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Danger of antibiotic resistance in shigellosis
186
Danger of antibiotic resistance in shigellosis SIR,-Dr Williams and Dr Richards (June 2, p 1343) suggest that single-dose ciprofloxacin is useful for diarrhoeal disease due to Shigella sonnei infection. We wish to call attention to antibiotic resistance in this disease. Shigellae have become resistant to most antimicrobial agents used in its treatment.1,2 In most developing countries antibiotics are available without prescription, and there should be public awareness about the misuse of antibiotics. We have investigated drug resistance in Shigella strains prospectively in a rural area near Ankara (Sflexneri in 21 patients; S sonnei in 8; S boydii in 1).3 Comparison with data from the same region in 19814 showed that the resistance to shigellae had increased:
emphasise that antibiotics should be used mainly in severe shigella dysentery (particularly that due to S dysenteriae). On the other hand, the World Health Organisation recommends antibiotic therapy only for S dysenteriae, which is the agent responsible for severe shigellosis.5 Antibiotics should be used with care in this disease because of the danger of antibiotic resistance. We wish
to
Department of Paediatrics, Medical Centre Hospital, Turkish Health and Therapy Foundation, 06510 Fmok, Ankara, Turkey
I. SAFA KAYA UĞUR DILMEN DURSUN ALI SENSES
1. Kaya IS, Ceyhan M, Dilmen U, et al Therapy for shigellosis J Pediatr 1989, 115: 168. 2. Mitra AK, Kabir I, Hossain MA. Pivmecillinam-resistant Shigella dysenteriae type 1 infection m Bangladesh Lancet 1990; i: 1461-62 3. Ceyhan M, Dilmen U, Korten V, Mert A Shigella diarrhoea and treatment Lancet 1988; ii: 45-46 4. Berkman D. The serotypes and antibiotic resistance of shigellae. Çocuk Sağl Hast Derg
1983, 26: 277-86 5. World Health
Organisation. A manual for the treatment of acute diarrhoea, programme the control of diarrhoel disease. WHO/CDD/Ser/80.2, 1984.
Fluoroquinolone-resistance in thermophilic Campylobacter spp isolated from stools of Spanish patients SIR,-Dr Endtz and his colleagues (March 31, p 787) report resistance to fluoroquinolones in campylobacter strains isolated from man and poultry products in the Netherlands. We report our findings in Spanish patients with diarrhoea. Before 1987, no campylobacter strains isolated in our laboratory demonstrated resistance to fluoroquinolones. In 1988, however, 3/126 strains (2-3%) and in 1989 5/146 (3-4%) showed resistance to nalidixic acid, ciprofloxacin, and norfloxacin; all resistant strains were identified as C jejuni. Resistance to erythromycin was detected in 17-6% of C coli strains and in only 1-4% of C jejuni.l The appearance of resistance to the fluoroquinolones in our country has been reported by ourselves2 and accords with the findings in other countries.3 C jejuni strains, originally susceptible to norfloxacin, may become resistant during the course of treatment.4 This finding has been substantiated by Segreti et al,5who observed that in patients with enteritis up to 20% C jejuni strains that were susceptible to ciprofloxacin before treatment became resistant to this antibiotic. Despite the fact that most strains studied in vitro are highly
susceptible to the fluoroquinolones (minimum inhibitory concentration below 05 µg/ml), spontaneous mutations produced during in vivo administration are selective for a resistant population. Although total resistance to the fluoroquinolones is unusual, one-step resistance occurs (either spontaneously or by induction), with a frequency of 1 in 107 to 1 in 108. This facilitates the selection of resistant strains because of the large bacterial population in the faeces of patients with enteritis due to thermophilic campylobacter. We have no evidence of the use of fluoroquinolones or their derivatives in veterinary practice in our country. We believe, therefore, that our rates of resistance, which are lower than those
reported by Endtz et al, are the result of the indiscriminate use of these antibiotics for the treatment of non-specific bacterial infections in man. We therefore think the use of fluoroquinolones should be controlled in man as well as, if possible, in animals, to preserve the efficacy of these antibiotics in the acute diarrhoea due to
thermophilic Campylobacter spp.
