Rifampin: Mechanisms of Action and Resistance

Wehrli, W.

doi:10.1093/clinids/5.supplement_3.s407

Cited by 324 publications

(212 citation statements)

References 35 publications

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“…The rifampin-associated mutation frequency of R. equi-sensitive strain ATCC 33701 (MIC 0.125 g/ml) was nearly 10 Ϫ8 in each of three independent selection experiments on agar plates containing either 1, 10, or 100 g of rifampin per ml. This frequency was similar to the 10 Ϫ7 in vivo rifampin-associated mutation frequency in R. equi (21) or to the 10 Ϫ7 to 10 Ϫ8 in vitro rifampin-associated mutation frequencies observed in S. aureus (1) or other pyogenic bacteria such as Streptococcus pneumoniae, N. meningitidis, and Streptococcus pyogenes. The six mutants obtained were all highly resistant to rifampin (MICs, Ͼ256 g/ml), regardless of the rifampin concentration on which the mutant was grown.…”

Section: Resultssupporting

confidence: 80%

Characterization of Mutations in the rpoB Gene Associated with Rifampin Resistance in Rhodococcus equi Isolated from Foals

Fines

Pronost²,

Maillard³

et al. 2001

J Clin Microbiol

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Treatment with a combination of erythromycin and rifampin has considerably improved survival rates of foals and immunocompromised patients suffering from severe pneumonia caused by Rhodococcus equi. Frequently, because of monotherapy, emergence of rifampin-resistant strains has been responsible for treatment failure. Using consensus oligonucleotides, we have amplified and sequenced the rifampin resistance (Rif r )-determining regions of 12 rifampin-resistant R. equi strains isolated from three foals and of mutants selected in vitro from R. equi ATCC 3701, a rifampin-susceptible strain. The deduced amino acid sequences compared to those of four rifampin-susceptible R. equi strains showed several types of mutations. In 3 of the 10 strains isolated from one foal, His526Asn (Escherichia coli numbering) and Asp516Val mutations were associated with low-level resistance (rifampin MIC, 2 to 8 g/ml), whereas His526Asp conferred high-level resistance (rifampin MIC, 128 g/ml) in the 7 remaining strains. In strains from the two other foals, His526Asp and Ser531Leu mutations were found to be associated with high-level and low-level resistance, respectively. The in vitro mutants, highly resistant to rifampin, harbored His526Tyr and His526Arg substitutions. As described in other bacterial genera, His526, Ser531, and Asp516 are critical residues for rifampin resistance in R. equi, and the resistance levels are dependent on both the location and the nature of the substitution.

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Section: Resultssupporting

confidence: 80%

Characterization of Mutations in the rpoB Gene Associated with Rifampin Resistance in Rhodococcus equi Isolated from Foals

Fines

Pronost²,

Maillard³

et al. 2001

J Clin Microbiol

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“…Rifampin is well known for the development of singlestep resistance [32]. In contrast to the specimens obtained at 30 min, 3 h and 12 h, SEM of the rifampinimpregnated catheter removed at 24 h showed an increased number of adhering bacteria surrounded by a typical bio®lm.…”

Section: Discussionmentioning

confidence: 76%

Use of scanning electron microscopy to investigate the prophylactic efficacy of rifampin-impregnated CSF shunt catheters

Kockro

Hampl

Jansen

et al. 2000

Journal of Medical Microbiology

113

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Infection continues to be one of the major complications of cerebrospinal¯uid (CSF) shunting procedures, and is caused mainly by skin-derived bacteria. Production of an extracellular bio®lm plays an important role in the pathogenesis of shunt-associated infections by protecting bacteria from immune mechanisms and antibiotics. So far, removal of the original shunt and implantation of a new shunting device has been the only successful treatment for most patients. As an alternative strategy to prevent CSF infections, a rifampin-impregnated silicone catheter was designed to provide high initial and long-lasting (>60 days) release of bactericidal drug. To investigate the pathophysiological mechanism of its function, this new device was investigated both in vitro and in a rodent model of CSF infection by scanning electron microscopy (SEM) and bacterial culture. Staphylococcus epidermidis (10 8 cfu=ml) and S. aureus (10 4 cfu=ml) served as test strains. SEM demonstrated that, in contrast to the unloaded catheters, initial bacterial adherence on the catheter surface could be reduced to a few single cells, which did not show visible signs of proliferation. Bacterial cultures obtained simultaneously were all sterile, showing that adherent bacteria were killed immediately by the rifampin released from the catheter. Although rifampin incorporation into silicone polymers was not able to prevent initial bacterial adhesion completely, subsequent colonisation could be prevented.

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“…Kill-curve studies of the five most effective antibiotics showed good killing of the test strains within 8 h; however, at 24 h complete regrowth to a density greater than the initial inoculum occurred with rifampin, and partial regrowth occurred with coumermycin. Despite the high level of inhibitory activity of rifampin, rapid emergence of resistance to rifampin by Metr S. aureus has been reported by other investigators (1,9,22). Vancomycin, teicoplanin, and ciprofloxacin were highly bactericidal at 24 h, killing greater than 98% of the inoculum.…”

Section: Discussionmentioning

confidence: 91%

Comparison of the activities of coumermycin, ciprofloxacin, teicoplanin, and other non-beta-lactam antibiotics against clinical isolates of methicillin-resistant Staphylococcus aureus from various geographical locations

Aldridge¹,

Janney²,

Sanders³

1985

Antimicrob Agents Chemother

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One hundred clinical isolates of methicillin-resistant (Metr) Staphylococcus aureus from five different geographical origins were tested for their susceptibility to 12 non-li-lactam antibiotics by the broth microdilution technique recommended by the National Committee for Clinical Laboratory Standards.Coumermycin and rifampin showed the highest activity with of MIC90s of 0.032 jig/ml for each compound. No resistance was found to coumermycin, whereas a single Metr S. aureus strain was found to be resistant to rifampin. Ciprofloxacin, vancomycin, and teicoplanin were the next most active compounds with MIC90s of 0.25, 0.5, and 0.5 ,ug/ml, respectively. Norfloxacin was less active, with an MIC90 of 1.0 ,ug/ml. Amikacin was the most active aminoglycoside tested, whereas high levels of resistance were found to tobramycin and gentamicin. Doxycycline and chloramphenicol showed variable results. Geographical variations in results were seen with doxycycline, chloramphenicol, and aminoglycosides. Kill-curve studies showed that coumermycin, ciprofloxacin, teicoplanin, vancomycin, and rifampin were highly bactericidal; more than 90% of the inoculum was killed within 8 h.

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Rifampin: Mechanisms of Action and Resistance

Cited by 324 publications

References 35 publications

Characterization of Mutations in the rpoB Gene Associated with Rifampin Resistance in Rhodococcus equi Isolated from Foals

Characterization of Mutations in the rpoB Gene Associated with Rifampin Resistance in Rhodococcus equi Isolated from Foals

Use of scanning electron microscopy to investigate the prophylactic efficacy of rifampin-impregnated CSF shunt catheters

Comparison of the activities of coumermycin, ciprofloxacin, teicoplanin, and other non-beta-lactam antibiotics against clinical isolates of methicillin-resistant Staphylococcus aureus from various geographical locations

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