nafcillin

nafcillin
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
Width	200
Tradename	Unipen, Nallpen, others
Drugs.com	monograph, nafcillin
MedlinePlus	a685020
Pregnancy AU	B1
Routes of administration	Intravenous, intramuscular
Bioavailability	n/a
Protein bound	70–90%
Metabolism	Liver
Elimination half-life	0.5–1.5 hours
Excretion	Bile, Urine
CAS number	985-16-0
PubChem	8982
DrugBank	DB00607
ChemSpiderID	8639
UNII	0Z5D3G5Q4K
KEGG	D07970
ChEBI	7453
ChEMBL	31
NIAID ChemDB	007625
ATC prefix	J01
ATC suffix	CF06
Legal AU	S4
Legal CA	Rx-only
Legal UK	POM
Legal US	Rx-only
Legal EU	Rx-only
Legal status	Rx-only

nafcillin. It is a narrow-spectrum beta-lactam antibiotic of the penicillin class, specifically a penicillinase-resistant antistaphylococcal penicillin. Primarily used to treat infections caused by penicillinase-producing staphylococci, it is a critical agent for managing serious conditions like bacteremia, endocarditis, and osteomyelitis. Its clinical utility is largely confined to methicillin-sensitive Staphylococcus aureus (MSSA) infections, as it is ineffective against methicillin-resistant Staphylococcus aureus (MRSA).

Medical uses

Nafcillin is indicated for the treatment of severe infections caused by susceptible strains of penicillinase-producing Staphylococcus aureus. Key clinical applications include bacteremia, infective endocarditis, and deep-seated infections such as osteomyelitis and septic arthritis. It is often preferred over vancomycin for MSSA bacteremia and endocarditis due to potential superior efficacy and reduced nephrotoxicity. The drug is not active against enterococci, Streptococcus pneumoniae with reduced penicillin susceptibility, or gram-negative organisms like Escherichia coli.

Adverse effects

Common adverse effects involve phlebitis and local irritation at the intravenous infusion site. Hypersensitivity reactions, ranging from skin rash to severe anaphylaxis, can occur, as with other penicillins. Significant adverse effects include interstitial nephritis, which may present with eosinophilia and acute kidney injury, and neutropenia, particularly with prolonged high-dose therapy. Cases of ''Clostridioides difficile''-associated diarrhea have been reported, though less frequently than with broader-spectrum agents.

Mechanism of action

As a beta-lactam antibiotic, nafcillin exerts its bactericidal effect by inhibiting bacterial cell wall synthesis. It binds to and inactivates specific penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. This inactivation disrupts the final transpeptidation step of peptidoglycan synthesis, leading to the formation of a defective cell wall and eventual osmotic lysis of the bacterium. Its isoxazolyl side chain confers stability against hydrolysis by staphylococcal penicillinase, an enzyme produced by many strains of Staphylococcus aureus.

Pharmacology

Nafcillin is administered parenterally via intravenous or intramuscular routes, as it is poorly absorbed from the gastrointestinal tract. It is highly protein-bound, primarily to albumin, which can influence its distribution and activity. The drug undergoes significant hepatic metabolism and is primarily excreted in the bile, with a smaller fraction eliminated unchanged in the urine; dosage adjustment is generally not required for renal impairment. Its elimination half-life is approximately one hour, necessitating frequent dosing to maintain therapeutic serum levels.

History

Nafcillin was developed in the early 1960s by Wyeth Laboratories as part of a concerted effort to create semisynthetic penicillins resistant to penicillinase. This research was driven by the growing clinical problem of penicillin resistance among Staphylococcus aureus isolates in hospitals worldwide. Its introduction provided a critical therapeutic alternative to methicillin, another early penicillinase-resistant penicillin. The drug received approval from the U.S. Food and Drug Administration and has remained a staple agent for serious staphylococcal infections, though its use has been impacted by the global rise of MRSA.

Society and culture

Nafcillin is marketed under trade names including Unipen and Nallpen. It is classified as a penicillin and carries a Boxed warning regarding the risk of severe hypersensitivity reactions. The drug is on the World Health Organization's List of Essential Medicines, underscoring its importance in basic healthcare systems. Its role has been studied in major clinical trials, such as those comparing it to vancomycin for Staphylococcus aureus bacteremia, conducted by institutions like the National Institutes of Health. Manufacturing has been associated with companies including Pfizer and Sandoz.

Category:World Health Organization essential medicines Category:Penicillin antibiotics Category:Antibiotics