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Biomedical subjects

M Barza

Publications and source records attributed to M Barza.

At least 73 records · Page 4Linked to original sources
PubMed1987

The inoculum effect with gram-negative bacteria in vitro and in vivo.

The in-vitro MICs and MBCs of ciprofloxacin, cefoperazone, ceftazidime, ceftriaxone, gentamicin and imipenem were measured for five strains each of Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa with standard and high inocula. The MBC was raised more than the MIC at the higher inoculum for all the drugs except ciprofloxacin. However, the MBC of imipenem against P. aeruginosa was increased relatively little at the higher inoculum in contrast to the findings with other beta-lactam drugs. In a rabbit model of endophthalmitis both cefoperazone and imipenem were markedly more bactericidal against a high inoculum of K. pneumoniae than would have been predicted from the results of in-vitro time kill curve studies. We conclude that the therapeutic relevance of the inoculum effect remains to be proved.

Animals↗
PubMed1987

Effect of broad-spectrum parenteral antibiotics on composition of intestinal microflora of humans.

We compared the effects of four beta-lactam drugs with widely differing antibacterial and pharmacological properties on the composition of the intestinal flora. Cefoxitin, piperacillin, cefoperazone, and aztreonam were given intravenously for 9 days to healthy volunteers. Cefoperazone reduced the numbers of aerobic and anaerobic bacteria to undetectable levels. At the other extreme, cefoxitin had little effect on the normal flora. Aztreonam markedly reduced the numbers of aerobes, whereas piperacillin had a variable effect on both aerobic and anaerobic bacteria. There was extensive overgrowth of enterococci in subjects given cefoxitin or aztreonam, which have little activity against this species, and of yeasts in subjects given cefoperazone or piperacillin. Cefoperazone reached concentrations of 2,727 to 8,840 micrograms/g in the feces, whereas the other agents were generally undetectable. These results show that the new beta-lactam antibiotics produce widely varying effects on the fecal microflora after parenteral administration and that these effects are consistent with the antibacterial and pharmacological properties of the drugs.

Adult↗
PubMed1987

Effect of lipid composition and liposome size on toxicity and in vitro fungicidal activity of liposome-intercalated amphotericin B.

Intercalation of amphotericin B into liposomes at a 10 mol% drug/lipid ratio decreased its cytotoxicity by 3- to 90-fold in cultured murine cells and reduced its lethality by 2- to 8-fold in a median lethal dose (LD50) test in mice when compared with the commercial deoxycholate-solubilized drug (LD50 = 2.3 mg/kg). The cytotoxicity and lethality of the liposomal preparations were a function of their lipid composition and diameter. There was no correlation between the reduction of toxicity in the tissue culture assay and the reduction of lethality in the LD50 test. The rank order of reduction of lethality was sterol-containing liposomes greater than solid liposomes greater than fluid liposomes. In general, small sterol-containing vesicles were less lethal than large vesicles of the same composition. Intercalation of amphotericin B in sterol or solid liposomes increased not only the LD50 but also the time to death. The organ distribution of amphotericin B 24 h after intravenous administration was similar whether the drug was given as the commercial deoxycholate preparation or in liposomes. Finally, there were no differences among any of the formulations in their fungicidal activity against Candida tropicalis and Saccharomyces cerevisiae in vitro. The lesser and slower lethality of the liposomal and detergent-solubilized drug suggests that the mechanism by which liposomes reduce the lethality of amphotericin B is by slowing its rate of transfer to a sensitive cellular target.

Amphotericin B↗
PubMed1987

Effect of broad-spectrum parenteral antibiotics on "colonization resistance" of intestinal microflora of humans.

Studies with animals have shown that the normal intestinal microflora protects against colonization by new strains ("colonization resistance") and that this protective effect may be related to the anaerobic component of the microflora. However, colonization resistance has not been shown in humans. We administered cefoxitin, piperacillin, cefoperazone, and aztreonam intravenously to healthy subjects for 9 days and monitored the acquisition of new isolates in the fecal flora. Seven of sixteen antibiotic-treated subjects but none of four untreated controls became colonized by gram-negative bacilli. However, there was no correlation between colonization and the particular drug given or the extent of suppression of anaerobes or of any other component of the fecal microflora. Cefoxitin and piperacillin were associated with the greatest increases in the numbers of drug-resistant bacteria and in fecal beta-lactamase content. The results of this study support the concept that colonization resistance occurs in humans and is diminished by antibiotic administration but fail to support the hypothesis that resistance is related to the anaerobic microflora.

