in Seattle, on a standardized single-disk method for antibiotic susceptibility testing ".. . consolidate(s) and update(s) previous descriptions of the method and provide(s) a concise outline for its performance and interpretation." Clinical microbiologists were relieved that finally a disk diffusion method had been standardized, could be used with ease, and provided reliable results as compared with minimum inhibitory concentration tests. The pivotal role of Hans Ericsson's theoretical and practical studies (H. Ericsson and G. Svartz-Malmberg, Antibiot. Chemother. 6:41-74, 1959), as well as earlier reports by some of the authors of the publications cited, must be mentioned as a matter of fairness. Most of the recommendations given are still valid today even though some of the antimicrobial agents are obsolete, new ones have been added, some zone sizes had to be modified, and new media were designed for Haemophilus influenzae and Neisseria gonorrhoeae. Recommendations of the National Committee for Clinical Laboratory Standards continue to be based on this publication; the "Kirby-Bauer" method is, among the many disk methods used in other countries, still the one that has been researched most thoroughly and updated continuously.

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.

Variational quantum algorithms are promising applications of noisy intermediate-scale quantum (NISQ) computers. These algorithms consist of a number of separate prepare-and-measure experiments that estimate terms in a Hamiltonian. The number of terms can become overwhelmingly large for problems at the scale of NISQ hardware that may soon be available. We use unitary partitioning (developed independently by Izmaylov et al. [J. Chem. Theory Comput. 16, 190 (2020)]) to define variational quantum eigensolver procedures in which additional unitary operations are appended to the ansatz preparation to reduce the number of terms. This approach may be scaled to use all coherent resources available after ansatz preparation. We also study the use of asymmetric qubitization to implement the additional coherent operations with lower circuit depth. Using this technique, we find a constant factor speedup for lattice and random Pauli Hamiltonians. For electronic structure Hamiltonians, we prove that linear term reduction with respect to the number of orbitals, which has been previously observed in numerical studies, is always achievable. For systems represented on 10-30 qubits, we find that there is a reduction in the number of terms by approximately an order of magnitude. Applied to the plane-wave dual-basis representation of fermionic Hamiltonians, however, unitary partitioning offers only a constant factor reduction. Finally, we show that noncontextual Hamiltonians may be reduced to effective commuting Hamiltonians using unitary partitioning.

accurate method for antibiotic assay of clinical specimens. Appl. Microbiol. 14:170-177. 1966.-Large glass plates are used for this modified agar-well diffusion assay method, allowing up to 81 replications on a single plate. With a specially designed agar punch, it is possible to prepare the small agar wells very quickly. The saving in serum resulting from fewer replications of standards with the large plates, and the small volume of the agar wells, makes it economically feasible to use pooled human serum for the standard antibiotic solutions. Methods are described for preparing the standard solutions, and for providing controls for the deterioration of standards and unknowns. Procedures for preparing and maintaining the commonly used assay organisms are presented. Serum specimens are tested directly rather than diluting them to a narrow range of antibiotic concentrations. This is possible because of a procedure for calculations that recognizes the curvilinear relationship between zone sizes and antibiotic concentrations. Adaptation of this method to a number of the commonly used antibiotics is described. With this method, it has been possible to test large numbers of clinical specimens in a minimal time, and with accuracy consistently better than 10%.

Ampicillin and amoxicillin (a-amino-p-hydroxybenzyl penicillin) were administered orally in 500-mg doses to eight fasting volunteers in a comparative study in which pharmacokinetic techniques were used. The absorption of amoxicillin was significantly better, as demonstrated by a higher mean peak serum concentration of 7.6 Ag/ml as compared to 3.2 ,ug/ml for ampicillin, an average "area under the curve"that was approximately double that of ampicillin, and an 8-hr urinary recovery for amoxicillin of 60% as compared to 34% for ampicillin. Serum half-lives were the same for the two antibiotics, with values of 60.3 (±3.3) min for ampicillin and 61.3 (±5.6) min for amoxicillin. The latter drug gave measurable concentrations in the blood at 8 hr in all of eight volunteers, as compared to only three of eight with ampicillin.Amoxicillin (BRL-2333, a-amino-p-hydroxybenzyl penicillin) is a semisynthetic penicillin that is comparable to ampicillin in antibacterial spectrum and in vitro activity but yields higher concentrations in the blood after equivalent oral doses (3,(16)(17)(18). Neu and Winsheil reported an average peak concentration in serum of 7.6 ,g/ml after oral administration of 500 mg of amoxicillin to volunteers, as compared to 3.8 Aug/ml for ampicillin (17). Considerably higher peak blood concentrations, 10.8 ,g/ml for amoxicillin and 6.3 ,ug/ml for ampicillin, were found with the same doses in another study (3). Further, only a 20% difference in the urinary recovery of the two agents was noted in one of the studies, as compared with 37% in the other (3,17). Peak serum concentrations of ampicillin attained after 500 mg orally as reported in the literature have ranged from 1.5 to 6.3 jAg/ml (2, 3,8,[13][14][15]17). Because of these inconsistencies and the desire to get more complete information regarding the precise pharmacokinetics of these two ampicillins, including the comparative half-lives, the present study was carried out. MATERIALS AND METHODSEight healthy adult male volunteers received two 250-mg capsules of amoxicillin and of commercially available ampicillin (Beecham Pharmaceuticals) in crossover fashion, with an interval of 7 days or more between the two parts of the study. The volunteers reported to the laboratory after an overnight fast and were instructed to empty their bladders. They were then given the antibiotic capsules with 100 ml of water, and were allowed no food during the first 3 hr of the experiment. Blood samples taken at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 hr, and samples of urine collected between 0 to 4 and 4 to 8 hr, were assayed for antibiotic content by use of a previously described agar-well diffusion technique, with Bacillus stubtilis as the test organism (1). Appropriate standards were prepared in pooled human serum and urine on the morning of each study, with the use of antibiotic powders provided by Beecham Research Laboratories. Specimens and standards were frozen at -20 C, and all assays were carried out within a few days of collection of the samples.The serum levels of...

