Pharmacokinetics of ciprofloxacin in the human eye: a clinical study and population pharmacokinetic analysis.

Ciprofloxacin, a fluoroquinolone antibiotic active against a wide variety of bacteria, is one of a few antibiotics which enters the human eye after oral administration. However, little is known about its pharmacokinetics in the human eye. One or two oral doses of 750 mg of ciprofloxacin (at a 12-h interval) were administered to 48 patients at various times prior to ocular surgery. Clotted blood, aqueous, and vitreous were collected at surgery, and the concentrations of ciprofloxacin were assayed by high-performance liquid chromatography. Our data were combined with those of others, and a population pharmacokinetic analysis was conducted. The concentrations of ciprofloxacin in both aqueous and vitreous were lower than those in serum and peaked at a later time. The pharmacokinetics of ciprofloxacin in aqueous and vitreous were fitted to a compartmental model in which the antibiotic was transferred into and out of the two compartments (aqueous and vitreous) by first-order processes. Population pharmacokinetic software, P-Pharm, was used to calculate the mean half-lives of the loss of ciprofloxacin from aqueous and vitreous, which were 3.5 and 5.3 h, respectively. At steady state, the mean ratios of then concentrations in aqueous and vitreous to the concentrations in serum were 23 and 17%, respectively. After the administration of one or two doses of 750 mg of ciprofloxacin, the concentrations in both aqueous and vitreous in a number of patients were lower than the MICs at which 90% of isolates are inhibited (0.5 mg/liter) for common intraocular bacterial pathogens. Simulations of concentrations in the eye after the administration of higher doses (1,500 mg of ciprofloxacin as a single dose, two doses of 750 mg 2 h apart, and 750 mg every 6 h) indicated that in approximately 20% of patients the concentrations would still be below 0.5 mg/liter. Although oral ciprofloxacin may be a beneficial adjunctive therapy, the use of oral ciprofloxacin alone may not be adequate for perioperative prophylaxis or for treatment of bacterial endophthalmitis.

Ciprofloxacin treatment does not influence course or relapse rate of reactive arthritis and anterior uveitis.

OBJECTIVE: To assess the efficacy of ciprofloxacin in the treatment of reactive arthritis (ReA) and anterior uveitis (AU) in a double-blind, randomized, placebo-controlled trial. METHODS: Seventy-two patients participated in this study, 56 with ReA and 42 with AU (26 patients had both ReA and AU). Ciprofloxacin (750 mg twice a day) was administered for 12 months with a 12-month followup. End points of the study included time to disease relapse and measures of disease severity. RESULTS: There was no difference between groups in time to disease relapse, joint inflammation, number of joints and enthesis involved in patients with ReA, or signs and symptoms of AU. CONCLUSION: Long-term treatment of ReA and AU with ciprofloxacin made no statistically significant difference to the natural history of these diseases or their severity.

Patterns of peri-operative prophylaxis for cataract surgery: a survey of Australian ophthalmologists.

BACKGROUND: Although peri-operative prophylaxis to prevent endophthalmitis is commonly practised by ophthalmologists, no one method has clearly been demonstrated to be more effective than another. We surveyed 570 Fellows of the Royal Australian College of Ophthalmologists to determine what their methods of prophylaxis were and whether these differed for patients who developed endophthalmitis. METHODS: The questionnaire asked about the types of antibiotics and other methods of prophylaxis used before, during and after cataract surgery. Of those who reported cases of endophthalmitis, we asked specifically about the methods of prophylaxis used for those patients. RESULTS: The response was 89% and the incidence of endophthalmitis was calculated as 0.11%. There was little difference in the methods of prophylaxis used by those who reported endophthalmitis compared with others, but pre-operative antibiotics were used more commonly by those who reported the disease (P = 0.06). Surgeons who had practised for 20 years or more reported a lower rate of endophthalmitis than others, as did those who performed more than 300 cataract operations per year. However the pattern of prophylaxis used by these two sub-groups was quite divergent. Differences in the methods of prophylaxis had no bearing on the development of endophthalmitis, with the exception that subconjunctival antibiotics were used less often in those patients who developed the disease (P = 0.03). CONCLUSIONS: The results of the present study provide no clear answer regarding appropriate peri-operative prophylaxis. The wide range of prophylactic regimens used suggests that no one method is superior to another. Formal case-controlled studies are required to identify which method would be most efficacious.

