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Biomedical subjects

M Barza

Publications and source records attributed to M Barza.

At least 37 records · Page 2Linked to original sources

The effect of cleaning and disinfection of soft contact lenses on corneal infectivity in an animal model.

PURPOSE: Bacterial contamination of previously worn soft contact lenses, especially at sites of lens deposits, might play a role in the pathogenesis of lens-associated bacterial keratitis. We studied the effects of three commercial contact lens cleaners and disinfectants in a rabbit model to determine whether cleaning and disinfection reduced infectivity. METHODS: Duragel 75 soft contact lenses, designed to fit the eyes of rabbits, were worn by rabbits under tarsorrhaphies, then were removed and cleaned in one of three cleaner and disinfectant solutions according to the manufacturers' instructions. The lenses were contaminated by overnight incubation in a suspension of 10(8) Pseudomonas aeruginosa/ml and were placed under tarsorrhaphies on the eyes of fresh rabbits. The rabbits were observed for two weeks for signs of infection. Control rabbits wore new, uncleaned but contaminated lenses or worn, uncleaned but contaminated lenses. RESULTS: The rates of infection with the three commercial cleaner and disinfectant solutions ranged from 18% (two of 11) to 31% (four of 13); these incidences were not significantly different from one another or from the 19% (three of 16) incidence with new, contaminated but uncleaned lenses. By contrast, when worn, uncleaned but contaminated lenses were placed in rabbits' eyes, seven of eight were infected, a rate that is significantly higher than that of the other four groups (P = .0003). CONCLUSIONS: These data indicate that the three commercial lens cleaner and disinfectant solutions were of similar efficacy in reducing the infectivity of contaminated contact lenses to a level similar to that of new, unworn lenses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Challenges to antibiotic activity in tissue.

The most important determinants of antibiotic efficacy in infectious sites are the pharmacokinetic profile of the drug, the biochemical characteristics of the local environment, and the susceptibility of the infecting microorganisms under local growth conditions. The role of these variables is fairly clear for extracellular infections but not for intracellular infections or tissues as a whole. Many agents, including the macrolides, azalides, lincosamides, and quinolones, are concentrated within cells--notably, phagocytic cells. The mechanisms and pharmacokinetics of accumulation as well as the subcellular localization of accumulated drug are poorly understood in most instances. High intracellular drug concentrations do not necessarily translate into potent anti-infective activity. Many drugs with high intracellular concentrations are weak bases that accumulate within acidic lysosomes, where their activity may be reduced; the site at which drug accumulation is greatest may differ from that at which the microbe is found; and slow rates of intracellular growth may lessen the susceptibility of microbes to a variety of agents. Nevertheless, some drugs display good antimicrobial activity within cells. Future studies must better identify the determinants of this activity and clarify the clinical utility of drugs that reach high intracellular levels.

Animals↗

Pharmacokinetics of newer cephalosporins after subconjunctival and intravitreal injection in rabbits.

Pharmacologic considerations suggest that third-generation cephalosporins might penetrate the vitreous humor better after periocular injection and might be eliminated less readily after intravitreous injection than older agents. We studied the sodium salts of ceftizoxime, ceftriaxone, and ceftazidime, and of an investigational cephalosporin, cefepime, in rabbits. After a single subconjunctival injection in animals with normal eyes, vitreous levels ranged from 3 to 13 mg/L. After five subconjunctival injections in rabbits with infected eyes, vitreous concentrations ranged from 12 to 34 mg/L. These concentrations are not appreciably greater than those found with older beta-lactams. The vitreous half-life of the four drugs after intravitreous injection varied from 5.7 to 20 hours in rabbits with uninflamed eyes and from 9.4 to 21.5 hours in rabbits with infected eyes. Except for ceftizoxime, the half-lives were substantially longer than those for older beta-lactams and suggest predominantly anterior route elimination. Vitreous penetration of these new agents after subconjunctival injection does not appear to be sufficient to overcome the need for intravitreous injections in the treatment of endophthalmitis. However, the longer vitreous half-lives of some of the newer agents may be useful if the drugs are to be given intravitreally.

Animals↗

Ocular penetration of ceftriaxone, ceftazidime, and vancomycin after subconjunctival injection in humans.

Vancomycin (25 mg), ceftriaxone (125 mg), and ceftazidime (100 mg) were given by subconjunctival injection before vitrectomy to patients with uninfected eyes. Most of the patients had diabetic vitreous hemorrhage with or without traction retinal detachments, and some had rhegmatogenous retinal detachments with proliferative vitreoretinopathy. Samples of vitreous were obtained by pars plana vitrectomy at intervals from 46 minutes to 4 hours 13 minutes after the subconjunctival injection. The median vitreous concentrations of all three drugs were below the limit of detection. Vitreous concentrations of these drugs after a single subconjunctival injection are exceedingly low.

