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Y F Jin

Publications and source records attributed to Y F Jin.

At least 19 recordsLinked to original sources
PubMed2001

Effect of hydrophobicity and molecular mass on the accumulation of fluoroquinolones by Staphylococcus aureus.

Ten novel fluoroquinolones, with similar chemical structures but differing antibacterial activities and hydrophobicities, were studied to evaluate the role of the physical properties of quinolones on their accumulation and antibacterial activity for Staphylococcus aureus. Six of the 10 agents and tosufloxacin were more active against quinolone-susceptible and -resistant S. aureus than the remaining four agents and several piperazinyl fluoroquinolones. Changes to the side chains of the pyrollidinyl substituent at the R7 position alone made little difference to the MICs. Comparison of MICs of agents that were structurally identical apart from the R1 substituents, confirmed that a t-butyl group confers enhanced activity against S. aureus over a cyclopropyl or ethyl group at this position. The steady-state concentrations (SSCs) of the 10 novel quinolones accumulated by wild-type S. aureus did not correlate with their MICs or chemical structures. There was no apparent relationship between logP of the quinolone and accumulation by S. aureus F77; however, accumulation was positively correlated with molecular mass for 9/10 agents (r = 0.745) confirming that high molecular mass is not a barrier to accumulation in S. aureus. For all 10 agents, the presence of carbonyl cyanide m-chlorophenylhydrazone (CCCP) increased the concentration of quinolone accumulated by SA-1199, suggesting that NorA was inhibited. The fold increase of the SSC in the presence of CCCP did not correlate with hydrophobicity, but the SSC of agents with either an ethyl or cyclopropyl group at R1 was increased two- to three-fold in the presence of CCCP, suggesting that affinity for the NorA efflux pump may be influenced by quinolone structure.

Anti-Infective Agents↗
PubMed1999

Quinolone accumulation by Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli.

The accumulation of nalidixic acid and 14 fluoroquinolones over a range of external drug concentrations (10-100 mg/L; c. 25-231 microM) into intact cells of Escherichia coli KL-16, Staphylococcus aureus NCTC 8532, Pseudomonas aeruginosa NCTC 10662 and spheroplasts of E. coli was investigated. The effect of 100 microM carbonyl cyanide m-chlorophenyl hydrazone (CCCP) upon the concentration of quinolone accumulated by intact cells and spheroplasts of E. coli was also determined. Except for pefloxacin, there was an increase in the concentration of the six quinolones examined accumulated by E. coli, despite a reduction in fluorescence at alkaline pH. For ciprofloxacin the partition coefficient (P(app)) was constant despite an increase in the pH; however, the P(app) for nalidixic acid decreased significantly with an increase in pH. The concentration of nalidixic acid, ciprofloxacin and enrofloxacin accumulated by E. coli and S. aureus increased with an increase in temperature up to 40 degrees C and 50 degrees C, respectively. Above these temperatures the cell viability decreased. With an increase in drug concentration there was, for intact E. coli and 12/15 agents, and for S. aureus and 10/15 agents, a linear increase in the concentration of drug accumulated. However, for P. aeruginosa and 13/15 agents there was apparent saturation of an accumulation pathway. Assuming 100% accumulation into intact cells of E. coli, for 10/14 fluoroquinolones < or = 40% was accumulated by spheroplasts. CCCP increased the concentration of quinolone accumulated but the increase varied with the agent and the bacterial species. The variation in the effect of CCCP upon accumulation of the different quinolones into E. coli could result from chemical interactions or from different affinities of the proposed efflux transporter for each quinolone. Overall, these data suggest that accumulation of most quinolones into E. coli and S. aureus proceeds by simple diffusion, but that P. aeruginosa behaves differently.

Anti-Infective Agents↗
PubMed1999

Antimicrobial activity and accumulation of moxifloxacin in quinolone-susceptible bacteria.