No abstract

temperature by use of an ultrafiltration method previously described (3). The concentrations of antibiotics used were those commonly found in the blood during therapy: 5 ,g/ml for gentamicin and tobramycin, S and 15 Ajg/ml for kanamycin, and 15 ,ug/ml for streptomycin. Pooled serum from healthy donors containing the antibiotic under study was adjusted to a pH of 7.4 to 7.5 by bubbling 5.0% CO2 through it. Then 15.4 ml of this 97% serum solution was put in the upper of two glass chambers, which were clamped tightly with a single layer of cellophane membrane (Union Carbide Corp., Dialysis Membrane 1-7u) between them. Ultrafiltration was carried out in an incubator at 37 C by the application of a vacuum to the lower chamber, and yielded 0.8 ml of filtrate within 45 min. By removing 1.0 ml from the upper chamber when 0.4 ml of filtrate had been collected, a midpoint specimen was available for antibiotic assay which corresponded to 100% serum because of the loss of water during filtration. The concentrations of antibiotic in this midpoint serum specimen, and in the protein-free ultrafiltrate, were determined by use of an agar well assay method with Bacillus subtilis ATCC 6633 as the test organism (2). Appropriate standard curves for the microbiological assay were prepared by dissolving known amounts of the antibiotic standards in fresh, pooled human serum and in antibiotic-free filtrate obtained by filtration of pooled serum. Impermeability of the cellophane membrane as a cause of apparent protein binding was investigated by ultrafiltration of buffered saline solutions of the antibiotics (6). The antibiotic standards used in these studies and their suppliers were gentamicin (Schering Corp.), tobramycin (Eli Lilly & Co.), kanamycin (Bristol Laboratories), and streptomycin (Canalco). RESULTSPercent binding was calculated by dividing the difference between the antibiotic concentrations in the serum and filtrate specimens by the serum concentration and multiplying by 100 (3). The numbers of separate ultrafiltrations performed and averaged were 9 for gentamicin, 8 for tobramycin, 12 for kanamycin at 5 Ag/ml, 6 for kanamycin at 15 ,ug/ml, and 6 for streptomycin. These ultrafiltration experiments with gentamicin and tobramycin in 100% human serum demonstrated no evidence of protein binding, with mean values of -2.0 and -2.1%, respectively (Table 1). Kanamycin experiments yielded values of +2.8% at 5,ug/ml and -0.7% at 15,ug/ml, whereas streptomycin was 35.4% bound at a serum concentration of 15,ug/ml. Membrane trapping as a cause of apparent protein binding was found to be negligible (retention <3.

Fosfomycin, an antibiotic discovered in Spain, has a unique chemical structure and pharmacologic features that are promising for clinical therapy. It is only partially absorbed orally, with relatively low blood levels. Intramuscularly, however, absorption is complete with peak blood levels 3–5 times as high as orally, and rapid intravenous injections give serum concentrations almost twice as high as intramuscularly. Some accumulation occurs with all three routes, and concentrations in excess of 1,000 μg/ml are consistently obtained in the urine with parenteral doses every 6 h. The serum half-life is 1.5–2 h, urinary excretion is by glomerular filtration, the antibiotic is not bound to serum proteins, and the volume of distribution is large. Diffusion into tissues and body fluids is good. Thus, the pharmacologic characteristics of fosfomycin along with its low toxicity make it comparable in these respects to other well-established antibiotics.