Service of Microbiology, Hospital Son Dureta, 07014-Palma de Mallorca, Spain
JORDI REINA PEDRO ALOMAR
1. Reina J, Gomez J, Alomar P. Implicaciones terapeuticas de la identificacion de especie dentro del genero Camphylobacter. Enf Infect Microbiol Clin (in press) 2. Rema J, Parras F, Alomar P Detección de cepas de Campylobacter jejum resistentes a las quinolonas: resistencia post-tratamiento Rev Esp Microbiol Clin 1989; 4: 318. 3. Olsson-Liljequist B, Mollby R. In vitro activity of norfloxacin and other antibacterial agents against gastro-intestinal pathogens isolated in Sweden. APMIS 1990, 98: 150-55. 4. Altwegg M, Bumess A, Zollinger-Iten J, Penner JL. Problems in identification of C jejum associated with acquisition of resistance to nalidixic acid J Clin Microbiol 5.
1987; 25: 1807-08 Segreti J, Goodman LJ, Hines DW, et al Emergence of high level ciprofloxacin resistance in Campylobacter isolates during a clinical trial. Interscience Conference on Antimicrobial Agents and Chemotherapy, Los Angeles, 1989, p 118.
Vaccination
against Helicobacter pylori urease
SIR,-Dr Sidebotham and Dr Baron (Jan 27, p 193) and Dr Guslandi (March 24, p 728) suggest an important role for Helicobacter pylori urease in the pathogenesis of gastric ulceration, whereas Dr Mooney and colleagues (May 19, p 1232) show that this enzyme contributes to the acid resistance of H pylori, and hence to the organism’s survival in the gastric mucosa. Microbial ureases have proved important in the pathogenesis of various conditions in man, including urinary tract infection, urolithiasis, catheter encrustation and blockage, ammoniacal nappy rash, and, perhaps, hepatic encephalopathy.’ We have reported the nucleotide and derived aminoacid sequences of the Hpylori urease genes,2 and have uncovered some curious facts about ureases, which may be of relevance to the control of urease-associated disease in man. All bacterial urease sequences reported so far not only show evidence of a common evolutionary origin but also are extraordinarily closely related to the sequence of a plant enzyme, the jackbean urease. The aminoacid sequences of the major urease subunits from Proteus mirabilis, Proteus vulgaris, Ureaplasma urealyticum, and H pylori are identical in over 50% of aminoacid residues to the jackbean urease.3-5This degree of similarity is unexpected, in view of the very distant phylogenetic relation between plants and bacteria. Indeed, one wonders whether it reflects horizontal gene transfer from a plant to a bacterium, or vice versa, during evolution. It is well known that antibodies to plant ureases can bind to bacterial ureases. Vaccination of various domestic animals with the jackbean urease produces antibodies that can inhibit bacterial ureases.6 Furthermore, vaccination with the plant enzyme stimulates growth in young chicks, lambs, rats, and pigs, and vaccination of hens with this enzyme enhances the growth of their progeny through passive transfer of maternal anti-urease.6 The growth-enhancing effect of early vaccination with jackbean urease is thought to result from the suppression of ureolytic ammonia production in the gut, which allows animals to conserve the energy usually needed for detoxification of absorbed ammonia.6 Mooney and colleagues suggest that urease inhibitors could be used to treat H pylori infection, and other workers have investigated the potential of urease inhibitors in the treatment of other urease-associated conditions.1 Why has there been so little interest in vaccination against ureolytic organisms in man, with microbial, or even plant, ureases? Indeed, the possibility of any form of vaccination against H pylori infection seems to have received little attention. Surely, a vaccine against gastritis and peptic ulceration should rate as one of the "vaccines we need but do not have", as discussed by Robbins (June 19, p 1436)? We suggest that the approach of anti-urease vaccination holds promise. In view of the widespread occurrence of urease in plant tissues, would a urease-
