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Vol. 25. Issue 7.
Pages 438-442 (January 2002)
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Vol. 25. Issue 7.
Pages 438-442 (January 2002)
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Erradicación de Helicobacter pylori en pacientes con úlcera péptica tras fracaso de dos tratamientos previos: estudio prospectivo guiado por cultivo
Helicobacter Pylori Eradication In Patients With Peptic Ulcer After Two Treatments Failure: A Prospective Culture-Guided Study
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Correspondencia: Dra. R. Vicente Lidón. C/ Rosa Chacel, 8, Esc. 1.a, 2.° B. 50015 Zaragoza.
, B. Siciliaa, S. Gallegoa, M.J. Revillob, J. Ducónsc, F. Gomollóna
a Servicios de Aparato Digestivo Hospital Universitario Miguel Servet. Zaragoza
b Servicios de Microbiología. Hospital Universitario Miguel Servet. Zaragoza
c Servicios de Unidad de Aparato Digestivo. Hospital San Jorge. Huesca
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IntroducciÓN

Menos de un 5% de los pacientes infectados por Helicobacter pylori precisa un tercer tratamiento erradicador al fracasar dos intentos previos. Existen relativamente pocos datos publicados en la bibliografía sobre la eficacia de estos tratamientos.

Objetivo

Analizar la efectividad de un tercer tratamiento erradicador de la infección por H. pylori, guiado por cultivo, tras el fracaso de dos tratamientos previos.

Pacientes Y Método

Cuarenta y dos pacientes consecutivos con diagnóstico previo de úlcera duodenal fueron incluidos en un estudio abierto, prospectivo y multicéntrico. Todos ellos presentaban fracaso documentado de dos intentos previos de erradicación (mediante test del aliento positivo), a todos se les realizó endoscopia y la infección fue confirmada por test de ureasa, histología y cultivo (Pylori Agar, Bio Mérieux, Francia). La sensibilidad a los antibióticos (metronidazol, amoxicilina, tetraciclina y claritromicina) se definió mediante E-test.

Asignamos cuádruple terapia (definida por protocolo) durante 14 días, guiada por cultivo, a 39 pacientes (un cultivo contaminado, un paciente rechazó el tratamiento y otro era alérgico a tetraciclina-amoxicilina y resistente a metronidazol y claritromicina), la cual consideraba los datos de sensibilidad de H. pylori a los diferentes antibióticos y la existencia previa de alergia a los mismos. Medimos el nivel de cumplimiento con el recuento de las pastillas y definimos erradicación ante la existencia de un test del aliento con urea 13C negativo a las 6 semanas de la finalización del tratamiento.

Resultados

Obtuvimos datos de susceptibilidad antibiótica en 41 pacientes, consiguiendo una erradicación global en el análisis por intención de tratamiento del 60% (24/40). Dieciocho cepas (43,9%) fueron resistentes a metronidazol; 21 (51,2%) a claritromicina, y 8 (19,5%) a ambos antibióticos. Ninguna cepa fue resistente a amoxicilina ni a tetraciclina. Usamos principalmente dos tipos de terapia cuádruple en 39 pacientes. A pesar del buen cumplimiento del tratamiento basado en omeprazol (20 mg/12 h), bismuto (120 mg/6 h), tetraciclinas (500 mg/6 h) y claritromicina (500 mg/12 h) (OBTC), obtuvimos éxito en erradicación en tan sólo 9/19 pacientes (47,4%; intervalo de confianza [IC], 24,4-71,1) (un paciente no acudió a la realización del test del aliento). Usando amoxicilina a dosis de 1.000 mg/12 h en lugar de claritromicina (OBTA) en 19 pacientes resistentes a dicho antibiótico, la efectividad fue de 14/19 (73,7%; IC, 48,8-90,9) Asignamos ciprofloxacino en un paciente alérgico a la amoxicilina y resistente a claritromicina y metronidazol, con lo que se consiguió su erradicación. No encontramos ningún factor clínico asociado a fallo de erradicación.

Conclusiones

A pesar de usar pautas cuádruples, de 14 días de duración y basadas en el cultivo previo, un tercer tratamiento fracasa a menudo en la erradicación de las cepas de H. pylori. La peor tasa de erradicación se obtuvo en pacientes con H. pylori sensible a todos los antibióticos, por lo que creemos que existen otros factores que influyen en la erradicación. Son necesarios estudios controlados que evalúen nuevas pautas terapéuticas en estos pacientes.

