In vitro antibiotic susceptibilities of ocular isolates in North and South America. In Vitro Antibiotic Testing Group.

PURPOSE: To assess the in vitro susceptibility of ocular bacterial isolates from North and South America to antiinfectives that are commonly used in the treatment of external ocular infection. METHODS: Ocular isolates (n = 1,291) from 12 laboratories in the United States, Canada, Mexico, and Argentina were tested for their susceptibility to ofloxacin, ciprofloxacin, norfloxacin, gentamicin, tobramycin, chloramphenicol, tetracycline, and erythromycin using both disk-diffusion and broth-dilution methods. RESULTS: When the results from disk-diffusion and broth-dilution testing were combined, the relative overall in vitro efficacy was (in decreasing order): ofloxacin, ciprofloxacin, norfloxacin, gentamicin, chloramphenicol, tobramycin, tetracycline, and erythromycin. Against gram-positive organisms it was: ofloxacin, ciprofloxacin equivalent to chloramphenicol, norfloxacin, tetracycline, gentamicin, and erythromycin equivalent to tobramycin. Against gram-negative organisms it was: ofloxacin equivalent to ciprofloxacin and norfloxacin, gentamicin, tobramycin, chloramphenicol, and tetracycline comparable to erythromycin. CONCLUSIONS: The fluoroquinolones ofloxacin, ciprofloxacin, and norfloxacin had higher overall in vitro efficacy than the other antibiotics tested. Of the fluoroquinolones, ofloxacin had the highest in vitro efficacy against gram-positive organisms. All three fluoroquinolones were equivalent in efficacy against gram-negative organisms.

Evaluation of therapeutic measures for treating endophthalmitis caused by isogenic toxin-producing and toxin-nonproducing Enterococcus faecalis strains.

PURPOSE: Management of endophthalmitis typically includes antibiotic combinations to arrest bacterial growth and antiinflammatory agents to limit inflammatory damage to sensitive tissues. Little research has been reported that systematically evaluates the contribution of each therapeutic component for treating infections caused by organisms of varying virulence. The authors determined the relative value of the antinflammatory corticosteroid, dexamethasone, as an intravitreal therapeutic adjunct for the treatment of infection caused by either Enterococcus faecalis expressing a cytolytic toxin previously shown to contribute to the course and severity of infection, or an otherwise identical strain of E. faecalis specifically attenuated in expression of the cytolytic toxin. METHODS: Endophthalmitis in rabbits was monitored using electroretinography (ERG). Eyes were infected with 100 colony forming units of either the cytolytic or the noncytolytic E. faecalis strain. Intravitreal ampicillin and gentamicin were administered at postinfection day 1, and intravitreal dexamethasone was either omitted or administered at day -1, 1, or 1.5. RESULTS: ERG B-wave amplitude declined precipitously throughout the course of infection with cytolytic toxin-producing E. faecalis, despite the administration of antibiotics and regardless of the time of dexamethasone administration. In fact, the ultimate course of infection caused by cytolytic E. faecalis did not differ from the course in untreated controls. In contrast, infections caused by specifically attenuated, noncytolytic strains of E. faecalis responded well to antibiotics augmented by antiinflammatory therapy when the latter was administered either 1 or 1.5 days after the initiation of infection. In these cases, no loss in ERG B-wave response was observed. CONCLUSIONS: These results underscore the importance of bacterial toxins in infectious diseases of the eye and their contribution to treatment failures. These results further suggest that in cases of endophthalmitis caused by toxin producing bacteria, significant improvement in clinical outcome will require specific therapeutic targeting of the toxins involved.

The effectiveness of a u-v toothbrush sanitizing device in reducing the number of bacteria, yeasts and viruses on toothbrushes.

