55
results it thus appears that triple therapy for 2 weeks may overcome metronidazole resistance; perhaps higher and more uniform gastric mucosal concentrations of antibiotics and of bismuth salts are achieved after longer treatment, and higher systemic concentrations may also ensue. In-vitro synergy between bismuth subcitrate and metronidazole has been observed against both metronidazole sensitive and resistant strains,l and this may contribute to the superiority of bismuth regimens against metronidazole-resistant
Hpylori. In our experience 2 weeks of a double amoxycillin/metronidazole may achieve a high eradication rate of metronidazolesensitive H pylori strains. However, 2 weeks of triple therapy with bismuth, amoxycillin, and metronidazole is to be preferred in the setting of metronidazole resistance or if sensitivity cannot be tested. This triple regimen corresponds to the anti-H pylorz regimen advocated by a working party at the 4th World Congress of
regimen
patterns were very different. Thus each patient had a unique strain that persisted when the isolate changed from being metronidazole sensitive to resistant. Preliminary results suggest that this resistance is not acquired by plasmid transfer.2 .2 We have achieved an H pylori eradication rate of over 90% in patients with metronidazole sensitive isolates by using a 2-week triple regimen, but our results in those with metronidazole-resistant organisms were disappointing (unpublished). Our eradication rate with omeprazole alone3or in combination with amoxycillin or TDB’ was low, as indeed was our success rate with pivampicillin and bismuth dual therapy.s Clearly what is now needed is a safe, effective, and cheap method of eradicating metronidazole-resistant H pylori. Department of Medicine.
G. D. BELL K. POWELL
Ipswich Hospital, Ipswich IP4 5PD, UK
Gastroenterology.2 Department of Microbiology, Brugmann University Hospital, B-1020 Brussels, Belgium
1.
dicitrato bismuthate and metronidazole combination Aliment Pharmacol Ther
YOURI GLUPCZYNSKI
1990, 4: 651-57. GD, Weil J, Powell K,
et al. Helicobacter pylori treated with combinations of dicitrato bismuthate and metronidazole: efficacy of different treatment regimens and some observations on the emergence of metronidazole resistance. Eur J Gastroenterol Hepatol 1991, 3: 819-22 3. Weil J, Bell GD, Powell K, et al Omeprazole and Helicobacter pylori: temporary suppression rather than true eradication. Aliment Pharmacol Ther 1991, 5: 309-13. 4. Bell GD, Powell K, Weil J, et al Experience with omeprazole in combination with either amoxycillin or colloidal bismuth subcitrate in patients metronidazoleresistant H pylori Eur JGastroenterol Hepatol 1991, 3: 923-26. 5. Weil J, Bell GD, Powell K, et al Eradication of Helicobacter pylori with pivampicillin alone or in combination with tripotassium dicitrato bismuthate Aliment Pharmacol Ther 1991; 5: 543-47.
2. Bell
tripotassium
Gastroenterology Unit, Nouvelle Clinique de la Basilique, Brussels
Weil J, Bell GD, Powell K, et al. Helicobacter pylori infection treated with tripotassium
ALAIN BURETTE
Glupczynski Y, De Wit J, Goutier S, Labbé M. Comparative study of the bactericidal activity of antibiotics and of colloidal bismuth subcitrate by time-kill curves against Helicobacter pylori. Microb Ecol Health Dis 1991; 4 (supply 184. 2. Editoral. Gastroenterologists in Sydney: histology and helicobacter Lancet 1990, 336:
1.
779-80.
SIR,-Our triple regimen for the eradication of Helicobacter is colloidal bismuth subcitrate 4 x 120 mg, amoxycillin 4 x 500 mg, and metronidazole 3 x 500 mg daily for 2 weeks. 63 % of our patients with metronidazole-resistant pretreatment isolates became free from H pylori.Eradication was verified by culture on gastric biopsy specimens taken 4 weeks and 6 months after the therapy. Decreasing H pylori antibody titres were also observed in patients who became H pylori negativeA higher eradication rate (91 %) was obtained when pretreatment strains were metronidazole susceptible. As in the study by Dr Logan and colleagues we found metronidazole-resistant post-treatment isolates in all patients who had not responded to the treatment. Although metronidazole resistance has an important role in treatment failures much of this resistance can be overcome with triple therapy of H pylori-positive patients for 2 weeks.