The antibacterial activity of moxifloxacin, compared with that of ciprofloxacin, was determined for five strains of Staphylococcus aureus, including one NorA-overproducing strain, two quinolone-susceptible strains of Streptococcus pneumoniae, four quinolone-susceptible strains of Haemophilus influenzae, and one strain each of quinolone-susceptible Escherichia coli, Pseudomonas aeruginosa and Moraxella catarrhalis. In addition, the accumulation of moxifloxacin and ciprofloxacin by the NCTC type strain of S. pneumoniae, H. influenzae, S. aureus, E. coli and P. aeruginosa was determined by a fluorescence method. For all strains, moxifloxacin accumulated to a lower concentration than ciprofloxacin. The concentrations of moxifloxacin accumulated ranged from 12 to 44 ng/mg dry cells. The lowest concentration was accumulated by S. pneumoniae NCTC 7465 and the highest concentration by S. aureus NCTC 8532. Increased expression of norA in S. aureus had no effect on the accumulation of moxifloxacin. Despite differences in the concentration of moxifloxacin accumulated by the different species, there was little difference between the MICs of this agent for each strain (0.06-0.5 mg/L), suggesting that the concentration accumulated by wild-type bacteria has little effect on the MIC.

Anti-Infective Agents↗
PubMed1997

Prevalence and mechanism of resistance to 'third-generation' cephalosporins in clinically relevant isolates of Enterobacteriaceae from 43 hospitals in the UK, 1990-1991.

In a UK survey of the occurrence of extended spectrum beta-lactamases, 96 hospitals submitted a total of 3951 non-selected, non-duplicate isolates of Enterobacteriaceae from 100 patients in each hospital, 206 of these cultures being mixed and, therefore, discarded. These isolates were initially screened for strains likely to produce extended-spectrum beta-lactamases (ESBLs) by MIC determination of beta-lactams followed by a bioassay, then disc approximation test and isoelectric focusing (IEF). Isolates were further examined using two pairs of PCR primers for both blaTEM and blaSHV genes. The ability of isolates to transfer resistance to both cefotaxime and ceftazidime by conjugation and transformation were examined. Four hundred and nine cefotaxime/ceftazidime-resistant isolates (10.9%) were identified from the 3745 submitted isolates, of which 338 (9.0%) were Enterobacteriaceae, 29 Escherichia coli, 35 Klebsiella spp. and seven Hafnia alveii. IEF suggested that 17 isolates produced an ESBL, which was confirmed in most cases by PCR and hydrolysis, five isolates produced an SHV enzyme by IEF, but not confirmed by PCR, and 11 had isoelectric points in the range 8-9 suggesting a possible AmpC enzyme. Only two isolates transferred the determinants. In the case of the Klebsiella spp., 19 of the 24 ceftazidime-resistant/clavulanate-sensitive isolates were positive by PCR for a blaSHV gene. No isolates were identified as carrying blaTEM, although eight isolates had isoelectric points of 5-6.3, suggesting the presence of a possible TEM beta-lactamase. The results for the H. alveii isolates suggest that either an AmpC-like enzyme or a transferable beta-lactamase which is not TEM/SHV is present. This study shows that a wide range of genotypically and phenotypically different isolates of Enterobacteriaceae producing ESBL-like enzymes is present throughout the UK at a frequency of about 1% of unselected isolates. It is important that surveillance of resistance to these clinically important antibiotics is maintained as the occurrence of localized or more widespread outbreaks caused by bacteria producing ESBLs is to be expected.

Cephalosporins↗
PubMed1997

Non-gyrA-mediated ciprofloxacin resistance in laboratory mutants of Streptococcus pneumoniae.

Two strains of Streptococcus pneumoniae, M4 (NCTC 7465, type strain) and M5 (clinical isolate), and their respective ciprofloxacin-resistant mutants, M4/C1, M5/C1 and M5/C3, were evaluated. All mutants were stable after one year's storage and all grew more slowly in Brain Heart Infusion broth than the parent. The MICs of ciprofloxacin, sparfloxacin and tosufloxacin were increased for the mutants of M4, whereas the mutants of M5 were less susceptible to ciprofloxacin only. The optimal bactericidal concentration (OBC) of each quinolone for all the strains was approximately ten-fold greater than the MIC. The OBCs for the mutants were increased for ciprofloxacin, but not for the other two quinolones. The DNA synthesis IC50 values of all quinolones correlated well with the MIC of each drug. All quinolones accumulated rapidly within all five strains; 10 mM magnesium chloride decreased the concentration of quinolone accumulated, but carbonyl cyanide m-chlorophenyl hydrazone had no effect. Mutant strains M4/C1, M5/C1 and M5/C3 accumulated less quinolone than their respective parent strains. DNA sequencing of those regions of gyrA and gyrB corresponding to the quinolone resistance-determining region in other bacteria did not reveal any differences between the parent and mutant strains.