Danger of antibiotic resistance in shigellosis SIR,-Dr Williams and Dr Richards (June 2, p 1343) suggest that single-dose ciprofloxacin is useful for diarrhoeal disease due to Shigella sonnei infection. We wish to call attention to antibiotic resistance in this disease. Shigellae have become resistant to most antimicrobial agents used in its treatment.1,2 In most developing countries antibiotics are available without prescription, and there should be public awareness about the misuse of antibiotics. We have investigated drug resistance in Shigella strains prospectively in a rural area near Ankara (Sflexneri in 21 patients; S sonnei in 8; S boydii in 1).3 Comparison with data from the same region in 19814 showed that the resistance to shigellae had increased:
emphasise that antibiotics should be used mainly in severe shigella dysentery (particularly that due to S dysenteriae). On the other hand, the World Health Organisation recommends antibiotic therapy only for S dysenteriae, which is the agent responsible for severe shigellosis.5 Antibiotics should be used with care in this disease because of the danger of antibiotic resistance. We wish
to
Department of Paediatrics, Medical Centre Hospital, Turkish Health and Therapy Foundation, 06510 Fmok, Ankara, Turkey
I. SAFA KAYA UĞUR DILMEN DURSUN ALI SENSES
1. Kaya IS, Ceyhan M, Dilmen U, et al Therapy for shigellosis J Pediatr 1989, 115: 168. 2. Mitra AK, Kabir I, Hossain MA. Pivmecillinam-resistant Shigella dysenteriae type 1 infection m Bangladesh Lancet 1990; i: 1461-62 3. Ceyhan M, Dilmen U, Korten V, Mert A Shigella diarrhoea and treatment Lancet 1988; ii: 45-46 4. Berkman D. The serotypes and antibiotic resistance of shigellae. Çocuk Sağl Hast Derg
1983, 26: 277-86 5. World Health
Organisation. A manual for the treatment of acute diarrhoea, programme the control of diarrhoel disease. WHO/CDD/Ser/80.2, 1984.
Fluoroquinolone-resistance in thermophilic Campylobacter spp isolated from stools of Spanish patients SIR,-Dr Endtz and his colleagues (March 31, p 787) report resistance to fluoroquinolones in campylobacter strains isolated from man and poultry products in the Netherlands. We report our findings in Spanish patients with diarrhoea. Before 1987, no campylobacter strains isolated in our laboratory demonstrated resistance to fluoroquinolones. In 1988, however, 3/126 strains (2-3%) and in 1989 5/146 (3-4%) showed resistance to nalidixic acid, ciprofloxacin, and norfloxacin; all resistant strains were identified as C jejuni. Resistance to erythromycin was detected in 17-6% of C coli strains and in only 1-4% of C jejuni.l The appearance of resistance to the fluoroquinolones in our country has been reported by ourselves2 and accords with the findings in other countries.3 C jejuni strains, originally susceptible to norfloxacin, may become resistant during the course of treatment.4 This finding has been substantiated by Segreti et al,5who observed that in patients with enteritis up to 20% C jejuni strains that were susceptible to ciprofloxacin before treatment became resistant to this antibiotic. Despite the fact that most strains studied in vitro are highly
susceptible to the fluoroquinolones (minimum inhibitory concentration below 05 µg/ml), spontaneous mutations produced during in vivo administration are selective for a resistant population. Although total resistance to the fluoroquinolones is unusual, one-step resistance occurs (either spontaneously or by induction), with a frequency of 1 in 107 to 1 in 108. This facilitates the selection of resistant strains because of the large bacterial population in the faeces of patients with enteritis due to thermophilic campylobacter. We have no evidence of the use of fluoroquinolones or their derivatives in veterinary practice in our country. We believe, therefore, that our rates of resistance, which are lower than those
reported by Endtz et al, are the result of the indiscriminate use of these antibiotics for the treatment of non-specific bacterial infections in man. We therefore think the use of fluoroquinolones should be controlled in man as well as, if possible, in animals, to preserve the efficacy of these antibiotics in the acute diarrhoea due to
thermophilic Campylobacter spp.