Adult↗

Anatomical barriers for antimicrobial agents.

It is often suggested that there are substantial anatomic barriers to the passage of antibiotics from the circulation into tissues and fluids of the body. In fact, most capillary beds are fenestrated and allow the passage of antimicrobial agents into tissue fluids fairly readily. At equilibrium, the mean concentrations of free (unbound) antibiotic in plasma and tissue fluids over the dosing interval are equal. However, the time to achieve equilibrium may range from minutes to days, depending on the ratio of surface area to volume of the tissue fluid compartment. There are several sites in the body in which nonfenestrated capillary beds pose appreciable barriers to the diffusion of antibiotics, namely the central nervous system, the eye and the prostate gland. Only lipid-soluble drugs traverse these capillaries readily. If the nonporosity of the capillaries were the only barrier to drug diffusion in these sites, the mean concentrations would eventually be equal to those in the plasma. However, in the central nervous system and the retina of the eye, transport pumps for organic anions combine with the effect of nonporous capillaries to produce concentrations which, even at equilibrium, are lower than those in the plasma. Bulk flow may also play a role in lowering drug concentrations in the cerebrospinal fluid. In the prostate gland, pH partition may cause mean concentrations in the prostatic secretions to differ from those in the plasma at equilibrium.

Anti-Bacterial Agents↗

Pharmacokinetics of antibiotics in shallow and deep compartments.

This paper reviews the influence of the type of capillary bed, type of compartment, and the presence of active transport systems, on the pharmacokinetics of antimicrobial agents in tissues and fluids of the body. In the absence of active transport or local degradation, the mean concentration or 'area under the curve' of free (unbound) drug in ordinary extravascular sites over the dosing interval at equilibrium is equal to that in the serum. Because the latter is easily measured, there should be no need to measure tissue concentrations except in unusual circumstances. Among the factors that will alter the relationship described above are active transport, pH partition, and bulk flow. Antibiotics such as the macrolides, lincosamines and quinolones may accumulate in high concentrations in cells containing lysosomes. There is some evidence that the intracellular sites may serve as a reservoir from which these drugs may later be released into tissue fluids, a phenomenon not taken into account in the relationships described above. Although knowledge of the in-vitro activity and local concentrations of antibiotics is of use in predicting therapeutic activity, many factors which are difficult to quantify in a given instance make precise correlations impossible. The inability of antibiotics alone to sterilize abscesses is probably not due to a problem in antibiotic penetration but to insusceptibility of the organisms and inefficacy of the phagocytes in an abscess. Similar processes operate to reduce the efficacy of antibiotics when treatment is delayed.

Animals↗

Soft tissue infections.

Several infectious processes ranging in severity from mild to overwhelming that affect the soft tissues are reviewed. Superficial infections such as impetigo, erysipelas, cellulitis, and subcutaneous bursitis are common and, for the most part, can be easily treated. Because suppurative tenosynovitis has the potential to destroy tendons, consultation with a hand surgeon should be obtained immediately. Mycobacterial and fungal tenosynovitis is usually chronic and patients present with a mass which, when excised and examined with appropriate stain and culture, reveals the unexpected diagnosis. Tropical myositis (muscle abscesses) is seen in temperate climates, primarily as a complication of AIDS. Necrotizing fasciitis and gas gangrene represent the hyperacute end of the spectrum of soft tissue restrictions. Although in most cases a history of trauma is present, spontaneous gas gangrene may arise from occult and colonic cancer. Patients do poorly unless immediate and extensive surgery is performed and appropriate antibiotics are given.

Bacterial Infections↗

Unusual manifestations of Yersinia enterocolitica infections diagnosed using novel methods.

We report the cases of two patients who had infections due to Yersinia enterocolitica. The first patient exhibited chronic recurrent fever, hepatic and splenic granulomas, and bone marrow abnormalities, and the second patient presented with enterocolitis with leukocytoclastic vasculitis of the skin. Cultures and agglutination titers were negative. Indirect immunofluorescence techniques with use of serotype-specific antisera and antisera to Yersinia outer-membrane proteins (Yops) were applied to biopsy specimens, and immunoblotting techniques for determining class-specific circulating antibodies to Yops were used for demonstrating these unusual manifestations of Y. enterocolitica infections.

Adult↗

An improved apparatus for transscleral iontophoresis of gentamicin.