Background

Less than 5% of patients with Helicobacter pylori need a third treatment after two treatment failures. Few data have been reported on the efficacy of these treatments.

Aim

To determine the effectiveness of a third, culture-guided, treatment of H. pylori infection after two unsuccessful attempts.

Patients and Methods

Forty-two consecutive patients with a diagnosis of peptic ulcer were included in an open prospective and multicenter study. After two unsuccessful attempts at eradication (demonstrated by positive urea breath test), all patients underwent endoscopy and H. pylori infection was confirmed by urease test, histology and culture (Pylori- Agar, Bio Merieux, France). Antibiotic susceptibility to metronidazole, amoxicillin, tetracycline and clarithromycin was defined by E-test. Thirty-nine patients received a twoweek quadruple culture-guided therapy defined by the protocol, which considered sensitivity data and previous allergies to antibiotics (one culture was contaminated, one patient refused treatment and one was allergic to tetracycline and amoxicillin and was resistant to metronidazole and clarithromycin). Compliance was monitored by pill counting and eradication was defined as a negative urea breath test six weeks after the end of treatment.

Results

Sensitivity data were obtained in 41 patients. Intention- to-treat analysis revealed that overall eradication was achieved in 60% (24/40). Eighteen strains (43.9%) were resistant to metronidazole, 21 (51.2%) were resistant to clarithromycin and 8 (19.5%) were resistant to both drugs. None of the strains were resistant to amoxicillin or tetracycline. We used mainly two kinds of quadruple therapy in the 39 patients. Despite good compliance with treatment based on omeprazole (20 mg/12 h), bismuth subcitrate (120 mg/ 6 h), tetracycline (500 mg/4 h) and clarithromycin (500 mg/ 12 h) (OBTC) eradication was achieved in only 9 of 19 patients (47.4%; CI: 24.4-71.1) (one patient failed to attend the urea breath test). Nineteen clarithromycin-resistant patients received amoxicillin (1,000 mg/12 h) instead of clarithromycin (OBTA) and this treatment was effective in 14 (73.7%; CI: 48.8-90.9). Eradication was achieved in one patient who was allergic to amoxicillin and resistant to clarithromycin and metronidazole and who received ciprofloxacin (500 mg/8 h) instead of clarithromycin (OBTCipro). No clinical factors associated with eradication failure were found.

Conclusions

Despite the use of two-week, high-dose, quadruple and culture-guided combinations of drugs, a third treatment was frequently unsuccessful. The lowest eradication rate was obtained in patients with H. pylori strains sensitive to all antibiotics; therefore, we believe that other factors could influence eradication rates. New prospective and randomized studies are needed in this subgroup of patients to find effective treatments.