Sixty-six sterile toothbrushes were exposed to one of the following microorganisms: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Bacillis subtilis, Serratia marcescens and Baker's yeast. The Pollenex DS60 Daily Dental Sanitizer was found to be effective in substantially reducing the number of retained bacteria and yeasts as compared to contaminated toothbrushes not treated with such a device. Different toothbrush types had different response rates. Seventy-two sterile toothbrushes were exposed to Herpes Simplex Virus, Type I and seventy-two sterile toothbrushes were exposed to Parainfluenza Virus, Type III. The Pollenex DS60 Daily Dental Sanitizer consistently killed both viruses on all of the toothbrushes treated. Both viruses were consistently retained on non-treated toothbrushes for at least 24 hours.

Coagulase-negative staphylococci in conjunctivitis and blepharitis.

Coagulase-negative staphylococcus (C-NS) are regarded as normal flora of the lids and conjunctiva. The ability of these organisms to cause conjunctivitis and blepharitis can be overlooked or disregarded. To elucidate the role of individual C-NS species in these eye diseases we compared Staphylococcus sp. isolated from the conjunctiva and lids of 50 healthy volunteers with 248 strains of Staphylococcus isolated from patients with staphylococcal conjunctivitis or blepharitis. S. epidermidis was the most frequent species isolated from the conjunctiva and lids of both groups. S. aureus was isolated only from infected patients. No individual C-NS species was found to be significantly associated with eye disease, but the colony count of C-NS after isolation was a useful indicator of conjunctivitis and blepharitis. The ability of Staphylococcus to ferment mannitol or mannose was associated with isolates only from infected patients.

Combined treatment of Acanthamoeba keratitis with propamidine, neomycin, and polyhexamethylene biguanide.

We developed an intensive treatment regimen of topical neomycin, propamidine, and polyhexamethylene biguanide that was tapered to a maintenance level over a 14- to 28-day period as toxicity developed. Since July 1991, we used this treatment on six eyes of five patients in whom Acanthamoeba keratitis was diagnosed clinically. All patients had positive cultures for microorganisms from their corneas or contact lens cases or had pathognomonic findings of pseudodendritic subepithelial infiltrates and radial keratone-uritis. After therapy, all patients improved within two to four weeks, with regression or resolution of neuritis and infiltrates, healing of epithelial defects, and lessening of pain. By three to four months, visual acuity had returned to 20/20 in all eyes. We believe the addition of polyhexamethylene biguanide to our treatment regimen in Acanthamoeba keratitis dramatically aided and hastened the clinical improvement in five consecutive patients and may, with early diagnosis, increase the number of medical cures.

Contribution of the pAD1-encoded cytolysin to the severity of experimental Enterococcus faecalis endophthalmitis.

The contribution of the pAD1-encoded cytolysin to Enterococcus faecalis virulence in an experimental endophthalmitis model was studied by using isogenic strains differing only in the location of transposon Tn917. The course of experimental endophthalmitis in New Zealand White rabbits was evaluated by postoperative reduction in retinal neuroresponsiveness, thin-section histopathology, and transmission electron microscopy. Infections caused by cytolytic E. faecalis resulted in 99% loss of retinal function at postoperative day 3, while isogenic, noncytolytic strains produced reductions of only 74.2%. Light microscopy revealed near-total destruction of retinal architecture at 24 h postinfection with cytolytic E. faecalis, while noncytolytic strains produced few or no destructive changes. Transmission electron microscopy revealed tissue destruction in retinal layers as early as 6 h postinfection with cytolytic E. faecalis. In vivo and in vitro growth rates of cytolytic and noncytolytic E. faecalis showed similar kinetics. These data demonstrate the contribution of the pAD1-encoded cytolysin to both the course and the severity of experimental E. faecalis endophthalmitis.

A hemolysin-encoding plasmid contributes to bacterial virulence in experimental Enterococcus faecalis endophthalmitis.

