The orally available cephalosporins are widely used as broad spectrum antibiotics for mild-to-moderate infections with susceptible organisms. Despite their widescale use, cases of drug induced liver disease from the cephalosporins are very rare, with only isolated case reports having been published.
The oral cephalosporins are available in both generic and trade formulations and include cefaclor (Ceclor, Raniclor: 2nd), cefadroxil (Duracef: 1st), cefdinir (Omnicef: 3rd), cefditoren (Spectracef: 3rd), cefixime (Suprax: 3rd), cefpodoxime (Vantin: 3rd), cefprozil (Cefzil: 2nd), ceftibuten (Cedax: 3rd), cephalexin (Keftab: Apo-Cephalex, Biocef, Keflex, NovoLexin, Nu-Cephalex: 1st), cefuroxime (Ceftin: 2nd), cephradine (Velosef: 1st), and loracarbef (Lorabid: 2nd). Cefuroxime and cephradine are also available in parenteral forms. The typical dose regimens for oral cephalosporins are 250 to 500 mg two to four times daily for 7 to 14 days. The oral cephalosporins are widely used in medicine for mild-to-moderate infections due to susceptible bacteria.
Oral cephalosporins can be associated with minor elevations in serum aminotransferase and alkaline phosphatase values, but these are generally mild, transient and not associated with symptoms or development of more severe liver injury. The frequency of these elevations is reported to be as high as 11%, but varies depending upon the frequency of monitoring, duration of therapy, and nature and severity of the underlying illness. Clinically apparent liver injury from oral cephalosporin use is rare, only isolated case reports having been published, and not all of the formulations have been linked to cases of liver injury. The clinical pattern of injury suggests that hepatotoxicity is largely a class effect from the cephalosporins, even though it is idiosyncratic and rare. The typical latency period has been 1 to 4 weeks with an abrupt onset of liver injury. The pattern of serum enzyme elevations is usually cholestatic, but mixed and hepatocellular instances have been reported. Liver injury is often accompanied by fever, rash and eosinophilia or other signs and symptoms of hypersensitivity. A history of penicillin allergy is not common.
Likelihood score: B (cephalosporins as a class are very likely but rare causes of clinically apparent liver injury, the association having been made largely with the most frequently used agents, such as cefazolin, cephalexin and ceftriaxone).
Mechanism of Injury
The mechanism of hepatic injury due to cephalosporins is unknown, but believed to be hypersensitivity and similar to that of other penicillins.
Outcome and Management
In most case reports, recovery has been rapid within 4 to 8 weeks with residual injury or persistent serum enzyme elevations. Among the few cases reported, none have been fatal.
References to oral cephalosporin induced liver injury are provided in the introductory Overview section on Cephalosporins.
|Medication:||Cefuroxime, 500 mg daily for 10 days|
|Severity:||3+ (jaundice and hospitalization)|
|Recovery:||More than 6 months|
|Other medications:||Fluticasone and salmeterol inhalant and albuterol (for asthma), insulin (diabetes), gabapentin (neuropathy), lisinopril and hydrochlorothiazide (hypertension), cyclobenzaprine and the combination of hydrocodone and acetaminophen (low back pain)|
|Time After Starting||Time After Stopping||ALT (U/L)||Alk P (U/L)||Bilirubin (mg/dL)||Other|
|Ten day course of cefuroxime: weeks 1-2|
|8 weeks||6 weeks||268||651||8.4||Jaundice and pruritus|
|9 weeks||8 weeks||264||595||7.1|
|Two courses of cephalexin: weeks 10-14|
|15 weeks||14 weeks||284||720||11.8|
|Five day course of cefuroxime: week 19|
|20 weeks||19 weeks||189||812||4.7||Erythema|
|21 weeks||20 weeks||191||859||3.6|
|22 weeks||21 weeks||176||717||2.1||Pruritus|
|6 months||6 months||111||428||1.0|
|7 months||7 months||69||174||0.7|
|8 months||8 months||74||217||1.0||Asymptomatic|
|15 months||15 months||42||169||0.7|
|18 months||18 months||32||131||0.4|
|20 months||20 months||35||119||0.4|
|DRUG||CAS REGISTRY NO||MOLECULAR FORMULA||STRUCTURE|