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Biblografía
[1.]
The Maastrich Consensus Report.
Current European concepts in the management of Helicobacter pylori.
Gut, 41 (1997), pp. 8-13
[2.]
J.A. Ducons, S. Santolaria, R. Guirao, M. Ferrero, M. Montoro, F. Gomollón.
Impact of clarithromycin resistance on the effectiveness of a regimen for Helicobacter pylori.
Aliment Pharmacol Ther, 13 (1999), pp. 775-780
[3.]
S.Y. De Boer, TH. Siem.
Four-day quadruple therapy as a routine treatment for Helicobacter pylori infection.
Aliment Pharmacol Ther, 11 (1997), pp. 1119-11121
[4.]
F. Gomollón, J.A. Ducons, L. Gimeno, J. Fuentes, S. García, J. Vera, et al.
The ideal therapy must be defined in each geographical area: experience with a quadruple therapy in Spain.
Helicobacter, 3 (1998), pp. 110-114
[5.]
J.P. Gisbert, D. Boixeda, C. Martín de Argila, C. Redondo, L. Moreno, V. Abraira.
Nuevas terapias triples de una semana de duración con metronidazol para la erradicación de Helicobacter pylori: claritromicina o amoxicilina como segundo antibiótico.
Med Clin (Barc), 110 (1998), pp. 1-5
[6.]
R.W.M. Van der Hulst, G.N.J. Tytgat.
Helicobacter pylori and peptic ulcer disease.
Scand J Gastroenterol, 31 (1996), pp. 10-18
[7.]
J.P. Gisbert, D. Boixeda, R. Aller, C. De la Serna, E. Sanz, C. Martín de Argila, et al.
Helicobacter pylori y hemorragia digestiva por úlcera duodenal: prevalencia de la infección, eficacia de tres terapias triples y papel de la erradicación en la prevención de la recidiva hemorrágica.
Med Clin (Barc), 112 (1999), pp. 161-165
[8.]
J. Danesh, R. Pounder.
Eradication of Helicobacter pylori and non-ulcer dyspepsia.
[9.]
I.R. Elizalde, F. Borda, C. Jara, A. Martínez, C. Rodríguez, J. Jiménez.
Eficacia de dos tratamientos consecutivos en la erradicación de Helicobacter pylori.
Anales Sis San Navarra, 21 (1998), pp. 83-88
[10.]
W. De Boer, W. Driessen, A. Jansz, G.N.J. Tytgat.
Effect of acid suppression on efficacy of treatment of Helicobacter pylori infection.
Lancet, 345 (1995), pp. 817-820
[11.]
W. De Boer, GN. Tytgat.
Treatment of Helicobacter pylori infection.
BMJ, 320 (2000), pp. 31-34
[12.]
B. Sicilia, E. Sierra, A. Lago, M. Villar, S. García, F. Gomollón.
Alto índice de erradicación de Helicobacter pylori en pacientes con úlcera duodenal tras fracaso de un tratamiento previo.
Med Clin (Barc), 115 (2000), pp. 641-643
[13.]
N. Chiba, R. Lahaie, R.N. Fedorak, R. Bailey, S.J. Van Veldhuyzen Zanten, B. Bernucci.
Helicobacter pylori and peptic ulcer disease. Current evidence for management strategies.
Can Fam Physician, 44 (1998), pp. 1481-1488
[14.]
N. Chiba, RH. Hunt.
Ulcer disease and Helicobacter pylori infection: aetiology and treatment.
Evidence based gastroenterology and hepatology,
[15.]
Y. Glupczynski.
Antimicrobial resistance in Helicobacter pylori: a global overview.
Acta Gastroenterol Belg, 61 (1998), pp. 357-366
[16.]
M. López-Brea, D. Domingo, I. Sánchez, T. Alarcón.
Evolution of resistance to metronidazole and clarithromycin in Helicobacter pylori clinical isolates from Spain.
J Antimicrob Chemother, 40 (1997), pp. 279-281
[17.]
D.Y. Graham, G.M. Lew, P.D. Klein, D.G. Evans, D.J. Evans, ZA. Saaed.
Effect of treatment of Helicobacter pylori infection on the long-term recurrence of gastric or duodenal ulcer: a randomised, controlled study.
Ann Intern Med, 116 (1992), pp. 705-708
[18.]
S.W. Hosking, T.K.W. Ling, S.C.S. Chung, M.Y. Yung, A.F. Cheng, J.J. Sung, et al.
Duodenal ulcer healing by eradication of Helicobacter pylori without anti-acid treatment: randomised controlled trial.
Lancet, 343 (1994), pp. 508-510
[19.]
J.P. Gisbert, D. Boixeda, C. Martín de Argila, I. Álvarez Baleriola, V. Abraira, A. García Plaza.
Unhealed duodenal ulcers despite Helicobacter pylori eradication.
Scand J Gastroentrol, 32 (1997), pp. 643-650
[20.]
W. DeBoer, GN. Tytgat.
How to treat Helicobacter pylori infection. Should treatment strategies be based on testing bacterial susceptibility? A personal viewpoint.
Eur J Gastroenterol Hepatol, 8 (1996), pp. 709-716
[21.]