Anti-Bacterial Agents↗
PubMed1987

Pasteurella multocida endophthalmitis.

We have recently seen an unusual case of endophthalmitis secondary to Pasteurella multocida infection. Unlike previously reported cases this patient had no previous history of animal bites or scratch wounds. Treatment included subconjunctival, parenteral, and intravitreal administration of ampicillin. Although the eye was sterilised, the patient's vision remained poor owing to the extensive amount of retinal necrosis.

Ampicillin↗
PubMed1987

Spontaneous inhibition of bacterial growth in experimental gram-negative endophthalmitis.

We compared the growth patterns of gram-negative bacilli in the vitreous humor (experimental endophthalmitis in rabbits) and in a subcutaneous site of infection (croton oil pouches in rats). In untreated animals, inoculation of Klebsiella pneumoniae or Pseudomonas aeruginosa into either site was followed by a period of rapid bacterial multiplication. Thereafter, the numbers of bacteria in the vitreous humor fell spontaneously, whereas those in the subcutaneous site remained stable. During treatment with antibiotics, there was a decline in the numbers of bacteria in both sites. However, once the drug had been eliminated, the numbers of bacteria remained low in the vitreous humor but increased in the subcutaneous site. These findings suggest that during the course of infection, there was depletion of an essential bacterial nutrient or accumulation of an antibacterial substance in the vitreous humor but not in the subcutaneous site. To examine some of these possibilities, we made biochemical measurements during the course of untreated infection. In general, the biochemical changes in the two sites were similar except that the pH fell to about 6.6-6.8 in the vitreous humor but remained above 7.0 in the subcutaneous site. None of the biochemical changes that we observed seemed likely to account for the spontaneous decline in bacterial numbers in the vitreous humor. Further study is warranted to determine the cause of the antibacterial effect in the vitreous humor during the course of experimental bacterial endophthalmitis.

Animals↗
PubMed1987

Effect of size and lipid composition on the pharmacokinetics of intravitreal liposomes.

We investigated the influence of size and lipid composition on the pharmacokinetic behavior of liposomes and their contents in the rabbit eye. Small and large unilamellar vesicles (SUV and LUV), prepared with and without cholesterol in the membrane, were injected intravitreally in rabbits. The vesicles were labelled with 125I and contained 51Cr-EDTA in the aqueous compartment. The mode of elimination of the vesicles from the vitreous humor is uncertain but may be via the anterior route; 51Cr-EDTA, like gentamicin, probably is eliminated by the anterior route. The rate of clearance of the lipid label appeared to be related to the size but not to the cholesterol content of the liposomes. Liposome-encapsulation prolonged the half-life of 51Cr-EDTA by up to 11-fold in the vitreous humor of normal eyes. The prolongation was greatest with cholesterol-containing vesicles, presumably because these are most stable, and was somewhat greater with large than with small vesicles. For SUV and LUV, the rate of elimination of 51Cr-EDTA from the normal eye was determined mainly by the rate of leakage from the liposomes, whereas for SUV-cholesterol and LUV-cholesterol, it was determined mainly by the rate of clearance of the liposomes themselves. Both 51Cr-EDTA and liposomes (125I label) had a shorter half-life in infected than in normal eyes. Encapsulation of 51Cr-EDTA prolonged its half-life by up to sevenfold in infected eyes; the effect was greatest with cholesterol-containing vesicles. These results suggest that both the structure of the liposome and the state of the eye may markedly affect the pharmacokinetic behavior of intravitreal liposomes.

Animals↗
PubMed1987

Transscleral iontophoresis of gentamicin in monkeys.

