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S G Amyes

Publications and source records attributed to S G Amyes.

At least 19 recordsLinked to original sources

Moxifloxacin sensitivity of respiratory pathogens in the United Kingdom.

The in vitro activity of moxifloxacin and comparator agents against respiratory isolates from a range of geographically distinct centres around the United Kingdom was investigated in the following study. Clinical isolates of Streptococcus pneumoniae (n = 257), Haemophilus influenzae (n = 399) and Moraxella catarrhalis (n = 253) were obtained between March 1998 and April 1999 from nine centres in the United Kingdom. Sensitivity was determined by testing each isolate for its minimum inhibitory concentration (MIC) by agar dilution. Against Streptococcus pneumoniae moxifloxacin and grepafloxacin were the most active (MIC90 = 0.25 mg/l). Trovafloxacin and sparfloxacin were the next most active (MIC90 = 0.5 mg/l) followed by levofloxacin and ciprofloxacin. MIC90 values of the six fluoroquinolones versus H. influenzae ranged from <0.0039 mg/l to 0.0625 mg/l and from <0.0039 mg/l to 0.5 mg/l for M. catarrhalis. The rank order of activity of the fluoroquinolones versus H. influenzae was moxifloxacin = trovafloxacin = grepafloxacin = sparfloxacin > ciprofloxacin > levofloxacin. Against M. catarrhalis the lowest MIC90 was that of grepafloxacin at 0.0625 mg/l followed by moxifloxacin, sparfloxacin, levofloxacin and ciprofloxacin. Trovafloxacin demonstrated the highest MIC90 at 0.5 mg/l. These results demonstrate that moxifloxacin has superior in vitro activity against respiratory tract pathogens than any other comparator quinolones available for clinical use.

Anti-Infective Agents↗

Diversity of Tn1546 elements in clinical isolates of glycopeptide-resistant enterococci from Scottish hospitals.

The Tn1546-related elements of 48 Van glycopetide-resistant enterococci were compared. Ten distinct Tn1546 types were identified with variation primarily due to IS1542 and IS1216V-like insertions. Clonal isolates frequently differed in their Tn1546 type, indicating instability of Tn1546-related elements. A putative hybrid promoter was identified, generated upstream of vanR by the insertion of IS1542. The presence of this hybrid promoter was associated with constitutive expression of the van genes and elevated teicoplanin resistance.

Anti-Bacterial Agents↗

Clonal spread of imipenem-resistant Pseudomonas aeruginosa in the intensive care unit of a Turkish hospital.

Pseudomonas aeruginosa may cause life-threatening infections, especially in nosocomial settings. Although carbapenems are considered as one of the most effective alternatives in antipseudomonal therapy, resistance to the carbapenem group of antibacterials is a growing problem. In the first 6 months of 1997, P. aeruginosa isolates that were resistant to almost all antipseudomonal agents including imipenem were recovered from various specimens from intensive, care unit (ICU) patients. Isolates with the same antibiogram profile caused a small outbreak in May 1997. A retrospective case-control study revealed that the major risk factors for infection/colonization with multiresistant P. aeruginosa were prolonged stay in the ICU (p<0.001), previous and lengthy imipenem usage (p<0.001 and p<0.0001, respectively), and mechanical ventilation (p<0.001). Analytical isoelectric focusing of the sonicates prepared from the isolates showed that each isolate produced 1-5 beta-lactamases, enzymes with isoelectric points (pIs) of 5.1, 6.4, 8.5-8.7 being the most prevalent. DNA macrorestriction patterns of imipenem-resistant isolates were distinct from those of the imipenem-sensitive isolates recovered from ICU patients during the same interval and from the environmental isolates (controls). Thus, our results indicate that colonized patients appear to be the major source for cross-contamination of other patients and if imipenem is selected for empirical therapy, emergence of resistant strains should be anticipated and appropriate precautions taken.

Adolescent↗

Characterization of multi-drug resistant Salmonella typhi isolated from Pakistan.

Thirty-nine strains of Salmonella typhi, isolated in 1995 from four Districts in Pakistan, Rawalpindi, Islamabad, Kharian and Jehlem, were catalogued and examined. Chromosomal DNA from each isolate was digested with XbaI restriction endonuclease and subjected to pulsed-field gel electrophoresis. Three clonal variants comprising of 17-19 DNA fragments were identified. Antibiotic susceptibility testing identified that 37 of the S. typhi were resistant to chloramphenicol, trimethoprim and ampicillin. These antibiotic resistance genes were found to be located on one of four plasmids belonging to incompatibility group IncHI1 and ranging in size from 150-175 Kb. The genes responsible for this resistance in each case were the chloramphenicol acetyltransferase (CAT) type I, the dihydrofolate reductase (DHFR) type VII and the beta-lactamase TEM-1 respectively.

