245
Emerging quinolone resistance in campylobacters SIR,-Dr Rowe and colleagues (March 21,
p
740) again
recommend ciprofloxacin for the treatment of multiresistant typhoid fever. Quinolones are also useful for the empirical therapy of selected cases of travellers’ diarrhoea’ and food poisoning caused
by other salmonellae and Campylobacter spp,2 especially in elderly
immunocompromised individuals.3 The efficacy of these agents depends partly on the very low prevalence of resistance in such pathogens, which unlike Salmonella typhi are largely of animal origin. Quinolones are now available for veterinary use, and their consumption by poultry has been linked to the emergence of quinolone resistance in campylobacters isolated from human subjects in the Netherlands.’ Strains of salmonellae resistant to quinolones have been isolated from chickens in the UK.s We have been screening salmonellae and campylobacters for ciprofloxacin resistance since 1988. Between January, 1988, and December, 1991, we examined 46 820 stools from patients in the or
Oxford
area.
Of the 1332 Salmonella spp grown,
none
was
ciprofloxacin resistant. During the same period we isolated 1240 campylobacters. Until the end of 1990 all were ciprofloxacin sensitive. However, during 1991 we isolated 359 campylobacters, of which 11 (3%) were resistant to ciprofloxacin (minimum inhibitory concentration > 32 mg/1). The 11patients with resistant strains were followed up via their general practitioners. 6 gave a history of foreign travel in the previous month (4 to the Mediterranean area,1 to India, 1 to SE Asia and India). One patient had received ciprofloxacin in the week before stool sampling, suggesting that resistance may have emerged during therapy.6 It is reassuring that at present salmonellae isolated from patients in the Oxford area remain susceptible to ciprofloxacin. However, campylobacters and salmonellae share a common ecological niche in poultry, and widespread use of quinolones in that industry risks the promotion of resistance in salmonellae as well as campylobacters. The future role of quinolones in the treatment of non-typhoidal enteric infections in man depends on restriction of their use in animals. We thank Dr J. Webberley, department of microbiology, Worcester Royal Infirmary, for confirming ciprofloxacin resistance in the campylobacters.
Department of Bacteriology, John Radcliffe Hospital, Oxford OX3 9DU, UK
IAN BOWLER DAVID DAY
been described previously.2 In addition, all serum samples were tested for antibodies against L pneumophila serogroup 1 after absorption with a mixture of equal amounts of a clinical strain of Cjejuni (RH-240481) and C coli (CIP 7080). If an increased antibody concentration against L pneumophila was caused by crossreactions between Campylobacter and Legionella spp, the legionella antibody values should decrease substantially after absorption of the serum samples with C jejuni and C coli. Only one serum sample had a low positive antibody titre (64) against L pneumophila serogroup 1. No decrease in the antibody concentrations against L pneumophila serogroup 1 was seen in this serum after absorption with C jejuni and C coli. All other serum samples proved negative by MAT. These results show that crossreactions between L pneumophila serogroup 1 and C jejuni/coli are unlikely to occur with MAT. The antigen preparation for the indirect immunofluorescence technique (IFAT) described in Boswell’s and Cheesbrough’s letters were formalised yolk-sac antigens. For MAT, heat killed bacteria were used as the antigen. Previous investigations have shown good correlation between IFAT methods using formalised and heat treated cells (as recommended by CDC, Atlanta), respectively,3 and between IFAT and MAT.1 The lack of crossreactivity between Legionella and Campylobacter spp in our small study suggests that the formalised antigen (including flagellar antigens) from L pneumophila serogroup 1 crossreacts with Campylobacter to a higher degree than the heat stable O-antigen (mainly lipopolysaccharide). In addition, IFAT measures direct binding between antigens and antibodies, whereas MAT also measures the secondary occurrence of agglutination, which may tend to reduce the unspecific reactions by MAT, compared with IF. It could be argued that the serum samples used in this study were from patients infected with different serogroups of campylobacters that did not crossreact with Legionella. We have found, however, about 30 different serotypes of campylobacter between 100 consecutive Danish strains (unpublished data). It is therefore unlikely that a crossreaction would be missed because of an over-representation of non-crossreacting serotypes. Department of Clinical Microbiology, University of Copenhagen, Rigshospitalet and Statens Seruminstitut, 2300 Copenhagen, Denmark
LEIF PERCIVAL ANDERSEN