Beta-hemolysin production is a variable trait of the Lancefield group D streptococcus, Enterococcus faecalis. The E. faecalis hemolysin is encoded by large transmissible plasmids. The variable nature of this putative virulence factor provided an ideal system for testing its contribution in experimental endophthalmitis. In this study, isogenic E. faecalis strains were compared to determine whether the presence of the hemolysin-encoding plasmid affected the severity of disease in a rabbit endophthalmitis model. Experimental infections (n = 6) with 10(1)-10(4) E. faecalis organisms harboring the hemolysin-encoding plasmid resulted in a 98% loss of retinal function (by electroretinography [ERG]) and white reflex by postoperative day 3. By contrast, infections of similar numbers of plasmid-free E. faecalis organisms (n = 5) resulted in retention of some retinal function (23% per ERG) with a red reflex demonstrated on postoperative day 3. Results of light microscopy, slit-lamp examination, ERG, and indirect ophthalmoscopy indicated that infections with hemolysin-encoding plasmid-containing E. faecalis resulted in a more aggressive endophthalmitis compared with the endophthalmitis caused by plasmid-free E. faecalis. This is the first endophthalmitis model to the authors' knowledge that specifically evaluates bacterial virulence using isogenic strains.

Intraocular safety of ciprofloxacin.

Retinal toxicity resulting from the treatment of exogenous bacterial endophthalmitis with multiple antibiotics has increased the importance of evaluating the efficacy of new potent antibiotics for monotherapy. The retinal and corneal toxicity of ciprofloxacin hydrochloride, which is rapidly bactericidal against gram-positive and gram-negative bacteria, was evaluated in the rabbit eye. Retinal toxicity was dose-dependent in phakic and aphakic rabbit eyes as determined with electroretinography, light microscopy, and transmission electron microscopy. An intravitreal dose of greater than 100 micrograms also resulted in dose-dependent acute corneal toxicity in aphakic vitrectomized rabbit eyes. Results of instillation of ciprofloxacin directly into the anterior chamber of phakic rabbit eyes confirmed dose-dependent corneal toxicity. No retinal or corneal damage was observed in aphakic or phakic rabbit eyes after administration of an intravitreal dose of 100 micrograms. Results of electroretinography and light microscopy alone are insufficient to evaluate the retinal toxicity of antibiotics. Ultrasonic pachymetry is the best method of detecting probable associated corneal toxicity.

Ocular infections associated with Comamonas acidovorans.

Comamonas acidovorans (Pseudomonas acidovorans) is a ubiquitous gram-negative rod. Although generally considered nonpathogenic, we found C. acidovorans to be associated with six cases of ocular infections. The organism was the only isolate in three cases, whereas an association of other organisms was present in three cases. The multiple resistance patterns of these strains to antibiotic susceptibility testing emphasizes the need for culturing ocular infections. We recommend the identification and susceptibility testing of all ocular gram-negative rod isolates.

The comparative in vitro activity of ofloxacin and selected ophthalmic antimicrobial agents against ocular bacterial isolates.

The in vitro activity of ofloxacin, a new fluoroquinolone anti-infective agent, was evaluated against 419 ocular bacterial isolates of 55 species to determine its potential as a topical agent for the treatment of ocular infections. Other agents tested in this study, in which a modified tube-dilution procedure was used, include norfloxacin, gentamicin, tobramycin, chloramphenicol, and polymyxin B. Ofloxacin demonstrated good to excellent activity against a variety of gram-positive and gram-negative pathogens. The minimum inhibitory concentration against 90% of all bacterial strains tested (MIC90) of ofloxacin was 0.5 microgram/ml for Staphylococcus aureus and S. epidermidis, 2 micrograms/ml for Streptococcus pneumoniae, and 4 micrograms/ml for Pseudomonas aeruginosa. These species were more susceptible to ofloxacin than to any of the nonquinolones tested. The MIC90 of ofloxacin was lower than that of norfloxacin, another quinolone, against S. aureus, S. epidermidis, and St. pneumoniae and equal to that of norfloxacin against P. aeruginosa. Because of its broad spectrum of activity and excellent in vitro activity, we concluded that ofloxacin has the potential for development into a superior topical treatment for ocular infection.