Amino Acid Sequence↗
PubMed1996

Contributions of individual mechanisms to fluoroquinolone resistance in 36 Escherichia coli strains isolated from humans and animals.

Twenty-eight human isolates of Escherichia coli from Argentina and Spain and eight veterinary isolates received from the Ministry of Agriculture Fisheries and Foods in the United Kingdom required 2 to > 128 micrograms of ciprofloxacin per ml for inhibition. Fragments of gyrA and parC encompassing the quinolone resistance-determining region were amplified by PCR, and the DNA sequences of the fragments were determined. All isolates contained a mutation in gyrA of a serine at position 83 (Ser83) to an Leu, and 26 isolates also contained a mutation of Asp87 to one of four amino acids: Asn (n = 14), Tyr (n = 6), Gly (n = 5), or His (n = 1). Twenty-four isolates contained a single mutation in parC, either a Ser80 to Ile (n = 17) or Arg (n = 2) or a Glu84 to Lys (n = 3). The role of a mutation in gyrB was investigated by introducing wild-type gyrB (pBP548) into all isolates; for three transformants MICs of ciprofloxacin were reduced; however, sequencing of PCR-derived fragments containing the gyrB quinolone resistance-determining region revealed no changes. The analogous region of parE was analyzed in 34 of 36 isolates by single-strand conformational polymorphism analysis and sequencing; however, no amino acid substitutions were discovered. The outer membrane protein and lipopolysaccharide profiles of all isolates were compared with those of reference strains, and the concentration of ciprofloxacin accumulated (with or without 100 microM carbony cyanide m-chlorophenylhydrazone [CCCP] was determined. Twenty-two isolates accumulated significantly lower concentrations of ciprofloxacin than the wild-type E. coli isolate; nine isolates accumulated less then half the concentration. The addition of CCCP increased the concentration of ciprofloxacin accumulated, and in all but one isolate the percent increase was greater than that in the control strains. The data indicate that high-level fluoroquinolone resistance in E. coli involves the acquisition of mutations at multiple loci.

Animals↗
PubMed1995

A novel gyrB mutation in a fluoroquinolone-resistant clinical isolate of Salmonella typhimurium.

In order to study the role of gyrB in antibiotic resistance in post-ciprofloxacin therapy fluoroquinolone-resistant clinical isolates of Salmonella typhimurium, plasmid pBP548, which contains the Escherichia coli gyrB gene, was used in complementation studies. In a heterodiploid strain, the wild-type (quinolone sensitive) allele is dominant over the resistant allele therefore, eleven clinical isolates were complemented with gyrB encoded on pBP548. Only one transformant, L18pBP548, exhibited increased susceptibility to the quinolones nalidixic acid, ciprofloxacin and sparfloxacin. The amino acid sequence of the gyrase B protein from a wild-type and the pre-therapy S. typhimurium (deduced from the nucleotide sequence) was identical to that of E. coli from codons 436 to 470; however, a point mutation was identified in codon 463 of gyrB of the quinolone-resistant post-therapy isolate L18, giving rise to an amino acid substitution of serine to tyrosine.

Anti-Infective Agents↗
PubMed1995

Activity of biapenem (LJC 10627) against 51 imipenem-resistant bacteria and selection and characterisation of biapenem-resistant mutants.

For wild-type bacteria the activity of biapenem was similar to that of imipenem, but for 51 imipenem-resistant strains meropenem was more active than either. When penicillin-binding protein 2a (PBP 2a) was expressed in Staphylococcus aureus biapenem had reduced activity. Mutant bacteria with decreased susceptibility to biapenem were selected in agar. Most of the mutant Gram negative bacteria were unstable and readily reverted to susceptible. The mutant Proteus vulgaris and Pseudomonas aeruginosa lacked an outer membrane protein. Biapenem-resistant S. aureus could be selected only from MRSA.

Drug Resistance, Microbial↗
PubMed1994

Quinolone resistance in veterinary isolates of Salmonella.

