Dicloxacillin is an oral, second generation penicillin antibiotic that is used to treat bacterial infections caused by penicillinase-resistant staphylococci. Dicloxacillin has been linked to rare instances of clinically apparent, idiosyncratic liver injury.
Dicloxacillin (dye klox' a sil' in) is a second generation penicillin that is resistant to inactivation by penicillinases and is used to treat infections caused by penicillinase-producing bacteria. Like other penicillins, dicloxacillin is a beta lactam antibiotic that is believed to act by binding to the bacterial enzyme that is responsible for synthesizing peptidoglycans which are necessary for the intregity of the bacterial cell wall. Dicloxacillin was approved for use in the United States in 1968 and is still widely used to treat mild-to-moderate staphylococcal infections. To reduce development of drug resistant bacteria, dicloxacillin is recommended to treat or prevent only those infections that are proven or suspected to be caused by penicillinase-producing susceptible bacteria. Dicloxacillin is available in multiple generic forms as 250 and 500 mg capsules and as a suspension for pediatric use. The typical dose is 125 to 500 mg every 6 hours. Common side effects of dicloxacillin include nausea, diarrhea, stomatitis, skin rash and allergic reactions.
Dicloxacillin therapy has not been associated with serum enzyme elevations during treatment, but has been linked to rare instances of clinically apparent, cholestatic hepatitis. The typical time to onset is 1 to 6 weeks and the pattern of serum enzyme elevations is usually cholestatic, although cases with a mixed pattern have also been described (Case 1). The injury usually presents with jaundice and pruritus. Fever, rash and eosinophlia can occur, but are not prominent and autoantibodies are rarely detected. A similar pattern of injury occurs more frequently with flucloxacillin (also called floxacillin) and cloxacillin, oral isoxazolyl penicillins similar in structure and activity to dicloxacillin, but never approved for use or available in the United States. Similar cholestatic hepatitis arising 1 to 6 weeks after starting therapy occurs with other penicillins.
Likelihood score: B (highly likely but rare cause of clinically apparent liver injury).
The cause of the idiosyncratic, cholestatic hepatitis following dicloxacillin therapy is not known. Allergic manifestations (rash, fever and eosinophilia) are not common and the liver injury is usually not accompanied by signs or symptoms of penicillin hypersensitivity. However, the rapid recurrence of injury with reexposure suggests a hypersensitivity mechanism, perhaps in response to the beta lactam ring. Injury occurs more frequently in older patients. Too few cases of dicloxacillin hepatotoxicity have been reported to comment on possible HLA associations, such as the link to HLA-B*57:01 which has been made to flucloxacin.
In the few cases that have been described, cholestasis has been prolonged, but all patients recovered within 6 to 12 weeks without residual injury. Reexposure appears to be associated with recurrence of injury, often with a shortened latency period. The idiosyncratic liver injury from dicloxacillin has not been linked to acute liver failure, chronic injury or the vanishing bile duct syndrome (although these have been described with flucloxacillin). Prednisone has been used to treat the cholestatic liver injury, but its effects are unclear while its side effects can be serious. Patients should be told to avoid reexposure to the penicillinase-resistant penicillins, including nafcillin and oxacillin.
References to dicloxacillin-induced liver injury are given in the overview section on Penicillinase-Resistant Penicillins (updated 03 January 2018).
|Severity:||3+ (jaundice and hospitalization)|
|Latency:||Two to three weeks|
|Recovery:||Complete in 3 months|
|Time After Starting||Time After Stopping||AST* (U/L)||Alk P* (U/L)||Bilirubin* (mg/dL)||Other|
|0||Dicloxacillin given for 5 days|
|3 weeks||2 weeks||225||218||3.8||Eosinophils=487|
|4 weeks||3 weeks||325||230||8.0|
|5 weeks||4 weeks||50||150||10.3|
|7 weeks||6 weeks||45||165||11.8|
|9 weeks||8 weeks||110||5.0|
|12 weeks||11 weeks||70||135||1.8|
|13 weeks||12 weeks||65||120||1.1|
|14 weeks||13 weeks||38||60||0.5|
|DRUG||CAS REGISTRY NO||MOLECULAR FORMULA||STRUCTURE|