Topical application of all-trans-retinoic acid. A look at the cornea and limbus.

A 0.1% all-trans-retinoic acid in petroleum-base ointment was applied daily in eight normal rabbit eyes. Epithelial samples were collected from the cornea and limbus of six rabbits by impression cytology at 3- to 4-day intervals. Cytological changes were followed for 21 days and the eyes subsequently harvested for histochemical, scanning electron microscopic (SEM), and transmission electron microscopic (TEM) analysis of corneal and limbal structures. Two rabbits were treated with 0.1% all-trans-retinoic acid for 24 days without impression cytology until the 21st day. On the 24th day these eyes were harvested for similar studies. Impression cytology studies of the corneal epithelium demonstrated perinuclear halos and vacuolization of the cytoplasm. Additionally, vacuolization of the cytoplasm was observed by TEM, with attendant extrusion of the cytoplasmic contents and a subjective increase in surface microvilli as seen by SEM. Histochemical analysis revealed mucinlike staining of the corneal epithelium.

Acanthamoeba keratitis and infectious crystalline keratopathy.

Two cases of Acanthamoeba keratitis and infectious crystalline keratopathy, occurring simultaneously, are presented. Three and 12 months after initiating topical corticosteroid therapy in cases 1 and 2, respectively, alpha-hemolytic Streptococcus viridans was cultured from each cornea. Topical corticosteroid therapy was initiated for the treatment of an annular stromal opacity, presumably secondary to herpes simplex keratitis. Acanthamoeba was identified in culture following penetrating keratoplasty in case 1, and Acanthamoeba polyphaga, Acanthamoeba rhysodes, and Acanthamoeba castellanii were identified using indirect fluorescent antibody staining in case 2. Histopathologic examination and electron microscopy demonstrated sheets of cocci within stromal lamellae characteristic of infectious crystalline keratopathy and double-walled encysted organisms typical of Acanthamoeba. These case reports alert one to the possibility of developing bacterial keratitis, such as infectious crystalline keratopathy, following the use of topical corticosteroids for the treatment of Acanthamoeba keratitis.

An anterior limbal approach to vitrectomy for the surgical management of infectious endophthalmitis.

We present two cases illustrating a surgical approach to the diagnosis and treatment of infectious endophthalmitis following extracapsular cataract extraction with insertion of a posterior chamber lens. In both cases, a vitrectomy was initiated through a limbal approach after clearing the anterior chamber, thus allowing improved visualization of the vitreous cavity. The vitrectomy probe was then passed through a peripheral iridotomy, the peripheral posterior capsule and/or zonules, and into the anterior vitreous. The peripheral iridotomy allowed access to the vitreous cavity for an anterior vitrectomy. The entire anterior chamber and vitreous aspirate was then analyzed for culture and sensitivity. This technique minimizes the risks of pars plana vitrectomy for endophthalmitis by improving visualization and possibly decreasing the risk of retinal detachment.

Ovarian cysts in women on chronic intermittent haemodialysis.

In a consecutive material of 42 female patients, who were treated with intermittent dialysis for chronic renal failure between May 1964 and Nov. 1971, 21 developed ovarian cysts. The cysts were found only among the 29 women, who had menstrual periods from commencement of dialysis (16 cases) or who started menstruating on dialysis after a period of secondary amenorrhoea (13 cases). No cysts were found in the remaining 13 patients, who had amenorrhoea throughout, and of whom 6 were in all probability postmenopausal. Seven of the 21 patients with ovarian cysts had pronounced symptoms, necessitating acute surgery in 4. Fourteen asymptomatic cases were diagnosed at routine gynaecological examination, which was performed at regular intervals in all patients. There is strong evidence suggesting that the development of ovarian cysts was somehow related to the dialytic treatment and neither to the uraemic state nor to the nature of the primary renal disease. The mechanism by which dialytic treatment may be opertional in the development of this hitherto undescribed complication is discussed, but no clear-cut explanation can be given.