Activities of β-Lactams and Macrolides against Helicobacter pylori

Abstract

A continuous-culture system (chemostat) was used to study the activities of β-lactam antimicrobial agents, clarithromycin, and 14-OH-clarithromycin against slowly growing Helicobacter pylori NCTC 11637. H. pylori was grown to steady state before exposure to these antimicrobial agents at ×8 the MIC. The bactericidal actions of combinations of amoxicillin and clarithromycin were also studied. Viable counts (numbers of CFU per milliliter) were determined at 2-h intervals for 12 h and at 20 h after the addition of antibiotics. The effects of pH changes (6.5 to 7.4) on the activities of amoxicillin, clarithromycin, and the combination of these against H. pylori NCTC 11637 were also studied. Viable counts following exposure to ampicillin, cefixime, ceftazidime, cefuroxime, cefotaxime, azlocillin, and piperacillin at 20 h showed bacteriostatic activity. Imipenem, meropenem, amoxicillin, clarithromycin, and 14-OH-clarithromycin reduced the viable counts by 3 log10 CFU/ml (≥99.9% killing). Imipenem was the most rapidly bactericidal against H. pylori NCTC 11637. Results of the pH experiments showed that amoxicillin was bactericidal at pHs 6.5 to 7.4. Clarithromycin was bactericidal at pH 7.0 to 7.4 but was bacteriostatic at pH 6.5. The combination of amoxicillin and clarithromycin was bactericidal at pHs 6.5 and 7.0. A batch culture (flask system) was also used to investigate 12 strains of H. pylori for their susceptibilities to β-lactams, clarithromycin, and/or 14-OH-clarithromycin in order to determine whether results from the chemostat model can be reproduced with batch cultures. Results of the chemostat time-kill kinetic study were reproducible in our batch culture flask system. The role of carbapenems in the eradication ofH. pylori should be investigated.

The status of antimicrobial resistance of Helicobacter pylori in eastern Europe

“…Resistance of Helicobacter pylori to metronidazole has been associated with a drop in efficacy of 15–50% for regimens involving nitroimidazoles; and clarithromycin resistance has a higher negative impact on treatment outcome, with a drop in efficacy from 92% to 50% in triple regimens including newer macrolides [1–4]. Recently, the resistance of H. pylori to amoxicillin, tetracycline and ciprofloxacin has been recognized [3,5–8]. While many studies have focused on H. pylori resistance patterns worldwide, there are still few reports concerning this topic in the eastern part of Europe.…”

“…efficacy from 92% to 50% in triple regimens including newer macrolides [1][2][3][4]. Recently, the resistance of H. pylori to amoxicillin, tetracycline and ciprofloxacin has been recognized [3,[5][6][7][8]. While many studies have focused on H. pylori resistance patterns worldwide, there are still few reports concerning this topic in the eastern part of Europe.…”

Dose‐dependent inhibition of CYP3A activity by clarithromycin during Helicobacter pylori eradication therapy assessed by changes in plasma lansoprazole levels and partial cortisol clearance to 6β‐hydroxycortisol

“…Drug interactions between clarithromycin and concomitant medications may be harmful to patients undergoing H pylori eradication therapy, but the interaction between clarithromycin and proton pump inhibitors may be beneficial rather than harmful for H pylori eradication. Because the bactericidal effects of clarithromycin and amoxicillin against H pylori have been shown to be potentiated during less acidic conditions than the bactericidal effects during highly acidic conditions, 12,13 the clarithromycin-induced elevations in plasma concentrations of proton pump inhibitors and the resultant potentiation in their antisecretory effects may underlie a higher H pylori eradication rate for the triple therapy with omeprazole, amoxicillin, and clarithromycin than those for the dual therapy with omeprazole and amoxicillin. However, it remains obscure whether clarithromycin would elicit a potentially beneficial drug interaction with proton pump inhibitors other than omeprazole (eg, lansoprazole) during the triple-drug H pylori eradication therapy.…”

In vitro Antibacterial and Morphological Effects of the Urushiol Component of the Sap of the Korean lacquer tree (Rhus verniciferaStokes) onHelicobacter pylori

“…Because antibiotics have different minimal inhibitory concentrations depending upon pH (15, 16), H. pylori eradication regimens using antibiotics need to include proton pump inhibitors. However, the minimal inhibitory concentration values of urushiol revealed minimal differences under different pH conditions.…”