Ciprofloxacin in renal failure.
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Biomedical subjects
Publications and source records attributed to J D Williams.
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A cross-over study was performed comparing serum kinetics and urinary excretion in six healthy, fasting volunteers after ingestion of comparable amounts of lenampicillin, bacampicillin and amoxycillin. Venous blood samples and urine samples were taken at intervals for 6 and 12 h respectively post-tablet ingestion and assayed for free ampicillin or amoxycillin concentration with Bacillus subtilis as indicator organism. The most rapid Tmax and the highest Cmax were achieved with lenampicillin. The AUC was similar for lenampicillin, bacampicillin and amoxycillin as was the total percentage urinary recovery of antibiotic. Potential pharmacokinetic advantage of orally administered lenampicillin and bacampicillin compared to comparable doses of amoxycillin are higher peak serum concentrations (12.0 mg/l lenampicillin; 9.7 mg/l bacampicillin; 7.6 mg/l amoxycillin) and more rapid time to peak concentration (0.6 h lenampicillin; 0.7 h bacampicillin and 1.4 h amoxycillin).
The pharmacokinetics of teicoplanin were studied in 20 subjects with varying degrees of renal function after administration of a single 200 mg intravenous dose. Pharmacokinetic parameters were calculated with a three compartment open model and by non-compartmental analysis. The elimination half-life increased as creatinine clearance decreased (rs = -0.87, P less than 0.001). The distribution volume was 1.0 (+/- 0.3) 1/kg of actual body weight and did not vary with changes in creatinine clearance. In normal subjects the main route of elimination was renal. The plasma clearance of teicoplanin correlated with creatinine clearance (rs = 0.91, P less than 0.001). At lower levels of creatinine clearance the variation in elimination half-life was such that we recommend individualization of the teicoplanin dosage following the measurement of the drug concentration in plasma.
The inhibitory activity of penem FCE 22101 was compared with those of imipenem and other relevant antibiotics against over 500 clinical isolates of Gram-positive cocci and anaerobes. The relative bactericidal activities of FCE 22101 and imipenem were compared by a killing curve method. FCE 22101 showed good inhibitory activity against most aerobic Gram-positive cocci although generally less than imipenem. A substantial number of Staphylococcus aureus isolates (43%) were highly susceptible to imipenem (MIC less than 0.0015 mg/l); the mode MIC for FCE 22101 was 0.06 mg/l. Methicillin-resistant Staph. aureus (MRSA) were often slightly more susceptible to FCE 22101 than to imipenem. Streptococci were more susceptible to imipenem than to FCE 22101; mode MICs for group A streptococci were 0.003 and 0.03 mg/l and for enterococci 1 and 4 mg/l, respectively. The anaerobic organisms tested were equally susceptible to both FCE 22101 and imipenem. Imipenem and FCE 22101 showed similar bactericidal activity at a concentration equivalent to 4 x MIC. Fully susceptible staphylococci were killed rapidly by both compounds, whereas less susceptible isolates, especially MRSA, were killed slowly. Streptococci, other than Str. pneumoniae, were also killed relatively slowly. Bacteroides fragilis group organisms were rapidly killed by both FCE 22101 and imipenem.
The in-vitro activity of the new carbapenem, meropenem, was compared with that of imipenem, five other beta-lactams, chloramphenicol and ciprofloxacin against 223 isolates of Haemophilus influenzae. This number included 115 ampicillin-susceptible, and 56 beta-lactamase positive isolates and 52 beta-lactamase negative isolates with reduced susceptibility to ampicillin. The activities of chloramphenicol and ciprofloxacin did not vary between groups of isolates delineated by their susceptibility to ampicillin. In contrast with ampicillin and piperacillin, the two carbapenems and three cephalosporins tested showed no reduction in activity against beta-lactamase producing isolates. beta-Lactam concentrations required for inhibition of 50% and 90% of beta-lactamase negative isolates with reduced susceptibility to ampicillin (MIC greater than or equal to 1 mg/l) were increased in comparison with similar concentrations required for the ampicillin-susceptible group. The differences in meropenem and imipenem activities between these two groups were much smaller than those observed for each of the other beta-lactams. MICs of meropenem were consistently the lower of the two carbapenems for all isolates. In addition, there were no notable increases in the concentrations of meropenem required for inhibition of the isolates least susceptible to imipenem (MIC greater than or equal to 4 mg/l), suggesting that differences in penetration and/or target-binding properties exist not only between the carbapenems and other beta-lactams, but also between meropenem and imipenem.
