- H.W. Gerritsen (1)
- A.W. Giessen van de (1)
- W.H. Goessens (1)
- R.J. Hassing (1)
- A.H. Havelaar (1)
- M.G.J. Koene (1)
- S.L. Lameris (1)
- D.J. Mevius (2)
- J.W. Mouton (1)
- M.W.F. Nielen (1)
- W. Pelt van (1)
- N. Phillips (1)
- L. Randall (1)
- M.L.M. Salverda (1)
- R. Sebille van (1)
- A.A.M. Stolker (1)
- C. Teale (1)
- A. Verbon (1)
- R.S. Wegh (1)
- G. Wu (1)
Decreased ciprofloxacin susceptibility in Salmonella Typhi and Paratyphi infections in ill-returned travellers: the impact on clinical outcome and future treatment options
Hassing, R.J. ; Goessens, W.H. ; Mevius, D.J. ; Pelt, W. van; Mouton, J.W. ; Verbon, A. ; Genderen, P.J. - \ 2013
European Journal of Clinical Microbiology and Infectious Diseases 32 (2013)10. - ISSN 0934-9723 - p. 1295 - 1301.
enterica serotype typhi - beta-lactamase - fever - pharmacokinetics - pharmacodynamics - reevaluation - multicenter - breakpoints - resistant - nepal
The emergence of decreased ciprofloxacin susceptibility (DCS) in Salmonella enterica serovar Typhi and serovar Paratyphi A, B or C limits treatment options. We studied the impact of DCS isolates on the fate of travellers returning with enteric fever and possible alternative treatment options. We evaluated the clinical features, susceptibility data and efficacy of empirical treatment in patients with positive blood cultures of a DCS isolate compared to patients infected with a ciprofloxacin-susceptible (CS) isolate in the period from January 2002 to August 2008. In addition, the pharmacokinetic and pharmacodynamic parameters of ciprofloxacin, levofloxacin and gatifloxacin were determined to assess if increasing the dose would result in adequate unbound fraction of the drug 24-h area under the concentration-time curve/minimum inhibitory concentration (ƒAUC(0-24)/MIC) ratio. Patients with DCS more often returned from the Indian subcontinent and had a longer fever clearance time and length of hospital stay compared to patients in whom the initial empirical therapy was adequate. The mean ƒAUC(0-24)/MIC was 41.3¿±¿18.8 in the patients with DCS and 585.4¿±¿219 in patients with a CS isolate. For DCS isolates, the mean ƒAUC0-24/MIC for levofloxacin was 60.5¿±¿28.7 and for gatifloxacin, it was 97.9¿±¿28.0. Increasing the dose to an adequate ƒAUC(0-24)/MIC ratio will lead to conceivably toxic drug levels in 50% of the patients treated with ciprofloxacin. Emerging DCS isolates has led to the failure of empirical treatment in ill-returned travellers. We demonstrated that, in some cases, an adequate ƒAUC(0-24)/MIC ratio could be achieved by increasing the dose of ciprofloxacin or by the use of alternative fluoroquinolones.
Comprehensive analysis of B-Lactam antibiotics including penicillins, cephalosporins and carbapenems in poultry muscle using liquid chromatography coupled to tandem mass spectrometry
Berendsen, B.J.A. ; Gerritsen, H.W. ; Wegh, R.S. ; Lameris, S.L. ; Sebille, R. van; Stolker, A.A.M. ; Nielen, M.W.F. - \ 2013
Analytical and Bioanalytical Chemistry 405 (2013)24. - ISSN 1618-2642 - p. 7859 - 7874.
