Third line treatment for Helicobacter pylori: a prospective, culture-guided study in peptic ulcer patients.

BACKGROUND: A third line treatment is needed in roughly 5% of patients infected with Helicobacter pylori. Few data have been reported on efficacy of treatment regimens in these patients. METHODS: A prospective trial was designed to study the effectiveness of third line treatment of H. pylori infection in ulcer patients. Two-week quadruple, culture-guided, combinations were used in 31 consecutive patients. Susceptibility to metronidazole and clarithromycin were studied by E-test, and thereafter a predetermined treatment regimen was used. Compliance was evaluated by pill count, and eradication defined by negative urea breath test at 6 weeks. RESULTS: Two main quadruple regimens were used in 29 patients. In spite of good compliance, the combination of omeprazole, tetracycline, bismuth and clarithromycin (OTBC) showed an eradication rate (per protocol analysis) of 36% (five out of 14; CI: 12.8-64.9), and if amoxycillin was used (OTBA) the rate was 67% (eight out of 12; CI: 34.9-90.1). The difference was not significant. No clinical factor was found to be associated with failure to eradicate. CONCLUSIONS: Third line treatment often fails to eradicate H. pylori infection. New strategies need to be developed and tested for this common clinical situation.

Impact of clarithromycin resistance on the effectiveness of a regimen for Helicobacter pylori: a prospective study of 1-week lansoprazole, amoxycillin and clarithromycin in active peptic ulcer.

BACKGROUND: Clarithromycin is a key antimicrobial in the combinations used to cure Helicobacter pylori infections, so there is a need to define the impact of in vitro resistance on in vivo results. METHODS: A prospective trial was designed to study the effectiveness of the 1-week combination of lansoprazole, clarithromycin and amoxycillin in 102 consecutive patients with active peptic ulcer. The pre-treatment and post-treatment sensitivity to amoxycillin, metronidazole and clarithromycin were studied by E-test, and H. pylori status was defined by histology, culture and urease test at diagnosis and one month after treatment, and by urea-breath test 2 months after treatment. RESULTS: The eradication rate (intention-to-treat analysis) was 77% (95% CI: 69-86). No clinical factor was found to be different between eradicated and non-eradicated patients. Clarithromycin-resistant strains were found in 10 (10%; CI: 5-17) patients. The eradication rate was 20% (CI: 3-56) in these patients vs. 83% (CI: 75-91) in patients harbouring clarithromycin-sensitive strains (P < 0.001). A logistic-regression analysis confirmed clarithromycin resistance as the only factor associated with treatment failure. CONCLUSIONS: Clarithromycin resistance significatively impairs the effectiveness of the combination of lansoprazole, amoxycillin, and clarithromycin. The 80% efficacy goal will be difficult to reach in areas with high (>10%) primary clarithromyicin resistance, if currently recommended proton pump inhibitor-triple therapies are used.

Factors affecting the variation in antibiotic resistance of Helicobacter pylori over a 3-year period.

Strains of Helicobacter pylori, isolated from 300 patients between 1996 and 2000 were tested for their sensitivity to clarithromycin, metronidazole and amoxycillin. Primary resistances (95% CI) were 9. 7% for clarithromycin and 21.7% for metronidazole. No strains were resistant to amoxycillin. There was no significant difference between the number of resistant strains in the male and female groups. Clarithromycin resistance was more common in older patients (P<0.01) and metronidazole resistance was more common in patients with peptic ulcer compared with patients with chronic gastritis (P<0. 05). Logistic regression analysis confirmed these results.

Breath test is very reliable for diagnosis of Helicobacter pylori infection in real clinical practice.

AIMS: To determine the accuracy of the most common available tests for the diagnosis of Helicobacter pylori infection in an unselected and untreated population of patients. PATIENTS AND METHODS: Prospective study including 314 unselected patients from a population of 814 patients referred for upper endoscopy at one hospital. H. pylori infection was diagnosed by rapid urease test (RUT), histology, culture and 13C-urea-breath test (UBT) and serum IgG (EIA). H. pylori infection was defined as positive if culture or at least two of the other tests were positive. RESULTS: The prevalence of H. pylori infection in this population was 72%. The diagnostic test with the greatest combination of sensitivity (97%) and specificity (100%) was the UBT. EIA had a good sensitivity (96%), but it was the test with the least specificity (71%). RUT, histology and culture showed a high specificity (>98%) but a sensitivity lower than 90%. In elderly patients (>65 years old, n=120), UBT was also the test with the greatest combination of sensitivity (94%) and specificity (100%). CONCLUSIONS: In conditions of real clinical practice the 13C-urea-breath test is a reliable test for H. pylori diagnosis, both in young and elderly patients.

