药物信息为Macrodantin (nitrofurantoin macrocrystals) (Procter & Gamble Pharmaceuticals): CLINICAL PHARMACOLOGY

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  • Macrodantin is a larger crystal form of Furadantin® (nitrofurantoin). The absorption of Macrodantin is slower and its excretion somewhat less when compared to Furadantin. Blood concentrations at therapeutic dosage are usually low. It is highly soluble in urine, to which it may impart a brown color.

    Following a dose regimen of 100 mg q.i.d. for 7 days, average urinary drug recoveries (0-24 hours) on day 1 and day 7 were 37.9% and 35.0%.

    Unlike many drugs, the presence of food or agents delaying gastric emptying can increase the bioavailability of Macrodantin, presumably by allowing better dissolution in gastric juices.

  • Microbiology: Nitrofurantoin is bactericidal in urine at therapeutic doses. The mechanism of the antimicrobial action of nitrofurantoin is unusual among antibacterials. Nitrofurantoin is reduced by bacterial flavoproteins to reactive intermediates which inactivate or alter bacterial ribosomal proteins and other macromolecules. As a result of such inactivations, the vital biochemical processes of protein synthesis, aerobic energy metabolism, DNA synthesis, RNA synthesis, and cell wall synthesis are inhibited. The broad-based nature of this mode of action may explain the lack of acquired bacterial resistance to nitrofurantoin, as the necessary multiple and simultaneous mutations of the target macromolecules would likely be lethal to the bacteria. Development of resistance to nitrofurantoin has not been a significant problem since its introduction in 1953. Cross-resistance with antibiotics and sulfonamides has not been observed, and transferable resistance is, at most, a very rare phenomenon.

    Nitrofurantoin, in the form of Macrodantin, has been shown to be active against most strains of the following bacteria both in vitro and in clinical infections (see INDICATIONS AND USAGE):

    • Gram-Positive Aerobes
      • Staphylococcus aureus
      • Enterococci (e.g., Enterococcus faecalis)
    • Gram-Negative Aerobes
      • Escherichia coli

    NOTE: Some strains of Enterobacter species and Klebsiella species are resistant to nitrofurantoin.

    Nitrofurantoin also demonstrates in vitro activity against the following microorganisms, although the clinical significance of these data with respect to treatment with Macrodantin is unknown:

    • Gram-Positive Aerobes
      • Coagulase-negative staphylococci
      • (including Staphylococcus epidermidis and
      • Staphylococcus saprophyticus)
      • Streptococcus agalactiae
      • Group D streptococci
      • Viridans group streptococci
    • Gram-Negative Aerobes
      • Citrobacter amalonaticus
      • Citrobacter diversus
      • Citrobacter freundii
      • Klebsiella oxytoca
      • Klebsiella ozaenae

    Nitrofurantoin is not active against most strains of Proteus species or Serratia species. It has no activity against Pseudomonas species.

    Antagonism has been demonstrated in vitro between nitrofurantoin and quinolone antimicrobial agents. The clinical significance of this finding is unknown.

  • Dilution techniques:

  • Quantitative methods are used to determine antimicrobial minimal inhibitory concentrations (MIC's). These MIC's provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MIC's should be determined using a standardized procedure. Standardized procedures are based on a dilution method1 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of nitrofurantoin powder. The MIC values should be interpreted according to the following criteria:

    MIC (μg/mL)Interpretation
    ≤ 32Susceptible (S)
    64Intermediate (I)
    ≥ 128Resistant (R)

    A report of "Susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the urine reaches the concentrations usually achievable. A report of "Intermediate" indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of "Resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the urine reaches the concentrations usually achievable; other therapy should be selected.

    Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard nitrofurantoin powder should provide the following MIC values:

    MicroorganismMIC (μg/mL)
    E. coli ATCC 259224-16
    S. aureus ATCC 292138-32
    E. faecalis ATCC 292124-16
  • Diffusion techniques:

  • Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 300 μg nitrofurantoin to test the susceptibility of microorganisms to nitrofurantoin.

    Reports from the laboratory providing results of the standard single-disk susceptibility test with a 300 μg nitrofurantoin disk should be interpreted according to the following criteria:

    Zone Diameter (mm)Interpretation
    ≥ 17Susceptible (S)
    15-16Intermediate (I)
    ≤ 14Resistant (R)

    Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for nitrofurantoin.

    As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 300 μg nitrofurantoin disk should provide the following zone diameters in these laboratory test quality control strains:

    MicroorganismZone Diameter (mm)
    E. coli ATCC 2592220-25
    S. aureus ATCC 2592318-22
  • Drug Information Provided by National Library of Medicine (NLM).
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