Twenty-seven nalidixic acid-resistant (MIC > or = 256 mg/L) isolates of salmonella from veterinary sources were also less susceptible to fluoroquinolones (range of MICs of ciprofloxacin, 0.12-2 mg/L). Six isolates were cross-resistant to one or more chemically unrelated antibacterial agents. The concentrations of enrofloxacin that inhibited DNA synthesis by 50% were similar to the MIC values for 23 of 27 isolates, suggesting a mutation in gyrA. Insertion of pNJR3-2 (gyrA) in nine of 20 isolates increased susceptibility to quinolones, suggesting that resistance was due to mutation in gyrA. Five of 27 isolates had reduced levels of accumulation of enrofloxacin. Two of the five also had increased susceptibility to quinolones when pNJR3-2 was introduced. None of the outer membrane protein profiles of the resistant isolates differed from those of sensitive control strains. Three of 27 isolates had differences in lipopolysaccharide profiles compared to control strains. Although the MIC of ciprofloxacin was less than the recommended UK break point concentrations for most isolates, the increasing incidence of quinolone-resistance in salmonella from veterinary sources is a matter of concern.

Animals↗
PubMed1994

Activity of Bay y3118 against quinolone-susceptible and -resistant gram-negative and gram-positive bacteria.

The activity of Bay y3118 against laboratory strains of bacteria, including those with mutations in gyrA, with decreased expression of outer membrane proteins, and/or that are multiply resistant, and 121 selected clinical isolates, including highly fluoroquinolone-resistant bacteria from Spain and Argentina, was determined. Bay y3118 was extremely active (MICs, < or = 1 microgram/ml) against all bacteria, including quinolone-resistant laboratory strains. However, Bay y3118 was less active against 46 of 121 quinolone-resistant clinical isolates, such that > or = 16 micrograms of Bay y3118 per ml was required to inhibit 3 isolates. The concentration of Bay y3118 required to inhibit DNA synthesis by 50% correlated well with the MIC. Bay y3118 had accumulation kinetics similar to those of previously studied fluoroquinolones, e.g., ciprofloxacin, and there was a 50% decrease in the steady-state concentration in those members of the family Enterobacteriaceae that lacked porin proteins. Magnesium chloride at 20 mM apparently abolished the accumulation of Bay y3118 into Escherichia coli and reduced the level of accumulation into other gram-negative bacteria and Staphylococcus aureus. Carbonyl cyanide m-chlorophenylhydrazone at 100 microM enhanced the accumulation of Bay y3118 into E. coli, but it had a minimal effect on accumulation into S. aureus.

Anti-Infective Agents↗
PubMed1993

Activity of 13 beta-lactam agents combined with BRL 42715 against beta-lactamase producing gram-negative bacteria compared to combinations with clavulanic acid, tazobactam and sulbactam.

The activity of six cephalosporins, six penicillins and one monobactam combined with BRL 42715, clavulanic acid, sulbactam or tazobactam at 0.1, 0.5, 1, 2, 5 and 10 mg/L was determined for 45 beta-lactamase producing Gram-negative bacteria. The combination of BRL 42715 with any of the agents was more active than any of the other inhibitor and beta-lactam combinations. Unlike the other beta-lactamase inhibitors, BRL 42715 enhanced the activity of the beta-lactams for strains that constitutively expressed Richmond & Sykes Class I beta-lactamase and against strains expressing extended-spectrum plasmid-mediated beta-lactamases.

Anti-Bacterial Agents↗
PubMed1993

Ciprofloxacin resistance in clinical isolates of Salmonella typhimurium obtained from two patients.

Two patients (patients A and B) infected with Salmonella typhimurium failed ciprofloxacin therapy, and the posttherapy isolates had reduced susceptibilities to quinolones; 6 of 11 isolates from patient B were also cross-resistant to chemically unrelated agents. No transferable resistance, chloramphenicol-acetylating enzymes, or beta-lactamases were detected. For 13 of 14 isolates, the concentrations of ciprofloxacin that inhibited DNA synthesis by 50% were similar to the MICs, suggesting a mutation in gyrA. Insertion of pNJR3-2 (gyrA) in the posttherapy isolate from patient A and 5 of 11 of the posttherapy isolates from patient B resulted in lower quinolone MICs, also suggesting that resistance was due to a mutation in gyrA. Three of the five isolates also had reduced levels of accumulation of quinolones. All six cross-resistant isolates from patient B had reduced levels of accumulation of quinolones, but only one isolate had increased susceptibility when pNJR3-2 was inserted. Despite the lack of OmpF seen in five isolates from patient B, there was no correlation with decreased levels of quinolone accumulation. All isolates had identical smooth lipopolysaccharide profiles. The mechanism of apparently reduced accumulation has yet to be determined.

