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• W2046884192 abstract "The provocative article by Professor Radostits poses several important questions regarding relationships between the use of fluoroquinolone antimicrobials in poultry and the world-wide emergence of strains of campylobacter exhibiting resistance to this group of antimicrobials.1.Radostits OM. Fluoroquinolone resistance trends and animal drug use: a retrospective analysis. Int J Infect Dis 2004;8:187–9.Google Scholar In particular the author has drawn attention to possible anomalies in the data of Endtz and colleagues, that demonstrated an increase in resistance to fluoroquinolones from 0% in 1982 to 11% in 1989 in human isolations of Campylobacter jejuni in the Netherlands following the licensing of this group of antimicrobials for use in poultry, cattle and pigs in 1987.2.Endtz H.P. Ruijs G.J. vanKilgeren B. Jansen W.H. vander Reyden T. Mouton R.P. Quinolone resistance in Campylobacter isolated from man and poultry following the introduction of fluoroquinolones in veterinary medicine.J. Antimicrob. Chemother. 1991; 27: 199-208Crossref PubMed Scopus (469) Google Scholar Radostits has questioned the validity of these and other data. This is because strains of C. lari are intrinsically resistant to nalidixic acid and resistance to this antimicrobial was used in many laboratories as a preliminary screen for differentiating between Campylobacter lari and Campylobacter jejuni/Campylobacter coli. By this logic, strains with resistance to nalidixic acid were often classified as C. lari without recourse to further tests. As all strains of Campylobacter spp. that exhibit resistance to fluoroquinolones are invariably resistant to nalidixic acid, strains of C. jejuni with such resistance may have been ‘missed’. On this basis the conclusions of Endtz and colleagues relating to fluoroquinolone usage in food-producing animals may be incorrect, and the 0% baseline of fluoroquinolone resistance in campylobacter in the USA in 19913.US FDA Center for Veterinary Medicine (CVM). Notice of opportunity for hearing for proposal to withdraw approval of new animal drug application for enrofloxacin. Code of the Federal Register 65, No. 211: 64954-5. 31 October, 2000.Google Scholar may have been false. Fortunately Endtz and colleagues were well aware of this possibility. As they were unable to distinguish between quinolone-resistant C. coli and C. lari using conventional methods, a range of additional tests were performed on all quinolone-resistant strains tested in their study and in addition, the results of identification and biotyping were confirmed by the WHO Collaborating Centre for Campylobacter Infections. By these tests none of the quinolone-resistant strains were identified as C. lari. Thus, although the possibility that a very small number of strains of C. jejuni/C. coli isolated from poultry and humans in the Netherlands between 1982 and 1989 may have been missed cannot be totally excluded, the findings of Endtz and colleagues are sound and the conclusions perfectly justifiable. These results and conclusions have subsequently been reinforced by reports from numerous countries throughout the world. Data for human isolates of C. coli and C. jejuni from Denmark, the UK, the USA, Italy, Finland, the Netherlands, France, Austria and Spain have demonstrated increases in the incidence of resistance to fluoroquinolones from <1% to between 10% (UK) and 80% (Spain) following the licensing of such antibiotics for use in food animals, predominantly poultry, in the respective countries in the 1980s and 1990s.4.Engberg J. Aarestrup F.M. Taylor D.E. Gerner-Smidt P. Nachamkin I. Quinolone and macrolide resistance in Campylobacter jejuni and C. coli: resistance mechanisms and trends in human isolates.Emerg. Infect. Dis. 2001; 7: 102-105Crossref Scopus (546) Google Scholar More recent data from the UK have shown an increase of the incidence of fluoroquinolone-resistant isolates of C. jejuni from humans from 10% in 1993–96 to 21% in 2003. Again, the use of fluoroquinolones in poultry was considered an important contributory factor, although foreign travel was also