beta-lactamase - quantitative-analysis - ceftiofur resistance - escherichia-coli - european-union - bovine muscle - kidney tissue - enterobacteriaceae - salmonella - mechanisms
A comprehensive method for the quantitative residue analysis of trace levels of 22 ß-lactam antibiotics, including penicillins, cephalosporins, and carbapenems, in poultry muscle by liquid chromatography in combination with tandem mass spectrometric detection is reported. The samples analyzed for ß-lactam residues are hydrolyzed using piperidine in order to improve compound stability and to include the total residue content of the cephalosporin ceftifour. The reaction procedure was optimized using a full experimental design. Following detailed isotope labeling, tandem mass spectrometry studies and exact mass measurements using high-resolution mass spectrometry reaction schemes could be proposed for all ß-lactams studied. The main reaction occurring is the hydrolysis of the ß-lactam ring under formation of the piperidine substituted amide. For some ß-lactams, multiple isobaric hydrolysis reaction products are obtained, in accordance with expectations, but this did not hamper quantitative analysis. The final method was fully validated as a quantitative confirmatory residue analysis method according to Commission Decision 2002/657/EC and showed satisfactory quantitative performance for all compounds with trueness between 80 and 110 % and within-laboratory reproducibility below 22 % at target level, except for biapenem. For biapenem, the method proved to be suitable for qualitative analysis only.
Virulence genes in bla (CTX-M) Escherichia Coli isolates from chickens and humans
Randall, L. ; Wu, G. ; Phillips, N. ; Coldham, N. ; Mevius, D.J. ; Teale, C. - \ 2012
Research in Veterinary Science 93 (2012)1. - ISSN 0034-5288 - p. 23 - 27.
beta-lactamase - ctx-m - diarrhea - resistance - strains - toxin - south
The aim of this study was to determine the presence of virulence genes in isolates of CTX-M Escherichia coli from diseased chickens, from healthy chickens and from urinary tract infections in people. Three CTX-M E. coli strains from three different instances of disease in poultry (two of which were E. coli related) were tested for blaCTX-M sequence type and replicon type. Additionally, they were tested for the presence of 56 virulence genes (encoding fimbriae, adhesins, toxins, microcins and iron acquisition genes) using a micro-array. Results were compared to the virulence genes present in isolates from 26 healthy chickens and from 10 people with urinary tract infections. All genes found in isolates from diseased birds, including the astA (heat stable toxin) and tsh (temperature sensitive haemagglutinin) genes which have previously been associated with colibacillosis in chickens, were also present in isolates from healthy birds. However, 6/10 of the virulence genes found were exclusive to isolates from humans. Genes exclusive to chicken isolates included ireA (sidephore receptor), lpfA (long polar fimbriae), mchF (microcin transporter protein) and tsh whilst genes exclusive to human isolates included ctdB (cytolethal distending toxin), nfaE (non-fimbrial adhesion), senB (plasmid encoded enterotoxin) and toxB (toxin B). The results support previous findings that CTX-M E. coli strains in chickens are generally different from those causing disease in humans, but genes such as astA and tsh in isolates from diseased birds with colisepticaemia were also present in isolates from healthy birds
Risk profile on antimicrobial resistance transmissible from food animals to humans
Geenen, P.L. ; Koene, M.G.J. ; Blaak, H. ; Havelaar, A.H. ; Giessen, A.W. van de - \ 2010
Bilthoven : RIVM (Rapport / Rijksinstituut voor Volksgezondheid en Milieu 330334001/2010) - 118
dierhouderij - antibioticaresistentie - risicogedrag - gezondheidsgevaren - risicobeheersing - campylobacter jejuni - staphylococcus aureus - bèta-lactamase - bacteriën - zoönosen - animal husbandry - antibiotic resistance - risk behaviour - health hazards - risk management - beta-lactamase - bacteria - zoonoses
In de dierhouderij worden antibiotica veelvuldig gebruikt, waardoor antibioticaresistentie toeneemt, zowel bij zoönotische als bij commensale bacteriën. Dit heeft geleid tot bezorgdheid over de risico’s van overdracht van resistente zoönotische bacteriën en resistentiegenen van voedselproducerende dieren naar de mens en de mogelijke gevolgen daarvan voor de volksgezondheid en de gezondheidszorg. Dit rapport bevat een risicoprofiel, hetgeen bedoeld is om risicomanagers te informeren over de beschikbare kennis met betrekking tot dit potentiële gezondheidsrisico, als een eerste stap in het proces van risicomanagement. 3 gevaren dienen als voorbeeld in dit risicoprofiel: 1. quinolone-resistente Campylobacter jejuni; 2. veegerelateerde MRSA (v-MRSA); 3. ESBL-producerende bacteriën.
