352
pattern was identical for each strain and conformed to OMP-type 4 as defined by Granoff et al.5 However, we did not discriminate between the two possible subtypes 4H and 4L. With a modified Stokes method the isolates were resistant to chloramphenicol, ampicillin, tetracycline, and erythromycin, but susceptible to cefuroxime, cefotaxime, and rifampicin. The agar dilution minimum inhibitory concentrations to chloramphenicol were between 32 and 64 J.1g/ml. P-lactamase and chloramphenicol acetyl transferase enzyme activities were detected. Resistances to chloramphenicol and ampicillin were cotransferred from five of the strains to a susceptible, recombination-deficient strain of H influenzae under ampicillin selecrion. A plasmid of about 50 kb (about 32 MD), as judged from agarose gel electrophoresis of an EcoRI-digest, was isolated from one such transconjugant but not from any of the donors (ie, the clinical isolates). These results imply that the DNA carrying the resistance genes was transferable and capable of extrachromosomal replication. Plasmids of size 38-50 MD encoding ampicillin and chloramphenicol resistance have also been detected in transconjugants from H influenzae type b isolated from patients in Spain.6 However, whether these plasmids are related to those described here remains to be established. Vigilance for chloramphenicol/ampicillin resistant strains must be maintained because transferable resistance such as we describe may spread. In fact the laboratory at Oxford is currently studying another two isolates of H influenzae type b obtained from different cases of invasive disease acquired in Britain. Public Health Laboratory, St Luke’s Hospital, Guildford GU1 3NT, UK
CHRISTOPHER A.
Public Health Laboratory, John Radcliffe Hospital, Oxford
DERRICK W. CROOK WILMA A. G. KRAAK IOANNA D. DIMOPOULOU EILEEN C. ANDERSON WRIGHT W. NICHOLS MARY P. E. SLACK
J. BRIGHTMAN
Department of Neurology, Royal Surrey County Hospital,
PETER R. BARKER
Guildford
1. Machka K,
Braveny I, Dabernat H,
et
al. Distribution and resistance patterns of
Haemophilus influenzae: a European cooperative study. Eur J Clin Microbiol Infect Dis 1988; 7: 14-24.
Amp=ampicillin, Ch=chloramphenicol, Tmp=trimethoprim, Smx=sulphamethoxazole, G=gentamicin, Nor=norfloxacin, Clp = clprofloxacln Sens=sensitive, Mod sens= moderately sensitive, Res = resistant. TABLE II-CLINICAL RESPONSE TO ANTIBIOTICS
7 days), and in 7 they were still positive after another 5 days of co-trimoxazole (three tablets every 12 h for 5 days). On sensitivity testing by the Stokes method (table I) resistance to two or more antibiotics was observed in 157 (89-7%) of the 175 strains of S typhi tested. All the strains were phage type 51, biotype 1. At first chloramphenicol, ampicillin, co-trimoxazole, and furazolidone were used, but with poor response. Subsequent patients were randomly allocated to gentamicin, norfloxacin, both drugs, or ciprofloxacin. The clinical response is summarised in table 11. Patients not responding to other drugs or who had complications were treated with ciprofloxacin. The complication rate was low (gastrointestinal bleeding 28%, delirium 16%, and salmonella hepatitis 35%). Only 2 patients relapsed later (8 and 15 weeks after treatment) and repeat blood cultures yielded S typhi with sensitivity patterns identical to those in the primary illness. Follow-up stool cultures, done in 60 patients, were all negative. 0 agglutinin titres against S typhi did not rise significantly in 92-1% of cases, probably because of early use of antibiotics.1 One interesting observation was that defervescence did not aways happen after 3-4 weeks, as stated in older textbooks; in 12 cases it continued unabated for 6 or 7 weeks if suitable therapy was over
given. Although the first case of chloramphenicol-resistant S typhi was reported in 1950Z there are few reports of epidemics of resistant enteric fever.3-5 The unique features of the Calcutta epidemic were multiresistant S typhi strains; onset of fever abrupt and lasting for longer, blood cultures often being positive even 2-5 weeks after onset of fever, indicating persistent bacteraemia; a rare phage type, S typhi type 51 being unusual in this part of the world (Prakash K, personal communication); and the clinical response to ciprofloxacin. The quinoline group of antimicrobials may be a useful addition to drugs against S typhi.
not
Campos J, Garcia-Tornel S, Sanfelu I. Susceptibility studies of multiple resistant Haemophilus influenzae isolated from paediatric patients and contacts. Antimicrob Agents Chemother 1984; 25: 706-09. 3. Campos J, Garcia-Tornel S, Gairi Tahull JM. Invasive infections caused by multiply resistant Haemophilus influenzae type b. JPediatrics 1984; 104: 162. 4. van Alphen L, Riemens T, Polman J, Hopman C, Zanen HC. Homogeneity of cell envelope protein subtypes lipopolysaccharides serotypes, and biotypes among Haemophilus influenzae tybe b from patients with meningitis in the Netherlands. J Infect Dis 1983; 148: 75-81. 5. Granoff DM, Barenkamp SJ, Munson RS. Outer membrane protein subtypes for epidemiologic investigation of Haemophilus influenzae type b disease. In: Sell SH, Wright PF, eds. Haemophilus influenzae: epidemiology, immunology, and prevention of disease. New York: Elsevier, 1982: 43-55. 6. Campos J, Chanyangam M, deGroot R, Smith AL, Tenover FC, Reig R. Genetic relatedness of antibiotic resistance determinants in multiply resistant Haemophilus influenzae. J Infect Dis 1989; 160: 810-17. 2.
