A continuous-culture system (chemostat) was used to study the activities of
beta-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 x8 the MI
C. The bactericidal actions of combinations of amoxicillin and clarithromyc
in were also studied. Viable counts (numbers of CFU per milliliter) were de
termined at 2-h intervals for 12 h and at 20 h after the addition of antibi
otics. The effects of pH changes (6.5 to 7.4) on the activities of amoxicil
lin, clarithromycin, and the combination of these against H. pylori NCTC 11
637 were also studied. Viable counts following exposure to ampicillin, cefi
xime, ceftazidime, cefuroxime, cefotaxime, azlocillin, and piperacillin at
20 h shelved bacteriostatic activity. Imipenem, meropenem, amoxicillin, cla
rithromycin, and 14-OH-clarithromycin reduced the viable counts by 3 log(10
) CFU/ml (greater than or equal to 99.9% killing). Imipenem was the most ra
pidly bactericidal against H. pylori NCTC 11637, Results of the pH experime
nts showed that amoxicillin was bactericidal at pHs 6.5 to 7.4. Clarithromy
cin 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 str
ains of H. pylori for their susceptibilities to beta-lactams, clarithromyci
n, and/or 14-OH-clarithromycin in order to determine whether results from t
he chemostat model can be reproduced with batch cultures. Results of the ch
emostat time-kill kinetic study were reproducible in our batch culture flas
k system. The role of carbapenems in the eradication of H. pylori should be
investigated.