Antibiotic prophylaxis for the prevention of late infections of prosthetic joints.

Late infection of prosthetic joints as a result of the haematogenous spread of an organism from a remote site with the seeding of that organism on the bone-implanted prosthesis interface is a well-documented but rare complication of prosthetic joint surgery. However, the use of antibiotic prophylaxis is such cases is controversial. The details of 67 previously reported cases of late infection have been reviewed in conjunction with the details of a series of 43 patients, and observations and recommendations regarding antibiotic prophylaxis are made upon the basis of these accumulated data.

A comparison of aztreonam and imipenem induction of class I beta-lactamase in Enterobacter cloacae ATCC 13047.

Aztreonam and imipenem were shown to induce Class I beta-lactamase in Enterobacter cloacae ATCC 13047 to a similar extent. Quantitatively, however, aztreonam was far less efficient as an inducer than imipenem. Optimum induction by aztreonam required a concentration of 200 mg/l, which was 800-fold greater than the concentration of 0.25 mg/l of imipenem which resulted in the optimum induction. The differences in the concentrations of aztreonam and imipenem that gave optimum induction were related to the inherent antibacterial activities of the antibiotics when these were determined under the conditions of broth culture. The beta-lactamase activity of sonicated cell samples following induction was inhibited by the presence of aztreonam but not by imipenem. The inhibition was overcome by first washing the cell samples from induced cultures and then incubating the sonicates for a prolonged period at 4 degrees C. It is proposed that the phenomena of an optimum inducing concentration and the interference with the assay of beta-lactamase by the presence of residual antibiotic demonstrated in this study with aztreonam and imipenem would be of relevance when applied more broadly to studies of beta-lactamase induction. In particular these would have a profound effect on the results of studies which attempt to compare the efficacy of beta-lactams as inducers of Class I beta-lactamase.

The penicillins.

The penicillins are among the most useful antibiotics despite the increasing problem of bacterial resistance. The authors review the various penicillins available in Australia and emphasise the rationale for their use and the mechanisms of bacterial resistance to these agents.

Comparison of glycine enhancement with cefoxitin induction of class 1 beta-lactamase production in Enterobacter cloacae ATCC 13047.

The presence of either glycine or cefoxitin in the growth medium resulted in an increase in the beta-lactamase activity of cultures of Enterobacter cloacae ATCC 13047. Although the beta-lactamases produced as a result of either glycine enhancement or cefoxitin induction were identical there were striking differences in the kinetics of beta-lactamase production. The increased production of beta-lactamase which resulted from enhancement by glycine occurred late in the growth cycle whereas, with cefoxitin induction, the maximum production of beta-lactamase occurred early in logarithmic-phase growth. After the peak activity was reached the beta-lactamase activity appeared to decline with both processes. However, the mechanism of the apparent fall in the intracellular beta-lactamase activity was different with glycine enhancement and cefoxitin induction. In glycine enhanced cultures the fall presumably was due to leakage of intracellular beta-lactamase into the culture medium whereas with cefoxitin induced cultures there was dilution of beta-lactamase activity by bacterial protein derived from an increase in cell numbers after the cessation of induction. High extra-cellular levels of beta-lactamase activity were observed in cultures enhanced by glycine, whereas little beta-lactamase activity was detected in the medium when the cultures were induced by cefoxitin. The findings demonstrate that there are considerable differences between glycine enhancement and cefoxitin induction, but a final mechanism common to both processes exists which results in the production of identical beta-lactamases by E. cloacae ATCC 13047.

The effect of casein derivatives on glycine enhancement of beta-lactamase production in Enterobacter cloacae ATCC.13047.