pylori
Department of Bacteriology and Immunology and Gastroenterological Unit, Second Department of Medicine, University of Helsinki, 00290 Helsinki, Finland
HILPI RAUTELIN TIMO U. KOSUNEN KARI SEPPÄLÄ
H, Seppala K, Renkonen OV, et al Role of metronidazole resistance in therapy of Helicobacter pylori infections. Antimicrob Agents Chemother (m press). Seppala K, Kosunen TU, Sipponen P, Valtonen V. Decrease of Helicobacter pylori antibodies reflects successful eradication therapy. World Congress of Gastroenterology, Sydney, 1990; abstr
1. Rautelin
2
agree with Dr Logan and colleagues that premetronidazole resistance is a major influence on the eradication rate of any regimen that includes metronidazole’ and that antral biopsy should be done routinely for in-vitro metronidazole sensitivity testing in patients in whom Helicobacter pylori eradication therapy is indicated. However, referring to one of our studies,’ Logan et al state "others have reported eradication rates of up to 79% with bismuth and metronidazole alone, but since metronidazole sensitivity was not determined after treatment, that treatment itself may have promoted the emergence of metronidazole-resistant H pylori". We can now report2 that in a series of 104 patients with metronidazole-sensitive pre-treatment H pylori isolates, eradication with a combination of tripotassium dicitrato bismuthate (TDB) and metronidazole failed in 21 cases. So far 14 of those 21 patients have had a repeat post-treatment gastroscopy and antral biopsy, and in all 14 the organism has become metronidazole resistant. 5 pairs of samples have been studied by DNA fingerprinting (HeaIIIribopattem); the intra-pair chromosomal DNA fmgerprints were identical but the inter-pair
SIR,-We
treatment
Pruritus
as
presenting sign of cervical rib
SIR,-I report two cases of an identical localised pruritus which proved to be the presenting symptom of cervical rib. A 22-year-old man (patient 1) and a 58-year-old woman (patient 2) complained for two and eleven months, respectively, of intense and persistent pruritus that was located on the left flexor aspect of the elbow and proximal forearm. Pruritus was present throughout the day and both patients denied any trauma or relation to sun exposure. They had no history of mental disorder, seemed to be emotionally stable, and denied taking any drug. Sleep was disturbed by pruritus in patient 2. On examination the itching skin was grossly normal. Laboratory tests were uninformative. Neurological examination was normal in both patients, as were electromyography and nerve conduction velocity of ulnar and median nerves in patient 2. A biopsy specimen of the skin was microscopically normal and the number of mastocytes was not increased in patient 1, but patient 2 refused biopsy. Radiography of the vertebral spine showed hypertrophy of the transverse process of C7 in patient 1 and a monolateral, supernumerary short cervical rib in patient 2. Treatment with diclofenac, gangliosides, and cervical physiotherapy substantially improved pruritus after one and a half weeks. Six months later patient 2 had intense and disabling cervico-brachialgia, paraesthesias and restricted motion, and Raynaud-like symptoms of the left forearm. Surgical resection of the cervical rib was followed by complete resolution of the symptoms including pruritus. There is little evidence that nerve injury causes pruritus.1 In our patients, however, the presence of the cervical rib, either in its monolateral incomplete form (type III) or in the form of a hypertrophy of the transverse process of C7 (type 1),2 seemed to be related to the localised pruritus, probably through a peripheral
compressive neuropathy. Cervical rib is diagnosed rarely since in 80% of cases it is symptomlessAll patients complaining of pruritus of the elbow and forearm
even
in the absence of any skin
lesions, should have
radiography of the cervical spine. Department of Dermatology, University of Genoa, Genoa, Italy
FRANCO RONGIOLETTI
1. Bernhard J. Clinical aspects of pruritos. In: Fitzpatrick TB, Eisen AZ, Wolff K, et al, eds. Dermatology in general medicine. New York: McGraw-Hill, 1987: 78-90. 2. Schwartz SI. Principles of surgery, 4th ed. New York: McGraw-Hill, 1984 640-42.
