Stability of beta-lactam antibiotics containing N-methylthiotetrazole side-chain.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R Wise.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
One gram each of moxalactam and cefotaxime and 0.5 g of ceftriaxone was administered intravenously to six volunteers. The pharmacokinetics and tissue penetration (as measured by a blister fluid model) were studied. The initial (i.e. 15 min) concentrations of the agents were 89.7 mg/l, 101 mg/l and 55 mg/l for ceftriaxone, moxalactam and cefotaxime respectively. The serum half-lives differed considerably, being 8.8, 2.8 and 1.2 h respectively. All agents penetrated the blister fluid rapidly the maximum penetration being found with ceftriaxone, namely 32.7 mg/l.
Ticarcillin was compared with metronidazole in the prevention of wound infection after appendicectomy. Two hundred nine patients with a diagnosis of acute appendicitis were admitted to a prospective, randomized study and received 500 mg of metronidazole or 5 g of ticarcillin intravenously before operation. Those patients with gangrenous or perforated appendices received two additional doses of the trial drug at 8 hourly intervals. The overall incidence of wound infections in both the metronidazole and the ticarcillin groups was 9 percent. There were no intraabdominal abscesses. Metronidazole abolished anaerobic wound infections. All the early wound infections (between 2 and 4 days after operation) occurred in patients with gangrenous or perforated appendices. We conclude that ticarcillin is as effective as metronidazole in the prevention of wound infection after appendicectomy, but in high-risk patients, (those with gangrenous or perforated appendices) longer courses of antibiotics should be employed.
Blood cultures from 140 patients with chest infections were examined for the presence of pneumococcal antigen by both latex particle agglutination and counterimmunoelectrophoresis. Twenty-three samples (15 patients) were positive for pneumococcal antigen by counterimmunoelectrophoresis, of which 21 samples (13 patients) yielded Streptococcus pneumoniae in culture. Thirty-three samples (20 patients) were positive by latex particle agglutination, of which 24 samples (15 patients) were culture positive. The sensitivities and specificities were calculated and it was concluded that latex particle agglutination was the better test for the determination of the presence of pneumococcal capsular polysaccharide.
Thirty patients undergoing elective abdominal surgery were given 1 g amoxycillin plus 0 . 2 g clavulanic acid as a single intravenous injection at varying times prior to the operation. Sterile assay discs were placed on the peritoneal surface in order to measure peritoneal fluid levels of each agent. Simultaneous serum levels were also measured. A total of 44 simultaneous serum and peritoneal samples were analysed. There was rapid penetration of both agents into peritoneal fluid. The mean peritoneal fluid levels of amoxycillin were 84% (S.D. 34) of the serum level and 66% 42) for clavulanic acid. The peritoneal levels of both agents declined in parallel to the serum levels (the half-lives all being about 1 h) and the ratio of amoxycillin: clavulanic acid in serum and peritoneal fluid was similar to that as administered.
Temocillin is a new penicillin combining activity against Gram-positive organisms, beta-lactamase stability and an exceptionally long half-life. In patients with normal renal function the half-life was approximately 4-6 h and this increased to 30 h in patients with severe renal failure. It is suggested that unlike other penicillins this compound may give adequate antibacterial concentration with once daily dosing in subjects with normal renal function; this will certainly require reduction in subjects with severely impaired renal function.
Sulbactam, a beta-lactamase inhibitor, was given as a single agent to 12 subjects with varying degrees of renal dysfunction. The half-life in normal subjects was 1.1 h and increased to 21.3 h in those with terminal renal failure. Sulbactam together with ampicillin was given to a further five subjects. It was concluded that if the two agents are given together, the plasma ratio of one to the other will remain constant whatever the renal function.