A new method for the manufacture of a heated factor VIII concentrate of high specific activity (2-6 IU factor VIII:C/mg protein) has been developed. Addition of heparin to cryoprecipitate extract at acid pH precipitated fibrinogen and fibronectin. Factor VIII was then recovered from the supernatant by precipitation with glycine and sodium chloride. After re-solution and desalting on Sephadex G-25, the concentrate was sterile-filtered and lyophilised. The dried product was stable to heating in the final container at 80 degrees C for 72 h. Data from 25 consecutive batches of concentrate prepared from 1,200-1,500 kg plasma pools are presented. The mean final yield of heated product was 190 IU factor VIII:C/kg plasma. The concentrate has been found to be safe and effective in clinical use.
Serious complications of urinary tract infection, such as papillary necrosis or perinephric abscess, occur more frequently in diabetic patients. However, severe bilateral renal parenchymal infection with multiple intrarenal abscesses is not well recognized. We described an 18-year-old insulin-dependent diabetic woman with such infection, in whom renal imaging showed progression to a major perinephric abscess, but only after 5 weeks of intensive antibiotic therapy. Complete recovery followed surgical drainage and no renal cortical scarring was present on computerized tomographic scan 18 months later.
Thirty four infants with chronic lung disease of prematurity were reviewed and divided into two groups on the appearance of the chest radiograph. Type 1 disease (n = 19) was defined as homogeneous or patchy ill defined opacification in the lungs without coarse reticulation, and type 2 disease (n = 11) had the classical appearance of bronchopulmonary dysplasia. Four patients could not be classified. We conclude that type 1 disease represents typical chronic lung disease of premature infants, and type 2 is usually complicated by pulmonary interstitial emphysema. As no infant with type 1 disease died, its histopathological basis is unknown.
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Interstitial fluid pressures, as a possible function of limb load, were measured at 2 sites within the digital coronary dermis of both cranial digits in 10 standing horses. Fluid pressure changes and digital load measurements were simultaneously detected and recorded by use of, respectively, modified wick-in-needle and force plate transducers coupled to a microcomputer. Mean pressures, recorded at limb loads between 50 and 80 kg, were 2.29 +/- 3.17 mm of Hg at the toe and 2.49 +/- 5.91 mm of Hg at the heel. Mean pressures, recorded between 150 and 180 kg, were 5.01 +/- 5.23 mm of Hg at the toe and 1.28 +/- 7.69 mm of Hg at the heel. These data indicate that, in the static limb, no statistically significant change in interstitial fluid pressure occurs at loads up to 180 kg.
