The Toronto Consensus for the Treatment of Helicobacter pylori Infection in Adults.

BACKGROUND & AIMS: Helicobacter pylori infection is increasingly difficult to treat. The purpose of these consensus statements is to provide a review of the literature and specific, updated recommendations for eradication therapy in adults. METHODS: A systematic literature search identified studies on H pylori treatment. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an online platform, finalized, and voted on by an international working group of specialists chosen by the Canadian Association of Gastroenterology. RESULTS: Because of increasing failure of therapy, the consensus group strongly recommends that all H pylori eradication regimens now be given for 14 days. Recommended first-line strategies include concomitant nonbismuth quadruple therapy (proton pump inhibitor [PPI] + amoxicillin + metronidazole + clarithromycin [PAMC]) and traditional bismuth quadruple therapy (PPI + bismuth + metronidazole + tetracycline [PBMT]). PPI triple therapy (PPI + clarithromycin + either amoxicillin or metronidazole) is restricted to areas with known low clarithromycin resistance or high eradication success with these regimens. Recommended rescue therapies include PBMT and levofloxacin-containing therapy (PPI + amoxicillin + levofloxacin). Rifabutin regimens should be restricted to patients who have failed to respond to at least 3 prior options. CONCLUSIONS: Optimal treatment of H pylori infection requires careful attention to local antibiotic resistance and eradication patterns. The quadruple therapies PAMC or PBMT should play a more prominent role in eradication of H pylori infection, and all treatments should be given for 14 days.

Feasibility of amlodipine besylate, chloroquine phosphate, dapsone, phenytoin, pyridoxine hydrochloride, sulfadiazine, sulfasalazine, tetracycline hydrochloride, trimethoprim and zonisamide in SyrSpend(®) SF PH4 oral suspensions.

The objective of this study was to evaluate the feasibility of 10 commonly used active pharmaceutical ingredients (APIs) compounded in oral suspensions using an internationally used suspending vehicle (SyrSpend(®) SF PH4 liquid): (i) amlodipine, (as besylate) 1.0mg/mL; (ii) chloroquine phosphate,15.0 mg/mL; (iii) dapsone, 2.0 mg/mL; (iv) phenytoin, 15.0 mg/mL; (v) pyridoxine hydrochloride, 50.0 mg/mL; (vi) sulfadiazine, 100.0 mg/mL; (vii) sulfasalazine, 100.0 mg/mL; (viii) tetracycline hydrochloride, 25.0 mg/mL; (ix) trimethoprim, 10.0 mg/mL; and (x) zonisamide, 10.0 mg/mL. All suspensions were stored both at controlled refrigeration (2-8 °C) and controlled room temperature (20-25 °C). Feasibility was assessed by measuring the percent recovery at varying time points throughout a 90-day period. API quantification was performed by high-performance liquid chromatography (HPLC-UV), via a stability-indicating method. Given the percentage of recovery of the APIs within the suspensions, the expiration date of the final products (API+vehicle) was at least 90 days for all suspensions with regard to both the controlled temperatures. This suggests that the vehicle is stable for compounding APIs from different pharmacological classes.

Development and validation of an HPLC method for tetracycline-related USP monographs.

A novel reversed-phase HPLC method was developed and validated for the assay of tetracycline hydrochloride and the limit of 4-epianhydrotetracycline hydrochloride impurity in tetracycline hydrochloride commercial bulk and pharmaceutical products. The method employed L1 (3 µm, 150 × 4.6 mm) columns, a mobile phase of 0.1% phosphoric acid and acetonitrile at a flow rate of 1.0 mL/min, and detection at 280 nm. The separation was performed in HPLC gradient mode. Forced degradation studies showed that tetracycline eluted as a spectrally pure peak and was well resolved from its degradation products. The fast degradation of tetracycline hydrochloride and 4-epianhydrotetracycline hydrochloride in solution was retarded by controlling the autosampler temperature at 4 °C and using 0.1% H3 PO4 as diluent. The robustness of the method was tested starting with the maximum variations allowed in the US Pharmacopeia (USP) general chapter Chromatography <621>. The method was linear over the range 80-120% of the assay concentration (0.1 mg/mL) for tetracycline hydrochloride and 50-150% of the acceptance criteria specified in the individual USP monographs for 4-epianhydrotetracycline hydrochloride. The limit of quantification for 4-epianhydrotetracycline hydrochloride was 0.1 µg/mL, 20 times lower than the acceptance criteria. The method was specific, precise, accurate and robust.

