Bacteroides Fragilis Resistant to Metronidazole After Long-Term Therapy

Ingham, H. R.; Eaton, S.; Venables, C W; Adams, Pamela

doi:10.1016/s0140-6736(78)90655-4

Cited by 99 publications

(26 citation statements)

References 7 publications

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“…This was also demonstrated in our patient who remained febrile while being treated with metronidazole for 7 days and who became apyretic 3 days after metronidazole was changed to piperacillin-tazobactam. It is believed that exposure to metronidazole can lead to the development of metronidazole-resistant mutants (12,16). In contrast, in the present report, a metronidazole-resistant Prevotella sp.…”

contrasting

confidence: 84%

Bacteremia Caused by a Metronidazole-Resistant Prevotella sp. Strain

Mory¹,

Carlier

Alauzet³

et al. 2005

J Clin Microbiol

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Metronidazole resistance among Prevotella spp. is rare. We report here the first case of bacteremia due to a high-level metronidazole-resistant Prevotella sp. responsible for treatment failure. CASE REPORTA 78-year-old man with a past history of non-insulin-dependent diabetes mellitus and diverticulitis was hospitalized because of fever and altered clinical status. Physical examination was normal and no abnormalities were revealed by a systematic computed tomography scan of the abdomen. Laboratory studies revealed a white blood cell count of 28,000 cells/mm 3 (90% polymorphonuclear leukocytes), a C-reactive protein level of 139 mg/liter, and a blood glucose level of 2 g/liter. Three sets of blood culture samples were collected in BACTEC Plus Aerobic/F medium and BACTEC Plus Anaerobic/F medium (BACTEC 9000 system; Becton Dickinson, Le Pont de Claix, France). The patient was treated empirically with intravenous cefotaxime (1 g three times daily) and ofloxacin (200 mg twice daily). Blood cultures taken at the admission detected the presence of Escherichia coli (susceptible to both antibiotics used) and Streptococcus anginosus (susceptible to cefotaxime). Urine and lower respiratory tract samples remained negative after quantitative bacteriologic cultures. On day 7, the patient remained febrile and new blood cultures (three sets) were taken while intravenous metronidazole (500 mg three times daily) and teicoplanin (400 mg once daily) were added.A strictly anaerobic, nonmotile, gram-negative rod was the only bacterium detected in the three anaerobic blood culture vials of the three sample sets taken on day 7. In vitro susceptibility testing was performed by using a standard disk diffusion method on brucella agar supplemented with 5% sheep blood, 1 mg of vitamin K 1 /liter, and 5 mg of hemin/liter (7). Metronidazole susceptibility was determined by using 16-g metronidazole Neo-Sensitabs (Rosco Diagnostica, Taastrup, Denmark). According to the criteria of the Comité de l'Antibiogramme de la Société Française de Microbiologie for susceptibility testing of anaerobes (7), the isolate was considered susceptible to amoxicillin-clavulanate, piperacillin-tazobactam, cefoxitin, imipenem, chloramphenicol, clindamycin, and metronidazole after 48 h of incubation. It was also intermediate to cefotaxime and resistant to ofloxacin. ␤-lactamase production was demonstrated by using a nitrocefin test (Cefinase; bioMérieux, Marcy-l'Etoile, France). Using an Etest method (13), we found a MIC ratio of Ͼ500 for cefotaxime/ cefotaxime-clavulanic acid and ceftazidime/ceftazidime-clavulanic acid, suggesting the presence of an extended-spectrum ␤-lactamase.It has been shown that metronidazole resistance may be only detected after prolonged incubation time (9, 12). Plates were therefore incubated for additional 48 h. This permitted us to observe that small colonies began to appear inside the metronidazole inhibition zone after 72 h and became more numerous after 96 h. The same phenomenon was also observed within the ellipse area of a metronidaz...

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confidence: 84%

Bacteremia Caused by a Metronidazole-Resistant Prevotella sp. Strain

Mory¹,

Carlier

Alauzet³

et al. 2005

J Clin Microbiol

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“…Therefore, it is not known whether this strain became resistant in this patient during repeated treatments or whether the patient was infected with a resistant strain. The development of refractive resistance of T. vaginalis to metronidazole in this case and other patients would receive support from a recent report showing that a strain of Bacteroides fragilis developed resistance to this compound during long-term therapy (10).…”

Section: Resultsmentioning

confidence: 55%

Strain of Trichomonas vaginalis Resistant to Metronidazole and Other 5-Nitroimidazoles

