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Increase of ciprofloxacin resistance in Campylobacter species in Styria, Austria
Zbl. Bakt. 281, 471--474 (1994) © Gustav Fischer Verlag, Stuttgart . Jena . New York
Increase of Ciprofloxacin Resistance in Campylobacter species in Styria, Austria GEBHARD FEIERL, ANDREA PSCHAID, BIRGIT SIXL, and EGON MARTH Institute of Hygiene, Karl-Franzens-Universitat Graz, Austria (Chair: o. Univ. Prof. DDr. E. Marth) Received December 31, 1993 . Revision received February 25, 1994 . Accepted April 28, 1994
Abstract Salmonella spp. and thermophilic Campylobacter spp. are the most important diarrheacausing pathogens in the area investigated in Styria, Austria. The isolation rate of Campylobacter in the more than 62,000 stool specimens investigated in the six-year period between 1988 and 1993 ranged between 1.90% in 1988 and 3.58% in 1991. The testing of susceptibility to nalidixic acid has been an usual characteristic for species identification. Nalidixic acid-resistant strains were rare in 1988-1990, but in the summer of 1991, we found an increasing number of these isolates. At the same time, we learnt about the increasing use of enrofloxacin in veterinary medicine, especially in the poultry industry, and therefore we started routine testing of Campylobacter spp. susceptibility to ciprofloxacin in 1992. In 1992, the resistance rate to ciprofloxacin was already 16.9%, rising to 22.1 % in 1993.
Methods Isolation and susceptibility testing were performed by using the routine media and methods. In order to verify our ciprofloxacin testing results obtained with the aid of agar diffusion, we conducted an additional E test (AB Biodisk) on 78 isolates in 1993. Only in 2 isolates, a clear-cut classification by agar diffusion was impossible, and according to the recommendations of NCCLS (12), these two strains were classified as moderately sensitive by the E test.
Results and Discussion In the years 1988-1989, a dramatic increase in salmonella infecions in humans, largely due to S. enteritidis PT 4, could be seen in Austria. The National Salmonella Centre of Austria in Graz reported a rise in total numbers of human salmonella isolates from 3,475 in 1988 to 6,047 in 1989, and up to 13,520 in 1992.
472
G. Feierl, A. Pschaid, B. Sixl, and E. Marth
Facing this epidemic situation, the Austrian gouvernment passed legislation on poultry hygiene the so-called "Gefliigelhygieneverordnung", which became effective in 1. 1. 1992. In this statutory order with the force of law, quality control, measures of hygiene, obligatory testing of poultry prior to slaughter and other procedures were established for the poultry industry. A side-effect of this regulation was an increasing use of antibiotics in prevention and therapy in the poultry industry and especially enrofloxacin was administered preferentially. Salmonella infections in humans are showing a downward tendency now, the total number of human salmonella-isolates having decreased to 11,336 in 1993. But on the other side, the number of infections caused by Campylobaeter spp. is constant and the rate of resistance to ciprofloxacin is now more than 20%. In the last 6 years (1988-1993), 62,023 stool specimens were investigated in our laboratory and 1,608 campylobacter isolates were found. The mean isolation rate was 2.59%. The development of ciprofloxacin resistance in the last two years is shown in Fig. 1. Taking into consideration the nalidixic acid test results, a conclusion about ciprofloxacin resistance can be drawn also for the years before the actual testing was started. 25%
II
Resistance to nalidixic
•
Resistance to ciprofloxoc,n
acid
-------~~~~~~-
20% 15% 10% 5% 0%
198f
1989
1990
1991
1992
1993
Fig. 1. Nalidixic acid and ciprofloxacin resistance in thermophilic campylobacter isolated from human stools Figure 2, showing the situation in several European countries (1-10, 14-16), demonstrates that the increase in ciprofloxacin resistance is not only a local phenomen in Styria. While there are few to no problems with resistance in the Scandinavian COuntries, it seems to be much more prevalent in southern European countries. Recent reports have shown ciprofloxacin resistance rates of Campylabaeter spp. of 32% in Greece (4) and even 55% in Spain (11). Several studies confirming our results attribute this development to the use of enrofloxacin in veterinary medicine, especially in the poultry industry (6, 7, 13). Another reason, in our view much less significant, is the administration of quinolones in human medicine or the development of resistance in the course of quinolone therapy. However, sensitivity to nalidixic acid can no longer be used as the only diagnostic criterion in order to differentiate between Campylabaeter lari and Campylabaeter coli. Additional tests are required.
