Colo-Pro: a pilot randomised controlled trial to compare standard bolus-dosed cefuroxime prophylaxis to bolus-continuous infusion-dosed cefuroxime prophylaxis for the prevention of infections after colorectal surgery.

Standard bolus-dosed antibiotic prophylaxis may not inhibit growth of antibiotic resistant colonic bacteria, a cause of SSIs after colorectal surgery. An alternative strategy is continuous administration of antibiotic throughout surgery, maintaining concentrations of antibiotics that inhibit growth of resistant bacteria. This study is a pilot comparing bolus-continuous infusion with bolus-dosed cefuroxime prophylaxis in colorectal surgery. This is a pilot randomised controlled trial in which participants received cefuroxime bolus-infusion (intervention arm) targeting free serum cefuroxime concentrations of 64 mg/L, or 1.5 g cefuroxime as a bolus dose four-hourly (standard arm). Patients in both arms received metronidazole (500 mg intravenously). Eligible participants were adults undergoing colorectal surgery expected to last for over 2 h. Results were analysed on an intention-to-treat basis. The study was successfully piloted, with 46% (90/196) of eligible patients recruited and 89% (80/90) of participants completing all components of the protocol. A trialled bolus-continuous dosing regimen was successful in maintaining free serum cefuroxime concentrations of 64 mg/L. No serious adverse reactions were identified. Rates of SSIs (superficial and deep SSIs) were lower in the intervention arm than the standard treatment arm (24% (10/42) vs. 30% (13/43)), as were infection within 30 days of operation (41% (17/43) vs 51% (22/43)) and urinary tract infections (2% (1/42) vs. 9% (4/43)). These infection rates can be used to power future clinical trials. This study demonstrates the feasibility of cefuroxime bolus-continuous infusion of antibiotic prophylaxis trials, and provides safety data for infusions targeting free serum cefuroxime concentrations of 64 mg/L. Trial registration: NCT02445859 .

Quantification and prediction of skin pharmacokinetics of amoxicillin and cefuroxime.

The purpose of this project was to develop and validate a pharmacokinetic model and to quantify the rate and extent of distribution between plasma and skin of two beta-lactam antibiotics, amoxicillin (AMX) and cefuroxime (CFX), which are frequently administered systemically to treat skin and skin structure infections. Dosing regimens are usually based on plasma concentration, however, concentrations at the target site are better correlated with the effect. For each antibiotic, three different i.v. bolus doses were administered to three female rabbits according to a randomized cross-over design and plasma samples were collected serially. Skin concentrations were obtained by continuous microdialysis. Skin and unbound plasma concentrations were fitted simultaneously using a semi-physiological model and the transfer constants plasma/skin (K(in)) and skin/plasma (K(out)) were estimated. K(in) and K(out) were then used to predict skin concentrations from the plasma levels obtained from an oral administration of AMX or from an i.v. bolus of CFX. The predicted skin profiles were similar to those measured by microdialysis during the actual experiments. In conclusion, this study shows that it is possible to generate a reasonable prediction of skin pharmacokinetics from any plasma level once a careful characterization of the transfer process between plasma and skin has been made.

Activity of FCE 22891 compared with cefuroxime axetil and cefixime in pulmonary and subcutaneous infections in mice.

The therapeutic activity of FCE 22891 was compared with that of two new oral cephalosporins, cefuroxime axetil and cefixime against Streptococcus pneumoniae respiratory infection and subcutaneous abscesses induced by mixed aerobes and anaerobes in mice. In experimental pneumonia FCE 22891 was the most active antibiotic. In aerobic abscesses FCE 22891 proved the most active agent in infections induced by methicillin susceptible and resistant Staphylococcus aureus while all three compounds were very active, against Str. pyogenes. In abscesses caused by Gram-negative bacteria, FCE 22891 showed good and constant efficacy. Cefixime was the most active drug against the two susceptible strains of Escherichia coli and Enterobacter cloacae and also against resistant Esch. coli but was inactive against a strain of Ent. cloacae that produced cephalosporinase. Cefuroxime axetil was less active than the other two drugs against Gram-negative bacteria with adequate efficacy only against a susceptible strain of Ent. cloacae. FCE 22891 was more effective than cefixime and cefuroxime axetil in preventing and reducing the size of abscesses induced by Bacteroides fragilis 101. We conclude that FCE 22891, despite its short half life of 6 min in mice, exerts comparable and sometimes better activity than the two oral cephalosporins characterized by longer half lives.

Comparison of ceftazidime, cefuroxime and methicillin in the treatment of Staphylococcus aureus endocarditis in rabbits.

Ceftazidime, cefuroxime and methicillin proved equally effective in the therapy of experimental Staphylococcus aureus endocarditis in rabbits with a dosing regimen of 40 mg/kg intramuscularly at 8-hourly intervals for three days. Treated animals all demonstrated a thousand to 10,000-fold reduction in the levels of bacteria in the vegetations compared with untreated controls. In-vitro sensitivities of the organism to the test antibiotics were not predictive of therapeutic efficacy in vivo.

Cefuroxime in soft tissue infections and septicaemia.

Data are presented on the absorption, antibacterial activity, clinical efficacy and side effects of cefuroxime in 33 cases with proven bacterial infection in soft tissues and in patients with septicaemia. The drug was administered mainly intramuscularly (i.m.) but also intravenously (i.v.). Peak serum concentrations 1 h after an injection of 750 mg cefuroxime i.m. were between 16-25 mug/ml. After 8 h the levels were mostly < 4 mug/ml in patients with normal renal function. I.v. injection gave only slightly higher maximum serum level obtained was approximately 40 mug/ml. No accumulation of the drug occurred in patients with normal renal function. Cefuroxime was active against all the gram-positive bacteria isolated from our patients as well as most of the gram-negatives. The clinical effect was satisfactory in 96%. The drug was well tolerated. Side effects were slight and relatively few.