JETTE BANGSBORG
1. Collins
MT, Lind K, Aalund O, McDonald J, Frederiksen W. Correlation between microagglutination and indirect fluorescent-antibody test for antibodies to 10 Legionellaceae antigens In: Thornberry C, Balows A, Feeley JC, Jacubowski W, eds. Legionella. Proceedings from the 2nd International Symposium. ASM, Washington 1984. 2. Andersen LP, Gaarslev K. Campylobacter jejuni/coli: Elevated IgA and IgM antibodies during acute infection. In Ruiz-Palacios GM, Calva E, Ruiz-Palacios BR. Campylobacter V. Istituto Nacional de la Nutricion, Mexico 1991. 3. Wilkinson HW, Brake BJ. Formalin-killed versus heat-killed Legionella pneumophila serogroup 1 antigen in the indirect immunofluorescence assay for legionellosis. J Clin Microbiol 1982; 16: 979-81. the
1. Ericson CD, Johnson PC, Dupont HL, et al. Ciprofloxacin or trimethoprimsulphamethoxazole as initial therapy for travellers’ diarrhoea. Ann Intern Med 1987; 106: 216-20. 2. Editorial. Quinolones in acute non-travellers’ diarrhoea. Lancet 1990; 336: 282. 3. Asperilla MO, Smego RA, Scott LK. Quinolone antibiotics in the treatment of salmonella infections. Rev Infect Dis 1990; 5: 873-89. 4. Endtz HP, Mouton PR, Van Der Reyden T, et al. Fluoroquinolone resistance in Campylobacter spp isolated from human stools and poultry products. Lancet 1990; 335: 787. 5. Piddock LJV, Wray C, McClaren I, et al. Quinolone resistance in Salmonella spp: veterinary pointers. Lancet 1990; 336: 125. 6. Segreti J, Gootz TD, Goodman LJ, et al. High level quinolone resistance in clinical isolates of Campylobacter jejum. J Infect Dis 1992; 165: 667-70.
Crossreactions between
Legionella Campylobacter spp
and
SIR,-Dr Boswell and Dr Kudesia (Jan 18, p 191) and Dr Cheesbrough and colleagues (Feb 15, p 429) report crossreactions between Legionella and Campylobacter spp in serology. We use a micro-agglutination technique (MAT) to detect antibodies against L pneumophila subgroup 1--6, L micdadei, L bozemamï, and L dunwffii.1 Titres above 16 (L pneumophila serogroup 1 and 3-6, L midadei, and L dumoffÙ) or over 64 (L pneunwphila serogroup 2, and L bozemanÙ) are judged positive (99% specificity cut-off). A four-fold rise in antibody titres to 128 or more is regarded as diagnostic. 48 serum samples from 34 patients with acute C jejuni/coli infection confirmed by positive stool culture were tested for MAT antibodies against L pneumophila serogroup 1 as the clinically most important pathogen within the family Legionellaceae. Antibody concentrations against C jejunifcoli in these serum samples have
Axillary node dissection in
breast
cancer
SiR,—The mixed reception given to our report on axillary dissection in operable breast cancer1 was an indication that such treatment is controversial. Unfortunately the trial Dr Cabanes and colleagues (May 23, p 1245) report will not persuade many sceptics because not only was the surgery different between the groups, but also so was the administration of adjuvant therapy. Nevertheless, Cabanes did demonstrate that the morbidity associated with surgical clearance and axillary irradiation was similar in terms of lymphoedema, which occurred in only 16% of patients. Because adjuvant therapy was given only to those with histological proof of axillary nodal involvement, which was undetermined in the irradiated group, whether the survival benefits for the group who underwent axillary clearance were the result of local or systemic treatment is not clear. However, there are data showing the survival benefits of axillary clearance. In the second Guy’s Wide Excision Trial patients with operable cancers, without clinical evidence of axillary nodal metastases, were treated by either radical mastectomy or wide excision.2 Both groups received postoperative irradiation, but the
Emerging quinolone resistance in campylobacters SIR,-Dr Rowe and colleagues (March 21,
p
740) again
recommend ciprofloxacin for the treatment of multiresistant typhoid fever. Quinolones are also useful for the empirical therapy of selected cases of travellers’ diarrhoea’ and food poisoning caused
by other salmonellae and Campylobacter spp,2 especially in elderly
immunocompromised individuals.3 The efficacy of these agents depends partly on the very low prevalence of resistance in such pathogens, which unlike Salmonella typhi are largely of animal origin. Quinolones are now available for veterinary use, and their consumption by poultry has been linked to the emergence of quinolone resistance in campylobacters isolated from human subjects in the Netherlands.’ Strains of salmonellae resistant to quinolones have been isolated from chickens in the UK.s We have been screening salmonellae and campylobacters for ciprofloxacin resistance since 1988. Between January, 1988, and December, 1991, we examined 46 820 stools from patients in the or
Oxford
area.