The quality of drugs in private pharmacies in Lao PDR: a repeat study in 1997 and 1999.

OBJECTIVE: To present a repeated test of the quality of ampicillin, tetracycline, chloroquine and ASA from private pharmacies in Laos in 1997 and 1999, and to discuss the quality in relation to the National Drug Policy Programme. METHOD: A total of 115 of 214 licensed private pharmacies were selected in Savannakhet province, a pilot province in the Lao National Drug Policy Programme. The four drugs, if available, were collected at each pharmacy. Thirty tablets of each drug were taken from a selected container. In 1997, 366 samples were analysed and three hundred in 1999. Identity, assay (content of active component) and measurement of weight variation tests were performed. Drug quality was compared mainly according to the standards of the British and United States' pharmacopoeias. RESULTS: The percentage of substandard drugs decreased significantly from 46% to 22% between 1997 and 1999 (P< 0.001). Substandard ampicillin and tetracycline were reduced significantly from 67% to 9% and from 38% to 12%, respectively (P < 0.001). In total, 3% vs 1% contained no active ingredient, 12% vs 4% had too little or too much active ingredient, and 35% vs 14% had weight variation outside pharmacopoeial limits. CONCLUSION: Drug quality was improved. However, the prevalence of substandard drugs was still unacceptably high, which may result in adverse clinical effect or treatment failure for individual patients.

Nested designs in ruggedness testing.

Nested designs were performed in order to execute a ruggedness test according to the United States Pharmacopeia definition for ruggedness, in which mainly non-procedure related factors are examined. Several nested designs have been executed on a high performance liquid chromatography assay to determine tetracycline and related substances in bulk samples of tetracycline. Factors such as different laboratories, analysts, instruments, columns, days and batches were examined. The interpretation methods described in the literature were found to cause problems. In these methods the variances of the examined factors are estimated from the calculated mean square values and from the equation for the expected mean squares. Very frequently, negative variance estimates were obtained. Their absolute values were found to be dependent on the influence of the factor examined below it in the design, on the examined response. Therefore an alternative interpretation method for nested designs, based on pooled variances, was proposed and found to be appropriate to use for ruggedness testing purposes. Both approaches, the one from the literature and the one proposed here, were tested on simulated data coming from a nested design with four factors and on the experimentally measured data.

Evaluation of tetracycline raw materials and finished products found on the Kenyan market.

Contents of tetracycline, its degradation products (epitetracycline, epianhydrotetracycline, anhydrotetracycline) and a fermentation impurity (2-acetyl-2-decarboxamidotetracycline) were determined in four raw materials, 12 batches of six ointment products, four eye ointment products and nine batches of five capsule products, all sampled from the Kenyan market. The analytical method was liquid chromatography on a column packed with a poly(styrenedivinyl-benzene) material (8-microns PLRP-S 100 A). All raw materials and finished products had tetracycline contents and impurity levels within the prescribed compendial limits.

The efficacy of percutaneous tetracycline instillation for sclerosis of recurrent thyroid cysts: a multivariate analysis.

A dichotomy exists in the literature concerning the efficacy of sclerosing agent tetracycline hydrochloride for treatment of thyroid cysts. However, the studies vary in patient selection and none employed a statistical method for simultaneous analysis of multiple factors that might affect the outcome of therapy. We, therefore, studied the efficacy of percutaneous instillation of tetracycline for eradication of recurrent thyroid cysts, using a multivariate analysis. Thirty-seven patients with recurrent, cytologically benign thyroid cysts (not cured after 3 aspirations) were studied. Twenty-three patients were given tetracycline instillations [100 mg/ml, range (R): 1-4 ml]. The remainder underwent only repeated needle aspiration. They were followed for 33 +/- 12 (SD) months, R: 12-58 months. Cure was achieved in 21 out of 23 cases after tetracycline instillation within 2 +/- 1.7 months (R: 1-6 months) and in 12 out of 14 cases after aspiration alone within 9.9 +/- 11.3 months (R: 1-43 months, 4-10 aspirations). Multivariate survival analysis using the Cox proportional-hazards regression model demonstrated significantly shorter time interval before cure in the group with tetracycline instillation (p = 0.001). The volume, color or duration of cysts and levothyroxine (L-T4) treatment did not appear to influence the outcome of therapy. After initial cure by tetracycline instillation, 5 cases had relapse. Three were later cured by reinstillation of tetracycline or by repeated aspirations (R: 1-3 times). Complications of tetracycline instillation included brief episode of neck pain and development of a foreign body granuloma in a single patient. In conclusion, tetracycline instillation is a quick and effective procedure for treating recurrent thyroid cysts.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of prophylactic use of tetracycline after evacuation in abortion in Harare Central Hospital.