Bacterial Typing Techniques↗

Bactericidal and bacteriostatic activity of gemifloxacin against Acinetobacter spp. in vitro.

This study compared the in vitro bacteriostatic activity of gemifloxacin (SB-265805) and a panel of test antimicrobial agents against 100 clinical isolates of Acinetobacter spp. (47 Acinetobacter baumannii, 18 Acinetobacter anitratus, 18 Acinetobacter lwoffii, 13 Acinetobacter calcoaceticus and four other Acinetobacter spp.). Gemifloxacin (MIC(50/90) 0.06/16 mg/L) was more than eight-fold more potent than ciprofloxacin (0.5/>128 mg/L), two- to eight-fold more potent than grepafloxacin, moxifloxacin, levofloxacin, ofloxacin and gatifloxacin, and of similar potency to trovafloxacin and sparfloxacin. Cross-resistance was seen only within the quinolone group and did not extend to non-quinolone antimicrobials. The bactericidal activities of gemifloxacin and the six comparator quinolones were investigated by dose-response and time-kill studies against A. baumannii ATCC 19606 at their optimum bactericidal concentration (OBC) and at 4 x MIC. At the OBC there was no significant difference between the quinolones, but at 4 x MIC gemifloxacin showed superior activity, reducing the viable count by almost 2 log(10) in 30 min compared with a 1 log(10) reduction seen with the other drugs. This enhanced killing extended over 24 h, reducing cell numbers by >4 log(10). These data suggest that gemifloxacin has the potential to be of therapeutic value in the treatment of infection by Acinetobacter spp.

Acinetobacter↗

Sequence analysis of ARI-1, a novel OXA beta-lactamase, responsible for imipenem resistance in Acinetobacter baumannii 6B92.

The sequence of the bla(ARI-1) gene from imipenem-resistant Acinetobacter baumannii 6B92 has been determined. The structural gene encodes a 273-amino-acid protein which is most related to the OXA class D beta-lactamases. The conserved S-T-F-K and K-T-G motifs were identified in the ARI-1 protein sequence, also named OXA-23, but significantly, a point mutation (Y-->F) was identified in the Y-G-N conserved motif, also known to function in the active site.

Acinetobacter↗

New gene cassettes for trimethoprim resistance, dfr13, and Streptomycin-spectinomycin resistance, aadA4, inserted on a class 1 integron.

In a previous survey of 357 trimethoprim-resistant isolates of aerobic gram-negative bacteria from commensal fecal flora, hybridization experiments showed that 25% (90 of 357) of the isolates failed to hybridize to specific oligonucleotide probes for dihydrofolate reductase types 1, 2b, 3, 5, 6, 7, 8, 9, 10, and 12. Subsequent cloning and sequencing of a plasmid-borne trimethoprim resistance gene from one of these isolates revealed a new dihydrofolate reductase gene, dfr13, which occurred as a cassette integrated in a site-specific manner in a class 1 integron. The gene product shared 84% amino acid identity with dfr12 and exhibited a trimethoprim inhibition profile similar to that of dfr12. Gene probing experiments with an oligonucleotide probe specific for this gene showed that 12.3% (44 of 357) of the isolates which did not hybridize to probes for other dihydrofolate reductases hybridized to this probe. Immediately downstream of dfr13, a new cassette, an aminoglycoside resistance gene of the class AADA ¿ANT(3")(9)-I, which encodes streptomycin-spectinomycin resistance, was identified. This gene shares 57% identity with the consensus aadA1 (ant(3")-Ia) and has been called aadA4 (ant(3")-Id). The 3' end of the aadA4 cassette was truncated by IS26, which was contiguous with a truncated form of Tn3. On the same plasmid, pUK2381, a second copy of IS26 was associated with sul2, which suggests that both integrase and transposase activities have played major roles in the arrangement and dissemination of antibiotic resistance genes dfr13, aadA4, bla(TEM-1), and sul2.

Amino Acid Sequence↗

Isolation and characterization of glycopeptide-resistant enterococci from hospitalized patients over a 30-month period.