[Gammagraphy with sucralfate labelled with technetium in esophagitis]. / Gammagrafía con sucralfato marcado con tecnecio en la esofagitis.

In previous studies it has been reported that, after being labeled with technetium, sucralfate, an useful drug in peptic diseases, can be used to detect peptic lesions of the digestive tract. In this work we report our experience with this technique in the diagnosis of esophagitis. 25 studies (11 controls and 14 patients) were undertaken. Sucralfate scintigraphy was normal in the 11 control studies, and abnormal in 10 out of 14 patients. Scintigraphy was abnormal in peptic as well as caustic lesions.

Is 1-week treatment for peptic ulcer healing sufficient and safe?

OBJECTIVE: To confirm whether 1-week anti-Helicobacter therapy to achieve ulcer healing is sufficient and safe. METHODS: We retrospectively analyzed patients with peptic ulcer who were infected with Helicobacter pylori and treated with 3 different 7-day regimens, according to predefined protocols in 3 different centers in the same geographical area (Aragón, Spain). Three combinations commonly described in the literature were used: a) omeprazole (40 mg/24 h), tetracycline hydrochloride (2 g/24 h), colloidal bismuth subcitrate (480 mg/24 h) and metronidazole (750 mg/24 h) (OBTM, n = 105); b) omeprazole (40 mg/24 h), clarithromycin (1.5 g/24 h) and amoxicillin (3 g/24 h) (O40C1.5A3, n = 13); and c) omeprazole (40 mg/24 h), clarithromycin (1 g/24 h) and amoxicillin (2 g/24 h) (O40C1A2, n = 4). In all patients the diagnosis of peptic ulcer disease was confirmed endoscopically, and H. pylori infection was verified with urease testing and histological analysis. After treatment ended, no other antacids were allowed until after endoscopic examination to check eradication and ulcer healing. RESULTS: 122 patients were included (107 with duodenal ulcer, 12 with gastric ulcer and 3 with both). Compliance was good and side effects infrequent and mild. Eradication rates were 88.5% (93/105) in the OBTM group, 100% (13/13) with O40C1.5A3, and 75% (3/4) with O40C1A2. Healing was achieved in 98.16% (107/109) of the patients in whom the bacterial infection was eradicated, and in 23.07% (3/13) of those in whom it was not (p < 0.0001). No patient had any complications during the period without treatment. CONCLUSIONS: 1-week eradication therapy with previously described combinations commonly used in clinical practice achieves high ulcer healing rates with no complications in the period without antacid treatment. We consider that it is not necessary, at least in most patients, to prolong antacid therapy.

[Gammagraphy with labeled leukocytes as an activity and extension index of Crohn disease]. / Gammagrafía con leucocitos marcados como índice de actividad y extensión de la enfermedad de Crohn.

The knowledge of the location and extent of bowel involment and disease activity can be an important aspect on the evaluation of inflammatory bowel disease. Thirty five patients of Crohn's disease (CD) have been studied in this sense. We performed a total of 44 scintigraphic examinations using 99mTc-HMPAO labeled leukocytes and the results were compared with several clinical-biological indexes and with radiology and endoscopy. The Tc scan was the most sensitive (84.3%) and specific (100%) activity index and showed an excellent correlation with radiology and/or endoscopy in the assessment of extent of disease. Leukocyte scanning brought useful information for the management of stenosis in CD.

[Does eliminating Helicobacter pylori mean the healing of the duodenal ulcer? The results of a prospective study in Spain]. / Erradicar Helicobacter pylori significa cicatrizar la úlcera duodenal? Resultados de un estudio prospectivo en nuestro medio.

