Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022568 (keratitis)
 5,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eight pseudomonal species were involved in 106 invasive infections of the eye; all were community acquired. Eighteen percent of the total and 9% of the Pseudomonas aeruginosa strains were gentamicin resistant, as defined using conventional criteria. All 10 cases of "resistant" pseudomonal (nine P. aeruginosa) keratitis responded satisfactorily to treatment with gentamicin. The resistance breakpoint (defined by safe serum levels in parenteral therapy) for most P. aeruginosa is much lower than ocular gentamicin levels achievable by optimal local application. We argue for a specific ophthalmologic definition of antibiotic resistance in infections of the cornea and external eye. MIC quantitative determinations of ocular isolates would provide more useful information to ophthalmologists than conventional qualitative disc sensitivity testing.
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PMID:Gentamicin-resistant pseudomonal infection. Rationale for a redefinition of ophthalmic antimicrobial sensitivities. 278 30

An experimental Keratitis study of Aspergillus fumigatus was performed in 130 rabbits divided into 12 groups of ten animals each. Three antifungal drugs (myconazole, amphotericin B and pimaricin) were tested using two procedures (topical drops and subconjunctival injections) and two different concentrations (500 and 10 000 times the MIC). In each case, the drugs were applied every 3 h starting 14 h after inoculation. Miconazole was useful at 10 mg/ml concentration by topical drops and subconjunctival injections, but was less useful at 5 mg/ml. Amphotericin B was useful at 5 mg/ml concentration by topical drops and less useful at 2 mg/ml. No differences were found between the two concentrations by subconjunctival administration. Pimaricin was useful by topical drops at 50 mg/ml concentration and less useful at 10 mg/ml as well as by subconjunctival injections.
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PMID:Chemotherapy of Aspergillus fumigatus keratitis: an experimental study. 388 74

This study was conducted to determine the therapeutic efficacy of 3.0 mg/ml ciprofloxacin administered concurrently with one of two salts of prednisolone for the treatment of experimental pseudomonal keratitis. Rabbit corneas were injected intrastromally with Pseudomonas aeruginosa ATCC strain 27853. Sixteen hr after injection, rabbits were randomly divided into four treatment groups (3 rabbits, 6 eyes per group): 1) ciprofloxacin plus prednisolone acetate; 2) ciprofloxacin plus prednisolone phosphate; 3) ciprofloxacin only; 4) untreated. Signs of inflammation were graded in a masked fashion by slit lamp examination (SLE) and by estimating polymorphonuclear leukocyte (PMN) numbers in corneas 27 hr after injection. SLE scores and PMN numbers were significantly lower (P < 0.02) in eyes receiving either salt of prednisolone plus ciprofloxacin compared to the untreated controls. In contrast, SLE scores and PMN numbers were not significantly different in eyes treated with ciprofloxacin alone, compared to untreated controls (P > 0.13). No viable bacteria were recovered from any eye treated with ciprofloxacin (groups 1, 2, and 3). Ciprofloxacin concentrations in the aqueous humor of eyes in groups 1, 2, and 3 were greater than 15-fold higher than the MIC for P. aeruginosa 27853. These results suggest that either salt of prednisolone, when combined with ciprofloxacin, reduces ocular inflammation without affecting the antimicrobial efficacy of the antibiotic.
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PMID:Prednisolone acetate or prednisolone phosphate concurrently administered with ciprofloxacin for the therapy of experimental Pseudomonas aeruginosa keratitis. 834 70

This study was designed to measure the concentration of ofloxacin in aqueous humor after topical, oral and intravenous administration in 50 patients undergoing cataract extraction. In Group 1, ofloxacin 0.3% eyedrops were topically instilled ten times and the aqueous humor concentration was 2.73 +/- 0.88 microg/ml. In Group 2, ofloxacin 0.3% eyedrops were topically instilled six times and the aqueous humor concentration was 0.84 +/- 0.61 microg/ml. Aqueous humor concentration 12 hours after 200 mg oral dose in Group 3, was 0.38 +/- 0.12 microg/ml. In Group 4, patients were given ofloxacin as a single intravenous 200 mg dose and the aqueous humor concentration 2 hours after the end of infusion was 0.45 +/- 0.11 microg/ml. Concentrations were determined by high performance liquid chromatography (HPLC) with fluorescence detection. There was a significant difference between Group 1 and the other groups, but not between Group 2 and Groups 3, 4. It was concluded that ofloxacin penetrates the corneal and the blood-aqueous barriers and can achieve good aqueous levels when given topically and systematically. Ofloxacin can be applied topically for external bacterial infections such as conjunctivitis and keratitis. Systematically administered ofloxacin reached higher levels than the MIC for some bacteria which cause endophthalmitis.
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PMID:The penetration of ofloxacin into human aqueous humor given by various routes. 959 May 93