In February 1996, a Hospital Infection Control Practices Advisory Committee-style screening program was commenced to isolate and subsequently characterize glycopeptide-resistant enterococci (GRE) from patients at a hospital trust in Glasgow, Scotland. Over the next 30 months, GRE were isolated from 154 patients. GRE were isolated from patients in traditionally high-risk areas such as the renal unit and intensive care unit and also in areas considered to be lower risk, including medical wards and associated long-stay geriatric hospitals. The majority (90%) of isolates were Enterococcus faecium vanB. The remaining isolates consisted of seven E. faecalis (vanA), three E. gallinarum (vanC), and a further six E. faecium (five vanA, one both vanA and vanB) isolates. Analysis of SmaI-digested DNA by pulsed-field gel electrophoresis revealed that 34 of 40 (85%) VanB E. faecium isolates were identical or closely related, while 11 of 13 (85%) VanA GRE were distinct. High-level aminoglycoside resistance was seen in less than 8% of isolates. VanB E. faecium isolates were almost uniformly resistant to ampicillin and tetracycline. In this study, GRE have been isolated over a prolonged period from a broad range of patients. Glycopeptide resistance within the study hospital trust appeared to be mainly due to the clonal dissemination of a single strain of E. faecium VanB.

Aminoglycosides↗

High prevalence of extended spectrum beta-lactamase production among Klebsiella pneumoniae strains isolated at a University Hospital in Turkey.

Beta-lactam susceptibility and beta-lactamase patterns of a random sample of 44 Klebsiella pneumoniae strains that had been isolated from nosocomial infections at Dokuz Eylül University Hospital in Izmir, were investigated. All strains were amoxycillin resistant but in the presence of clavulanic acid 26 became sensitive. Similarly 39 of the strains were resistant to ceftazidime and cefotaxime; clavulanic acid restored sensitivity to ceftazidime in 28 and to cefotaxime in 25 of these resistant strains. Extended spectrum beta-lactamase (ESBL) production was positive in 84% of the isolates as determined by the double disk synergy test. Isoelectric focusing revealed that each strain produced one to four beta-lactamases, pI 7.6 enzymes being the most prevalent. Other enzymes with pIs of 8.4, 8.2, 5.4, 7.8 were also detected. Resistance to ceftazidime was transferred from 18 of the 44 isolates to the recipient Escherichia coli K-12 at 37 degrees C. The transconjugants were examined for their plasmid content and the plasmids were characterized by their size and resistance profile. Fourteen different restriction pattern groups were identified with Eco R1. The results indicate a high prevalence of ESBL production in nosocomial K. pneumoniae isolates in Izmir and have major implications concerning the clinical use of later generation cephalosporins.

Anti-Bacterial Agents↗

Beta-lactamase patterns and betalactam/clavulanic acid resistance in Escherichia coli isolated from fecal samples from healthy volunteers.

Fecal specimens from 50 healthy volunteers living in Izmir, Turkey, were examined for the presence of beta-lactamase producing Escherichia coli by selection on agar plates containing ampicillin (10 mg/L). Thirty-nine (78%) of the strains were ampicillin-resistant and ampicillin MIC50 values for these isolates were > or =1024 microg/ml (range 32- > or =1024 microg/ml). Ampicillin MIC values remained above 64 microg/ml in 16 (41%) strains despite addition of clavulanic acid (2 mg/L). Beta-lactamase production of the clavulanate-resistant strains was further investigated by analytical isoelectric focusing (pI). Enzymes with pIs of 5.4, 5.6, 7.4, 7.6 and >8.5 were detected. Sixty-nine percent of the isolates produced a pI 5.4 enzyme that cofocused with TEM-1. Beta-lactamase assays revealed that hyperproduction of these enzymes was the predominant mechanism for clavulanate resistance. Twelve (75%) of the isolates were able to transfer their ampicillin resistance. The ampicillin and ampicillin plus clavulanic acid MIC values of all transconjugants were above 256 microg/ml. Transferable ampicillin resistance was associated with resistance to other antibacterials at the following frequencies: tetracycline 92%, trimethoprim 83%, streptomycin 50%, gentamicin 25%, and chloramphenicol 8%. In conclusion, it has been suggested that commensal bacteria in normal populations make up the largest reservoir of antibiotic-resistant genes. Although the exact molecular mechanisms could not be determined, the current study shows that the incidence of ampicillin and clavulanic acid resistance is also high in commensal fecal flora.