On the natural and laboratory evolution of an antibiotic resistance gene
Salverda, M.L.M. - \ 2008
University. Promotor(en): Rolf Hoekstra, co-promotor(en): Arjan de Visser; John van der Oost. - [S.l.] : S.n. - ISBN 9789085049999 - 144
evolutie - bèta-lactamase - plasmiden - recombinatie - bacteriën - fenotypen - mutagenese - fylogenie - moleculaire genetica - selectie - antibioticaresistentie - evolution - beta-lactamase - plasmids - recombination - bacteria - phenotypes - mutagenesis - phylogeny - molecular genetics - selection - antibiotic resistance
TEM-1 ß-lactamase is one of the most notorious antibiotic resistance enzymes around. It exists at high frequencies in antibiotic-resistant bacteria around the world and confers resistance to ß-lactam antibiotics, including penicillins (e.g. ampicillin) and cephalosporins. The enzyme displays a remarkable phenotypic plasticity in response to the introduction of new drugs; within a few years after the clinical debut of most new ß-lactam antibiotics resistance conferring variants of TEM-1 are isolated. Such a shift in resistance phenotype is typically caused by just a few amino acid substitutions. Until today, more than 150 variants of TEM-1 with a unique amino acid sequence have been identified.
Because of the clear link between genotype and phenotype (i.e. level of resistance or fitness) and because of the ease of selecting for increased antibiotic resistance, TEM-1 has been used as a model in studies that seek new methods to optimize proteins. These studies combine the power of in vitro mutagenesis and in vivo selection and have resulted in a wealth of information about which mutations can increase resistance when the enzyme is exposed to an antibiotic that it initially hydrolyzes inefficiently. At a later stage, these techniques were adopted and used to repeat and predict the natural evolution of TEM-1 under various selective conditions. Recently, TEM-1 is increasingly being used as an experimental model for the study of fundamental evolutionary questions, particularly those that benefit from the direct relationship between genotype and phenotype.
In this thesis, both the natural and laboratory evolution of TEM-1 are studied. The aim of the laboratory work is to increase our understanding of the way in which adaptive mutations interact. For this purpose, TEM-1 is mutagenized using error-prone PCR, which creates variation in the resulting copies of the TEM-1 gene. Mutated gene-copies are placed in bacteria which are subsequently selected for increased resistance to cefotaxime (an antibiotic that TEM-1 hydrolyzes poorly). By repeating this process multiple times in independent experiments, the mutations and mutational trajectories involved in the increase of cefotaxime resistance are studied. At a fundamental level, this has lead to a better understanding of the nature of mutation interaction and its consequences for evolutionary contingency and constraint. Evidence indicating that certain ‘silent’ mutations (i.e. mutations that alter the codon sequence but not the amino acid that the respective codon encodes) can also play a role in increased resistance was found in these data as well.
A phylogenetic study of the sequences of the ~150 different TEM-alleles that have been isolated in hospitals and clinics so far indicates that recombination has played a significant role in the evolution of TEM-alleles, contrary to what is often assumed. Furthermore, amino acid substitutions present in these clinical isolates are compared to those found in laboratory evolution studies of TEM-1, in order to investigate to what extent laboratory evolution can be used as a predictive tool for the natural evolution of antibiotic resistance genes. This overview indicates that laboratory evolution very accurately repeats the natural evolution of TEM-1. Based on these findings, predictions are made about substitutions that may appear in future clinical TEM-isolates, and directions are given how laboratory evolution can be exploited as a predictive tool most efficiently.