Cephazolin, the latest parenteral cephalosporin produced by substitution of heterocyclic groups on the 7-aminocephalosporanic acid (7-ACA) nucleus, became available for clinical use in the U.K. in 1974. Its history is traced from the original Sardinian mould (1945) through isolation of cephalosporin C (1953) and 7-ACA (1962) to its discovery (1969) and subsequent clinical use. Its mode of action is examined and its bactericidal nature confirmed. MICs of over 500 common pathogens are used to define its spectrum. The cut-off point for sensitivity and resistance is taken as 20 mg. per l. With 30 μg. discs zone sizes ≤ 14 mm. indicate resistance. The clinical relevance of MICs and attainable serum and urine levels is examined by relating them to clinical response in 12 patients. A disc study compares cephazolin with 4 other available cephalosporins, namely cephaloridine, cephalothin, cephalexin and cephradine. Many major discrepancies indicate that they are not interchangeable. The laboratory and clinical implications are discussed, including the need for local policy decisions regarding choice of preparation. The change from a parenteral to an oral form should be preceded by a sensitivity test against the causal organism. The validity of using a single representative disc is questioned and the use of phrases such as ‘sensitive to the cephalosporins’ deprecated. Cephazolin is potent, broad-spectrum and bactericidal and is potentially life-saving in serious hospital infections. The cephalosporins rival the aminoglycosides as ‘best-guess’ primary choice and are preferable in pregnancy, the puerperium and in pulmonary infections. Within the group cephazolin will seriously challenge or even oust cephaloridine and cephalothin.

The new aminoglycoside antibiotic, tobramycin, was used for treatment of gram-negative and staphylococcal infection in 38 neonates, infants, and children in a pediatric surgical unit. Levels of drug in serum after administration by intramuscular, intravenous, and intraperitoneal routes were monitored, and control of infections was generally good within the therapeutic range of 2.0-10.0 mug/ml with a standard dosage regimen of approximately 5 mg/kg per day. Impairment of renal function and concurrent lincomycin therapy were important factors causing variation of levels in serum outside this range. Levels of tobramycin in cerebrospinal fluid after intraventricular instillation varied greatly in one patient, but were satisfactory in another. Clinical and bacteriological assessment of results indicated only two failures of treatment, although infection with a known resistant organism supervened in three cases. Screening for renal, hepatic, and hematological toxicity revealed only one case of transient and reversible renal impairment. Response to tobramycin therapy was generally rapid and satisfactory in a group of young patients with moderately severe infections, many of which were complicated by the presence of a congenital anomaly.

The susceptibilities of various clinical isolates to tobramycin were studied, and the applicability of these data to clinical situations was evaluated. The bactericidal nature of tobramycin was confirmed by killing curves, and the minimal inhibitory concentrations for 500 common pathogens were used to define its spectrum. Isolates inhibited by less than or equal to 5 mug/ml were considered to be sensitive to tobramycin. The clinical response of some patients was examined in relation to the minimal inhibitory concentration for the infecting organism and the serum and urine levels of tobramycin. The activity of tobramycin was compared with that of gentamicin against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Tobramycin was at least twice as active as gentamicin against P. aeruginosa. The effectiveness of tobramycin against S. aureus and E. coli was compared with that of other commonly used antibiotics, and its clinical role as an alternative to gentamicin in the "best guess" treatment of septicemia was considered. Lincomycin is often added to counter the ineffectiveness of tobramycin against streptococci and anaerobes such as Bacteroides species, but this combination was antagonistic against E. coli when tested in vitro by the checkerboard technique and its graphical display, the isobologram. Tobramycin was essentially similar to gentamicin in laboratory characteristics and clinical application but was more active against P. aeruginosa in general and against gentamicin-resistant strains in particular.

No abstract