Epidemic multiresistant enteric fever in eastern India
SiR,-During an epidemic of enteric fever in Calcutta 201 patients treated between August and October, 1989, after which the incidence seemed to wane. The average age was 24 years (range 2-60) and 48-7% were males. Almost every patient presented with sudden onset of remittent fever. A few came to hospital with icterus (25%) and lower gastrointestinal bleeding (20%). There were no localising features though the spleen could be palpated in 33. Salmonella typhi was found on blood culture in 175 cases; the other 26 were treated on clinical suspicion alone. Blood cultures were positive 2-34 days (mean 13) after the onset of fever. In 32 patients cultures were positive even after chloramphenicol therapy (21 g were
TABLE I-ANTIBIOTIC SENSITIVITY TESTING
We thank Dr K. Prakash (National Salmonella Research Laboratory, New Delhi) for help with phage typing.
Command Hospital and Pathology Laboratory Calcutta 700027, India
(EC),
A. C. ANAND V. K. KATARIA WARYAM SINGH S. K. CHATTERJEE
1. Parker MT. Enteric infections:
typhoid and paratyphoid fevers. In: Smith GR, ed Topley and Wilson’s principles of bacteriology, virology and immunity, 7th ed, vol III. London: Edward
Arnold,
1984: 407-33.
2. Colquhoun J, Weetch RS. Resistance to chloramphenicol developing during treatment of typhoid fever. Lancet 1950; ii: 621. 3. Olarte J, Cialindo E. S typhi resistant to chloramphenicol, ampicillin and other antimicrobial agents: strains isolated during an extensive typhoid fever epidemic in Mexico. Antimicrob Ag Chemother 1973; 4: 597-99. CKJ, Vimla KM. Transferable chloramphenicol resistance m S typhi Nature 1973; 239: 109. 5. Agarwal KC, Panhotra BR, Mahanta J, Arya VK, Garg RK. Typhoid fever due to chloramphenicol resistant S typhi associated with R-plasmid. Indian J Med Res
4. Panicker
1981; 73: 484-88.
pattern was identical for each strain and conformed to OMP-type 4 as defined by Granoff et al.5 However, we did not discriminate between the two possible subtypes 4H and 4L. With a modified Stokes method the isolates were resistant to chloramphenicol, ampicillin, tetracycline, and erythromycin, but susceptible to cefuroxime, cefotaxime, and rifampicin. The agar dilution minimum inhibitory concentrations to chloramphenicol were between 32 and 64 J.1g/ml. P-lactamase and chloramphenicol acetyl transferase enzyme activities were detected. Resistances to chloramphenicol and ampicillin were cotransferred from five of the strains to a susceptible, recombination-deficient strain of H influenzae under ampicillin selecrion. A plasmid of about 50 kb (about 32 MD), as judged from agarose gel electrophoresis of an EcoRI-digest, was isolated from one such transconjugant but not from any of the donors (ie, the clinical isolates). These results imply that the DNA carrying the resistance genes was transferable and capable of extrachromosomal replication. Plasmids of size 38-50 MD encoding ampicillin and chloramphenicol resistance have also been detected in transconjugants from H influenzae type b isolated from patients in Spain.6 However, whether these plasmids are related to those described here remains to be established. Vigilance for chloramphenicol/ampicillin resistant strains must be maintained because transferable resistance such as we describe may spread. In fact the laboratory at Oxford is currently studying another two isolates of H influenzae type b obtained from different cases of invasive disease acquired in Britain. Public Health Laboratory, St Luke’s Hospital, Guildford GU1 3NT, UK
CHRISTOPHER A.
Public Health Laboratory, John Radcliffe Hospital, Oxford
DERRICK W. CROOK WILMA A. G. KRAAK IOANNA D. DIMOPOULOU EILEEN C. ANDERSON WRIGHT W. NICHOLS MARY P. E. SLACK
J. BRIGHTMAN
Department of Neurology, Royal Surrey County Hospital,
PETER R. BARKER
Guildford
1. Machka K,
Braveny I, Dabernat H,
et
al. Distribution and resistance patterns of
Haemophilus influenzae: a European cooperative study. Eur J Clin Microbiol Infect Dis 1988; 7: 14-24.
