Nafcillin

Nafcillin sodium is a narrow-spectrum[1] beta-lactam antibiotic[2] of the penicillin class. As a beta-lactamase-resistant penicillin, it is used to treat infections caused by Gram-positive bacteria, in particular, species of staphylococci that are resistant to other penicillins.

Nafcillin

Clinical data
AHFS/Drugs.com	Monograph
MedlinePlus	a685019
Pregnancy category	US: B (No risk in non-human studies)
Routes of administration	IM, IV
ATC code	J01CF06 (WHO)
Legal status
Legal status	In general: ℞ (Prescription only)
Pharmacokinetic data
Protein binding	90%
Metabolism	<30% hepatic
Elimination half-life	0.5 hours
Excretion	Biliary and renal
Identifiers
IUPAC name (2S,5R,6R)-6-[(2-ethoxy-1-naphthoyl)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
CAS Number	985-16-0^Y
PubChem CID	8982
DrugBank	DB00607^Y
ChemSpider	8634^Y
UNII	SY07234TTS
ChEBI	CHEBI:7447^Y
ChEMBL	ChEMBL1443^Y
CompTox Dashboard (EPA)	DTXSID8023343
ECHA InfoCard	100.005.174
Chemical and physical data
Formula	C21H22N2O5S
Molar mass	414.48 g·mol^−1
3D model (JSmol)	Interactive image
SMILES O=C(O)[C@@H]3N4C(=O)[C@@H](NC(=O)c2c1ccccc1ccc2OCC)[C@H]4SC3(C)C
InChI InChI=1S/C21H22N2O5S/c1-4-28-13-10-9-11-7-5-6-8-12(11)14(13)17(24)22-15-18(25)23-16(20(26)27)21(2,3)29-19(15)23/h5-10,15-16,19H,4H2,1-3H3,(H,22,24)(H,26,27)/t15-,16+,19-/m1/s1^Y Key:GPXLMGHLHQJAGZ-JTDSTZFVSA-N^Y
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Nafcillin is considered therapeutically equivalent to oxacillin, although one retrospective study found greater rates of hypokalemia and acute kidney injury in patients taking nafcillin compared to patients taking oxacillin.[3]

Indications

Nafcillin is indicated in the treatment of staphylococcal infections, except those caused by MRSA.[4]

U.S. clinical practice guidelines recommend either nafcillin or oxacillin as the first-line treatment of choice for staphylococcal endocarditis in patients without artificial heart valves.[5]

Side-effects

As with all penicillins, serious life-threatening allergic reactions can occur.

Milder side-effects include:

• Hypokalemia[6]
• Nausea and vomiting
• Diarrhea, often due to suppression of normal gastrointestinal bacteria, which, on occasion, leads to a more serious super-infection with an organism like Clostridium difficile
• Abdominal pain
• Yeast infections (thrush) affecting the mouth and tongue or vagina
• Agranulocytosis, neutropenia

Interactions

There is evidence that nafcillin induces cytochrome P-450 enzymes, specifically CYP2C9. Several drugs with a narrow therapeutic window, such as warfarin and nifedipine, are metabolized by CYP2C9.[7]

Nafcillin contains salts added as stability media. These added salts could cause edema or fluid accumulation. It would be prudent to avoid this medication if there were a concern for a congestive heart failure or kidney disease.

References

1. Palmer DL, Pett SB, Akl BF (March 1995). "Bacterial wound colonization after broad-spectrum versus narrow-spectrum antibiotics". Ann. Thorac. Surg. 59 (3): 626–31. doi:10.1016/0003-4975(94)00992-9. PMID 7887701.
2. Tan AK, Fink AL (January 1992). "Identification of the site of covalent attachment of nafcillin, a reversible suicide inhibitor of beta-lactamase". Biochem. J. 281 (1): 191–6. doi:10.1042/bj2810191. PMC 1130660. PMID 1731755.
3. Viehman, J. Alexander; Oleksiuk, Louise-Marie; Sheridan, Kathleen R.; Byers, Karin E.; He, Peimei; Falcione, Bonnie A.; Shields, Ryan K. (May 2016). "Adverse Events Lead to Drug Discontinuation More Commonly among Patients Who Receive Nafcillin than among Those Who Receive Oxacillin". Antimicrobial Agents and Chemotherapy. 60 (5): 3090–3095. doi:10.1128/AAC.03122-15. PMC 4862451. PMID 26976858.
4. Pham P, Bartlett JG (January 2, 2009). "Nafcillin". Point-of-Care Information Technology ABX Guide. Johns Hopkins University. Retrieved on July 10, 2009. Freely available with registration.
5. Bonow RO, Carabello BA, Kanu C, et al. (August 2006). "ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): developed in collaboration with the Society of Cardiovascular Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons". Circulation. 114 (5): e84–231. doi:10.1161/CIRCULATIONAHA.106.176857. PMID 16880336.
6. JA Mohr. (1979). Nafcillin-associated hypokalemia. JAMA
7. Lang CC, Jamal SK, Mohamed Z, Mustafa MR, Mustafa AM, Lee TC (June 2003). "Evidence of an interaction between nifedipine and nafcillin in humans". Br J Clin Pharmacol. 55 (6): 588–90. doi:10.1046/j.1365-2125.2003.01789.x. PMC 1884262. PMID 12814453.