Cefuroxime was given during operation to 95 patients undergoing 106 total joint replacements (hip 69: knee 37). Two regimes were used. Either 1 g was given intravenously with induction of anaesthesia and then two intramuscular injections of 1 g 6 and 12 h later, or 1.5 g was given intravenously with induction and two injections of 750 mg each intramuscularly 6 and 12 h later.

SummaryIn a prospective, randomized, double‐blind, multicentre trial the effect of antenatal treatment with betamethasone phosphate was compared with placebo in the prevention of the respiratory distress syndrome (RDS) in preterm infants. The dose of betamethasone was 4 mg every 8 h for six doses, unless delivery occurred. The 251 women who were enrolled gave birth to 262 liveborn infants, 130 in the betamethasone and 132 in the placebo group; the two groups were evenly matched in most respects. The diagnosis of RDS in the newborn was confirmed by two independent assessors. Seven of the 130 infants in the betamethasone group and 16 of the 132 in the placebo group developed RDS. In infants whose mothers had received at least three injections, RDS was also less frequent in the steroid group than in the placebo group (3/104 and 10/104 respectively; P<0·05). There was a significant reduction of RDS in those born between 24 h and 6 days after entry into the trial (0/30 and 8/45 respectively; P<0·05). The largest difference in frequency of RDS occurred in the subgroup of infants born before 34 weeks gestation, within 8 days of trial entry, and whose mothers had received at least three injections (0/27 steroid group and 7/32 placebo group; P=0·03), and there were also significantly fewer neonatal deaths (2/27 and 13/32, respectively; P<0·01) in this subgroup. Betamethasone did not provoke earlier delivery. Premature rupture of the membranes and maternal hypertension did not seem to contraindicate the use of steroids: there was no increase in maternal or neonatal sepsis nor in stillbirth in hypertensive pregnancies in the steroid group. Neonatal jaundice was significantly less frequent in the steroid (55/129) than in the placebo group (81/127; P<0·01) but not in the subgroups born before 34 completed weeks gestation.

The penetration of ceftazidime into bone was determined by measuring the volume of distribution of 14C-ceftazidime in infected and non-infected bone of adult mongrel dogs. The volume of distribution in non-infected cortical bone was 0.114 +/- 0.011 l/kg (mean +/- S.E.M.) and increased significantly in non-infected immature callus to 0.484 +/- 0.13 l/kg (P less than 0.05). In the presence of infection, the volume of distribution in non-infected cortical bone was 0.144 +/- 0.05 l/kg, and significantly higher in infected reactive cortical bone, 0.453 +/- 0.07 (P less than 0.05). We conclude that ceftazidime penetrates infected and non-infected bone and that this penetration is greater into immature bone.

This paper presents the results of adding the antibiotic cefuroxime to CMW bone cement in a group of patients undergoing total hip or knee replacement, in which the levels of cefuroxime were assayed in the blood, wound drainage fluid, urine and surplus bone cement.

100 patients with acute tracheitis, tracheobronchitis or bronchitis were randomly allocated to receive inhaled beclomethasone dipropionate (BDP) 100 micrograms qds or placebo as an adjunct to oral antihistamine and a tetracycline antibiotic. 2 patients were withdrawn from analysis, leaving 49 patients in each group. There was no evidence that inhaled BDP conferred any benefit or detriment on the progress of the condition as assessed by daily symptom scores and weekly clinic visits for up to 2 weeks. The same conclusion maintains when the patients were subdivided into two grades of severity as assessed by the physician when the patient first presented. Inhaled BDP would seem to have no role in the inflammatory process associated with those acute infections of presumed viral origins.

A randomized study was carried out in 396 patients requiring inhalation therapy for chronic obstructive lung disease to assess whether a modified, breath-activated device for drug delivery ('Rotahaler') was more effective than the current standard model in opening the hard gelatin cartridge containing the drug in powder form ('Rotacaps'). 'Rotacaps' packaged in two different ways, one specially designed to protect them against environmental changes, were also compared. Patients were asked to open 5 cartridges of each type with each of the two devices. The modified 'Rotahaler' failed to open only 0.7% of both types of 'Rotacaps' whereas the standard model failed to open 13.6% of the foil-packed type and 16.9% of those from a special polypropylene container. There was a statistically significant difference between the two 'Rotahaler' devices and between the two types of 'Rotacaps' in the standard device. More patients preferred the modified 'Rotahaler' (160) than the standard (75). The results did not depend upon age, sex, nationality of the patients or previous 'Rotahaler' experience. It is concluded that the modifications substantially improve the performance of the 'Rotahaler' and should make it easier for patients to use.

The extraction of ceftazidime has been measured in bone by means of the outflow dilution technique following injection into the perfused nutrient artery of the canine tibia. The instantaneous extraction was found to be 0.71 +/- 0.18 and the net extraction was 0.55 +/- 0.25 (mean +/- S.D. n = 5). The extraction of this antibiotic is relatively high and this experiment demonstrates the fact that antibiotics leave capillaries in bone and pass into the fluid spaces where they can act on pathogenic organisms.

Cefuroxime is a broad spectrum cephalosporin antibiotic. An intravenous injection of cefuroxime 1.5 g was administered to 25 patients after induction of anaesthesia for cholecystectomy. Concentrations of antibiotic were measured and the mean levels in microgram/ml found to be: serum 120.5, common bile duct bile 42.8, gallbladder bile 5.4, gallbladder wall 39.2. The drug levels exceeded the minimum inhibitory concentrations for most organisms commonly encountered in the biliary tract. There was no difference in cefuroxime levels in bile from functioning or non-functioning gallbladders. It is suggested that the diffusion of antibiotic into and out of the inflamed gallbladder is similar to that in abscesses and in experimental tissue cages. No side effects, toxicity or wound infections occurred.