results it thus appears that triple therapy for 2 weeks may overcome metronidazole resistance; perhaps higher and more uniform gastric mucosal concentrations of antibiotics and of bismuth salts are achieved after longer treatment, and higher systemic concentrations may also ensue. In-vitro synergy between bismuth subcitrate and metronidazole has been observed against both metronidazole sensitive and resistant strains,l and this may contribute to the superiority of bismuth regimens against metronidazole-resistant
Hpylori. In our experience 2 weeks of a double amoxycillin/metronidazole may achieve a high eradication rate of metronidazolesensitive H pylori strains. However, 2 weeks of triple therapy with bismuth, amoxycillin, and metronidazole is to be preferred in the setting of metronidazole resistance or if sensitivity cannot be tested. This triple regimen corresponds to the anti-H pylorz regimen advocated by a working party at the 4th World Congress of
regimen
patterns were very different. Thus each patient had a unique strain that persisted when the isolate changed from being metronidazole sensitive to resistant. Preliminary results suggest that this resistance is not acquired by plasmid transfer.2 .2 We have achieved an H pylori eradication rate of over 90% in patients with metronidazole sensitive isolates by using a 2-week triple regimen, but our results in those with metronidazole-resistant organisms were disappointing (unpublished). Our eradication rate with omeprazole alone3or in combination with amoxycillin or TDB’ was low, as indeed was our success rate with pivampicillin and bismuth dual therapy.s Clearly what is now needed is a safe, effective, and cheap method of eradicating metronidazole-resistant H pylori. Department of Medicine.
G. D. BELL K. POWELL
Ipswich Hospital, Ipswich IP4 5PD, UK
Gastroenterology.2 Department of Microbiology, Brugmann University Hospital, B-1020 Brussels, Belgium
1.
dicitrato bismuthate and metronidazole combination Aliment Pharmacol Ther
YOURI GLUPCZYNSKI
1990, 4: 651-57. GD, Weil J, Powell K,
et al. Helicobacter pylori treated with combinations of dicitrato bismuthate and metronidazole: efficacy of different treatment regimens and some observations on the emergence of metronidazole resistance. Eur J Gastroenterol Hepatol 1991, 3: 819-22 3. Weil J, Bell GD, Powell K, et al Omeprazole and Helicobacter pylori: temporary suppression rather than true eradication. Aliment Pharmacol Ther 1991, 5: 309-13. 4. Bell GD, Powell K, Weil J, et al Experience with omeprazole in combination with either amoxycillin or colloidal bismuth subcitrate in patients metronidazoleresistant H pylori Eur JGastroenterol Hepatol 1991, 3: 923-26. 5. Weil J, Bell GD, Powell K, et al Eradication of Helicobacter pylori with pivampicillin alone or in combination with tripotassium dicitrato bismuthate Aliment Pharmacol Ther 1991; 5: 543-47.
2. Bell
tripotassium
Gastroenterology Unit, Nouvelle Clinique de la Basilique, Brussels
Weil J, Bell GD, Powell K, et al. Helicobacter pylori infection treated with tripotassium
ALAIN BURETTE
Glupczynski Y, De Wit J, Goutier S, Labbé M. Comparative study of the bactericidal activity of antibiotics and of colloidal bismuth subcitrate by time-kill curves against Helicobacter pylori. Microb Ecol Health Dis 1991; 4 (supply 184. 2. Editoral. Gastroenterologists in Sydney: histology and helicobacter Lancet 1990, 336:
1.
779-80.
SIR,-Our triple regimen for the eradication of Helicobacter is colloidal bismuth subcitrate 4 x 120 mg, amoxycillin 4 x 500 mg, and metronidazole 3 x 500 mg daily for 2 weeks. 63 % of our patients with metronidazole-resistant pretreatment isolates became free from H pylori.Eradication was verified by culture on gastric biopsy specimens taken 4 weeks and 6 months after the therapy. Decreasing H pylori antibody titres were also observed in patients who became H pylori negativeA higher eradication rate (91 %) was obtained when pretreatment strains were metronidazole susceptible. As in the study by Dr Logan and colleagues we found metronidazole-resistant post-treatment isolates in all patients who had not responded to the treatment. Although metronidazole resistance has an important role in treatment failures much of this resistance can be overcome with triple therapy of H pylori-positive patients for 2 weeks.
