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Biomedical subjects

C S Lewin

Publications and source records attributed to C S Lewin.

At least 37 records · Page 2Linked to original sources
PubMed1990

Assessment of the interaction between ciprofloxacin and teicoplanin in vitro and in neutropenic patients.

The interactions of ciprofloxacin and teicoplanin were investigated against methicillin-sensitive and methicillin-resistant Staphylococcus aureus and Staph. epidermidis isolated during a clinical trial of the efficacy of this combination. In-vitro studies of the combination of ciprofloxacin and teicoplanin found no evidence of any antagonism between these two drugs in terms of inhibition of bacterial multiplication, as determined by Fractional Inhibitory Concentration Indices, and lethality. Clinical use of teicoplanin plus ciprofloxacin as empirical therapy in 29 febrile neutropenic patients revealed an overall response rate of 75%. Response rate for staphylococcal infections, which accounted for 53% of isolated pathogens, was 80%. No serious adverse drug reactions were seen. Our results show that both in vitro, and in the treatment of febrile neutropenic patients, teicoplanin plus ciprofloxacin is an effective anti-staphylococcal combination.

Adult↗
PubMed1990

DNA breakdown by the 4-quinolones and its significance.

DNA breakdown occurred in Escherichia coli KL16 exposed to nalidixic acid, ciprofloxacin or norfloxacin. However DNA breakdown does not seem to be the cause of the lethality of the 4-quinolones because it still occurred under conditions which abolished the lethality of nalidixic acid. Furthermore, no correlation was found between the amount of DNA breakdown and the rate of death of bacteria caused by the three 4-quinolones. Similarly, DNA breakdown did not occur when recB or recC mutants were treated with nalidixic acid despite both mutants being killed by the drug, again suggesting that DNA breakdown is not the cause of bacterial death. Since recB and recC mutants lack exonuclease V, this enzyme may be responsible for the DNA breakdown observed in bacteria treated with 4-quinolones.

Ciprofloxacin↗
PubMed1990

Conditions required for the bactericidal activity of fleroxacin and pefloxacin against Escherichia coli KL 16.

Pefloxacin and fleroxacin showed biphasic bactericidal activity against Escherichia coli KL16 in nutrient broth. Bacteriostatic concentrations of chloramphenicol, an inhibitor of protein synthesis, and rifampicin, an inhibitor of RNA synthesis, could not completely abolish the bactericidal activity of either drug. Pefloxacin and fleroxacin were also active against non-dividing E. coli KL16. Therefore, pefloxacin and fleroxacin are able to kill bacteria which are not dividing nor actively synthesising protein or RNA.

Anti-Infective Agents↗
PubMed1990

Conditions required for the bactericidal activity of 4-quinolones against Serratia marcescens.

The conditions required to kill Serratia marcescens with nalidixic acid, ciprofloxacin, norfloxacin or ofloxacin were determined in nutrient broth and in phosphate-buffered saline. They were found to be similar to the conditions required for these 4-quinolones to kill Escherichia coli. Bacterial RNA synthesis and bacterial cell division were essential for the bactericidal activity of nalidixic acid but all three fluoroquinolones were bactericidal against non-dividing S. marcescens. However, as with E. coli, bacterial RNA synthesis was essential for the bactericidal activity of norfloxacin though this was not required to kill S. marcescens with ciprofloxacin or ofloxacin.

Anti-Bacterial Agents↗
PubMed1990

Bactericidal action of PD127,391, an enhanced spectrum quinolone.

The 4-quinolone PD127,391 displays a biphasic effect on Escherichia coli, Staphylococcus aureus and S. epidermidis in nutrient broth. It is as active as ciprofloxacin in terms of its optimum bactericidal concentration against E. coli. However, against staphylococci it is six times as active as ciprofloxacin or any other 4-quinolone previously investigated. Although protein and RNA synthesis are not required for bactericidal activity, cell division is essential.

4-Quinolones↗
PubMed1990

Antibacterial activity of fluoroquinolones in combination with zidovudine.

Since patients with AIDS may receive fluoroquinolones concurrently with zidovudine, the antibacterial interaction of these drugs was investigated. No evidence was found of antagonism between zidovudine and ciprofloxacin, DR-3355, enoxacin, lomefloxacin or ofloxacin against enterobacteria, staphylococci or Pseudomonas aeruginosa. Furthermore, the bactericidal activity of the fluoroquinolones against selected enterobacteria in nutrient broth was not affected by a clinically achievable concentration of zidovudine. It seems unlikely that zidovudine will have an adverse effect on the antibacterial activity of the fluoroquinolones in patients with AIDS.

Anti-Infective Agents↗
PubMed1990

Mechanisms of zidovudine resistance in bacteria.

Unlike their parent strains, zidovudine-resistant derivatives of Escherichia coli KL16 and Salmonella typhimurium NCTC 5710 were found to be incapable of incorporating radiolabelled thymidine into their chromosomal DNA. Since incorporation was still prevented in the presence of EDTA, resistance to zidovudine was not associated with a permeability barrier, but appeared to result from the loss of thymidine kinase activity, required for the phosphorylation of zidovudine. Pseudomonas aeruginosa, which is intrinsically zidovudine-resistant, was also shown to be incapable of incorporating thymidine into its DNA, but Staphylococcus epidermidis SK360 and Staph. aureus E3T, which are also intrinsically zidovudine-resistant, possessed thymidine kinase activity. This suggests that two distinct mechanisms of resistance to zidovudine exist in bacteria. Zidovudine resistance did not appear to confer resistance to other antibacterial agents.

DNA, Bacterial↗
PubMed1990

Isolation of zidovudine resistant Escherichia coli from AIDS patients.