The pharmacokinetics of cefotetan following a 0.5 g intravenous dose were studied in 15 patients with varying degrees of renal failure. In patients with glomerular filtration rates (GFR) greater than 50 ml/min the serum half-life was between 3 and 5 h. The half-life increased to 15 h as the GFR fell to 10 ml/min. When the GFR was less than 10 ml/min the serum clearance of cefotetan was very variable, the half-life being between 15 and 50 h. Cefotetan was eliminated almost entirely by the kidneys. It is suggested that cefotetan 0.5 g 12-hourly is appropriate for patients with GFRs greater than 20 ml/min. For patients with GFRs between 10 and 20 ml/min 0.5 g every 24 h should avoid gross accumulation.
Explore the source record for details and available documents.
The intraperitoneal penetration of temocillin was studied following a 1 g iv injection in 28 patients undergoing elective gastrointestinal surgery. Temocillin penetrated rapidly and during the first hour post administration the peritoneal level was 48% of the serum level. The mean peritoneal level of temocillin over the period of the study (3.5 h) was 49.1 mg/l. It was concluded that 1 g of temocillin twice daily would achieve sufficiently high intraperitoneal levels to inhibit susceptible pathogens.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The hypothesis that the pharmacokinetics of amikacin are more predictable than those of gentamicin or tobramycin was studied. In a three-way crossover design 58 volunteers received 7.5 mg/kg amikacin by iv infusion and either 1.5 mg/kg or 1 mg/kg gentamicin and tobramycin. The mean half-life and mean serum concentration at 1 h for each drug was determined. No consistent significant difference was found between the pharmacokinetics of amikacin and the other two drugs.
The in vitro activity of Bay 09867, a new quinoline derivative, was compared with those of norfloxacin, nalidixic acid, ceftazidime, cefaclor, cefuroxime, gentamicin, and other antimicrobial agents, when appropriate, against 410 recent clinical isolates. The minimal inhibitory concentrations of Bay 09867 for 90% of Enterobacteriaceae, Pseudomonas aeruginosa, Haemophilus influenzae, Neisseria gonorrhoeae, streptococci, Staphylococcus aureus, and Bacteroides fragilis strains were between 0.008 and 2 micrograms/ml. Bay 09867 was considerably more active against the gram-negative bacteria tested than were other agents tested. Gentamicin-resistant Enterobacteriaceae, P. aeruginosa, and methicillin-resistant S. aureus were highly susceptible to Bay 09867. Strains less susceptible to nalidixic acid and norfloxacin tended to be less susceptible to Bay 09867. The protein binding of Bay 09867 was about 20%.
A combination of 3 g of ticarcillin and 200 mg of clavulanic acid was administered intravenously to six healthy male volunteers, after which the concentrations of these agents in serum and blister fluid were measured. The ratio of the two drugs in serum varied from 15:1 (ticarcillin-clavulanic acid) at the time of administration to 28:1 at 30 min and 62:1 at 5 h after injection. Both agents penetrated blister fluid rapidly, the ratio being 33:1 at 1 h and 66:1 at 3 h. The elimination rates of these agents were different, but for each compound they were similar in serum and blister fluid.
The intraperitoneal penetration of cefotetan was studied after a 1-g intravenous injection in 25 patients undergoing elective gastrointestinal surgery. Levels of peritoneal fluid were high within 10 min after administration and increased to 44% of the serum levels after 30 min, rising to 115% at 3 h. The mean concentration of cefotetan between 3 and 5 h after administration was 32.3 micrograms/ml. These findings suggest that 1 g of cefotetan administered before abdominal surgery would result in intraperitoneal cefotetan levels necessary to inhibit susceptible pathogens for 5 h or more.
Twenty-five patients undergoing elective intraabdominal surgery received either 1 or 2 g of ampicillin together with 1 g of sulbactam intravenously before surgery. The peritoneal levels of the agent were measured. Both compounds penetrated peritoneal fluid readily; the mean percentage of penetration by ampicillin was 92%; that of sulbactam was 96%. After 1 g of each agent, the peritoneal levels of sulbactam were 47% greater than those of ampicillin. Our results suggest that 2 g of ampicillin plus 1 g of sulbactam should provide peritoneal levels that would inhibit most susceptible beta-lactamase-producing pathogens encountered in intraabdominal sepsis.