In a single-blinded study, two groups of 10 healthy subjects were given cephapirin or cephalothin by continuous intravenous infusion for 5 days, 0.5 g every 6 hr for the first day and then 1.0 g every 6 hr for 4 days. Eight of the cephalothin subjects and two of the cephapirin subjects developed phlebitis. Phlebitis was more severe in the cephalothin group and developed more rapidly, necessitating vein changes six times more often than in the cephapirin group. The less irritating properties of cephapirin demonstrated in this study indicate it may be the more useful cephalosporin analogue for intravenous therapy.Of the two parenteral cephalosporins available, cephalothin is usually preferred for the treatment of infections requiring high intravenous doses because cephaloridine in doses over 2 g daily may be nephrotoxic (Loridine® package insert, Eli Lilly & Co.). The incidence of phlebitis with cephalothin, however, has been reported to be as high as 50%, depending on dosage and technique (5-8). The manufacturer's package insert recommends alternating veins or adding hydrocortisone to solutions containing more than 4 g of cephalothin to reduce the incidence of thrombophlebitis.Cephapirin sodium, a new cephalosporanic acid derivative, shows evidence of being perhaps less chemically irritating than cephalothin (la, 2, 4) while having essentially the same spectrum and level of antibacterial activity (1-3). In the course of studying systemic tolerance to cephapirin, we took the opportunity to determine also the local tolerance of this drug relative to that of cephalothin by giving the drugs in identical fashion by continuous intravenous infusion. For the first 24 hr, 0.5-g amounts of the drugs in 250 ml of normal saline were infused over each 6-hr period; then the dosage was raised to 1.0 g in 250 ml every 6 hr for the remaining 4 days. During each 6-hr period, flow rates were kept as uniform as possible. To simulate the clinical situation, 21-gauge needles and an intravenous infusion apparatus commonly used in hospitals (Metriset) were employed. MATERIALS AND METHODSThe physician in residence at the institution started all infusions and kept them going at a constant rate around the clock for 5 days with the aid of technicians. He examined infusion sites at least once every day and graded phlebitis as absent, mild, moderate, or severe, depending on the degree of any swelling, redness, tenderness, discoloration, induration, or sclerosing of veins. The subject's comments regarding pain or discomfort were elicited without the use of leading questions. The physician decided when infusion sites should be changed.Because cephapirin went into solution more rapidly on reconstitution and was usually a darker color than cephalothin, it was not possible to blind the physician and paramedical staff as to drug identity. Subjects, however, were kept unaware of which drug they were receiving, and care was taken not to influence their subjective reactions during the study.

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Case records of 1,098 patients treated with amikacin at 79 research centers in 10 countries in a program of worldwide clinical trials were reviewed. Of the 697 patients eligible for use in evaluation of efficacy of the drug, 81% were cured, as evidenced by clinical remission and eradication of the infecting pathogen. The usual dosage was 7.5 mg/kg administered intramuscularly at 12-hr intervals. This dosage was modified in patients with renal impairment. Amikacin was effective in 90% of 322 patients with genitourinary infections, 85% of 97 patients with septicemia, 70% of 73 patients with infections of skin, soft tissue, or bone (excluding burns), and 69% of 68 patients with infections of the lower respiratory tract. Amikacin was effective in treatment of 88% of 85 infections due to gentamicin-resistant pathogens. The drug was generally well tolerated, and no side effects were reported in 80.6% of the 1,098 patients evaluated. Amikacin shares with other aminoglycosides the risk of ototoxicity and nephtotoxicity; previous exposure to gentamicin was a major factor in the development of such adverse effects. Other adverse reactions were relatively infrequent and in most cases were characterized as mild and transient.

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From the results from over 150 clinical trials of netilmicin 3376 completed patient treatment courses have been reviewed to assess its efficacy and safety. Fourteen-hundred and twenty-three patients with 2273 infections caused by 2322 pathogens were evaluable for treatment efficacy. Favourable clinical responses were observed in 90% of the infections treated. Eighty-three per cent of the causative pathogens were eliminated from the infection sites. Netilmicin's safety was evaluated in all patients. Nephrotoxicity considered to be probably netilmicin-related occurred in 1.7% of the patients, and was possibly related in an additional 5.2%. Auditory toxicity was probably netilmicin-related in 1.6% and possibly related in 1.9% of the patients. Vestibular toxicity, probably or possibly drug-related, was observed in 0.62% of the patients. Extensive clinical trials with netilmicin have confirmed its excellent efficacy and safety profile.