Our earlier work showed that glycine enhancement of class I beta-lactamase production in Enterobacter cloacae ATCC.13047 was greater on Isosensitest Agar than on other laboratory media. In the present study it was demonstrated that Casein Hydrolysate was the constituent of Isosensitest Agar which was necessary for glycine enhancement of beta-lactamase production. Also, a comparison of the effect of casein and casein derivatives on glycine enhancement of beta-lactamase production showed that acid hydrolysis of casein was a prerequisite for glycine enhancement of beta-lactamase production. Enterobacter cloacae ATCC.13047 failed to grow on a medium containing casein, and glycine enhancement of beta-lactamase production did not occur on a medium containing tryptic hydrolysate of casein. The effect on beta-lactamase production of variations in the concentrations of both Casein Hydrolysate and glycine was examined by titration of both components in a chequerboard fashion. Beta-lactamase production was influenced by the concentrations of both Casein Hydrolysate and glycine. This inter-relationship indicated that there was a balance between the concentrations of Casein Hydrolysate and glycine and that alterations in this balance modified beta-lactamase production. The significance of the observations is discussed in relation to the factors which influence glycine enhancement of beta-lactamase production in Enterobacter cloacae ATCC.13047.

Enhancement of beta-lactamase production by glycine in Enterobacter cloacae ATCC.13047.

Beta-lactamase production in Enterobacter cloacae ATCC.13047 was enhanced by glycine, and the degree of enhancement was dependent on the concentration of glycine and the medium used. Maximum enhancement occurred with a concentration of 0.05 moles/l of glycine, and of 4 media examined enhancement was greatest on Isosensitest Agar. Enhanced beta-lactamase production evoked by glycine was compared with that following induction by various concentrations of cefoxitin. The amount of beta-lactamase produced under conditions of maximum glycine enhancement was higher than that produced by cultures fully induced by cefoxitin. Other differences in the characteristics of the enhancement of beta-lactamase production by glycine and beta-lactamase induced by cefoxitin suggested that the mechanisms of the 2 phenomena were different. The significance of this finding in terms of the interpretation of in vitro antimicrobial sensitivity tests with beta-lactam antibiotics is discussed.

A case of Japanese B encephalitis imported into the United Kingdom.

A case of acute encephalomyelitis, serologically proven to be due to Japanese B encephalitis virus, is reported. The patient, a 35-year-old woman, contracted the disease whilst in Hong Kong but presented in the United Kingdom. She required ventilatory support and was given high-dose steroids. She recovered from the illness but died after a period of four months from respiratory/cardiac arrest.

The relative values of serum immuno-reactive trypsin concentration and total amylase activity in the diagnosis of mumps, chronic renal failure, and pancreatic disease.

Fasting serum concentrations of trypsin and amylase activity have been compared in 107 subjects, including 18 controls and patients with mumps, acute pancreatitis, chronic pancreatitis, cancer of the pancreas, and chronic renal failure. There was no significant correlation between amylase activity and trypsin concentrations in any of these groups. In all 12 patients with acute pancreatitis and all 16 with chronic renal failure the serum immuno-reactive trypsin concentrations were elevated. Amylase activity was increased in 87% (20 out of 23) of patients with mumps, but only 13% (3 out of 23) had hypertrypsinaemia suggesting subclinical pancreatitis. In 18 patients with chronic pancreatitis low levels of serum trypsin were measured in 11 (61%), reflecting a decrease in pancreatic acinar mass. In contrast, serum amylase was normal or raised in all 18. Subnormal values of the trypsin to amylase ratio was obtained in 15 (83%). Trypsin levels in 20 patients with carcinoma of the pancreas were abnormal in 11 (55%). Six (30%) had abnormal amylase levels. It is concluded that it is more useful to measure the serum trypsin concentration than the amylase activity in the diagnosis of both mumps-pancreatitis and chronic pancreatic disease and that the trypsin to amylase ratio is more sensitive than either enzyme alone in the diagnosis of chronic pancreatitis.