Zidovudine-resistant Escherichia coli were isolated from faecal samples from 6 out of 11 AIDS patients receiving zidovudine. Resistance appeared to be due to the loss of thymidine kinase activity which is required for the phosphorylation of zidovudine to its active form. No zidovudine resistant enterobacteria were isolated from 30 control faecal samples. Hence, clinically, there appeared to be a high correlation between the development of zidovudine-resistance in E. coli and exposure to zidovudine (chi 2: 11.77, P less than 0.001). However the development of zidovudine resistance does not appear to be associated with cross-resistance to other antimicrobial agents as the zidovudine-resistant E. coli did not display a high degree of resistance to other antibacterials.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Susceptibility of bacterial isolates from AIDS patients to six fluoroquinolones.

The susceptibilities to ciprofloxacin, DR-3355 (S-(-)-ofloxacin), enoxacin, lomefloxacin, ofloxacin and PD127,391 of 69 significant bacterial isolates from HIV-positive patients at the City Hospital, Edinburgh have been determined. With the exception of the enterococci, most of the strains tested (including staphylococci, Escherichia coli and Pseudomonas aeruginosa) were susceptible to the fluoroquinolones. Ciprofloxacin was the most active of the clinically available drugs followed by ofloxacin, lomefloxacin and enoxacin. PD127,391 and DR-3355, the new fluoroquinolones tested, were at least as active as ciprofloxacin. Hence bacterial infections in AIDS patients should respond to fluoroquinolone therapy.

4-Quinolones↗
PubMed1990

In vitro activities of 4-quinolones against the fish pathogen Aeromonas salmonicida.

The activities of five fluorinated 4-quinolones, namely, sarafloxacin, enrofloxacin, PD127391, PD117596, and CI934, against the fish pathogen Aeromonas salmonicida were investigated and compared with that of oxolinic acid. The results indicated that with the exception of CI934, these drugs are more active than oxolinic acid in terms of MIC. No inoculum effect was observed, but the drugs were less active at 10 degrees C than at 22 degrees C. The presence of 3% of NaCl caused an increase in drug activity. Resistance to the drugs appeared to be fairly stable, with only a small decrease in activity after 10 successive passages of the test strains on drug-free tryptone soya agar.

Aeromonas↗
PubMed1989

Bactericidal activity of enoxacin and lomefloxacin against Escherichia coli KL16.

Enoxacin and lomefloxacin were found to display a biphasic response when their bactericidal activities were investigated against Escherichia coli KL16 in nutrient broth. Although enoxacin required bacterial protein and RNA synthesis to exert bactericidal activity, it was able to kill non-dividing bacteria. On the other hand, the protein synthesis inhibitor chloramphenicol and the RNA synthesis inhibitor rifampicin did not abolish enoxacin's killing activity against Escherichia coli KL16 in nutrient broth. Lomefloxacin was also shown to be active against non-dividing Escherichia coli KL16.

Anti-Infective Agents↗
PubMed1989

Conditions required for the antibacterial activity of zidovudine.

In a study to determine the conditions required for its antibacterial activity, zidovudine was found to be bactericidal against Escherichia coli and Salmonella typhimurium in nutrient broth over 6 h. Zidovudine was also found to be active against ten clinical isolates of Salmonella and Escherichia coli at 1 mg/l, which is a clinically achievable concentration of the drug. Bacterial protein synthesis was required for the bactericidal activity of zidovudine against both Escherichia coli and Salmonella typhimurium. Zidovudine was found to be inactive against non-dividing bacteria, as it was unable to kill bacteria of either species when they were suspended in PBS.

Bacteria↗
PubMed1989

4-quinolones and the SOS response.

The SOS DNA repair system is induced in bacteria treated with 4-quinolones. However, whether the response exacerbates or repairs the damage caused by these drugs is still unclear. The recA13 and the recB21 mutations impair recombination repair and render bacteria unable to induce the SOS response when treated with nalidixic acid or other agents that affect DNA synthesis. However, UV treatment induces the SOS response in recB21 mutants but not in recA13 mutants. Both these mutants are hypersensitive to nalidixic acid and, therefore, either recombination repair or SOS repair would appear to repair DNA damage caused by the drug. However, since the lexA3 mutation (which also renders bacteria incapable of inducing the SOS response without affecting recombination repair) had no effect on the susceptibility of bacteria to nalidixic acid, the SOS response neither contributes to nor repairs DNA damage caused by the drug. Consequently, it would seem that the hypersensitivity of the recA13 and recB21 mutants to nalidixic acid is due to their deficiency in recombination repair. This view was confirmed by testing a recA430 mutant that is recombination-repair proficient but SOS repair-deficient and finding it to be no more sensitive to nalidixic acid than its parent. Thus it would appear that, although induced by nalidixic acid treatment, the SOS DNA repair system does not play any role in bacterial responses to the damage caused by the drug. In contrast, the recombination repair system does repair damage caused by nalidixic acid.

Anti-Infective Agents↗
PubMed1989

Interactions of the 4-quinolones with other antibacterials.

The effect of sub-inhibitory concentrations of 16 antibacterials on the bactericidal activity of the 4-quinolones nalidixic acid, ciprofloxacin and ofloxacin against Escherichia coli KL16 in nutrient broth was investigated. Sub-inhibitory concentrations of rifampicin, clindamycin, chloramphenicol, erythromycin or tetracycline antagonised the bactericidal activity of the 4-quinolones. Conversely, all seven aminoglycosides tested enhanced the bactericidal activity of the 4-quinolones whereas the cell wall antagonists, azlocillin, mezlocillin, ceftazidime and vancomycin had no effect on the bactericidal activity of the 4-quinolones.

Anti-Bacterial Agents↗