implicated in a significant number of infections.7.Campylobacter Sentinel Surveillance Scheme Collaborators. Ciprofloxacin resistance in Campylobacter jejuni: case-case analysis as a tool for elucidating risks at home and abroad. J Antimicrob Chemother 2002;50:561–68.Google Scholar It is widely accepted that an important source of campylobacter causing infections in humans world-wide is poultry. The implications from studies quoted above are that fluoroquinolone resistance in C. jejuni and C. coli from cases of human infection in many countries and the use of fluoroquinolones in food animals, particularly poultry, are inextricably linked. These conclusions are reinforced by findings from Australia, a country that has not allowed the use of fluoroquinolones in food animals and where domestically-acquired campylobacter infections are susceptible to these antimicrobials.5.Unicomb L. Ferguson J. Riley T.V. Collignon P. Fluoroquinolone resistance in Campylobacter absent from isolates, Australia.Emerg. Infect. Dis. 2003; 9: 1482-1483Crossref PubMed Scopus (55) Google Scholar Thus, although increases in the occurrence of resistance to fluoroquinolones in isolations of campylobacter from humans and the licensing/use of such compounds in food animals and particularly poultry is for the most part temporal, the conclusion that such increases are linked to fluoroquinolone usage in this animal species is fully justifiable. As Radostits points out, the contribution of foreign travel in the occurrence of fluoroquinolone-resistant strains of campylobacter from cases of infection in humans cannot be overlooked. In a study in the USA reported in 1999, a significant proportion of patients infected with isolates with resistance to fluoroquinolones had acquired their infections abroad.6.Smith K.E. Besser J.M. Hedberg C.W. et al.Quinolone-resistant Campylobacter jejuni infections in Minnesota, 1992–1998.N Engl. J. Med. 1999; 340: 1525-1532Crossref PubMed Scopus (545) Google Scholar Similarly in the UK, 55% of campylobacter infections acquired abroad in the period 1 April 2000 to 31 May 2001 were resistant to ciprofloxacin compared with 10% of UK-acquired strains.7.Campylobacter Sentinel Surveillance Scheme Collaborators. Ciprofloxacin resistance in Campylobacter jejuni: case-case analysis as a tool for elucidating risks at home and abroad. J Antimicrob Chemother 2002;50:561–68.Google Scholar More recently, in the USA both eating poultry outside the home and foreign travel have been identified as risk factors for infections with fluoroquinolone-resistant campylobacter.8.Kassenbourg HD, Smith KE, Vugia DJ, et al. Fluoroquinolone-resistant campylobacter infections: eating poultry outside the home and foreign travel are risk factors. Clin Infect Dis 2004, in press.Google Scholar However, what is not clear is whether patients infected with fluoroquinolone-resistant strains following foreign travel had acquired their infections from contaminated poultry meat in the countries visited, or resistance had arisen as a result of the use of such antimicrobials in human medicine in the countries concerned. For patients from the UK the most commonly-visited foreign country was Spain,7.Campylobacter Sentinel Surveillance Scheme Collaborators. Ciprofloxacin resistance in Campylobacter jejuni: case-case analysis as a tool for elucidating risks at home and abroad. J Antimicrob Chemother 2002;50:561–68.Google Scholar where fluoroquinolone-resistant campylobacters are endemic in poultry and where 80% of strains from cases of human infection in 2000 were ciprofloxacin-resistant.4.Engberg J. Aarestrup F.M. Taylor D.E. Gerner-Smidt P. Nachamkin I. Quinolone and macrolide resistance in Campylobacter jejuni and C. coli: resistance mechanisms and trends in human isolates.Emerg. Infect. Dis. 2001; 7: 102-105Crossref Scopus (546) Google Scholar However, in a study of patients from the USA who acquired their infections with fluoroquinolone-resistant campylobacter whilst in Thailand, where fluoroquinolones are allegedly not used in poultry, prophylactic treatment with ciprofloxacin for travellers’ diarrhoea may have been an important contributory factor.9.Kuschner