Abstract
BackgroundFlucloxacillin is an established cause of liver injury. Despite this, there are a lack of published data on both the strength of association after adjusting for potential confounders, and the absolute incidence among different subgroups of patients.ObjectivesTo assess the relative and absolute risks of liver injury following exposure to flucloxacillin and identify subgroups at potentially increased risk.MethodsA cohort study between 1 January 2000 and 1 January 2012 using the UK Clinical Practice Research Datalink, including 1 046 699 people with a first prescription for flucloxacillin (861 962) or oxytetracycline (184 737). Absolute risks of experiencing both symptom-defined (jaundice) and laboratory-confirmed liver injury within 1–45 and 46–90 days of antibiotic initiation were estimated. Multivariable logistic regression was used to estimate 1–45 day relative effects.ResultsThere were 183 symptom-defined cases (160 prescribed flucloxacillin) and 108 laboratory-confirmed cases (102 flucloxacillin). The 1–45 day adjusted risk ratio for laboratory-confirmed injury was 5.22 (95% CI 1.64–16.62) comparing flucloxacillin with oxytetracycline use. The 1–45 day risk of laboratory-confirmed liver injury was 8.47 per 100 000 people prescribed flucloxacillin (95% CI 6.64–10.65). People who received consecutive flucloxacillin prescriptions had a 1–45 day risk of jaundice of 39.00 per 100 000 (95% CI 26.85–54.77), while those aged >70 receiving consecutive prescriptions had a risk of 110.57 per 100 000 (95% CI 70.86–164.48).ConclusionsThe short-term risk of laboratory-confirmed liver injury was >5-fold higher after a flucloxacillin prescription than an oxytetracycline prescription. The risk of flucloxacillin-induced liver injury is particularly high within those aged >70 and those who receive multiple flucloxacillin prescriptions. The stratified risk estimates from this study could help guide clinical care.
Highlights
Flucloxacillin is an antibiotic of the penicillin class that has a broad range of uses in the treatment of Gram-positive bacterial infections, including skin and soft tissue infections, respiratory tract infections, urinary tract infections, meningitis and prophylaxis during surgery.[1]
Previous work has shown flucloxacillin to be associated with liver injury at a frequency of 8 per 100000 people exposed within the general population.[4,5,6]
For the analysis of the association between flucloxacillin and liver injury, all relative effects were calculated as odds ratios, which given the rarity of the Between 1 January 2000 and 1 January 2012, 1073894 people aged 18 years and over were identified in Clinical Practice Research Datalink (CPRD) who received a first prescription for either flucloxacillin or oxytetracycline and had been registered in the database for at least 6 months (Figure 2)
Summary
Flucloxacillin is an antibiotic of the penicillin class that has a broad range of uses in the treatment of Gram-positive bacterial infections, including skin and soft tissue infections, respiratory tract infections, urinary tract infections, meningitis and prophylaxis during surgery.[1] First available in 1960, case reports appeared in the 1980s of an adverse drug reaction in which the patient developed serious liver injury, which in some cases could be fatal.[2] While commonly and increasingly prescribed in the UK,[3] flucloxacillin is not marketed in the USA and some European countries, where alternative therapies perceived to have a better safety profile are used (such as dicloxacillin). Previous work has shown flucloxacillin to be associated with liver injury at a frequency of 8 per 100000 people exposed within the general population.[4,5,6] Liver injury may occur up to 45 days from initiation of treatment, can be prolonged and is characterized by a predominantly cholestatic pattern of liver test results, and symptoms including jaundice. There are a lack of published data on both the strength of association after adjusting for potential confounders, and the absolute incidence among different subgroups of patients
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