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Dicloxacillin exerts a bactericidal action against penicillin-susceptible microorganisms during the state of active multiplication. All penicillins inhibit the biosynthesis of the bacterial cell wall.
The drugs in this class are highly resistant to inactivation by staphylococcal penicillinase and are active against penicillinase-producing and non-penicillinase-producing strains of Staphylococcus aureus. The penicillinase-resistant penicillins are active in vitro against a variety of other bacteria.
Susceptibility Plate Testing
Quantitative methods of susceptibility testing that require measurements of zone diameters or minimal inhibitory concentrations (MICs) give the most precise estimates of antibiotic susceptibility. One such procedure has been recommended for use with discs to test susceptibility to this class of drugs. Interpretations correlate diameters on the disc test with MIC values.
A penicillinase-resistant class disc may be used to determine microbial susceptibility to dicloxacillin.
TABLE I shows the interpretation of test results for penicillinase-resistant penicillins using the FDA Standard Disc Test Method (formerly Bauer-Kirby-Sherris-Turck method) of disc bacteriological susceptibility testing for staphylococci with a disc containing 5 micrograms of methicillin sodium.
With this procedure, a report from a laboratory of "susceptible" indicates that the infecting organism is likely to respond to therapy. A report of "resistant" indicates that the infecting organism is not likety to respond to therapy. A report of "intermediate" susceptibility suggests that the organism might be susceptible if high doses of the antibiotic are used, or if the infection is confined to tissues and fluids (eg, urine) in which high antibiotic levels are attained.
In general, all staphylococci should be tested against the penicillin G disc and against the methicillin disc. Routine methods of antibiotic susceptibility testing may fail to detect strains of organisms resistant to the penicillinase-resistant penicillins. For this reason, the use of large inocula and 48-hour incubation periods may be necessary to obtain accurate susceptibility studies with these antibiotics. Bacterial strains which are resistant to one of the penicillinase-resistant penicillins should be considered resistant to all of the drugs in the class.
|Standardized Disc T.S. Method Of Bacteriological Susceptibility Testing Using a Class Disc Containing 5 Micrograms Of Methicillin Sodium|
|Diameters of Zone
at least 14mm
|Diameters of Zone
10 - 13mm
|Diameters of Zone
less than 10mm
Methicillin sodium is readily destroyed by gastric acidity and must be administered by intramuscular or intravenous injection. The isoxazolyl penicillins (cloxacillin, dicloxacillin and oxacillin) and nafciliin are more acid-resistant and may be administered orally.
Absorption of the isoxazolyl penicillins after oral administration is rapid but incomplete: peak blood levels are achieved in 1-1.5 hours. In one study, after ingestion of a single 500 mg oral dose, peak serum concentrations range from 5-7 micrograms/milliliter for oxacillin, from 7.5- 14.4 mg/ mL for cloxacillin and from 10-17 mg/mL for dicloxacillin.
Oral absorption of cloxacillin, dicloxacillin, oxacillin and nafcillin is delayed when the drugs are administered after meals.
Once absorbed, the penicillinase-resistant penicillins bind to serum protein, mainly albumin. The degree of protein binding reported varies with the method of study and the investigator (see TABLE 2).
|Penicillinase-Resistant Penicillins Percent Protein Binding ± SD|
|Methicillin||37.3 ± 7.9|
|Nafcillin||89.9 ± 1.5|
|Oxacillin||94.2 ± 2.1|
|Cloxacillin||95.2 ± 0.5|
|Dicloxacillin||97.9 ± 0.6|
The penicillinase-resistant penicillins vary in the extent to which they are distributed in the body fluids. With normal doses, insignificant concentrations are found in the cerebrospinal fluid and aqueous humor. All the drugs in this class are found in therapeutic concentrations in the pleural, bile and amniotic fluids.
The penicillinase-resistant penicillins are rapidly excreted, primarily as unchanged drug in the urine by glomerular filtration and active tubular secretion The elimination half-life for dicloxacillin is about 0.7 hour. Nonrenal elimination includes hepatic inactivation and excretion in bile.
Last reviewed on RxList: 12/8/2004
This monograph has been modified to include the generic and brand name in many instances.
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