Comparative efficacy of new investigational agents against Helicobacter pylori.
BACKGROUND
Emergence of antibiotic resistant Helicobacter pylori has necessitated the identification of alternate therapies for the treatment of this infection.


OBJECTIVE
To assess the in vitro efficacy of two investigational agents: DMG-MINO CL 344 (a N,N-dimethylglycylamido derivative of minocycline), and davercin, a cyclic carbonate of erythromycin A as compared to older antibiotics (clarithromcyin, azithromycin, minocycline, tetracycline, ofloxacin, ciprofloxacin, cefixime) against clinical isolates of H. pylori.


METHODS
Testing was performed using the agar dilution method approved by the NCCLS subcommittee on antimicrobial susceptibility testing, Helicobacter pylori working group. Under these guidelines, Mueller-Hinton agar containing 5% aged sheep blood was used. All incubations were done under CampyPak Plus conditions for 72 h at 37 degrees C. The drug concentrations in the agar ranged from 0.016 to 16 microg/mL. Twenty-one clarithromycin-resistant and 16 clarithromycin-susceptible clinical isolates of H. pylori obtained from patients with duodenal ulcer were used. H. pylori ATCC 43504 was used as the control in all determinations.


RESULTS
Against clarithromycin susceptible isolates, all antimicrobial agents except the fluoroquinolones were highly effective. Against clarithromycin-resistant H. pylori, the MIC50/MIC90 values showed that the tetracyclines and cefixime were the most efficacious agents. The fluoroquinolones and macrolides were ineffective. Macrolide cross-resistance was detected.


CONCLUSIONS
Macrolide cross-resistance prevents the use of this entire class of antimicrobials when clarithromycin resistance is present. Tetracyclines and cefixime are possible alternative agents for the treatment of H. pylori infection in these patients.
Osato
M S
MS
Department of Medicine, Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USA. mosato@bcm.tmc.edu
Reddy
S G
SG
Piergies
A A
AA
Bochenek
W J
WJ
Testa
R T
RT
Graham
D Y
DY
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D004917:Erythromycin / Q000031:analogs & derivatives / Q000494:pharmacology*; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; C085305:9-(N,N-dimethylglycylamido)minocycline; C029784:erythromycin A cyclic 11,12-carbonate; D004917:Erythromycin; D008911:Minocycline