Meingassner

Thurner

1979

Antimicrob Agents Chemother

138

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A strain of Trichomonas vaginalis , recently isolated from a patient afflicted with recurrent symptomatic trichomoniasis, showed resistance to metronidazole, tinidazole, and nimorazole in vitro as well as in vivo. In a serial dilution test using cysteine monohydrochloride-peptone-liver infusion-maltose medium, T. vaginalis IR-78 was only resistant under aerobic conditions. Under anaerobic conditions it was as susceptible as the normal reference strain. The minimal lethal concentrations of metronidazole, tinidazole, and nimorazole for IR-78 were 100, 50, and 50 ,ug/ml aerobically and 0.4,0.4, and 0.2 ,g/ml anaerobically, respectively.The efficacy of metronidazole, tinidazole, and nimorazole was assessed in vivo by oral administration to mice simultaneously infected with IR-78 both subcutaneously and intraperitoneally. The CD5o (dose needed to cure 50% of infections) of each compound was significantly higher for the subcutaneous than for the intraperitoneal infection. In contrast, there was little difference in CD50 for these infections in mice inoculated with a susceptible trichomonas strain. The CD50's for all three compounds against intraperitoneal and subcutaneous infections with IR-78 were 2 to >70 times higher than for susceptible strain E. Both forms of infection with IR-78 could always be cured with therapeutically acceptable doses of tinidazole and nimorazole; subcutaneous infections could not be cured with tolerated doses of metronidazole.

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“…and many anaerobic bacteria. Since metronidazole is supposed to penetrate extensively into central nervous system (CNS), it has been described in literature as being responsible for both peripheral (1) and central (2-6) neurotoxicity, especially after a prolonged use of metronidazole (7). In both cases, symptoms and lesions on magnetic resonance imaging may spontaneously regress after discontinuation of treatment.…”

mentioning

confidence: 99%

Metronidazole and Hydroxymetronidazole Central Nervous System Distribution: 1. Microdialysis Assessment of Brain Extracellular Fluid Concentrations in Patients with Acute Brain Injury

Frasca

Dahyot‐Fizelier

Adier

et al. 2014

Antimicrob Agents Chemother

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The distribution of metronidazole in the central nervous system has only been described based on cerebrospinal fluid data. However, extracellular fluid (ECF) concentrations may better predict its antimicrobial effect and/or side effects. We sought to explore by microdialysis brain ECF metronidazole distribution in patients with acute brain injury. Four brain-injured patients monitored by cerebral microdialysis received 500 mg of metronidazole over 0.5 h every 8 h. Brain dialysates and blood samples were collected at steady state over 8 h. Probe recoveries were evaluated by in vivo retrodialysis in each patient for metronidazole. Metronidazole and OH-metronidazole were assayed by high-pressure liquid chromatography, and a noncompartmental pharmacokinetic analysis was performed. Probe recovery was equal to 78.8% ؎ 1.3% for metronidazole in patients. Unbound brain metronidazole concentration-time curves were delayed compared to unbound plasma concentration-time curves but with a mean metronidazole unbound brain/plasma AUC 0 -ratio equal to 102% ؎ 19% (ranging from 87 to 124%). The unbound plasma concentration-time profiles for OH-metronidazole were flat, with mean average steady-state concentrations equal to 4.0 ؎ 0.7 g ml ؊1 . This microdialysis study describes the steady-state brain distribution of metronidazole in patients and confirms its extensive distribution. Metronidazole, a nitroimidazole antibiotic, is useful for treating infections by Bacteroides spp. and many anaerobic bacteria. Since metronidazole is supposed to penetrate extensively into central nervous system (CNS), it has been described in literature as being responsible for both peripheral (1) and central (2-6) neurotoxicity, especially after a prolonged use of metronidazole (7). In both cases, symptoms and lesions on magnetic resonance imaging may spontaneously regress after discontinuation of treatment. While the pathogenesis as yet remains unclear, the most likely hypothesis is an axonal swelling due to metronidazoleinduced vasogenic edema, which could be linked to an impairment of vitamin B 1 action, because of metronidazole conversion to a thiamine analog (8). Thus, characterizing the distribution of metronidazole in cerebral tissue may contribute to managing the dosing regimen in order to prevent side effects while preserving maximal antibacterial efficiency.Differences in anatomy, enzymatic activity or bulk-flow exist between blood-brain-barrier (BBB) and blood-cerebrospinal fluid (CSF) barrier (9), which could result in differences in drug distribution between the CSF and brain extracellular fluid (ECF). Current metronidazole doses rely on a few studies that show an extensive distribution of metronidazole into the CSF (10-12). However, most of the previous CSF pharmacokinetic studies of metronidazole used nonspecific microbiological assays that cannot distinguish parent drug from metabolites (13-16) and at present no study has explored the distribution of metronidazole in the brain ECF.Intracerebral microdialysis is the state-of-the-art in ...

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Bacteroides Fragilis Resistant to Metronidazole After Long-Term Therapy

Cited by 99 publications

References 7 publications

Bacteremia Caused by a Metronidazole-Resistant Prevotella sp. Strain

Bacteremia Caused by a Metronidazole-Resistant Prevotella sp. Strain

Strain of Trichomonas vaginalis Resistant to Metronidazole and Other 5-Nitroimidazoles

Metronidazole and Hydroxymetronidazole Central Nervous System Distribution: 1. Microdialysis Assessment of Brain Extracellular Fluid Concentrations in Patients with Acute Brain Injury

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