Chemistry:Nafcillin
Nafcillin sodium is a narrow-spectrum,[1] second-generation 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 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 approved by the FDA for use in treating Staphylococcus infections, including strains resistant to other penicillin-class antibiotics. One notable exception is that Nafcillin is not indicated for treatment of MRSA cases.
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.[4]
Side-effects
Milder side-effects include:
- Hypokalemia[5]
- 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 Clostridioides 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.[6]
Mechanism of Action
Nafcillin, like other β-lactams, targets bacterial cell wall synthesis during cell growth and division. As a penicillin-class antibiotic, the molecule binds to penicillin binding proteins (PBP) in both the cytoplasm and cytoplasmic membrane. Binding of Nafcillin to PBP's inhibits the proteins' transpeptidase and carboxypeptidase functions, both essential for bacterial cell wall synthesis.[7]
This mechanism is effective against gram-positive bacteria, whose cell walls are composed of thick layers of peptidoglycan, a matrix composed of carbohydrates and amino acids. By inhibiting the synthesis of certain bacterial cell walls, penicillin class drugs, including Nafcillin, make the bacterial cell vulnerable to different osmotic pressures and solutes, killing the cell.
References
- ↑ "Bacterial wound colonization after broad-spectrum versus narrow-spectrum antibiotics". The Annals of Thoracic Surgery 59 (3): 626–631. March 1995. doi:10.1016/0003-4975(94)00992-9. PMID 7887701.
- ↑ "Identification of the site of covalent attachment of nafcillin, a reversible suicide inhibitor of beta-lactamase". The Biochemical Journal 281 (Pt 1): 191–196. January 1992. doi:10.1042/bj2810191. PMID 1731755.
- ↑ "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. May 2016. doi:10.1128/AAC.03122-15. PMID 26976858.
- ↑ "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. August 2006. doi:10.1161/CIRCULATIONAHA.106.176857. PMID 16880336.
- ↑ "Nafcillin-associated hypokalemia". JAMA 242 (6): 544. August 1979. doi:10.1001/jama.1979.03300060046028. PMID 448989.
- ↑ "Evidence of an interaction between nifedipine and nafcillin in humans". British Journal of Clinical Pharmacology 55 (6): 588–590. June 2003. doi:10.1046/j.1365-2125.2003.01789.x. PMID 12814453.
- ↑ PubChem. "Nafcillin" (in en). https://pubchem.ncbi.nlm.nih.gov/compound/Nafcillin#section=Biological-Half-Life.
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