Of the 1332 Salmonella spp grown,
none
was
ciprofloxacin resistant. During the same period we isolated 1240 campylobacters. Until the end of 1990 all were ciprofloxacin sensitive. However, during 1991 we isolated 359 campylobacters, of which 11 (3%) were resistant to ciprofloxacin (minimum inhibitory concentration > 32 mg/1). The 11patients with resistant strains were followed up via their general practitioners. 6 gave a history of foreign travel in the previous month (4 to the Mediterranean area,1 to India, 1 to SE Asia and India). One patient had received ciprofloxacin in the week before stool sampling, suggesting that resistance may have emerged during therapy.6 It is reassuring that at present salmonellae isolated from patients in the Oxford area remain susceptible to ciprofloxacin. However, campylobacters and salmonellae share a common ecological niche in poultry, and widespread use of quinolones in that industry risks the promotion of resistance in salmonellae as well as campylobacters. The future role of quinolones in the treatment of non-typhoidal enteric infections in man depends on restriction of their use in animals. We thank Dr J. Webberley, department of microbiology, Worcester Royal Infirmary, for confirming ciprofloxacin resistance in the campylobacters.
Department of Bacteriology, John Radcliffe Hospital, Oxford OX3 9DU, UK
IAN BOWLER DAVID DAY
been described previously.2 In addition, all serum samples were tested for antibodies against L pneumophila serogroup 1 after absorption with a mixture of equal amounts of a clinical strain of Cjejuni (RH-240481) and C coli (CIP 7080). If an increased antibody concentration against L pneumophila was caused by crossreactions between Campylobacter and Legionella spp, the legionella antibody values should decrease substantially after absorption of the serum samples with C jejuni and C coli. Only one serum sample had a low positive antibody titre (64) against L pneumophila serogroup 1. No decrease in the antibody concentrations against L pneumophila serogroup 1 was seen in this serum after absorption with C jejuni and C coli. All other serum samples proved negative by MAT. These results show that crossreactions between L pneumophila serogroup 1 and C jejuni/coli are unlikely to occur with MAT. The antigen preparation for the indirect immunofluorescence technique (IFAT) described in Boswell’s and Cheesbrough’s letters were formalised yolk-sac antigens. For MAT, heat killed bacteria were used as the antigen. Previous investigations have shown good correlation between IFAT methods using formalised and heat treated cells (as recommended by CDC, Atlanta), respectively,3 and between IFAT and MAT.1 The lack of crossreactivity between Legionella and Campylobacter spp in our small study suggests that the formalised antigen (including flagellar antigens) from L pneumophila serogroup 1 crossreacts with Campylobacter to a higher degree than the heat stable O-antigen (mainly lipopolysaccharide). In addition, IFAT measures direct binding between antigens and antibodies, whereas MAT also measures the secondary occurrence of agglutination, which may tend to reduce the unspecific reactions by MAT, compared with IF. It could be argued that the serum samples used in this study were from patients infected with different serogroups of campylobacters that did not crossreact with Legionella. We have found, however, about 30 different serotypes of campylobacter between 100 consecutive Danish strains (unpublished data). It is therefore unlikely that a crossreaction would be missed because of an over-representation of non-crossreacting serotypes. Department of Clinical Microbiology, University of Copenhagen, Rigshospitalet and Statens Seruminstitut, 2300 Copenhagen, Denmark
LEIF PERCIVAL ANDERSEN