R.A. Trofa A.F. Thomas R.J. et al.Use of azithromycin for the treatment of Campylobacter enteritis in travellers to Thailand, an area where ciprofloxacin resistance is prevalent.Clin. Infect. Dis. 1995; 21: 536-541Crossref PubMed Scopus (222) Google Scholar It also should be realised that the use of fluoroquinolone antimicrobials in food-production animals and the appearance of resistance is not confined to campylobacter. In the UK, the appearance and spread of muliple drug-resistant strains of Salmonella enterica serotype Typhimurium definitive phage type (DT) 104 (=DT104) with additional decreased susceptibility to ciprofloxacin was temporally linked to the licensing of fluoroquinolone compounds for use in food production animals in 1993.10.Threlfall E.J. Ward L.R. Rowe B. Increasing incidence of resistance to trimethoprim and ciprofloxacin in epidemic Salmonella typhimurium DT 104 in England and Wales.Eurosurv. 1997; 2: 81-84Google Scholar In 1999 the use of a fluoroquinolone-containing compound for the treatment of cattle infected with multiple-resistant DT104 was demonstrated to be an important factor in the development of resistance to quinolones in such strains, which subsequently caused over 100 infections in humans.11.Walker R.A. Lawson A.J. Lindsay E.A. Ward L.R. Wright P.A. Bolton F.J. Wareing D.R. Corkish J.D. Davies R.H. Threlfall E.J. Decreased susceptibility to ciprofloxacin in outbreak-associated multiresistant Salmonella typhimurium DT104.Vet. Rec. 2000; 147: 395-396Crossref PubMed Scopus (64) Google Scholar The message from the above reports is that the use of antimicrobials such as the fluoroquinolones is inextricably linked to the development of resistance in target organisms. When the organisms are zoonotic, and when the antimicrobials are used in food animals, then such animals will eventually harbour resistant organisms capable of causing disease in humans. Likewise, the use of antimicrobials such as the fluoroquinolones in human medicine will also promote the development of resistance. When such antimicrobials are used in an indiscriminate manner, as for example for the prophylaxis of syndromes such as traveller’s diarrhoea, then resistant organisms will emerge and proliferate in the human host. Retrospectively, the licensing of fluoroquinolone antimicrobials for use in food production animals on a worldwide scale may have been unwise, as such usage has undoubtedly resulted in the appearance and spread in food animals of strains of campylobacter and salmonella capable of causing disease in humans. However the indiscriminate use of this important group of antimicrobials in human medicine is also to be deplored, and has probably contributed not only to the high incidence of ciprofloxacin-resistant campylobacter in Thailand,9.Kuschner R.A. Trofa A.F. Thomas R.J. et al.Use of azithromycin for the treatment of Campylobacter enteritis in travellers to Thailand, an area where ciprofloxacin resistance is prevalent.Clin. Infect. Dis. 1995; 21: 536-541Crossref PubMed Scopus (222) Google Scholar but also to the appearance and spread of strains of S. typhi and S. paratyphi A with decreased susceptibility to ciprofloxacin in several countries in the Indian sub-continent.12.Threlfall E.J. Skinner J.A. Ward L.R. Detection of decreased in vitro susceptibility to ciprofloxacin in Salmonella enterica serotypes Typhi and Paratyphi A.J. Antimicrob. Chemother. 2001; 8: 740-741Crossref Google Scholar To combat antimicrobial resistance in pathogens such as campylobacter and salmonella, principles of prudent usage should be applied at all times in both veterinary and human medicine. I am grateful to staff of the Health Protection Agency Campylobacter and Helicobacter Reference Unit for providing data relating to the incidence of fluoroquinolone-resistant campylobacter in the UK in humans in 2003, and for critically reading this manuscript. Conflict of interest: No conflicting interest declared." @default.
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• W2046884192 title "Fluoroquinolone-resistant Campylobacter infections and animal drug use" @default.
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