Ciprofloxacin Resistance in Campylobacter species 1985 Austria Germany SwiUerland Sweden Norway Finland Netherlands England Italy Spain Greece
1986
1987
0,0%
1989
1988
1990
473
1991
1992
0,0% 8,5%
1,9%-3%
4,9%
13,0%
29,8%
0,0% 0,0% 3.4% 0,7% 0,0% 9,0%
0,0%
11,0%
8,0%
0,0%
0,0%
0,0%
2,3%
3,4%
I
24,5% 32,2%
Fig. 2. Ciprofloxacin resistance in Campylobacter spp.: distribution in Europe
The resistance pattern of Campylabacter spp. should be tested to evaluate the epidemiological situation in the area in question. The use of enrofloxacin in prophylaxis and therapy in veterinary medicine should be handled restrictively; limitations to its use should be considered. However, in most cases campylobacter-associated diarrhea is self-limiting and mild. Antibiotic therapy is generally not required. In systemic infections or persistance of the organism, macrolides are the therapeutic agents of choice, with still low resistance rates (1992: 1.34% and 1993: 0.84°;;,).
References 1. Adler-Mosca, H. and M. Altwegg: Fluoroquinolone resistance in Campylobacter jejuni
and Campylobacter coli isolated from human faeces in Switzerland. J. Infect 23 (1991) 341-342 2. Bar, W., G. Fricke, and H. Goossens: Distribution of serotypes and biotypes of thermophilic Campylobacters in the Federal Republic of Germany: A comparison with other countries. Zbl. Bakt. 271 (1989) 127-134 3. Bowler, 1. and D. Day: Emerging quinolone resistance in campylobacters. Lancet 340 (1992) 245 4. Chatzipanagiotou, S., E. Papavasiliou, and E. Malamou-Lada: Isolation of Campylobacter jejuni strains resistant to nalidixic acid and fluoroquinolones from children with diarrhea in Athens, Greece. Eur. ]. Clin. Microbiol. Infect. Dis. Vol. 12 (1993) 566-568 5. Crotti, D., E. Pacifico, S. Brodi, and S. Rossi: Detection of resistance among Campylobacter spp. The case of quinolones. Alpe Adria Microbiology Journal 2 (1993) 115-121 6. Endtz, H. P., G. j. Ruijs, B. Klingeren, W. H. Jansen, T. Reyden, and R. P. Mouton: Quinolone resistance in campylobactcr isolated from man and poultry following the introduction of fluoroquinolones in veterinary medicine. J. Antimicrob. Chemother. 27 (1991) 199-208 7. Endtz, H. P., R. P. Mouton, T. Reyden, G. j. Ruijs, M. Biever, and B. Klingeren: Fluoroquinolone resistance in Campylobacter spp. isolated from human stools and poultry products. Lancet .335 (1990) 787
474
G. Feierl, A. Pschaid, B. Sixl, and E. Marth
8. Hirschi, A. M., D. Wolf, j. Berger, and M. L. Rotter: In vitro Susceptibility of Campylobacter jejuni and Campylobacter coli isolated in Austria to erythromycin and ciprofloxacin. Zbl. Bakt. 272 (1990) 443-447 9. Kapperud, G., j. Lassen, S. M. Ostroff, and S. Aasen: Clinical Features of sporadic Campylobacter infections in Norway. Scand. J. Infect. Dis. 24 (1992) 741-749 10. McIntyre, M. and M. Lyons: Resistance to ciprofloxacin in Campylobacter spp. Lancet 341 (1992) 188 11. Navarro, F., E. Mira, C. Izquierdo, B. Mirelis, and G. Prats: Increased resistance of enteropathogens to fluoroquinolones in Barcelona, Spain. Eur. J. Clin. Microbiol. Infect. Dis. Vol. 12 (1993) 645-646 12. NCCLS Vol 12 NO. 20 Dec, M 100-S4: (M2-A4) 13. Perez- Trallero, E., M. Urbieta, C. L. Lopategui, C. Zigorraga, and I. Ayestaran: Antibiotics in veterinary medicine and public health. Lancet 342 (1993) 1371-1372 14. Rautelin, H., O. Renkonen, and T. U. Kosunen: Emergence of fluoroquinolone resistance in Campylobacter jejuni and Campylobacter coli in subjects from Finland. Antimkrobial Agents and Chemotherapy 35 (1991) 2065-2069 15. Reina, j., N. Borrell, and A. Serra: Emergence of resistance to erythromycin and flu oroquinolones in thermotolerant Campylobacter strains isolated from feces 1987-1991. Eur. J. Clin. Microbiol. Infect. Dis. Vol. 11 (1992) 1163-1165 16. Sjogren, E., B. Kaijser, and M. Werner: Antimicrobial susceptibilities of Campylobacter jejuni and Campylobacter coli isolated in Sweden: a 10-year follow-up report. Antimicrob. Agents Chemother. 36 (1992) 2847-2849
Dr. Gebhard Feierl, Hygiene-Institut der Universitat Graz, Universitatsplatz 4, A-8010 Graz, Austria
Increase of Ciprofloxacin Resistance in Campylobacter species in Styria, Austria GEBHARD FEIERL, ANDREA PSCHAID, BIRGIT SIXL, and EGON MARTH Institute of Hygiene, Karl-Franzens-Universitat Graz, Austria (Chair: o. Univ. Prof. DDr. E. Marth) Received December 31, 1993 . Revision received February 25, 1994 . Accepted April 28, 1994
Abstract Salmonella spp. and thermophilic Campylobacter spp. are the most important diarrheacausing pathogens in the area investigated in Styria, Austria. The isolation rate of Campylobacter in the more than 62,000 stool specimens investigated in the six-year period between 1988 and 1993 ranged between 1.90% in 1988 and 3.58% in 1991. The testing of susceptibility to nalidixic acid has been an usual characteristic for species identification. Nalidixic acid-resistant strains were rare in 1988-1990, but in the summer of 1991, we found an increasing number of these isolates. At the same time, we learnt about the increasing use of enrofloxacin in veterinary medicine, especially in the poultry industry, and therefore we started routine testing of Campylobacter spp. susceptibility to ciprofloxacin in 1992. In 1992, the resistance rate to ciprofloxacin was already 16.9%, rising to 22.1 % in 1993.