The authors previously found that positively charged substances are less well-transported into the vitreous humor by transscleral iontophoresis than are negatively charged substances. There was more bubble formation in the eye cup with positively charged than with negatively charged substances. The authors hypothesized that these bubbles might account for the poorer conductance of the positively charged species by causing interruptions of the current. Therefore, the authors developed a modified eye cup in which the diameter of the fluid column was larger than that in the old device (1.0 rather than 0.5 mm). This modification allowed larger voltage to be applied than with the older device, because bubbles could be more easily cleared from the conjunctiva than with the narrower-bore eye cup. Although the efficiency of the apparatus was the same with the two eye cups (micrograms per milliliter in vitreous humor divided by milliampere minutes of current applied), vitreal concentrations of gentamicin with the modified eye cup were fourfold higher than with the older eye cup (83 versus 19 micrograms/ml; P < 0.001). These studies suggest that modifying the eye cup to permit easier removal of bubbles resulted in improved delivery of gentamicin into the ocular humors.

Animals↗

Use of quinolones for treatment of ear and eye infections.

Malignant otitis externa is a severe, necrotizing infection of the external auditory canal which is sometimes fatal. The traditional antimicrobial treatment has usually been the combination of an antipseudomonal beta-lactam and an aminoglycoside, given intravenously for 4 to 8 weeks. Over 100 patients have been treated with a fluoroquinolone alone, most commonly ciprofloxacin given by mouth in a dosage of 750 mg b.i.d. for 6 to 12 weeks. About 90% of patients have been cured. Treatment with a quinolone has the advantage over older treatments that it can be given orally and has a low rate of side-effects. The ocular penetration of the fluoroquinolones has been studied in patients with unifected eyes. After the administration of a single dose of ciprofloxacin, pefloxacin, ofloxacin or norfloxacin, penetration into the aqueous humor, expressed as the ratio of the peak concentration in the aqueous humor to that in the serum, is about 20%. The penetration of ciprofloxacin into the vitreous humor, based primarily on the data from one report, is about 20%. The concentrations are likely to be higher after repeated doses or in the inflamed eye. Whether the concentrations achieved will be adequate for therapeutic or prophylactic purposes has not been determined.

4-Quinolones↗

Neuraminidase activity in acanthamoeba species trophozoites and cysts.

Acanthamoeba species, a widely distributed group of free-living amoeba, can infect humans and spread hematogenously after direct interaction with the mucosal surfaces. The mechanism underlying Acanthamoeba damage to the target cell is unknown. The authors report that trophozoites and cysts of Acanthamoeba species exhibit a neuraminidase activity that is membrane associated and released into the culture medium at the start of the logarithmic phase of growth. The enzyme activity is optimal at pH 5 and at 25-30 degrees C. Live parasites release sialic acid from human cells. Therefore, the neuraminidase of Acanthamoeba species could be relevant in the colonization and damage of the sialic acid-rich corneal epithelium and in the alterations of glycolipids associated with meningoencephalitis.

Acanthamoeba↗

Bacterial adherence to extended wear soft contact lenses.

The authors studied the adherence of Pseudomonas aeruginosa and Staphylococcus aureus to extended wear soft contact lenses (EWSCLs) with and without focal deposits using both a radiolabeling technique and electron microscopy. P. aeruginosa showed significant adherence to contact lenses in vitro. In contrast, S. aureus failed to show significant adherence to contact lenses in vitro (i.e., the radioactive uptake was not significantly above background). The extent of adherence of Pseudomonas was proportional to the number of focal deposits on the lenses. Results of electron microscopic examination showed the bacteria to be adherent primarily to large focal deposits (greater than or equal to 150 microns). There was no pseudomonal adherence to the small focal deposits (less than or equal to 50 microns) and little adherence to the areas in between the focal deposits. The authors hypothesize that worn lenses, especially those with large focal deposits, serve as a vehicle for the transport of P. aeruginosa to the cornea. This hypothesis could be a partial explanation for the high incidence of keratitis caused by P. aeruginosa in EWSCL patients.

Bacterial Adhesion↗

Therapy for shigellosis. II. Randomized, double-blind comparison of ciprofloxacin and ampicillin.

Ciprofloxacin, 500 mg every 12 h, was compared with ampicillin, 500 mg every 6 h, both given for 5 days, in the treatment of 121 adult males hospitalized with severe shigellosis. Treatment was randomized and double-blinded. At the completion of treatment, there was resolution or marked improvement in symptoms in 57 (95%) of 60 ciprofloxacin-treated patients, 23 (88%) of 26 ampicillin-treated patients infected with an ampicillin-susceptible strain of Shigella, and 15 (43%) of 35 ampicillin-treated patients infected with an ampicillin-resistant strain of Shigella (ampicillin-R group) (P less than .01, ciprofloxacin or ampicillin groups vs. ampicillin-R group). Bacteriologic failure was less common (P less than .025) in the ciprofloxacin group (0/60) than in the ampicillin (3/26, 12%) or ampicillin-R groups (5/35, 14%). Ciprofloxacin-treated patients had a mean of 29 stools during the study, compared with 46 for ampicillin-treated patients (P = .004). Thus ciprofloxacin seems to be an effective, and perhaps superior, alternative to ampicillin in treating patients with shigellosis.

Adult↗