A case of Scedosporium apiospermum keratitis was successfully treated with oral voriconazole and penetrating keratoplasty. Voriconazole levels in the aqueous humor were 53% of the levels in plasma and exceeded the MIC for the isolate by sevenfold.
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PMID:Keratitis caused by Scedosporium apiospermum successfully treated with a cornea transplant and voriconazole. 1273 97

Mycotic keratitis usually occurs in conjunction with trauma to the cornea. Scedosporium apiospermum, a dematiaceous fungus linked to the teleomorph Pseudallescheria boydii is not a common agent of mycotic keratitis. A 22-year old male patient with mycotic keratitis due to S. apiospermum is presented. In in vitro susceptibility testing, the isolate showed resistance against amphotericin B (minimum inhibitory concentration [MIC] 16 microg ml(-1)) but was susceptible to itraconazole (ITC) and fluconazole with MICs of 0.125 microg ml(-1) and 4 microg ml(-1), respectively. The patient was cured clinically after ITC treatment and surgical intervention. Azoles may be superior for eliminating S. apiospermum from infected ocular sites.
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PMID:Scedosporium apiospermum keratitis treated with itraconazole. 1296 42

The purpose of this study was to evaluate the influence of gamma-irradiation and dry heat sterilisation on the properties of a bioadhesive powder mixture containing ciprofloxacin and its corresponding ocular minitablets. The molecular weight characteristics of drum dried waxy maize starch (DDWM), employed as major component of the bioadhesive formulation, the decay kinetics of radicals, the rheological properties of the bioadhesive polymers and the microbial activity of ciprofloxacin were studied. The influence of the different sterilisation methods on the characteristics of the ocular minitablets was investigated by measuring the crushing strength, the friability, and the in vitro release of ciprofloxacin from the minitablets. Finally, the clinical value of the selected sterilised minitablets was evaluated in seven healthy volunteers. Both sterilisation methods similarly affected the properties of the bioadhesive formulation by inducing stable radicals and decreasing the molecular weight of DDWM, although no changes in the microbiological activity of ciprofloxacin were measured. An obvious influence of both sterilisation methods was observed in the in vitro release study. The crushing strength and friability of the minitablets were not significantly influenced by gamma-irradiation. Based on these data, gamma-irradiation was more adequate as sterilisation method for the bioadhesive ocular minitablets than dry heat sterilisation, because it affected the least the physical properties of the minitablets. Therefore, the gamma-sterilised minitablets were selected for an in vivo evaluation in seven volunteers. The concentration of ciprofloxacin in the tear film remained above its MIC value for the most common ocular pathogens for at least 8 h. Consequently, the gamma-irradiated minitablets containing ciprofloxacin can be considered as a promising formulation to treat bacterial keratitis and conjunctivitis.
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PMID:Effect of different sterilisation methods on the properties of bioadhesive powders and ocular minitablets, and clinical evaluation. 1532 25

Rapidly growing mycobacteria (RGM) have emerged as important human pathogens that can cause a variety of diseases. Thirty isolates of the pathogenic RGM were recovered from patients who attended King Chulalongkorn Memorial Hospital during 1997 and 2003. There were 16 isolates of Mycobacterium chelonae, ten isolates of M. fortuitum and four isolates of M. abscessus. Clinical data was available in only nine patients (five males and four females) including six M. chelonae, two M. abscessus, and one M. fortuitum. The mean age was 37 years (range: 13-62 years). The associated conditions were present in five patients including two diabetes, one HIV infection, one pregnancy, one SLE and one chronic renal failure. A wide spectrum of clinical features was observed. These included two chronic pulmonary infections, two post-traumatic wound infections, two disseminated infections, one lymphadenitis, one keratitis and respiratory colonization. AFB staining was positive in six patients (66.67%). The MIC of one M. chelonae and one M. abscessus were determined by Epsilon test. For M. chelonae, the MIC of clarithromycin, amikacin, ciprofloxacin, sulfamethoxazole and imipenem were 0.25, 2.0, 1.00, > 64, and 0.54 microg/ml, respectively. For M. abscessus, the MIC of clarithromycin, amikacin, ciprofloxacin, tetracycline and sulfamethoxazole were 0.016, 0.016, 0.038, > 16 and 0.002 microg/ml, respectively. Six of eight patients (75%) were initially treated with four first-line antituberculous drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) before obtaining the culture result. Of these, three patients with pulmonary and disseminated infections improved after a prolonged course of these combinations. The patients improved after switching to specific anti-RGM antibiotics. One patient died after 10 months of therapy of four anti-tuberculous drugs. One patient with post-traumatic wound infection was cured with surgical debridement and dicloxacillin. One patient improved after treatment as acute bronchitis with oral amoxicillin. An extensive review of the literature of RGM infections in Thailand is also presented.
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PMID:Rapidly growing mycobacteria in King Chulalongkorn Memorial Hospital and review of the literature in Thailand. 1640 50

