Objectives: National and international guidelines recommend empiric first-line treatments of individuals infected with Helicobacter pylori without prior antimicrobial susceptibility testing. For this reason, knowledge of primary resistance to first-line antibiotics such as clarithromycin is essential. We assessed the primary resistance of H. pylori in Germany to key antibiotics by molecular genetic methods and evaluated risk factors for the development of resistance. Methods: Gastric tissue samples of 1851 yet treatment-naïve H. pylori-positive patients were examined with real-time PCR or PCR and Sanger sequencing for mutations conferring resistance to clarithromycin, levofloxacin and tetracycline. Clinical and epidemiological data were documented and univariable and multivariable logistic regression analyses were conducted. Results: Overall primary resistances were 11.3% (210/1851) to clarithromycin, and 13.4% (201/1497) to levofloxacin; resistance to tetracycline (2.5%, 38/1497) was as low as combined resistance to clarithromycin/levofloxacin (2.6%, 39/1497). Female sex and prior antimicrobial therapies owing to unrelated bacterial infections were risk factors for clarithromycin resistance (adjusted OR (aOR) 2.3, 95% CI 1.6e3.4; and 2.6, 95% CI 1.5e4.5, respectively); older age was associated with levofloxacin resistance (aOR for those 65 years compared with those 18e35 years: 6.6, 95% CI 3.1e14.2). Conclusions: Clarithromycin might still be recommended in first-line eradication therapies in yet untreated patients, but as nearly every tenth patient may carry clarithromycin-resistant H. pylori it may be advisable to rule out resistance ahead of treatment by carrying out susceptibility testing or prescribing an alternative therapy.

1.When undergoing nucleophilic reactions with proteins, a-iodopropionic acid and its amide show greater specificity for SH groups than do iodoacetic acid and its amide.2. The kinetics and stereochemistry of the reactions of the D( +) and L( -) antipodes of a-iodopropionic acid and its amide with both cysteine and papain were investigated. The antipodes of the SH reagents reacted with these asymmetric SH compounds a t different rates. I n the reaction with papain, the L( -) antipode of the acid reacted faster than the D(+) antipode; the stereochemical preference was inverted when the amide was used, the D(+)antipode reacting faster than the L( -)antipode. 3.Arguing from the differing reactivities of the SH reagents and their antipodes and the pH dependence of the reaction rates, it has been suggested, that L( -)a-iodopropionic acid is specifically oriented onto the reaction center through the concerted attractive and repulsive actions of a cationic and an anionic group in the protein. These have been tentatively identified as a protonated imidazole residue and a carboxylate group respectively.4. Parallels between these stereospecific alkylations and the catalytic action of the enzyme are discussed.Gundlach, Stein, and Moore [1] demonstrated in their studies of the alkylation of ribonuclease with iodoacetic acid and iodoacetamide, that these "classic" sulfhydryl reagents do not react only with SH groups. Other nucleophiles present in proteins, such as amino, imidazolyl or thioether groups may also be alkylated. The extent of these side reactions depends on the reaction conditions. Our purpose in undertaking this work was to find SH reagents with higher selectivity for SH groups.Reasoning from a theory of Bunnett [a] it seemed likely, that this could be achieved by the introduction of polarizable substituents alpha to the halogen of halogen-alkyles. The possibility for the action of dispersion forces, which is introduced with the polarizable substituent, should specially favor the transition state for the reaction with the highly polarizable SH group. Steric, inductive or mesomeric effects of the a substituent would be expected to show the same influence on the reactions with all different nucleophilic groups.We tested this hypothesis using a series of derivatives of iodoacetamide with different substituents alpha to the iodine. With the methyl group as CI substituent i e . in the reaction of amino acids with a-iodopropionamide we observed an enhanced selectivity for SH groups as predicted by Bunnett's theory A further possibility for selective reactivity is contributed by a-substitution in iodoacetic acid derivatives ; the leaving group of the reagent is attached to an asymmetric carbon atom. One may expect specific interactions if the substrate itself is asymmetric since diastereomeric transition states are involved. This type of stereoselective reaction was shown for the first time by Heinrikson et al. [4,5]. They found, that the essential histidine (residue 12) of ribonuclease reacts preferentially with the D-...

Three-in-one capsule bismuth quadruple therapy is effective and safe for treatment of H. pylori infection in routine practice, irrespective of the patient's migrational background or the number of previous treatment failures.

Background Antimicrobial therapy is recommended to eradicate Helicobacter (H.) pylori in infected individuals. As first‐line treatments are empiric, knowledge of antimicrobial resistance is key to successful eradication. Aims We investigated primary resistance in an eastern German region to derive recommendations for eradication treatment. Methods We used molecular genetic methods to examine Helicobacter rapid urease test (RUT) positive gastric specimens of 533 patients from Berlin and the federal state of Brandenburg with allegedly no prior eradication treatment. Tissue samples were removed from RUT and screened by real‐time PCR for mutations conferring resistance to clarithromycin. In addition, 182 samples out of 533 were tested for resistance to levofloxacin and tetracycline. Results Primary resistances were 10.9% (58 out of 533) to clarithromycin; 13.7% (25/182) to levofloxacin; and 2.2% to tetracycline (4/182). Combined resistance to clarithromycin/levofloxacin was low (2.2%, 4/182). Female sex was significantly associated with clarithromycin resistance. Conclusion Clarithromycin may be a suitable first‐line antibiotic for about 90% of outpatients. A simple molecular test may help physicians avoid prescription of an ineffective first‐line regimen.