Amp=ampicillin, Ch=chloramphenicol, Tmp=trimethoprim, Smx=sulphamethoxazole, G=gentamicin, Nor=norfloxacin, Clp = clprofloxacln Sens=sensitive, Mod sens= moderately sensitive, Res = resistant. TABLE II-CLINICAL RESPONSE TO ANTIBIOTICS
7 days), and in 7 they were still positive after another 5 days of co-trimoxazole (three tablets every 12 h for 5 days). On sensitivity testing by the Stokes method (table I) resistance to two or more antibiotics was observed in 157 (89-7%) of the 175 strains of S typhi tested. All the strains were phage type 51, biotype 1. At first chloramphenicol, ampicillin, co-trimoxazole, and furazolidone were used, but with poor response. Subsequent patients were randomly allocated to gentamicin, norfloxacin, both drugs, or ciprofloxacin. The clinical response is summarised in table 11. Patients not responding to other drugs or who had complications were treated with ciprofloxacin. The complication rate was low (gastrointestinal bleeding 28%, delirium 16%, and salmonella hepatitis 35%). Only 2 patients relapsed later (8 and 15 weeks after treatment) and repeat blood cultures yielded S typhi with sensitivity patterns identical to those in the primary illness. Follow-up stool cultures, done in 60 patients, were all negative. 0 agglutinin titres against S typhi did not rise significantly in 92-1% of cases, probably because of early use of antibiotics.1 One interesting observation was that defervescence did not aways happen after 3-4 weeks, as stated in older textbooks; in 12 cases it continued unabated for 6 or 7 weeks if suitable therapy was over
given. Although the first case of chloramphenicol-resistant S typhi was reported in 1950Z there are few reports of epidemics of resistant enteric fever.3-5 The unique features of the Calcutta epidemic were multiresistant S typhi strains; onset of fever abrupt and lasting for longer, blood cultures often being positive even 2-5 weeks after onset of fever, indicating persistent bacteraemia; a rare phage type, S typhi type 51 being unusual in this part of the world (Prakash K, personal communication); and the clinical response to ciprofloxacin. The quinoline group of antimicrobials may be a useful addition to drugs against S typhi.
not
Campos J, Garcia-Tornel S, Sanfelu I. Susceptibility studies of multiple resistant Haemophilus influenzae isolated from paediatric patients and contacts. Antimicrob Agents Chemother 1984; 25: 706-09. 3. Campos J, Garcia-Tornel S, Gairi Tahull JM. Invasive infections caused by multiply resistant Haemophilus influenzae type b. JPediatrics 1984; 104: 162. 4. van Alphen L, Riemens T, Polman J, Hopman C, Zanen HC. Homogeneity of cell envelope protein subtypes lipopolysaccharides serotypes, and biotypes among Haemophilus influenzae tybe b from patients with meningitis in the Netherlands. J Infect Dis 1983; 148: 75-81. 5. Granoff DM, Barenkamp SJ, Munson RS. Outer membrane protein subtypes for epidemiologic investigation of Haemophilus influenzae type b disease. In: Sell SH, Wright PF, eds. Haemophilus influenzae: epidemiology, immunology, and prevention of disease. New York: Elsevier, 1982: 43-55. 6. Campos J, Chanyangam M, deGroot R, Smith AL, Tenover FC, Reig R. Genetic relatedness of antibiotic resistance determinants in multiply resistant Haemophilus influenzae. J Infect Dis 1989; 160: 810-17. 2.
Epidemic multiresistant enteric fever in eastern India
SiR,-During an epidemic of enteric fever in Calcutta 201 patients treated between August and October, 1989, after which the incidence seemed to wane. The average age was 24 years (range 2-60) and 48-7% were males. Almost every patient presented with sudden onset of remittent fever. A few came to hospital with icterus (25%) and lower gastrointestinal bleeding (20%). There were no localising features though the spleen could be palpated in 33. Salmonella typhi was found on blood culture in 175 cases; the other 26 were treated on clinical suspicion alone. Blood cultures were positive 2-34 days (mean 13) after the onset of fever. In 32 patients cultures were positive even after chloramphenicol therapy (21 g were
TABLE I-ANTIBIOTIC SENSITIVITY TESTING
We thank Dr K. Prakash (National Salmonella Research Laboratory, New Delhi) for help with phage typing.
Command Hospital and Pathology Laboratory Calcutta 700027, India
(EC),
A. C. ANAND V. K. KATARIA WARYAM SINGH S. K. CHATTERJEE
1. Parker MT. Enteric infections:
typhoid and paratyphoid fevers. In: Smith GR, ed Topley and Wilson’s principles of bacteriology, virology and immunity, 7th ed, vol III. London: Edward
Arnold,
1984: 407-33.
2. Colquhoun J, Weetch RS. Resistance to chloramphenicol developing during treatment of typhoid fever. Lancet 1950; ii: 621. 3. Olarte J, Cialindo E. S typhi resistant to chloramphenicol, ampicillin and other antimicrobial agents: strains isolated during an extensive typhoid fever epidemic in Mexico. Antimicrob Ag Chemother 1973; 4: 597-99. CKJ, Vimla KM. Transferable chloramphenicol resistance m S typhi Nature 1973; 239: 109. 5. Agarwal KC, Panhotra BR, Mahanta J, Arya VK, Garg RK. Typhoid fever due to chloramphenicol resistant S typhi associated with R-plasmid. Indian J Med Res
4. Panicker
1981; 73: 484-88.