A randomised controlled trial involving 140 non-septic incomplete abortions was performed to determine the efficacy of prophylactic tetracycline as practiced in these cases in Harare Central Hospital. The treatment group (62) received tetracycline (500 mg four times daily) for a week. The remainder acted as controls. No significant difference in sepsis rate between treatment and control groups was noted. The high sepsis recorded in the treatment group was thought to be due to poor compliance. A new prophylaxis regimen has been suggested.

PIP: The purpose of this randomized, controlled study was to determine the efficacy of tetracycline as a prophylactic antibiotic therapy in treating nonseptic, incomplete abortion patients in Zimbabwe. In 1984, the gynecology emergency unit of Harare Central Hospital admitted 3240 cases of incomplete abortion, of which 2891 were nonseptic on admission. For this prospective study, patients presenting with nonseptic, incomplete abortion (n = 140) from February through May 1985 were recruited at Harare Central. These patients were randomly divided into treatment and control groups, and all patients received aseptic evacuation procedures. Following evacuation, the treatment group (n = 62) was given tetracycline (500 mg 4 times daily to be taken for a week). The remainder (n = 78) acted as controls. Diagnosis for sepsis, based on defined parameters, was performed a week later by the author, who did not know the group to which the patient belonged. The majority of the patients in both groups were 15-24 years old and of parity 1-4. An overall sepsis rate of 35.6% was obtained in this study. No significant difference in sepsis rates between treatment and control groups was noted. The apparent higher proportion of sepsis recorded in the treatment group (25/62, or 40.32%) in comparison to the control group (23/78, or 29.5%) was not significant. Although all patients insisted they took their drugs as instructed, further questioning and counting of remaining capsules revealed that the majority (82.6%) had not taken any or part of the course; the patients who did complete the course had not followed the instructions properly. Thus, the lack of significant reduction in the sepsis rate with the use of prophylactic tetracycline was thought to be due to poor compliance. The author argued that this was due to the young age, low socioeconomic status, and lack of understanding of the regimen among the patients. Thus, it is suggested that tetracycline treatment be replaced with a cheap, single-dose, hospital-administered prophylaxis regimen, such as doxycycline, that covers a wide range of organisms.

[Mathematical model for the control and standardization of discs]. / Matematicheskaia model' kontrolia i standartizatsii diskov

Analysis of tetracycline and erythromycin diagnostic discs manufactured in the USSR showed their conformity with the requirements of the USA Federal Register. Comparison of the antibiotic amounts extracting and diffusing from the discs showed that as an average 92 and 90 per cent of the extracted amounts of erythromycin and tetracycline respectively diffused into the agar. Subsequently, it is desirable that on control testing of the disc quality both the similarity of the antibiotic content in the discs and the real amount of the antibiotic diffusing into the agar should be considered. A statistically reliable correlation between the values of the growth inhibition zones around the discs with definite and constant amounts of erythromycin, tetracycline or oxacillin and different resistance levels for every staphylococcal strain was found. On the basis of such a control system it is possible to divide the staphyloccal strains into the groups with high, low and intermediate resistance levels to the above antibiotics. However, it is not possible to use such data for accurate calculation of the value of the minimum inhibitory concentration of unknown strains because of a high value of the main error.

The second international reference preparation of lymecycline.

The second International Reference Preparation of Lymecycline was established. Nine laboratories in 8 countries collaborated in assaying its potency in terms of the first International Reference Preparation, of which stocks had become exhausted. The best estimate of potency was taken to be 948 IU/mg, which was the unweighted geometric mean of a total of 124 assays. On this basis, the International Unit of lymecycline was defined as the activity contained in 0.0010548 mg of the second International Reference Preparation.

The second international standard for tetracycline.

A second international standard has been established to replace the first International Standard for Tetracycline, stocks of which were depleted. The International Unit of tetracycline is defined as the activity contained in 0.00101833 mg of the second International Standard, corresponding to a potency of 982 IU/mg. These values were assigned on the basis of the results of an international collaborative assay carried out by laboratories in 19 countries. Most of the assays were by diffusion techniques; a few were by turbidimetric methods. Both procedures gave statistically valid assays but there was some heterogeneity of repeated estimations within a laboratory and also some heterogeneity of the mean estimates from each laboratory. The agreed defined potency was the unweighted mean of 281 individual assays; the confidence limits were 978-986 IU/mg.