AIM: To evaluate the predictive value of Helicobacter pylori eradication in the healing of duodenal ulcer. METHODS: A prospective study of 92 duodenal ulcer patients (diagnosed by endoscopy) with H. pylori infection demonstrated by rapid urease test, positive histology and culture. They were treated with a 7-day regimen of lansoprazole, clarithromycin and amoxicillin. Healing was evaluated in a follow-up gastroscopy performed one month after treatment had finished. Eradication was defined as negative urease test, histology and culture at 30 days and negative urea breath test at 60 days. RESULTS: Duodenal ulcer healing was observed in 85 patients (92.4%, CI 85-96.9). Eradication of H. pylori infection was the only variable independently associated with ulcer healing. Healing was observed in 97.2% of patients with H. pylori eradication versus 75% of those with persistent infection (p < 0.01; OR = 11.6; CI 95% = 2.06-65.9). CONCLUSION: Eliminating H. pylori infection favors duodenal ulcer healing and, from a clinical point of view, confirmation of H. pylori eradication almost always means healing of duodenal ulcer.

[Prevalence of peptic ulcer in smokers and non-smokers in Aragon]. / Prevalencia de úlcera péptica en fumadores y no fumadores en Aragón.

The present study has attempted to determine the prevalence of peptic ulcer (UP) in smokers and nonsmokers in the geographic region of Aragon (Spain) using a sample of 10,000 subjects, 1,897 with ulcer, 1,708 of them diagnosed by endoscopy. The prevalence of smokers is 42.4% (63% of males and 14% of females). The prevalence of peptic ulcer in smokers (26.87%) is double that of nonsmokers (13.38%) (p less than 0.05). In males, all of the locations (duodenal, duodenal + gastric and gastric) are more common among smokers than among nonsmokers. These differences do not exist in women, gastric ulcer being more common among nonsmokers. Complications were more frequent among smokers with ulcer (60%) than among nonsmokers with ulcer (40%).

The ideal therapy must be defined in each geographical area: experience with a quadruple therapy in Spain.

BACKGROUND: Multiple therapeutic combinations have been tested to determine the optimal regimen(s) for Helicobacter pylori eradication, leading to very different results depending on the geographical area. Our goal was to evaluate the efficacy of a "quadruple" therapy with omeprazole, tetracycline, bismuth and metronidazole in our area. MATERIALS AND METHODS: We investigate 106 consecutive patients with active peptic ulcer disease (duodenal, gastric or both) and Helicobacter pylori infection. One-week therapy with omeprazole 20 mg b.i.d., tetracycline hydrochloride 500 mg q.i.d., colloidal bismuth subcitrate 120 mg q.i.d., and metronidazole 250 mg t.i.d was prescribed. Between the days 30 and 40 after treatment ended follow-up endoscopy was performed. Eradication was defined as both negative urease test and histology. Between days 90 and 360 a 13C urea breath test was performed in 100 patients. RESULTS: Of the 106 patients in the study, 91 had duodenal ulcer, 12 had gastric ulcer, and 3 had both. Side effects were observed in 25% of the cases. Eradication was achieved in 87.7% (93/106; CI 79.9-93.3). Healing was obtained in 95.2% (100/105; CI 89.2-98.4); 97.8% (CI 92.4-99.7) in those eradicated and 75% (CI 42.8-94.5) in non-eradicated (p < .01). CONCLUSIONS: Quadruple therapy with omeprazole, tetracycline, bismuth subcitrate and metronidazole achieves healing rates up to 95-100%. The 87.7% eradication rate obtained suggests that the regimen we used is a reasonable therapeutic alternative in our area.

[Alpha-adrenergic receptors in the hepatic sinusoid of the rat and its relation to portal pressure]. / Receptores alfa-adrenérgicos del sinusoide hepático de la rata y su relación con la presión portal.

The presence of alpha-adrenergic receptors in the hepatic sinusoid of the rat, and its relation to portal pressure (PP), by local and systemic infusion of bolus doses of norepinephrine (NE) (1 microgram/100 g) and phentolamine (FA) (25 micrograms/100 g) have been studied. Fifty-five male Wistar rats with intact nerves have been used in 5 experiments. When NE is injected into the portal vein (PV), it provokes an immediate rise in PP, modified subsequently by the systemic effect is induced earlier and more intensely than if injected into PV. If FA is infused into PV, PP decreases and the effect of posterior infusion of NE is less marked. These results suggest the presence of alpha-adrenergic receptors in the hepatic sinusoid of the rat. When they are stimulated PP raises, indicating that basal PP is maintained not only because of hepatic arterial flow, but also through a distinct sympathetic tone.