Between December 1972 and December 1986, 83 patients with aneurysmal disease (n = 37) or dissection (n = 46) involving the ascending aorta underwent a variety of operations, including composite value-graft repairs (n = 39), separated replacements of the aortic valve and ascending aorta (n = 18), resuspension and graft replacement of the ascending aorta (n = 9), graft replacement of the ascending aorta only (n = 8), homograft root replacement (n = 3), aortic valve replacement with aortorrhaphy (n = 3), aotorrhaphy alone (n = 2), and use of a sutureless intraluminal prosthesis (n = 1). The inclusion method was used in nine patients. The hospital mortality rate was 10% for patients with annuloaortic ectasia, 21% (70% confidence interval 13% to 30%) for acute dissection, and 18% (70% confidence interval 14% to 22%) for the entire group. Logistic regression analysis showed age and cumulative bypass time to be significant for hospital death. The estimated 5-year survival rates are 69.5% +/- 7.2% and 67.0% +/- 9.0% and 10-year estimates are 34.6% +/- 10.6% and 61.4% +/- 9.8% for dissection and aneurysm, respectively. Patient survival was related to differing pathology and type of operation, and log-rank testing showed no differences at the 5% level. Attrition (17 late deaths) was mostly due to left ventricular dysfunction, myocardial infarction, or aneurysmal disease in ungrafted aorta. Actuarial freedom from thromboembolism in patients with prosthetic valves is 92.0% +/- 4.0% and 83.5% +/- 6.8% at 5 and 10 years. Freedom from all late graft and cardiac complications is 72.5% +/- 9.1% and 48.8% +/- 13.1% at 5 and 10 years for aneurysmal disease and 79.1% +/- 7.3% and 67.3% +/- 9.9% at 5 and 10 years for dissection. Reoperation in nine patients was required for pseudoaneurysms (n = 3), other aortic aneurysms (n = 3), persistent aortic regurgitation (n = 1), and obsolescent valve prosthesis (n = 2). Thus hospital mortality does not seem to be significantly related to the type of operation used for pathologic conditions of the ascending aorta unless cumulative bypass time exceeds about 2 hours. Many nonfatal late complications are associated with a prosthetic valve, but late death is due primarily to cardiac causes and residual disease in other parts of the aorta.
We have studied the in-vitro activity of erythromycin, vancomycin and pristinamycin against 1,006 clinical isolates comprising streptococci, staphylococci, Neisseria gonorrhoeae, Haemophilus influenzae and anaerobes. In-vitro studies show pristinamycin to inhibit staphylococci and streptococci, including erythromycin highly-resistant organisms, at a concentration of less than or equal to 0.78 mg/l. Although pristinamycin's mean MIC for streptococci is higher than that of erythromycin, pristinamycin is bactericidal, whereas erythromycin is bacteristatic against Streptococcus agalactiae and oral streptococci. Enterococci were less uniformly susceptible to pristinamycin: 58 of the 94 Enterococcus faecalis tested were resistant (MIC greater than or equal to 3.12 mg/l). 14 of the 15 isolates of Enterococcus faecium were inhibited by less than or equal to 1.56 mg/l pristinamycin. Pristinamycin showed poor activity against Haemophilus influenzae (mode MIC 1.56 and MIC90 of 3.12 mg/l) but all except two of the 100 Neisseria gonorrhoeae tested were inhibited by less than or equal to 0.78 mg/l pristinamycin. Pristinamycin inhibited all nine Clostridium spp. at less than or equal to 0.39 mg/l and 38 of 40 strains of anaerobic gram-positive cocci at less than or equal to 0.78 mg/l. It was less effective against the Bacteroides fragilis group: (MIC90 3.12 mg/l). Pristinamycin had poor bactericidal activity against the anaerobes tested.
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The comparative in vitro activity of A-56268 was studied using 1,006 clinical isolates including streptococci, enterococci, staphylococci, Neisseria gonorrhoeae, Haemophilus influenzae and anaerobes. A-56268 showed activity comparable to that of erythromycin and was more active than josamycin and roxithromycin against erythromycin-sensitive aerobic and facultatively anaerobic gram-positive cocci. A-56268 was the most active macrolide against Clostridium spp. and Neisseria gonorrhoeae. Josamycin was more active than either A-56268 or erythromycin against the anaerobic gram-positive cocci and the Bacteroides fragilis group. Staphylococci moderately resistant or resistant to erythromycin (MIC 3.12-50 mg/l) remained susceptible to josamycin but not the other macrolides.
An outbreak with a strain of methicillin-resistant Staphylococcus aureus began in The London Hospital in 1982 and continues to be associated with significant morbidity and mortality. This particular strain, termed epidemic methicillin-resistant S. aureus, is recognized by its characteristic antibiogram, phage-type and plasmid profile. In this outbreak various means of control have been attempted. Sideroom isolation did not curtail spread of the organism and containment was only achieved with the combination of extended screening, mupirocin for treatment of carriage and the use of an isolation ward.
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