Boer Wink A de, Tytgat Guido NJ.
Treatment of Helicobacter pylori infection.
BMJ, 320 (2000), pp. 31-33
[22.]
U. Peitz, A. Hackelsberger, P. Malfertheiner.
A practical approach to patients with refractory Helicobacter pylori infection, or who are re-infected after standard therapy.
Drugs, 57 (1999), pp. 905-920
[23.]
V. Rinaldi, A. Zullo, V. De Francesco, C. Hassan, S. Winn, V. Stoppino, al. el.
Helicobacter pylori eradication with proton pump inhibitor-based triple therapies and re-treatment with ranitidine bismuth citrate-based triple therapy.
Aliment Pharmacol Ther, 13 (1999), pp. 163-168
[24.]
R. Mera, J.L. Realpe, L.E. Bravo, J.P. DeLany, P. Correa.
Eradication of Helicobacter pylori infection with proton pump-based triple therapy in patients in whom bismuth-based triple therapy failed.
J Clin Gastroenterol, 29 (1999), pp. 51-55
[25.]
F. Gomollón, B. Sicilia, J.A. Ducons, E. Sierra, M.J. Revillo, M. Ferrero.
Third line treatment for Helicobacter pylori: a prospective, culture-guided study in peptic ulcer patients.
Aliment Pharmacol Ther, 14 (2000), pp. 1335-1338
[26.]
National Committee for Clinical Laboratory Standards (NCCLS).
Performance standards for antimicrobial susceptibility testing. Fourth Information Supplement. Villanova.
[27.]
J.P. Gisbert, J.L. Gisbert, S. Marcos, R.G. Gravalos, D. Carpio, JM. Pajares.
Seven-day rescue therapy after Helicobacter pylori treatment failure omeprazole, bismuth, tetracycline and vs. metronidazole ranitidine bismuth citrate, tetracycline and metronidazole.
Aliment Pharmacol Ther, 13 (1999), pp. 1311-1316
[28.]
F. Perri, V. Festa, R. Clementer, M.R. Villani, M. Quitadamo, N. Caruso, et al.
Randomized study of two «rescue» therapies for Helicobacter pylori-infected patients after failure of standard triple therapies.
Am J Gastroenterol, 96 (2001), pp. 58-62
[29.]
U. Peitz, A. Hackelsberger, P. Malfertheiner.
A practical approach to patients with refractory Helicobacter pylori infection, or who are re-infected after standard therapy.
Drugs, 57 (1999), pp. 905-920
[30.]
V. Rinaldi, A. Zullo, V. De Francesco, C. Hassan, S. Winn, V. Stoppino, al. el.
Helicobacter pylori eradication with proton pump inhibitor-based triple therapies and re-treatment with ranitidine bismuth citrate-based triple therapy.
Aliment Pharmacol Ther, 13 (1999), pp. 163-168
[31.]
R. Mera, J.L. Realpe, L.E. Bravo, J.P. DeLany, P. Correa.
Eradication of Helicobacter pylori infection with proton pump-based triple therapy in patients in whom bismuth-based triple therapy failed.
J Clin Gastroenterol, 29 (1999), pp. 51-55
[32.]
F. Gomollón, J.A. Ducons, M. Ferrero, J. García Cabezudo, R. Guirao, M.A. Simón, et al.
Quadruple therapy is effective for eradicating Helicobacter pylori after failure of triple proton pomp inhibitor-based therapy: a detailed prospective analysis of 21 consecutive cases.
Helicobacter, 4 (1999), pp. 222-225
[33.]
F. Megraud, N. Lehn, T. Lind, E. Bayerdorffer, C. O'Morain, R. Spiller, et al.
Antimicrobial susceptibility testing of Helicobacter pylori in a large multicentre trial: the MACH 2 study.
Antimicrob Agents Chemoter, 43 (1999), pp. 2747-2752
[34.]
N. Brouet, F. Guillon, E. Sauty, D. Lethuare, F. Megraud.
Survey of the in vitro susceptibility of Helicobacter pylori to antibiotics in France. Preliminary results [abstract].
Gastroenterology, 114 (1998), pp. A81
[35.]
J.P. Gisbert, S. Marcos, J.L. Gisbert, M. Pajares.
Helicobacter pylori eradication therapy is more effective in peptic ulcer than in non-ulcer dyspepsia.
Eur J Gastroenterol Hepatol, 13 (2001), pp. 1303-1307
[36.]
F. Gomollón, B. Sicilia.
Helicobacer pylori: strategies for treatment.
Expert Opin Investig Drugs, 10 (2001), pp. 1231-1241
[37.]
A. Pilotto, M. Franceschi, M. Rassu, F. Furlan, M. Scagnelli.
In vitro activity of rifabutin against strains of Helicobacter pylori resistant to metronidazole and clarithromycin.
Am J Gastroenterol, 95 (2000), pp. 833-834
Copyright © 2002. Elsevier España, S.L.. Todos los derechos reservados
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