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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.


Nitrofurantoin is a nitrofuran antimicrobial agent with activity against certain Gram-positive and Gram-negative bacteria.

Mechanism of Action

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 acromolecules. 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. Nitrofurantoin is bactericidal in urine at therapeutic doses. 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.

Interactions with Other Antibiotics

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

Development of Resistance

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

Aerobic and facultative Gram-positive microorganisms

Staphylococcus aureus
Enterococci (e.g. Enterococcus faecalis)

Aerobic and facultative Gram-negative microorganisms

Escherichia coli

NOTE: While nitrofurantoin has excellent activity against Enterococcus faecalis, the majority of Enterococcus faecium isolates are not susceptible to nitrofurantoin.

At least 90 percent of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for nitrofurantoin. However, the efficacy of nitrofurantoin in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled trials.

Aerobic and facultative Gram-positive microorganisms

Coagulase-negative staphylococci (including Staphylococcus epidermidis and Staphylococcus saprophyticus)
Streptococcus agalactiae

Group D streptococci

Viridans group streptococci

Aerobic and facultative Gram-negative microorganisms

Citrobacter amalonaticus
Citrobacter diversus

Citrobacter freundii

Klebsiella oxytoca

Klebsiella ozaenae

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

Susceptibility Test Methods

When available, the clinical microbiology laboratory should provide cumulative results of the in vitro susceptibility test results for antimicrobial drugs used in resident hospitals to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting the most effective antimicrobial.

Dilution techniques: Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure. Standardized procedures are based on a dilution method (broth or agar) (1) or equivalent with standardized inoculum concentrations and standardized concentrations of nitrofurantoin powder. The MIC values should be interpreted according to the criteria provided in Table 1.

Diffusion technique: Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure (2) requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 300 Ilg of nitrofurantoin to test the susceptibility of microorganisms to nitrofurantoin. The disk diffusion interpretive criteria are provided in Table 1.

Table 1: Susceptibility Interpretive Criteria for Nitrofurantoin

Pathogen Susceptibility Interpretive Criteria
Minimum Inhibitory Concentrations (μg/mL) Disk Diffusion (zone diameter in mm)
Enterobacteriaceae δ32 64 ε128 ε17 15-16 δ14
Staphylococcus spp. δ32 64 ε128 ε17 15-16 δ14
Enterococcus spp. δ32 64 ε128 ε17 15-16 δ14

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 physiologicallyconcentrated or in situations where a 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.

Quality Control: Standardized susceptibility test procedures require the use of quality control microorganisms to control the technical aspects of the test procedures (3). Standard nitrofurantoin powder should provide the following range of values noted in Table 2.

Table 2: Acceptable Quality Control Ranges for Nitrofurantoin

QC Strain Acceptable Quality Control Ranges
Minimum Inhibitory Concentration (μg/mL) Disk Diffusion (zone diameter in mm)
Escherichia coli ATCC 25922 4 – 16 20 -25
Enterococcus faecalis ATCC 29212 4 – 16 NAa
Staphylococcus aureus ATCC 29213 8 – 32 NAa
Staphylococcus aureus ATCC 25923 NAa 18-22
aNot applicable

Last reviewed on RxList: 10/18/2016
This monograph has been modified to include the generic and brand name in many instances.

Macrodantin - User Reviews

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