconjunctival injection, or combined therapy in a rabbit model of Staphylococcus aureus endophthalmitis. At equilibrium during intravenous infusion, concentrations in the aqueous humor, cornea, and choroid-retina were 25% to 30% of the serum level; in contrast, vitreous levels were only 2% of the serum concentration. Subconjunctival injection produced extremely high levels in the cornea and aqueous and moderate concentrations in the choroid-retina; vitreous penetration remained poor (<1 microgram/ml). Combined therapy offered little advantage in terms of concentrations in the aqueous or cornea and had a modest effect on levels in the choroid-retina. Vitreous concentrations showed a striking relation to serum levels with all regimens, including subconjunctival ones; although this could have been fortuitous, it suggests an important role for the hematogenous route in this model. Only those modes of delivery producing serum concentrations greater than 50 micrograms/ml consistently resulted in vitreous levels greater than 0.4 microgram/ml. The optimal therapy of bacterial endophthalmitis may require direct intravitreal injection of antibiotic.

Animals↗