Experiments in rabbits have shown that the novel technique of transscleral iontophoresis is a safe, effective, noninvasive way to produce high concentrations of antibiotics in the vitreous humor. The authors have now studied the effects of repeated transscleral iontophoresis in the eyes of cynomolgus monkeys. Six treatments with gentamicin sulfate, 1.5 mA for 10 min, were applied to both eyes of three monkeys over a 2-week period. The concentrations of gentamicin in the vitreous humor 24 hr after treatment were determined for each eye on three occasions. The mean concentration was 28 micrograms/ml (range, 11-44 micrograms/ml) after the first treatment and 12 micrograms/ml (range, 2-21 micrograms/ml) after the fifth treatment. Indirect ophthalmoscopy completed after the last treatment showed only small retinal burns up to 2.5 mm in diameter in four eyes in the area of the pars plana over which the electrode had been applied. Electroretinograms were normal after treatment. These experiments confirm the efficacy and safety of transscleral iontophoresis in the primate's eye and suggest that investigations of this potentially useful technique are warranted in humans.

Animals↗
PubMed1986

Transscleral iontophoresis of cefazolin, ticarcillin, and gentamicin in the rabbit.

Corneal iontophoresis produces high concentrations of drugs in the anterior segment but not in the vitreous humor of the phakic eye, presumably because transport is impeded by the lens-iris barrier. We have used two modifications to produce high levels of commonly used antibiotics in the vitreous humor of the phakic rabbit eye: the device is placed over the pars plana, circumventing the lens-iris barrier; the contact area of the column of fluid is kept small (less than or equal to 1 mm diameter) so as to provide a high current density. Applying 2 mAmp for 10 minutes, we were able to achieve mean vitreal concentrations of cefazolin, ticarcillin, and gentamicin of 94-207 micrograms/ml in the normal rabbit eye. Drug penetration showed a correlation with strength of current (0.1-2 mAmp) and with duration of iontophoresis (1-10 minutes) but not with concentration of the drug solution. Transscleral iontophoresis is a promising noninvasive technique to achieve high vitreal levels of charged solutes.

Animals↗
PubMed1986

Randomized prospective study comparing moxalactam and cefoxitin with or without tobramycin for the treatment of serious surgical infections.

The efficacy and toxicity of moxalactam were compared with the efficacy and toxicity of cefoxitin given with or without tobramycin to 109 patients with surgical infections. A total of 66 patients could be assessed for efficacy (33 patients in each group); 13 of the cefoxitin-treated patients also received tobramycin for at least 72 h. Most patients had intraabdominal infections; 17 had peritonitis, 14 had intraabdominal abscesses, and 7 had perforation of a gangrenous appendix. There were 15 patients with necrotizing soft-tissue infections. The predominant pathogens were members of the Enterobacteriaceae and Bacteroides fragilis. The cure rates were 79% (26 of 33 patients) for moxalactam and 88% (29 of 33 patients) for cefoxitin; the difference in cure rates was not statistically significant. In several patients, cultures of purulent intraabdominal exudates were negative, although bacteria were observed after Gram staining; this presumably reflected the potent activity of the antibiotic therapy which had been started before surgical drainage could be carried out. Adverse effects were observed in 18 of 44 assessable patients (41%) in the cefoxitin group and in 12 of 36 patients (33%) in the moxalactam group; the difference in the rates of adverse effects was not statistically significant. Our results suggest that moxalactam is similar in efficacy and toxicity to cefoxitin given with or without tobramycin for the treatment of serious surgical sepsis caused by a mixture of anaerobic and aerobic pathogens.

Adolescent↗
PubMed1985

Ocular toxicity of intravitreally injected liposomal amphotericin B in rhesus monkeys.

We determined whether liposome-intercalated amphotericin B was less toxic than commercial amphotericin B when injected intravitreally in the primate. Three rhesus monkeys were studied on each of three occasions. Each eye received increasing doses of amphotericin B (10, 20, or 30 micrograms) or liposome-intercalated amphotericin B (40, 80, or 120 micrograms) as a single intravitreal injection. There were often transient inflammatory changes in the anterior chamber and all eyes showed an acute cellular infiltrate in the vitreous humor after injection. These reactions had resolved by eight weeks after injection of the low or intermediate doses of amphotericin B (10 or 20 micrograms) or liposome-intercalated amphotericin B (40 or 80 micrograms) but left a mild vitreal infiltrate in the high-dose groups (30 micrograms of amphotericin B or 120 micrograms of liposome-intercalcated amphotericin B). Histologic examination at the end of the third experiment showed no abnormalities. These studies suggest that liposome incorporation reduces the toxicity of amphotericin B by at least fourfold and that as much as 30 micrograms of commercial amphotericin B may be tolerated by the intravitreal route in the rhesus monkey.

Amphotericin B↗