Methods Isolation and susceptibility testing were performed by using the routine media and methods. In order to verify our ciprofloxacin testing results obtained with the aid of agar diffusion, we conducted an additional E test (AB Biodisk) on 78 isolates in 1993. Only in 2 isolates, a clear-cut classification by agar diffusion was impossible, and according to the recommendations of NCCLS (12), these two strains were classified as moderately sensitive by the E test.
Results and Discussion In the years 1988-1989, a dramatic increase in salmonella infecions in humans, largely due to S. enteritidis PT 4, could be seen in Austria. The National Salmonella Centre of Austria in Graz reported a rise in total numbers of human salmonella isolates from 3,475 in 1988 to 6,047 in 1989, and up to 13,520 in 1992.
472
G. Feierl, A. Pschaid, B. Sixl, and E. Marth
Facing this epidemic situation, the Austrian gouvernment passed legislation on poultry hygiene the so-called "Gefliigelhygieneverordnung", which became effective in 1. 1. 1992. In this statutory order with the force of law, quality control, measures of hygiene, obligatory testing of poultry prior to slaughter and other procedures were established for the poultry industry. A side-effect of this regulation was an increasing use of antibiotics in prevention and therapy in the poultry industry and especially enrofloxacin was administered preferentially. Salmonella infections in humans are showing a downward tendency now, the total number of human salmonella-isolates having decreased to 11,336 in 1993. But on the other side, the number of infections caused by Campylobaeter spp. is constant and the rate of resistance to ciprofloxacin is now more than 20%. In the last 6 years (1988-1993), 62,023 stool specimens were investigated in our laboratory and 1,608 campylobacter isolates were found. The mean isolation rate was 2.59%. The development of ciprofloxacin resistance in the last two years is shown in Fig. 1. Taking into consideration the nalidixic acid test results, a conclusion about ciprofloxacin resistance can be drawn also for the years before the actual testing was started. 25%
II
Resistance to nalidixic
•
Resistance to ciprofloxoc,n
acid
-------~~~~~~-
20% 15% 10% 5% 0%
198f
1989
1990
1991
1992
1993
Fig. 1. Nalidixic acid and ciprofloxacin resistance in thermophilic campylobacter isolated from human stools Figure 2, showing the situation in several European countries (1-10, 14-16), demonstrates that the increase in ciprofloxacin resistance is not only a local phenomen in Styria. While there are few to no problems with resistance in the Scandinavian COuntries, it seems to be much more prevalent in southern European countries. Recent reports have shown ciprofloxacin resistance rates of Campylabaeter spp. of 32% in Greece (4) and even 55% in Spain (11). Several studies confirming our results attribute this development to the use of enrofloxacin in veterinary medicine, especially in the poultry industry (6, 7, 13). Another reason, in our view much less significant, is the administration of quinolones in human medicine or the development of resistance in the course of quinolone therapy. However, sensitivity to nalidixic acid can no longer be used as the only diagnostic criterion in order to differentiate between Campylabaeter lari and Campylabaeter coli. Additional tests are required.
