Resistance metronidazole

Preexisting antimicrobial resistance is an increasing cause of treatment failure and is estimated to account for up to 70% of all treatment failures. Geography is the most important factor in HP resistance. Metronidazole-resistant strains are more prevalent in Asia (85%) than North America (30%).15 Primary resistance to amoxicillin and tetracycline remains low in both the United States and Europe. Clarithromycin resistance rates are estimated to be approximately 10% in the United States. Another confounding factor when evaluating potential antibiotic resistance is that culture and sensitivity studies are not routinely performed with HP infection. 

Various studies demonstrate the successful use of tinida-zole for metronidazole-resistant trichomoniasis.19 Possible side effects include a metallic taste, dizziness, loss of coordination, seizures, severe diarrhea, darkened urine, nausea, vomiting, and a swollen or discolored tongue. 

Land KM, Johnson PJ. 1997. Molecular mechanisms underlying metronidazole resistance in trichomonads. Exper Parasitol 87 305-8. 

Rasoloson D,Tomkova E, Cammack R, et al. 2001. Metronidazole-resistant strains of Trichomonas vaginalis display increased susceptibility to oxygen. Parasitology 123 45-56. 

Zaidi SE, Yoshida 1, Butt F, Yusuf MA, Usmanghani K, Kadowaki M, Sugiyama T. (2009) Potent bactericidal constituents from Mallotus philippinensis against clarithromycin and metronidazole resistant strains of Japanese and Pakistani Helicobacter pylori. Biol Pharm Bull 32 631-636. 

Metronidazole is the treatment of choice. A single dose of 2 g is effective. Metronidazole-resistant organisms can lead to treatment failures. Tinidazole may be effective against some of these resistant organisms. 

Sobel JD, Nyirjesy P, Brown W Tinidazole therapy for metronidazole-resistant vaginal trichomoniasis. Clin Infect Dis 2001 33 1341. [PMID 11565074]... 

Ellis JE, Yarlett N, Cole D, Humphreys MJ, Lloyd D (1994b) Antioxidant defenses in the microaerophilic protozoan Trichomonas vaginalis comparison of metronidazole-resistant and sensitive strains. Microbiol-SGM 140 2489-2494... 

Fig-1 Metronidazole, l-(2-hydroxyethyl)-2-methyl-5-nitroimidazole, and side chains in positions 1 and 2 of related compounds tinidazole and ornidazole. Metronidazole and tinidazole are approved by the FDA for treatment of trichomoniasis, and ornidazole is used for this purpose outside the USA. Both tinidazole and ornidazole have been used with variable success in attempts to cure metronidazole-resistant infections... 

Surprisingly, monitoring of changes in metabolism and protein expression that accompany in vitro development of metronidazole resistance in I vaginalis (Rasoloson et al. 2002) revealed that the two types of resistance belong to a common multistep process, with aerobic resistance occurring at its earliest stage. 

Altered ferredoxin function or an insufficient amount of ferredoxin caused by defective transcription has been proposed to participate in mechanisms of aerobic resistance in I vaginalis (Yarlett et al. 1986b Quon et al. 1992). Down-regulated transcription of one of the two genes for ferredoxin was also reported in laboratory-induced metronidazole-resistant E. histolytica (Wassmann et al. 

Fig. 8 SDS-PAGE (a) and Western blot (b) analysis of the purified hydrogenosomal fractions isolated from the metronidazole-susceptible T. vaginalis strain TV 10-02 (P) and its metronidazole-resistant derivatives MR-3, MR-5, MR-30, MR-50, and MR-100 displaying the aerobic (3), early anaerobic (5), advanced anaerobic (30, 50), and fully developed anaerobic resistance (100) to metronidazole. Numbers in the designation of MR strains indicate the concentrations of metronidazole in ixg/ml at which the organisms multiply in culture. About 10 pg protein was loaded per line. PFOR pyruvate ferredoxin oxidoreduc-tase, a-STK a subunit of succinate thiokinase (hydrogenosomal enzyme not involved in metronidazole resistance used as control), Fdx ferredoxin. From Rasoloson et al. (2002) by courtesy of the Society of General Microbiology...

Fig. 10 Ultrastructure of hydrogenosomes of the T. foetus strain KV1-MR100 with fully developed metronidazole resistance (a,b) and of its drug-susceptible parent clone KV1 (c,d). Note the irregular shape, enlarged electron-dense core, and presence of tubular extensions (arrows) in hydrogenosomes of the drug-resistant strain. Bars 0.2 xm in a,b,c and 0.4 im in d. Original electron micrographs from the author (JK)...

Analysis of the data from the I vaginalis genome sequencing project indicates that the mechanisms involved in acquisition of metronidazole resistance by this parasite might be more complex than currently understood. 

Cudmore S, Delgaty KL, Hayward-McClelland SF, Petrin DP, Garber E (2004) Treatment of infections caused by metronidazole-resistant Trichomonas vaginalis. Clin Microbiol Rev 17 783-793... 

Ellis JE, Yarlett N, Cole D, Humphreys MJ, Lloyd D (1994) Antioxidant defenses in the microaerophilic protozoan Trichomonas vaginalis—comparison of metronidazole-resistant and sensitive strains. Microbiol-SGM 140 2489-2494 Haggoud A, Reysset G, Azeddoug H, Sebald M (1994) Nucleotide sequence analysis of two 5-nitroimidazole resistance determinants from Bacterioides strains and of a new insertion sequence upstream of the two genes. Antimicrob Agents Chemother 38 1047-1051... 

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