A detailed pharmacokinetic study of cefuroxime has been carried out. Levels of cefuroxime were determined in the blood, sputum, saliva, and urine of 23 patients receiving parenteral cefuroxime eight hourly for chest infections. Profiles were obtained after the first dose and on the final (fifth) day of treatment. Antibiotic levels in the sputum reached 0.8 mg/l within one hour of the first injection, and were maintained close to this value for six hours. There was a build-up by the fifth day, mean cefuroxime concentrations at this time reaching 1.8 mg/l. This concentration was maintained for a prolonged period. Salivary concentrations were detectable but low (maximum mean value was 0.6 mg/l). Concentrations of antibiotic were significantly higher in the serum than those observed after the same doses in volunteers. In the patients there was no build-up in serum levels between the first and fifth days. The data obtained explain the clinical efficacy of cefuroxime in the treatment of lower respiratory infections, and suggest that a 12-hour schedule may be feasible.

300 patients undergoing various operations were randomly allocated to receive, intra-incisionally, just before skin suture, either a solution of 1 g cephaloridine or Polybactrin aerosol. An equal number of patients were allocated to each group, and various factors likely to influence the incidence of wound infections were evenly distributed. 13 wound infections (9.8%) developed in the cephaloridine group and 28 (20.1%) in the Polybactrin group (p less than 0.02). In the former group, the infections were milder and there were 44 fewer patient-days of hospitalisation. The difference in infection rates for 'potentially contaminated and contaminated' operations was greater (p less than 0.01), in favour of cephaloridine. Other differences are discussed and some reasons for the superiority of cephaloridine over other agents (e.g., povidone-iodine, ampicillin) are advanced.

Cefuroxime is a new parenteral antibiotic with a wider spectrum of activity than earlier cephalosporins and is particularly active against Haemophilus influenzae, including strains resistant to ampicillin due to beta-lactamase production. From 18 centres, 274 patients suffering with 275 infections were treated with cefuroxime sodium using the standard regimen of 750 mg 8-hourly by intramuscular injection. The clinical results showed a 90% success rate in the patients with bronchopneumonia (105), 91% in patients with post-operative pneumonia (74), and 89% in the patients with acute exacerbations of chronic bronchitis (96). Renal function was closely monitored during therapy, and no adverse changes attributable to cefuroxime therapy were seen in any patient, including those who also received frusemide. Two patients (0.7%) developed a rash, although 8 penicillin-allergic patients were treated without incident. From these studies, it can be concluded that 750 mg cefuroxime 8-hourly is effective in the treatment of lower respiratory tract infections. It is suggested that the attributes of this antibiotic may offer several advantages over existing therapies.

The sensitivities to cefuroxime and cephradine of potentially pathogenic bacteria isolated in two British general hospitals comprising 900 beds have been assessed. In a three-month period 2537 strains were studied; 30 microgram cefuroxime discs were used with 2511 strains, and cephradine discs of the same strength were used with 2525 strains. The organisms were also examined routinely for sensitivity to other antibiotics. Overall, 91.7% of the isolates were sensitive to cefuroxime and 85.8% were inhibited by cephradine, the differences in percentage strain susceptibility to cefuroxime and cephradine being mainly a result of the greater activity of cefuroxime against the Gram-negative bacteria. The wide antibacterial effectiveness of cefuroxime should make it a useful antibiotic for the treatment of serious infections including those conditions in which the causative organism has not been identified.

The properties ofcephaloridine, cephalexin, cefuroxime and cephalothin were examinedin vitro after the Incorporation of each of them with CMW Type 1 bone cement. When bathed in buffer at body temperature, cement containing cephaloridme, cefuroxime or cephalothin lost antibacterial activity after thirty-five to eighty-five days whereas with cephalexin there was still activity after 185 days. Antibiotic passed rapidly out of the cement into the buffer for two days after immersion, then more slowly for some weeks; a total of between 23 and 32 per cent of antibiotic in the cement was eventually recovered from the bathing fluid. Hand mixing ofdry antibiotic powder and cement powder resulted In an even distribution of the antibiotic, the mixture being stable when stored at 4 degrees Celsius. In a group of nine patients undergoing total hip replacement, 500 milligrams or 1 gram of cephaloridine was mixed with each packet ofSimplex cement. All the urine passed by the patients, and the drainage fluid removed from the wound for the first forty-eight hours after operation, were collected and the amount of cephaloridine was assayed. Urine was collected from some patients for up to fourteen days after operation. Cephaloridine gradually leached out ofthe cement in vivo, and was subsequently found in the urine and drainage fluid in generally similar amounts. Between 1.6 and 3.6 per cent of antibiotic implanted with the cement was recovered during the period ofstudy, most ofit during the first forty-eight hours after operation.

Cefuroxime, a new cephalosporin antibiotic which is stable to most β-lactamases produced by Gram-negative bacteria, was given by bolus intravenous injection to six volunteers in doses of 500 mg and 750 mg. The concentrations of cefuroxime in serum and urine were measured at pre-determined times after injection and the data analysed by a two-compartment open system model. A serum concentration of 8 µg/ml was exceeded for 100.3 min (±18.3) after a 500 mg dose and for 144.5 min (±19.8) after 750 mg. The ultimate serum half-life was 1.1 h. Excretion of cefuroxime in the urine was almost complete in 24 h, the clearance being 150 ml/min/1.73 m2. About 45% was excreted through the renal tubules. The injections were well tolerated and no changes in haematological or biochemical values were seen. The resulting data are compared with those published for some other cephalosporins. It is concluded that the favourable pharmacokinetics, especially the high concentrations of unbound cefuroxime in the serum, are likely to aid effective therapy of human infection caused by sensitive bacteria.