Ciprofloxacin Resistance in Campylobacter species 1985 Austria Germany SwiUerland Sweden Norway Finland Netherlands England Italy Spain Greece
1986
1987
0,0%
1989
1988
1990
473
1991
1992
0,0% 8,5%
1,9%-3%
4,9%
13,0%
29,8%
0,0% 0,0% 3.4% 0,7% 0,0% 9,0%
0,0%
11,0%
8,0%
0,0%
0,0%
0,0%
2,3%
3,4%
I
24,5% 32,2%
Fig. 2. Ciprofloxacin resistance in Campylobacter spp.: distribution in Europe
The resistance pattern of Campylabacter spp. should be tested to evaluate the epidemiological situation in the area in question. The use of enrofloxacin in prophylaxis and therapy in veterinary medicine should be handled restrictively; limitations to its use should be considered. However, in most cases campylobacter-associated diarrhea is self-limiting and mild. Antibiotic therapy is generally not required. In systemic infections or persistance of the organism, macrolides are the therapeutic agents of choice, with still low resistance rates (1992: 1.34% and 1993: 0.84°;;,).
References 1. Adler-Mosca, H. and M. Altwegg: Fluoroquinolone resistance in Campylobacter jejuni
and Campylobacter coli isolated from human faeces in Switzerland. J. Infect 23 (1991) 341-342 2. Bar, W., G. Fricke, and H. Goossens: Distribution of serotypes and biotypes of thermophilic Campylobacters in the Federal Republic of Germany: A comparison with other countries. Zbl. Bakt. 271 (1989) 127-134 3. Bowler, 1. and D. Day: Emerging quinolone resistance in campylobacters. Lancet 340 (1992) 245 4. Chatzipanagiotou, S., E. Papavasiliou, and E. Malamou-Lada: Isolation of Campylobacter jejuni strains resistant to nalidixic acid and fluoroquinolones from children with diarrhea in Athens, Greece. Eur. ]. Clin. Microbiol. Infect. Dis. Vol. 12 (1993) 566-568 5. Crotti, D., E. Pacifico, S. Brodi, and S. Rossi: Detection of resistance among Campylobacter spp. The case of quinolones. Alpe Adria Microbiology Journal 2 (1993) 115-121 6. Endtz, H. P., G. j. Ruijs, B. Klingeren, W. H. Jansen, T. Reyden, and R. P. Mouton: Quinolone resistance in campylobactcr isolated from man and poultry following the introduction of fluoroquinolones in veterinary medicine. J. Antimicrob. Chemother. 27 (1991) 199-208 7. Endtz, H. P., R. P. Mouton, T. Reyden, G. j. Ruijs, M. Biever, and B. Klingeren: Fluoroquinolone resistance in Campylobacter spp. isolated from human stools and poultry products. Lancet .335 (1990) 787
474
G. Feierl, A. Pschaid, B. Sixl, and E. Marth
8. Hirschi, A. M., D. Wolf, j. Berger, and M. L. Rotter: In vitro Susceptibility of Campylobacter jejuni and Campylobacter coli isolated in Austria to erythromycin and ciprofloxacin. Zbl. Bakt. 272 (1990) 443-447 9. Kapperud, G., j. Lassen, S. M. Ostroff, and S. Aasen: Clinical Features of sporadic Campylobacter infections in Norway. Scand. J. Infect. Dis. 24 (1992) 741-749 10. McIntyre, M. and M. Lyons: Resistance to ciprofloxacin in Campylobacter spp. Lancet 341 (1992) 188 11. Navarro, F., E. Mira, C. Izquierdo, B. Mirelis, and G. Prats: Increased resistance of enteropathogens to fluoroquinolones in Barcelona, Spain. Eur. J. Clin. Microbiol. Infect. Dis. Vol. 12 (1993) 645-646 12. NCCLS Vol 12 NO. 20 Dec, M 100-S4: (M2-A4) 13. Perez- Trallero, E., M. Urbieta, C. L. Lopategui, C. Zigorraga, and I. Ayestaran: Antibiotics in veterinary medicine and public health. Lancet 342 (1993) 1371-1372 14. Rautelin, H., O. Renkonen, and T. U. Kosunen: Emergence of fluoroquinolone resistance in Campylobacter jejuni and Campylobacter coli in subjects from Finland. Antimkrobial Agents and Chemotherapy 35 (1991) 2065-2069 15. Reina, j., N. Borrell, and A. Serra: Emergence of resistance to erythromycin and flu oroquinolones in thermotolerant Campylobacter strains isolated from feces 1987-1991. Eur. J. Clin. Microbiol. Infect. Dis. Vol. 11 (1992) 1163-1165 16. Sjogren, E., B. Kaijser, and M. Werner: Antimicrobial susceptibilities of Campylobacter jejuni and Campylobacter coli isolated in Sweden: a 10-year follow-up report. Antimicrob. Agents Chemother. 36 (1992) 2847-2849
Dr. Gebhard Feierl, Hygiene-Institut der Universitat Graz, Universitatsplatz 4, A-8010 Graz, Austria