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Memórias do Instituto Oswaldo Cruz
Fundação Oswaldo Cruz, Fiocruz
ISSN: 1678-8060 EISSN: 1678-8060
Vol. 91, Num. 6, 1996
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Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 91(6),
Nov./Dec. 1996,
RESEARCH NOTE
Susceptibility of Helicobacter pylori to
Metronidazole in a Brazilian Population
Marco Salazar/+, Isabel Abalem, Claude Solari/*, Charisse
Rodriguez**, Luiz Luna**
Laboratorio de Enterobacterias, Departamento de
Bacteriologia, Instituto Oswaldo Cruz, Av. Brasil 4365, 21045-
900 Rio de Janeiro, RJ, Brasil *Hospital Universitario Gaffree
e Guinle, UNIRIO, Rio de Janeiro, RJ, Brasil **Setor de
Endoscopia Digestiva, Hospital do Andarai, Rio de Janeiro, RJ,
Brasil
+Corresponding author. Fax: +55-21-280.0754
Received 29 March 1996, Accepted 27 August 1996
Code Number: OC96143
Sizes of Files:
Text: 6.4K
Graphics: No associated graphics files
Key words: Helicobacter pylori - susceptibility -
metronidazole
Helicobacter pylori is strongly associated with
gastritis, ulcer disease and has recently been recognized as a
probable cofactor in the development of gastric cancer (F
Megraud & H Lamouliatte 1992 Dig Dis Sci 37: 769-772, E
Raws & G Tytgat 1990 Lancet i: 1233-1235, J Kang et
al. 1990 Gut 31: 476-480, A Nomura et al. 1991 N
England J Med 325: 1132-1136). Although the mechanism of
pathogenicity has not yet been fully clarified, there is
evidence to suggest that patients with Helicobacter-
associated peptic ulceration can be cured by antimicrobial
treatment directed towards eradication of this microrganism (R
Hopkins et al. 1996 Gastroenterol 110: 1244-1252). This
eradication is best achieved with triple antimicrobial
therapy. Among agents used in the therapy of infection are
metronidazole, bismuth salts, furazolidone, ciprofloxacin,
tetracycline, amoxicillin, erythromycin, roxithromycin,
azithromycin, and clarithromycin (L Resende et al. 1993
Braz J Med Biol Res 26: 1279-1289, G Cederbrant et al.
1994 J Antimicrob Chemother 34: 1025-1029, L Klein & S
Tanaka 1995 Ann Rep Med Chem 30: 151-158, Hopkins et
al. loc. cit.). However emergence of strains of H.
pylori-resistant to antimicrobial agents, specially
metronidazole, represents a drawback to therapeutic regimens
(European Study Group on Antibiotic Susceptibility of
Helicobacter pylori 1992 Eur J Clin Microbiol Infect
Dis 11: 777-781). In our country, the frequent use of
metronidazole could select resistant strains to this agent.
Various methods of susceptibility testing have determined
resistance to metronidazole and include agar dilution, disk
diffusion and the E-test (G Rubinstein et al. 1994 J
Antimicrob Chemother 34: 409-413, P Midolo et al. 1995
Diagn Microbial Infect Dis 21: 135-140).
The objective of this study was to determine the Minimum
Inhibitory Concentrations (MICs) of our strains to
metronidazole.
Forty strains of H. pylori isolated from dyspeptic
Brazilian patients who were not treated with any antimicrobial
therapy for H. pylori infection and were referred to
endoscopy service (Andarai Hospital, Rio de Janeiro) were
studied. Strains were stored in plastic vials at -70 C in
sterile defibrinated sheep blood before being tested.
MICs to metronidazole for H. pylori strains grown in
Brucella agar (Difco) supplemented with 10%
defibrinated sheep blood and 0.004% 2, 3, 5 -
tripheniltetrazolium chloride (TTC-Difco) (D Queiroz et al.
1987 J Clin Microbiol 25: 2378-2379) in a
microaerophilic atmosphere for 72 hr, were determined by E-
test (AB Biodisk, Sweden). E-test strip with antimicrobial
concentrations from 0.002 to 32 mg/l were assayed. The
bacterial inoculum was prepared in Brucella broth
(Difco) and adjusted to McFarland standard 0.5. The plates
were streaked with non-toxic swab three times, rotating the
plate approximately 90 degrees each time to ensure a
distribution of inoculum. The MIC was defined as the lowest
concentration at which there was completely inhibited growth.
The breakpoint of >=8 mg/l was used to indicate resistance (Y
Glupczynski et al. 1990 Lancet 335: 976-977).
The prevalence of metronidazole-resistant strains was 72.5%
(29/40). Twenty nine strains showed MIC >=32 mg/l whereas 11
strains showed MIC between 0.016 to 2 mg/l. In the present
study, the rate of metronidazole resistance was similar to
that observed in a previous Brazilian study (64.7%) (D Queiroz
et al. 1993 Am J Gastroenterol 88: 322-323), where the
MIC values to metronidazole were not mentioned.
On the other hand, comparing our results to the multicentre
European survey on metronidazole resistance (European Study
Group on Antibiotic Susceptibility of Helicobacter pylori
loc. cit.) we observe much higher resistance levels in
Brazil than in Europe. The resistance there varied from 7 to
49%, having the non-Caucasian groups the most elevated
percentage of resistance. Considering the MIC >=32 mg/l, we
found 100% of resistent strains while the European Group
detected 88.5% (108/122).
Due to its effective local (D Edwards 1986 Biochem
Pharmacol 35: 53-58) and even systemic activities (S Loft
et al. 1988 Clin Pharmacol Ther 43: 420-428), reaching
the gastric cells, metronidazole has been considered a
complement to the treatment of H. pylori infection
(Hopkins et al. loc. cit.). The occurrence of
metronidazole-resistant H. pylori strains has been
reported to be related to the earlier use of nitroimidazoles
(T Borody et al. 1988 Gastroenterol 94: A43, M Becx et
al. 1990 Lancet i: 539-540). In our country these
resistant strains can possibly be explained by frequent use of
this drug in the treatment of gynecological, parasitic and
urological infections; moreover, free distribution and reduced
costs in hospitals and medical centers indicate common
availability for the population.
Considering the present results in our country, it is
recommendable to perform susceptibility testing of H.
pylori strains to antimicrobial agents before initiating
treatment in order to avoid failure.
Acknowledgments: to Evaldo Soares da Silva and Sergio
Alves Azevedo for technical support.
Copyright 1996 Fundacao Oswaldo Cruz
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