Treatment of experimental Staphylococcus epidermidis endophthalmitis with oral trovafloxacin.

PURPOSE: To investigate the ocular pharmacokinetics and efficacy of oral trovafloxacin, a novel fluoroquinolone antibiotic, in Staphylococcus epidermidis endophthalmitis. METHODS: Albino rabbits (n = 20) were infected with an intravitreal inoculum of S epidermidis (1.0 x 10(8) colony-forming units [CFU/0.1 ml) and 24 hours later received a single oral dose of trovafloxacin (250 mg/kg). Serum and intraocular samples from infected and control (noninfected) eyes were obtained up to 24 hours after antibiotic administration for measurement of trovafloxacin levels. A second group of rabbits (n = 72) was infected intraocularly and randomized 24 hours later to oral trovafloxacin (250 mg/kg twice a day) for 6 days or no treatment (control). Treatment efficacy was assessed by vitreous culture, clinical examination, and histopathology. RESULTS: Following a single dose of trovafloxacin, maximal vitreous levels were achieved at 8 hours in infected eyes, with a penetration ratio of 36%. Vitreous levels were greater than 15 times the minimum inhibitory concentration of the strain employed. In animals with established endophthalmitis, treated eyes were sterilized after 5 days (P = .0495) compared with control eyes, which autosterilized at 14 days. Clinical and histologic examination revealed significant amelioration of anterior segment inflammation in treated eyes, although severe destruction of posterior segment structures occurred in both groups after 6 days of therapy. CONCLUSIONS: These data support trovafloxacin as a potential oral agent for treatment or prophylaxis of S epidermidis endophthalmitis, although retinal alterations that occur over the period required for vitreous sterilization suggest that it will not replace intravitreal therapy in established endophthalmitis.

Insights into the mechanism of catalysis by the P-C bond-cleaving enzyme phosphonoacetaldehyde hydrolase derived from gene sequence analysis and mutagenesis.

Phosphonoacetaldehyde hydrolase (phosphonatase) catalyzes the hydrolysis of phosphonoacetaldehyde to acetaldehyde and inorganic phosphate. In this study, the genes encoding phosphonatase in Bacillus cereus and in Salmonella typhimurium were cloned for high-level expression in Escherichia coli. The kinetic properties of the purified, recombinant phosphonatases were determined. The Schiff base mechanism known to operate in the B. cereus enzyme was verified for the S. typhimurium enzyme by phosphonoacetaldehyde-sodium borohydride-induced inactivation and by site-directed mutagenesis of the catalytic lysine 53. The protein sequence inferred from the B. cereus phosphonatase gene was determined, and this sequence was used along with that from the S. typhimurium phosphonatase gene sequence to search the primary sequence databases for possible structural homologues. We found that phosphonatase belongs to a novel family of hydrolases which appear to use a highly conserved active site aspartate residue in covalent catalysis. On the basis of this finding and the known stereochemical course of phosphonatase-catalyzed hydrolysis at phosphorus (retention), we propose a mechanism which involves Schiff base formation with lysine 53 followed by phosphoryl transfer to aspartate (at position 11 in the S. typhimurium enzyme and position 12 in the B. cereusphosphonatase) and last hydrolysis at the imine C(1) and acyl phosphate phosphorus.

Rhinoscleroma treated with ciprofloxacin: a case report.

Rhinoscleroma, a chronic progressive infection of the nose and associated structures caused by Klebsiella rhinoscleromatis, has posed a therapeutic dilemma since its identification in the late 1800s. Although a number of antibiotics have been found to be effective in this relapsing disorder, the lengthy duration of treatment can lead to problems with adverse effects and compliance, especially with the traditional therapies of streptomycin and tetracycline. We report on a patient with extensive nasal rhinoscleroma who achieved pathologic and bacteriologic resolution during treatment with oral ciprofloxacin after previous courses of tetracycline and trimethoprim-sulfamethoxazole. Ciprofloxacin may prove to be useful in the therapy of rhinoscleroma because it is convenient for oral administration, achieves good tissue levels, is concentrated in macrophages, and is generally well tolerated as long-term therapy. As mentioned in a recent review of patients with rhinoscleroma at the Mayo Clinic, the fluoroquinolones deserve further study as potentially highly effective agents for this uncommon but significant infectious condition.

What do family physicians in a prepaid group do in their offices?

Each family physician at the Permanente Group of San Diego was observed for one half-day. As with two earlier time studies, the time spent with each patient was tabulated to show the number of minutes used in each of the usual activity categories that are encompassed in a patient encounter. Previously, similar studies had been carried out with rural practitioners in Missouri (1965) and rural and urban physicians in New Zealand (1975). The Missouri physicians practicing in pre-Medicaid days spent less time doing administrative work than their counterparts in this study, but appreciably more time in treatment and preventive activities. The time utilization of the physicians in prepaid groups was remarkably similar to that of the physicians in the fee-for-service system in New Zealand.

What do New Zealand general practitioners do in their offices?

A third person physician observer timed 16 New Zealand general practitioners during a work day during summer months. Usual office hours for the 16 physicians occupied over seven hours, during which time the patient list averaged 26 persons. Greatest time span, 27 percent, used in diagnosis, but substantial time was spent in health education, counseling and administration. The distribution of patients' problems was greatest in respiratory disease, followed by musculoskeletal, dermatologic and urogenital. There is considerable similarity to practice patterns of rural physicians in Missouri, USA.