pylori
Department of Bacteriology and Immunology and Gastroenterological Unit, Second Department of Medicine, University of Helsinki, 00290 Helsinki, Finland
HILPI RAUTELIN TIMO U. KOSUNEN KARI SEPPÄLÄ
H, Seppala K, Renkonen OV, et al Role of metronidazole resistance in therapy of Helicobacter pylori infections. Antimicrob Agents Chemother (m press). Seppala K, Kosunen TU, Sipponen P, Valtonen V. Decrease of Helicobacter pylori antibodies reflects successful eradication therapy. World Congress of Gastroenterology, Sydney, 1990; abstr
1. Rautelin
2
agree with Dr Logan and colleagues that premetronidazole resistance is a major influence on the eradication rate of any regimen that includes metronidazole’ and that antral biopsy should be done routinely for in-vitro metronidazole sensitivity testing in patients in whom Helicobacter pylori eradication therapy is indicated. However, referring to one of our studies,’ Logan et al state "others have reported eradication rates of up to 79% with bismuth and metronidazole alone, but since metronidazole sensitivity was not determined after treatment, that treatment itself may have promoted the emergence of metronidazole-resistant H pylori". We can now report2 that in a series of 104 patients with metronidazole-sensitive pre-treatment H pylori isolates, eradication with a combination of tripotassium dicitrato bismuthate (TDB) and metronidazole failed in 21 cases. So far 14 of those 21 patients have had a repeat post-treatment gastroscopy and antral biopsy, and in all 14 the organism has become metronidazole resistant. 5 pairs of samples have been studied by DNA fingerprinting (HeaIIIribopattem); the intra-pair chromosomal DNA fmgerprints were identical but the inter-pair
SIR,-We
treatment
Pruritus
as
presenting sign of cervical rib
SIR,-I report two cases of an identical localised pruritus which proved to be the presenting symptom of cervical rib. A 22-year-old man (patient 1) and a 58-year-old woman (patient 2) complained for two and eleven months, respectively, of intense and persistent pruritus that was located on the left flexor aspect of the elbow and proximal forearm. Pruritus was present throughout the day and both patients denied any trauma or relation to sun exposure. They had no history of mental disorder, seemed to be emotionally stable, and denied taking any drug. Sleep was disturbed by pruritus in patient 2. On examination the itching skin was grossly normal. Laboratory tests were uninformative. Neurological examination was normal in both patients, as were electromyography and nerve conduction velocity of ulnar and median nerves in patient 2. A biopsy specimen of the skin was microscopically normal and the number of mastocytes was not increased in patient 1, but patient 2 refused biopsy. Radiography of the vertebral spine showed hypertrophy of the transverse process of C7 in patient 1 and a monolateral, supernumerary short cervical rib in patient 2. Treatment with diclofenac, gangliosides, and cervical physiotherapy substantially improved pruritus after one and a half weeks. Six months later patient 2 had intense and disabling cervico-brachialgia, paraesthesias and restricted motion, and Raynaud-like symptoms of the left forearm. Surgical resection of the cervical rib was followed by complete resolution of the symptoms including pruritus. There is little evidence that nerve injury causes pruritus.1 In our patients, however, the presence of the cervical rib, either in its monolateral incomplete form (type III) or in the form of a hypertrophy of the transverse process of C7 (type 1),2 seemed to be related to the localised pruritus, probably through a peripheral
compressive neuropathy. Cervical rib is diagnosed rarely since in 80% of cases it is symptomlessAll patients complaining of pruritus of the elbow and forearm
even
in the absence of any skin
lesions, should have
radiography of the cervical spine. Department of Dermatology, University of Genoa, Genoa, Italy
FRANCO RONGIOLETTI
1. Bernhard J. Clinical aspects of pruritos. In: Fitzpatrick TB, Eisen AZ, Wolff K, et al, eds. Dermatology in general medicine. New York: McGraw-Hill, 1987: 78-90. 2. Schwartz SI. Principles of surgery, 4th ed. New York: McGraw-Hill, 1984 640-42.