Ampicillin↗

The mechanism of ampicillin resistance in enterobacteriaceae isolated in Vellore.

Ampicillin resistance in clinical isolates of enterobacteriaceae has been on the increase in the last decade. A study was carried out to delineate the possible mechanisms of this resistance. The method employed was isoelectric focussing to observe the electrophoretic mobility of the enzyme responsible and this showed that TEM 1 betalactamase was the cause irrespective of the species.

Ampicillin Resistance↗

The persistence and clonal spread of a single strain of Acinetobacter 13TU in a large Scottish teaching hospital.

This study describes the persistence and spread of a single strain of Acinetobacter 13TU in a large Scottish teaching hospital. Acinetobacter spp. are reported with increasing frequency as a cause of nosocomial infection. The species most implicated in these infections is Acinetobacter baumannii. Following an outbreak of infection with Acinetobacter 13TU within the intensive therapy unit (ITU) of Edinburgh Royal Infirmary (ERI) during 1994-1995, the current epidemiological Acinetobacter situation within the hospital was monitored to determine whether or not control of infection procedures instigated at that time had been successful in controlling the outbreak. Sixty-eight strains of Acinetobacter spp were isolated from clinical specimens received from various wards in the ERI and other associated hospitals over a 7-month period. Each isolate was typed phenotypically by the API20NE system and genotypically by pulsed field gel electrophoresis (PFGE) in order to compare them with the previous outbreak strain. Fifty-three percent of the isolates collected were originally identified as A. junii by API 20 NE, of which 83% (mainly from ITU) were shown to be genotypically related to the previous outbreak strain. Subsequent tDNA fingerprinting of one of the original outbreak strains showed it to be a member of the genospecies 13TU and not A. junii as originally thought.

Acinetobacter↗

Epidemiology and control of vancomycin-resistant enterococci (VRE) in a renal unit.

This study reports an outbreak of infection and colonization caused by vancomycin-resistant enterococci (VRE) in the renal service of a large teaching hospital. The polymerase chain reaction and pulsed-field gel electrophoresis were used to study the epidemiology of 26/34 strains of vancomycin-resistant Enterococcus faecalis and Enterococcus faecium from the outbreak in comparison with five strains from other hospitals in Edinburgh and the Borders, and three from other wards in the Royal Infirmary. The study revealed a heterogeneous population of vancomycin-resistant E. faecalis. Over 60% of E. faecium isolates had matching pulsed-field gel electrophoresis patterns and all of these were of VanA phenotype. These results suggest that clonal spread of VanA phenotype E. faecium within and possibly between hospitals is the major vancomycin-resistant enterococcal problem in Edinburgh. Screening of patients and isolation of colonized and infected patients appear to have been successful in controlling the spread of VRE.

Anti-Bacterial Agents↗

The prevalence of Vibrio spp. in drinking water and environmental samples in Vellore South India.

The prevalence of Vibrio cholerae in drinking water, lakes and sewage outfalls during July and August 1996 in Vellore, India was determined. Drinking water samples were collected on single occasions from 12 sites in different geographic areas of the town where cholera had been reported. Samples of water, plankton and sediment were collected from fixed sites at three lakes on three occasions separated by at least 3 days during the course of the study. Samples from open sewers were taken from two representative sites in four areas of the town. Bacteria isolated from samples were identified by standard biochemical tests and isolated strains of V. cholerae tested for their ability to agglutinate O1 and O139 antisera. Water samples from lakes were also tested for the presence of V. cholerae O1 and O139 by fluorescent antibody staining. Non-O1, non-O139 strains of V. cholerae were detected in 41% of drinking water samples and 100% of water, sediment and plankton samples from the test lakes. Eighty-seven per cent of open sewers sampled contained viable non-O1, non-O139 V. cholerae. Fluorescent antibody staining gave positive results for V. cholerae O1 and O139 for all water samples from the three lake sites. Strains of Aeromonas spp. were isolated from 58% of drinking water samples and from 66% of sediment, 77% of plankton and 55% of water samples from lakes. All open sewers sampled contained Aeromonas spp. PCR amplification employing specific primers demonstrated that none of the non-agglutinating V. cholerae isolates contained the ctx operon. The non-O1, non-O139 V. cholerae isolates showed different patterns of antibiotic resistance to ampicillin, ciprofloxacin, chloramphenicol, tetracycline and trimethoprim.

Cholera↗