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Nafcillin

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Nafcillin Injection

Nafcillin Injection

CLINICAL PHARMACOLOGY

In a study of five healthy adults administered a single 500 mg dose of nafcillin by intravenous injection over seven minutes, the mean plasma concentration of the drug was approximately 30 mcg/mL at 5 minutes after injection. The mean area under the plasma concentration-versus-time curve (AUC) for nafcillin in this study was 18.06 mcg•h/mL.

The serum half-life of nafcillin administered by the intravenous route ranged from 33 to 61 minutes as measured in three separate studies.

In contrast to the other penicillinase-resistant penicillins, only about 30% of nafcillin is excreted as unchanged drug in the urine of normal volunteers, and most within the first six hours. Nafcillin is primarily eliminated by nonrenal routes, namely hepatic inactivation and excretion in the bile.

Nafcillin binds to serum proteins, mainly albumin. The degree of protein binding reported for nafcillin is 89.9 ± 1.5%. Reported values vary with the method of study and the investigator.

The concurrent administration of probenecid with nafcillin increases and prolongs plasma concentrations of nafcillin. Probenecid significantly reduces the total body clearance of nafcillin with renal clearance being decreased to a greater extent than nonrenal clearance.

The penicillinase-resistant penicillins are widely distributed in various body fluids, including bile, pleural, amniotic and synovial fluids. With normal doses insignificant concentrations are found in the aqueous humor of the eye. High nafcillin CSF levels have been obtained in the presence of inflamed meninges.

Renal failure does not appreciably affect the serum half-life of nafcillin; therefore, no modification of the usual nafcillin dosage is necessary in renal failure with or without hemodialysis. Hemodialysis does not accelerate the rate of clearance of nafcillin from the blood.

A study which assessed the effects of cirrhosis and extrahepatic biliary obstruction in man demonstrated that the plasma clearance of nafcillin was significantly decreased in patients with hepatic dysfunction. In these patients with cirrhosis and extrahepatic obstruction, nafcillin excretion in the urine was significantly increased from about 30 to 50% of the administered dose, suggesting that renal disease superimposed on hepatic disease could further decrease nafcillin clearance.

Microbiology

Penicillinase-resistant penicillins exert 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 strains of Staphylococcus aureus. The penicillinase-resistant penicillins are active in vitro against a variety of other bacteria.

Susceptibility Test Methods

When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas 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 based on dilution method1,2 (broth, agar or microdilution) or equivalent. It has been reported that determination of susceptibility or resistance of a microorganism to all penicillinase-resistant penicillins, including nafcillin, may be deduced by testing microorganisms against either oxacillin or cefoxitin.2 For this reason, routine dilution testing of nafcillin is not advised and susceptibility to nafcillin should be determined by dilution using standardized inoculum and concentrations of oxacillin according to the criteria in Table 1.1,2

Table 1: Staphylococcus aureus MIC Susceptibility Test Interpretive Criteria for Oxacillina

Pathogen Minimum Inhibitory Oxacillin Concentrations (mcg/mL)
Susceptible (S) Resistant (R)
Staphylococcus aureus ≤ 2.0 ≥ 4.0
a Staphylococcus aureus strains found to be “Susceptible” or “Resistant” to oxacillin by dilution testing can be considered to be “Susceptible” or “Resistant” to nafcillin.

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 procedure2,3 requires the use of standardized inoculum concentrations. It has been reported that determination of susceptibility or resistance of a microorganism to all penicillinase-resistant penicillins, including nafcillin, may be deduced by testing microorganisms against either oxacillin or cefoxitin.2 Disk diffusion results using cefoxitin have been shown to be more reproducible than those obtained with oxacillin,4,5 therefore cefoxitin is the preferred reagent for testing nafcillin susceptibility by diffusion. Reports from the laboratory providing results of the standard single-disk susceptibility test with a 30 microgram cefoxitin disk should be interpreted according to the following criteria in Table 2.

Table 2: Staphylococcus aureus Disk Diffusion Susceptibility Test Interpretive Criteria for Nafcillin Using a 30 mcg Cefoxitin Diska

Pathogen Disk DiffusionDiameters (mm)
Susceptible (S) Resistant (R)
Staphylococcus aureus ≥ 22 ≤ 21
a Staphylococcus aureus strains found to be “Susceptible” or “Resistant” to cefoxitin by disk diffusion can be considered to be “Susceptible' or “Resistant” to nafcillin.

A report of “Susceptible” indicates that the pathogen is likely to be inhibited by usually achievable concentrations of the antimicrobial compound in blood. A report of “Resistant” indicates that usually achievable concentrations of the antimicrobial compound in the blood are unlikely to be inhibitory and that other therapy should be selected.

Measurement of MIC or MBC and achieved antimicrobial compound concentrations may be appropriate to guide therapy in some infections. (See CLINICAL PHARMACOLOGY section for further information on drug concentrations achieved in infected body sites and other pharmacokinetic properties of this antimicrobial drug product.)

Quality Control

Standardized susceptibility test procedures require the use of laboratory control microorganisms to monitor and ensure the accuracy and precision of the supplies and reagents used in the assay, and the techniques of the individuals performing the test. Appropriate quality control organisms and acceptable corresponding ranges of oxacillin MICs obtained by dilution testing or inhibition zones around 30 mcg cefoxitin disks are provided in Table 3.

Table 3: In Vitro Susceptibility Test Quality Control Ranges for Oxacillin and Cefoxitin

Organism (ATTC #) Oxacillin MIC range (mcg/mL) Cefoxitin disk diffusion range (mm)
Staphylococcus aureus (29213) 0.12 - 0.5 Not applicable
Staphylococcus aureus (25923) Not applicable 23 - 29

REFERENCES

1. Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard- Eighth Edition. CLSI Document M07-A8 (ISBN 1-56238-689-1). Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, 2009.

2. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-First Informational Supplement. CLSI Document M100S21 (ISBN 1-56238-742-1). Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, 2011.

3. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard-Tenth Edition. CLSI Document M02-A10 (ISBN 1-56238-688-3). Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, 2009.

4. Palazzo ICV, Darini ALC. Evaluation of methods for detecting oxacillin resistance in coagulase-negative staphylococci including cefoxitin disc diffusion. FEMS Microbiol Lett 2006;257:299-305

5. Swenson JM, Tenover FC; Cefoxitin Disk Study Group. Results of disk diffusion testing with cefoxitin correlate with presence of mecA in Staphylococcus spp. J Clin Microbiol 2005;43:3818-23.

Last reviewed on RxList: 11/18/2011
This monograph has been modified to include the generic and brand name in many instances.

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