Quadruple therapy is effective for eradicating Helicobacter pylori after failure of triple proton-pump inhibitor-based therapy: a detailed, prospective analysis of 21 consecutive cases.

BACKGROUND: Data regarding the effectiveness of second-line treatment of Helicobacter pylori infection are limited, especially if microbiological studies are considered. METHODS AND PATIENTS: We conducted a prospective, uncontrolled study of a consecutive series of 21 peptic ulcer patients with failure of 1-week lansoprazole, amoxicillin, and clarithromycin. H. pylori status was evaluated by urease test, histology, culture, and urea breath test. Susceptibility to amoxicillin, clarithromycin, and metronidazole was studied by E-test. Cure of infection was defined as negative results from endoscopy-based tests 1 month after treatment and negative results from a urea breath test at 2 months. Treatment consisted of a 1-week combination of lansoprazole (30 mg bid), tetracycline (500 mg qid), metronidazole (500 mg tid), and bismuth subcitrate (120 mg qid). RESULTS: H. pylori was resistant to metronidazole in three cases, to clarithromycin in three cases, and to both clarithromycin and metroinidazole in an additional three patients. No resistance to amoxicillin was found. Eradication was obtained in 20 cases (95.2% confidence interval [CI], 76.2-99.9). The only patient in whom infection was not eradicated harbored a metronidazole-resistant (minimum inhibitory concentration > 32 micrograms/ml) strain. No significant side effects were reported. CONCLUSION: Quadruple therapy obtains a high eradication rate even in patients with clarithromycin- and metronidazole-resistant strains. Further randomized and controlled studies are warranted and are urgently needed.

¿Es suficiente y seguro un tratamiento de una semana para cicatrizar la úlcera péptica? / Is 1-week treatment for peptic ulcer healing sufficient and safe?

OBJETIVO: confirmar si la terapia anti-Helicobacter pylori de una semana de duración es suficiente y segura para cicatrizar la úlcera péptica. MATERIAL Y MÉTODOS: se analizan de forma retrospectiva pacientes con úlcera péptica e infección por Helicobacter pylori sometidos a tratamiento erradicador con diversas pautas de siete días, con protocolos predefinidos, en tres centros diferentes de la misma área geográfica (Aragón, España). Se han utilizando tres combinaciones de fármacos ampliamente utilizadas en la literatura: a) OBTM (n = 105) omeprazol (40 mg/día), clorhidrato de tetraciclina (2 g/día), subcitrato de bismuto coloidal (480 mg/día) y metronidazol (750 mg/día); b) 040C1.5A3 (n = 13) omeprazol (40 mg/día), claritromicina (1,5 g/día) y amoxicilina (3 g/día), y c) 04OClA2 (n = 4) omeprazol (40 mg/día), claritromicina (1 g/día) y amoxicilina (2 g/día). Todos ellos eran diagnosticados de úlcera péptica activa por endoscopia e infección por Helicobacter pylori mediante ureasa y confirmación histológica. Tras la semana de tratamiento el enfermo no recibió fármacos antisecretores hasta la revisión endoscópica, realizada entre 28-60 días de finalizar el tratamiento, donde se comprobó cicatrización y erradicación (ureasa e histología). RESULTADOS: ciento veintidós pacientes fueron incluidos (107 con úlcera duodenal, 12 con úlcera gástrica y tres con ambas simultáneamente). El cumplimiento del tratamiento fue bueno y los efectos secundarios escasos y leves. Las tasas de erradicación obtenidas eran 88,5 por ciento (93/105) para el grupo OBTM, 100 por ciento (13/13) para 040CI.5A3 y 75 por ciento (3/4) para 04OClA2. Habían cicatrizado el 98,16 por ciento (107/109) de los pacientes erradicados frente a un 23,07 por ciento (3/13) de los no erradicados (p < 0,0001). Ningún paciente presentó complicaciones en el periodo de tiempo sin tratamiento. CONCLUSIONES: el tratamiento erradicador de sólo una semana de duración con las pautas descritas, las más utilizadas en la práctica clínica, tiene una alta eficacia en la cicatrización de las lesiones sin existir complicaciones en el periodo de tiempo sin tratamiento. Por ello consideramos que no es necesario, al menos en la mayoría de los pacientes, prolongar el tratamiento antisecretor (AU)