William Kirby

A highly potent penicillin inactivator has been extracted from 7 strains of Staph. aureus (coagulase positive), all of which were naturally penicillin resistant. No such inhibitor was present in extracts of 7 penicillin sensitive strains of Staph. aureus.

OBJECTIVE To investigate the efficacy, safety, and tolerability of oral semaglutide added to insulin with or without metformin. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes uncontrolled on insulin with or without metformin were randomized to oral semaglutide 3 mg (N = 184), 7 mg (N = 182), or 14 mg (N = 181) or to placebo (N = 184) in a 52-week, double-blind trial. End points were change from baseline to week 26 in HbA1c (primary) and body weight (confirmatory secondary). Two estimands were defined: treatment policy (effect regardless of trial product discontinuation or rescue medication) and trial product (effect assuming trial product continuation without rescue medication) in randomized patients. RESULTS Oral semaglutide was superior to placebo in reducing HbA1c (estimated treatment difference [ETD] –0.5% [95% CI –0.7, –0.3], –0.9% [–1.1, –0.7], and –1.2% [–1.4, –1.0] for 3, 7, and 14 mg, respectively; P < 0.001) and body weight (ETD −0.9 kg [95% CI −1.8, −0.0], −2.0 kg [−3.0, −1.0], and −3.3 kg [−4.2, −2.3]; P = 0.0392 for 3 mg, P ≤ 0.0001 for 7 and 14 mg) at week 26 (treatment policy estimand). Significantly greater dose-dependent HbA1c and body weight reductions versus placebo were achieved with oral semaglutide at weeks 26 and 52 (both estimands). The most frequent adverse event with oral semaglutide was nausea (11.4–23.2% of patients vs. 7.1% with placebo; mostly mild to moderate). CONCLUSIONS Oral semaglutide was superior to placebo in reducing HbA1c and body weight when added to insulin with or without metformin in patients with type 2 diabetes. The safety profile was consistent with other glucagon-like peptide 1 receptor agonists.

BACKGROUND: Hepatitis B virus infection remains an important public health problem in the United States. Currently approved alum-adjuvanted vaccines require three doses and have reduced immunogenicity in adults, particularly in those who have diabetes mellitus, or are older, male, obese, or who smoke. METHODS: Phase 3 observer-blinded, randomized (2:1 HBsAg-1018 [HEPLISAV-B™]:HBsAg-Eng [Engerix-B®]), active-controlled trial in adults 18-70 years of age. HBsAg-1018 was administered intramuscularly at weeks 0 and 4 and placebo at week 24 and HBsAg-Eng at weeks 0, 4, and 24. The primary immunogenicity endpoint assessed the noninferiority of the seroprotection rate at week 28 in participants with type 2 diabetes mellitus. Secondary endpoints included seroprotection rates in the total trial population and by age, sex, body mass index, and smoking status. RESULTS: Among 8374 participants randomized, 961 participants in the per-protocol population had type 2 diabetes mellitus. In diabetes participants, the seroprotection rate in the HBsAg-1018 group at week 28 was 90.0%, compared with 65.1% in the HBsAg-Eng group, with a difference of 24.9% (95% CI: 19.3%, 30.7%), which met the prospectively-defined criteria for noninferiority and statistical significance. In the total study per-protocol population (N = 6826) and each pre-specified subpopulation, the seroprotection rate in the HBsAg-1018 group was statistically significantly higher than in the HBsAg-Eng group. CONCLUSION: Two doses of HBsAg-1018, administered over 4 weeks, induced significantly higher seroprotection rates than three doses of HBsAg-Eng, given over 24 weeks, in adults with factors known to reduce the immune response to hepatitis B vaccines as well as in those without those factors. With fewer doses in a shorter time, and greater immunogenicity, HBsAg-1018 has the potential to significantly improve protection against hepatitis B in adults at risk for hepatitis B infection. Trial Registration clinicaltrials.gov Identifier: NCT02117934.

The pharmacokinetics of cefazolin were compared with those of cephaloridine, cephalothin, cephalexin, and cephanone in healthy adult male volunteers. The concentration of cefazolin in serum was twice as high after im and iv injections as that of cephaloridine, and four times as high as that of cephalothin. An iv infusion of 0.5 g of cefazolin during a period of 20 min gave a peak level in blood of 118 μg/ml, as compared with 70 μg/ml ml after a l-g dose of cephalothin. Higher levels in blood persisted for more than 8 hr with the former as compared with only about 2 hr with the latter. Half lives in serum were 1.8, 1.1, and 0.5 hr for cefazolin, cephaloridine, and cephalothin, respectively. Lower renal clearance of cefazolin (64 mllmin per 1.73 m2) as compared with values of 125 and 274 for cephaloridine and cephalothin, was the factor mainly responsible for its higher and more prolonged levels in blood. Renal clearance of cefazolin was essentially the same as its serum clearance, and almost 100% of the dose administered was recovered in the urine within 24 hr. Features that might offset, to some extent, these favorable characteristics of cefazolin are its high rate of binding to protein (86%) and its small apparent volume of distribution (10 liter/l.73 m2).

The binding of four aminoglycoside antibiotics by human serum was investigated under controlled conditions of physiological pH and temperature, by means of an ultrafiltration technique. No serum binding was demonstrable for gentamicin, tobramycin, or kanamycin, whereas streptomycin was 35% bound. Previous conflicting studies are discussed, and some of the pharmacological implications are considered.