JETTE BANGSBORG
1. Collins
MT, Lind K, Aalund O, McDonald J, Frederiksen W. Correlation between microagglutination and indirect fluorescent-antibody test for antibodies to 10 Legionellaceae antigens In: Thornberry C, Balows A, Feeley JC, Jacubowski W, eds. Legionella. Proceedings from the 2nd International Symposium. ASM, Washington 1984. 2. Andersen LP, Gaarslev K. Campylobacter jejuni/coli: Elevated IgA and IgM antibodies during acute infection. In Ruiz-Palacios GM, Calva E, Ruiz-Palacios BR. Campylobacter V. Istituto Nacional de la Nutricion, Mexico 1991. 3. Wilkinson HW, Brake BJ. Formalin-killed versus heat-killed Legionella pneumophila serogroup 1 antigen in the indirect immunofluorescence assay for legionellosis. J Clin Microbiol 1982; 16: 979-81. the
1. Ericson CD, Johnson PC, Dupont HL, et al. Ciprofloxacin or trimethoprimsulphamethoxazole as initial therapy for travellers’ diarrhoea. Ann Intern Med 1987; 106: 216-20. 2. Editorial. Quinolones in acute non-travellers’ diarrhoea. Lancet 1990; 336: 282. 3. Asperilla MO, Smego RA, Scott LK. Quinolone antibiotics in the treatment of salmonella infections. Rev Infect Dis 1990; 5: 873-89. 4. Endtz HP, Mouton PR, Van Der Reyden T, et al. Fluoroquinolone resistance in Campylobacter spp isolated from human stools and poultry products. Lancet 1990; 335: 787. 5. Piddock LJV, Wray C, McClaren I, et al. Quinolone resistance in Salmonella spp: veterinary pointers. Lancet 1990; 336: 125. 6. Segreti J, Gootz TD, Goodman LJ, et al. High level quinolone resistance in clinical isolates of Campylobacter jejum. J Infect Dis 1992; 165: 667-70.
Crossreactions between
Legionella Campylobacter spp
and
SIR,-Dr Boswell and Dr Kudesia (Jan 18, p 191) and Dr Cheesbrough and colleagues (Feb 15, p 429) report crossreactions between Legionella and Campylobacter spp in serology. We use a micro-agglutination technique (MAT) to detect antibodies against L pneumophila subgroup 1--6, L micdadei, L bozemamï, and L dunwffii.1 Titres above 16 (L pneumophila serogroup 1 and 3-6, L midadei, and L dumoffÙ) or over 64 (L pneunwphila serogroup 2, and L bozemanÙ) are judged positive (99% specificity cut-off). A four-fold rise in antibody titres to 128 or more is regarded as diagnostic. 48 serum samples from 34 patients with acute C jejuni/coli infection confirmed by positive stool culture were tested for MAT antibodies against L pneumophila serogroup 1 as the clinically most important pathogen within the family Legionellaceae. Antibody concentrations against C jejunifcoli in these serum samples have
Axillary node dissection in
breast
cancer
SiR,—The mixed reception given to our report on axillary dissection in operable breast cancer1 was an indication that such treatment is controversial. Unfortunately the trial Dr Cabanes and colleagues (May 23, p 1245) report will not persuade many sceptics because not only was the surgery different between the groups, but also so was the administration of adjuvant therapy. Nevertheless, Cabanes did demonstrate that the morbidity associated with surgical clearance and axillary irradiation was similar in terms of lymphoedema, which occurred in only 16% of patients. Because adjuvant therapy was given only to those with histological proof of axillary nodal involvement, which was undetermined in the irradiated group, whether the survival benefits for the group who underwent axillary clearance were the result of local or systemic treatment is not clear. However, there are data showing the survival benefits of axillary clearance. In the second Guy’s Wide Excision Trial patients with operable cancers, without clinical evidence of axillary nodal metastases, were treated by either radical mastectomy or wide excision.2 Both groups received postoperative irradiation, but the