The anticancer agent miltefosine and the antifungal drug voriconazole were tested in vitro against Balamuthia mandrillaris, Acanthamoeba spp., and Naegleria fowleri. All three amebas are etiologic agents of chronic (Balamuthia, Acanthamoeba) or fulminant (Naegleria) encephalitides in humans and animals and, in the case of Acanthamoeba, amebic keratitis. Balamuthia exposed to <40 microm concentrations of miltefosine survived, while concentrations of >or=40 microM were generally amebacidal, with variation in sensitivity between strains. At amebastatic drug concentrations, recovery from drug effects could take as long as 2 weeks. Acanthamoeba spp. recovered from exposure to 40 microM, but not 80 microM miltefosin. Attempts to define more narrowly the minimal inhibitory (MIC) and minimal amebacidal concentrations (MAC) for Balamuthia and Acanthamoeba were difficult due to persistence of non-proliferating trophic amebas in the medium. For N. fowleri, 40 and 55 microM were the MIC and MAC, respectively, with no trophic amebas seen at the MAC. Voriconazole had little or no inhibitory effect on Balamuthia at concentrations up to 40 microg/ml, but had a strong inhibitory effect upon Acanthamoeba spp. and N. fowleri at all drug concentrations through 40 microg/ml. Following transfer to drug-free medium, Acanthamoeba polyphaga recovered within a period of 2 weeks; N. fowleri amebas recovered from exposure to 1 microg/ml, but not from higher concentrations. All testing was done on trophic amebas; drug sensitivities of cysts were not examined. Miltefosine and voriconazole are potentially useful drugs for treatment of free-living amebic infections, though sensitivities differ between genera, species, and strains.
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PMID:In-vitro activity of miltefosine and voriconazole on clinical isolates of free-living amebas: Balamuthia mandrillaris, Acanthamoeba spp., and Naegleria fowleri. 1657 14

Voriconazole (VRC) is an antifungal drug that effectively treats keratitis caused by yeasts and molds when administered orally. We retrospectively evaluated clinical outcomes and plasma and aqueous humor drug concentrations in five patients with fungal keratitis and one patient with posttraumatic endophthalmitis who were treated with VRC. VRC was administered either topically (1% eye drops every hour) or orally (400 mg twice a day). Plasma and aqueous humor samples from affected eyes were taken 12 h after oral administration or 1 h after eye drop application. The drug concentration was measured by liquid chromatography with UV or mass spectrometric detection. All six patients responded well to VRC treatment. The VRC concentration ranged from 2.93 to 3.40 mg/liter in the aqueous humor and from 3.20 to 4.20 mg/liter in the plasma after combined oral and topical treatment. Topical administration alone resulted in highly variable trough VRC concentrations of 0.61 to 3.30 mg/liter in the aqueous humor. VRC concentrations were above the MIC for Candida albicans Aspergillus fumigatus and clinical improvement was seen in all four patients with C. albicans and A. fumigatus keratitis. Combined orally and topically administered VRC resulted in aqueous humor drug concentrations of > or =2.93 mg/liter, which is above the VRC MIC for most fungi. Topical VRC treatment resulted in an aqueous humor drug concentration >0.61 mg/liter, which is above the MIC for most Candida species. The results from this small series of patients suggest that both topical and combined systemic and topical VRC therapy can be effective in treating fungal keratitis. Furthermore, the data provide preliminary support for initiation of VRC treatment with a combined topical and systemic administration until the causative fungus and its MIC are identified.
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PMID:Voriconazole concentration in human aqueous humor and plasma during topical or combined topical and systemic administration for fungal keratitis. 1706 May 17


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