Anti-Infective Agents↗
PubMed1993

Correlation of serum lipids, lipoproteins, lipid peroxide products and metals with coronary heart disease.

Serum lipids, lipoproteins, malondialdelyde (MDA) and metal levels were determined in 86 patients with coronary heart disease (CHD) proved angiographically and 33 controls subjects. Serum concentrations of TC, LDL-C, AI, MDA and Cu were significantly elevated and serum HDL-C, Zn and Mg contents were decreased markedly in patients. Correlation analyses indicated that the severity of coronary arterial lesions was related positively to serum TC, LDL-C, AI, MDA and Cu levels, and inversely to HDL-C levels; both the serum Cu and MDA contents were related positively to TC and LDL-C levels. These data suggest that serum Cu and MDA might have effects on the extent of CA lesions during the progress of atherosclerosis in patients with CHD.

Cholesterol↗
PubMed1992

[Effects erythropoietin on experimental anemia in rats with chronic renal failure].

Erythropoietin (EPO) is a glycoprotein hormone secreted by human kidney cells. Human EPO was induced from human embryo kidney cells, isolated and purified from medium by biochemical method in our laboratory. The hypoproliferative anemia in chronic renal failure (CRF) has been assumed to be the result of decreased EPO production by the damaged kidney and of the shortening of the survival of erythrocytes. In this study, CRF anemia was formed 9 weeks after the removal of five-sixths of the renal mass of rats. These anemic rats were divided into 6 groups: treated with different dosages of EPO or physiological saline. The results indicate that EPO has apparent effects on anemia in rats with CRF. It may stimulate erythropoiesis and improve the anemia state of rats with CRF. Hematological parameters (RBC, Hb, PLT, Ht and Rt) may be reverted to normal levels (P less than 0.001). The level of BUN and Cr were significantly decreased. The optimum dose of EPO was 1000 U/kg. All these results show that injection of EPO has therapeutic effect on anemia in rats with CRF. EPO showed no effect on normal rats.

Anemia↗
PubMed1990

In-vitro comparison of the post-antibiotic effect of vancomycin and teicoplanin.

The post-antibiotic effect (PAE) of teicoplanin was compared with that of vancomycin for five selected Gram-positive cocci. Two concentrations of each antibiotic were investigated, with the test organisms being exposed to each for both 1 and 2 h. At a concentration of 25 mg/l, teicoplanin had a greater PAE than vancomycin for the methicillin resistant staphylococci and Enterococcus faecalis strains tested. At a concentration of 5 mg/l, teicoplanin gave equal effects to those of vancomycin except for the strain of methicillin-resistant Staphylococcus aureus (MRSA) tested. The variation in the antibiotic exposure time gave only small changes in the PAE, except for the MRSA tested.

Enterococcus faecalis↗
PubMed1990

Correlations of blood lipids and lipoproteins with coronary artery disease documented by angiography.

A study of the relationships between serum TC, TG and HDL.C and selective coronary arteriography was carried out on 117 patients who were divided into groups according to the extent of artery stenosis. Normal control group consisted of 153 healthy subjects. There were no statistical differences in TC, TG, HDL.C, LDL.C, TC/HDL.C, LDL.C/HDL.C and TC-HDL.C/HDL.C between normal control group and the group with normal coronary arteriogram. LDL.C, TC/HDL.C, LDL.C/HDL.C, TC HDL.C/HDL.C rose and HDL.C decreased as the degree of coronary artery stenosis and the extent of stenosis increased, besides the medium and severe stenosis group. Analyses based on the correlation coefficients indicate that 3 compound indexes (TC-HDL.C/HDL.C, TC-HDL.C, LDL.C/HDL.C) are better in assessing CAD than single index such as LDL.C, HDL.C and TC. The results of our study showed that the 3 compound indexes might be regarded as important risk factors for CAD.

Adult↗