Service of Microbiology, Hospital Son Dureta, 07014-Palma de Mallorca, Spain
JORDI REINA PEDRO ALOMAR
1. Reina J, Gomez J, Alomar P. Implicaciones terapeuticas de la identificacion de especie dentro del genero Camphylobacter. Enf Infect Microbiol Clin (in press) 2. Rema J, Parras F, Alomar P Detección de cepas de Campylobacter jejum resistentes a las quinolonas: resistencia post-tratamiento Rev Esp Microbiol Clin 1989; 4: 318. 3. Olsson-Liljequist B, Mollby R. In vitro activity of norfloxacin and other antibacterial agents against gastro-intestinal pathogens isolated in Sweden. APMIS 1990, 98: 150-55. 4. Altwegg M, Bumess A, Zollinger-Iten J, Penner JL. Problems in identification of C jejum associated with acquisition of resistance to nalidixic acid J Clin Microbiol 5.
1987; 25: 1807-08 Segreti J, Goodman LJ, Hines DW, et al Emergence of high level ciprofloxacin resistance in Campylobacter isolates during a clinical trial. Interscience Conference on Antimicrobial Agents and Chemotherapy, Los Angeles, 1989, p 118.
Vaccination
against Helicobacter pylori urease
SIR,-Dr Sidebotham and Dr Baron (Jan 27, p 193) and Dr Guslandi (March 24, p 728) suggest an important role for Helicobacter pylori urease in the pathogenesis of gastric ulceration, whereas Dr Mooney and colleagues (May 19, p 1232) show that this enzyme contributes to the acid resistance of H pylori, and hence to the organism’s survival in the gastric mucosa. Microbial ureases have proved important in the pathogenesis of various conditions in man, including urinary tract infection, urolithiasis, catheter encrustation and blockage, ammoniacal nappy rash, and, perhaps, hepatic encephalopathy.’ We have reported the nucleotide and derived aminoacid sequences of the Hpylori urease genes,2 and have uncovered some curious facts about ureases, which may be of relevance to the control of urease-associated disease in man. All bacterial urease sequences reported so far not only show evidence of a common evolutionary origin but also are extraordinarily closely related to the sequence of a plant enzyme, the jackbean urease. The aminoacid sequences of the major urease subunits from Proteus mirabilis, Proteus vulgaris, Ureaplasma urealyticum, and H pylori are identical in over 50% of aminoacid residues to the jackbean urease.3-5This degree of similarity is unexpected, in view of the very distant phylogenetic relation between plants and bacteria. Indeed, one wonders whether it reflects horizontal gene transfer from a plant to a bacterium, or vice versa, during evolution. It is well known that antibodies to plant ureases can bind to bacterial ureases. Vaccination of various domestic animals with the jackbean urease produces antibodies that can inhibit bacterial ureases.6 Furthermore, vaccination with the plant enzyme stimulates growth in young chicks, lambs, rats, and pigs, and vaccination of hens with this enzyme enhances the growth of their progeny through passive transfer of maternal anti-urease.6 The growth-enhancing effect of early vaccination with jackbean urease is thought to result from the suppression of ureolytic ammonia production in the gut, which allows animals to conserve the energy usually needed for detoxification of absorbed ammonia.6 Mooney and colleagues suggest that urease inhibitors could be used to treat H pylori infection, and other workers have investigated the potential of urease inhibitors in the treatment of other urease-associated conditions.1 Why has there been so little interest in vaccination against ureolytic organisms in man, with microbial, or even plant, ureases? Indeed, the possibility of any form of vaccination against H pylori infection seems to have received little attention. Surely, a vaccine against gastritis and peptic ulceration should rate as one of the "vaccines we need but do not have", as discussed by Robbins (June 19, p 1436)? We suggest that the approach of anti-urease vaccination holds promise. In view of the widespread occurrence of urease in plant tissues, would a urease-