[a]. D Stewart, at al. Azlocillin: in vitro studies of a new semisynthetic penicillin. Antimicrob Agents Chemother. 1977 May;11(5):865-70.

Intro:

Azlocillin: in vitro studies of a new semisynthetic penicillin

Antimicrob Agents Chemother. 1977 May;11(5):865-70. doi: 10.1128/AAC.11.5.865.

D Stewart,  G P Bodey

PMID: 18083 DOI: 10.1128/AAC.11.5.865

Abstract

The activity of azlocillin, a new semisynthetic penicillin, was determined against 582 clinical isolates of gram-negative bacilli and gram-positive cocci. Over 75% of the isolates of Pseudomonas aeruginosa were inhibited at a concentration of 12.5 mug or less per ml. Azlocillin is also active against indole-negative and -positive Proteus spp., inhibiting 98 and 71%, respectively, at a concentration of 12.5 mug or less per ml. Isolates of Klebsiella spp. and Enterobacter spp. showed less susceptibility than isolates of Escherichia coli and Serratia spp. Gram-positive cocci except penicillin G-resistant Staphylococcus aureus were susceptible to azlocillin. Azlocillin failed to inhibit the growth of gram-negative bacilli when large inocula were used. It was more active in alkaline pH, but the type of medium used had little effect on its activity. Azlocillin was more active than mezlocillin, ticarcillin, and carbenicillin and as active as BLP-1654 against isolates of P. aeruginosa. It was not as active as mezlocillin against the majority of the other gram-negative bacilli.

[b]. S H Zinner, et al. In vitro and in vivo studies of three antibiotic combinations against gram-negative bacteria and Staphylococcus aureus. Antimicrob Agents Chemother. 1981 Oct;20(4):463-9.

Intro:

In vitro and in vivo studies of three antibiotic combinations against gram-negative bacteria and Staphylococcus aureus

Antimicrob Agents Chemother. 1981 Oct;20(4):463-9. doi: 10.1128/AAC.20.4.463.

S H Zinner,  J Klastersky,  H Gaya,  C Bernard,  J C Ryff

PMID: 6282192 DOI: 10.1128/AAC.20.4.463

Abstract

The activities of azlocillin, cefotaxime, and amikacin alone and in combination were evaluated in in vitro checkerboard studies, in infected neutropenic mice, and in human volunteers. The combination of cefotaxime plus amikacin was more synergistic in vitro than the Others against the Enterobacteriaceae tested, and the combination of azlocillin plus amikacin was more synergistic against Pseudomonas aeruginosa and Staphylococcus aureus. Survival of neutropenic mice infected with Escherichia coli and Klebsiella pneumoniae, respectively, was greater with azlocillin plus amikacin (24 of 40 and 11 of 40) and with cefotaxime plus amikacin (21 of 40 and 17 of 40) than with azlocillin plus cefotaxime (22 of 40 and 3 of 40; P less than 0.05). Median serum bactericidal activity in volunteers receiving these Antibiotics alone and in combination was greater than or equal to 1:8 with most agents and with all combinations tested against 10 strains each of E. coli, K. pneumoniae, P. aeruginosa, and S. aureus. These data suggest that clinical trials with combinations of azlocillin or cefotaxime plus amikacin deserve further study in febrile neutropenic patients.

[c]. Jennifer L Weisman, et al. Searching for new antimalarial therapeutics amongst known drugs. Chem Biol Drug Des. 2006 Jun;67(6):409-16.

Intro:

Searching for new antimalarial therapeutics amongst known drugs

Chem Biol Drug Des. 2006 Jun;67(6):409-16. doi: 10.1111/j.1747-0285.2006.00391.x.

Jennifer L Weisman 1,  Ally P Liou,  Anang A Shelat,  Fred E Cohen,  R Kiplin Guy,  Joseph L DeRisi

Affiliations collapse

Affiliation

1Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158-2542, USA.

PMID: 16882315 DOI: 10.1111/j.1747-0285.2006.00391.x

Abstract

The need to discover and develop new antimalarial therapeutics is overwhelming. The annual mortality attributed to malaria, currently approximately 2.5 million, is increasing due primarily to widespread resistance to currently used drugs. One strategy to identify new treatment alternatives for malaria is to examine libraries of diverse compounds for the possible identification of novel scaffolds. Beginning with libraries of drug or drug-like compounds is an ideal starting point because, in the case of approved drugs, substantial pharmacokinetic and toxicologic data should be available for each compound series. We have employed a high-throughput screen of the MicroSource Spectrum and Killer Collections, a library of known drugs, bioactive compounds, and Natural Products. Our screening assay identifies compounds that inhibit growth of Plasmodium falciparum cultured in human erythrocytes. We have identified 36 novel inhibitors of P. falciparum, of which 19 are therapeutics, and five of these drugs exhibit effective 50% inhibitory concentrations within similar ranges to therapeutic serum concentrations for their recently indicated uses: propafenone, thioridazine, chlorprothixene, perhexiline, and azlocillin. The findings we report here indicate that this is an effective strategy to identify novel scaffolds and therefore aid in antimalarial drug discovery efforts.