The serum concentrations of cephalothin were measured in nine patients with the various degree of renal impairment after administration of 4 g of cephalothin by intravenous injection or intravenous drip.
Five patients received a single 4 g of cephalothin by intravenous drip of two hours. Nearly same serum levels of cephalothin were obtained in the patients with creatinine clearance of 80 ml/min. and 37.5 ml/min. These serum half lives were 0.52 and 0.58 hours. Elevation of peak serum levels of cephalothin and prolongation of half lives were observed in the patients with creatinine clearance below 20 ml/min. Serum half lives of cephalothin were 1.31 hours in the patients with creatinine clearance of 18 ml/min., and 2.87 hours and 4.02 hours in two patients with below 10 ml/min. respectively.
Four patients received 4 g of cephalothin intravenously once a day for seven days. Serum cephalothin levels at 30 minutes after injection were 140-480 mcg/ml in the patient with GFR of 56.4 ml/min. and higher than 200 mcg/ml in three patients with creatinine clearance below 20 ml/min. Serum cephalothin concentrations at the time of next injection were about 1 mcg/ml in the patient with creatinine clearance of 11.2 ml/min. and 12-60 mcg/ml in two patients with below 10 ml/min., but not detectable in the patient with GFR of 56.4 ml/min.
Two patients with acute renal failure, one caused by acute pyelonephritis and the other by bacteremic shock of E. coli, were treated with daily 6 g of cephalothin. These infections were cured successfully without any side effect on recovery of renal failure.
We recommend the dosage of cephalothin for severe infections as follows : In the patients with moderately severe renal impairment should be administered the same dosage as in the normal. If creatinine clearance is about 20 ml/min., 4 g of cephalothin should be administered twice a day by intra-venous drip. If creatinine clearances are 10 to 20 ml/min. and below 10 ml/min., cephalothin should be administered 3 g twice and 4 g once a day intravenously, respectively.

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Bacteriological and clinical investigations have been performed on cefazolin (abbr. CEZ), a new anti-biotic of cephalosporin C family.
1) CEZ concentration in body fluids could be measured as more than 0.078 μg/ml by means of the thin-layer cylinder-plate method using B. subtilis PCI 219. Serum concentration of CEZ exhibited a peak of 20-26 μg/ml 1-2 hours after 500 mg of the antibiotic were injected intramuscularly, and the effective concentration of more than 0.5 μg/ml was maintained for longer than 8 hours. Urinary concentration of CEZ was measured simultaneously, and the value reached to 380-1, 200 μg/ml, recovery ratio being 48-68% within 16 hours. In the patient of renal insufficiency, however, the decline of blood concentration delayed, and the excretion ratio in urine tended to decrease. Biliary concentration of CEZ was 2. 7-20 μg/ml 2-5 hours after the intramuscular injection, and the transfer in bile appeared to be comparatively good.
2) CEZ sensitivity to various bacteria was measured by agar dilution method. Staphylococcus (except Methicillin-resistant strain), α-Streptococcus, β-Streptococcus, Pneumococcus, Corynebacterium diphtheriae, Neisseria gonorrhoeae and Neisseria meningitidis exhibited an extremely high sensitivity less than 1 μg/ml of MIC, while Hemophilus influenzae, E. coli, Klebsiella, Shigella and Salmonella a fair sensitivity less than 4 μg/ml of MIC. On the other hand, Enterococcus and Proteus-Providence demonstrated mostly a low sensitivity more than 17 μg/l of MIC, and Pseudomonas a resistance more than 142 μg/ml of MIC.
3) For the purpose of applying the CEZ sensitivity measurement method by a single disc method, the standard curves indicating the relationship between MIC and inhibitory diameter could be prepared respectively for the methods as follows : (a) conventional method by which an incubation is made overnight for 16 hours, (b) delayed assay by which a judgment is made after 24 hours, (c) rapid method by which a judgment is made 4 hours after 3-4 hours incubation with heavy inoculum, (d) rapid method by which a judgment is made 6 hours after 5-6 hours incubation similarly. In the case of Staphylococcus producing Cephalosporinase, however, an another judgment standard was supplemented necessarily, as the inhibition zone is more reduced with disc method than the MIC with dilution method.
4) Inactivating actions of Staphylococcus isolated from lesion ranged in order as Benzyl-penicillin> Cephaloridin>Cefazolin>Cephalexin.
5) CEZ presented a remarkable effectiveness in a case of bronchopneumonia due to Pneumococcus.

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