Case report links piperacillin-tazobactam re-exposure to severe liver injury

A 73-year-old man developed severe liver injury while receiving piperacillin-tazobactam, improved partially after the antibiotic was withdrawn, and then experienced a sharp biochemical deterioration when the drug was restarted. The sequence led clinicians to diagnose possible piperacillin-tazobactam-associated drug-induced liver injury (DILI), with the re-exposure producing a pronounced increase in aminotransferases, jaundice and impaired coagulation. The case report emphasizes the value of reconstructing medication timelines and communicating suspected adverse drug reactions when patients move between clinical teams, although the case cannot establish a causal relationship or estimate how frequently this reaction occurs.

The patient was admitted on 10 May 2026 after nine days of recurrent fever, altered consciousness and foaming at the mouth during febrile episodes. He had received intravenous levofloxacin at another hospital from 5 to 9 May without clinical improvement. On admission, his temperature was 39.5 °C and he was somnolent but responsive to voice. Blood tests showed normal liver biochemistry, including alanine aminotransferase (ALT) of 39.9 U/L, aspartate aminotransferase (AST) of 45.6 U/L, alkaline phosphatase (ALP) of 61.15 U/L, total bilirubin of 11.9 μmol/L and an international normalized ratio (INR) of 1.16. A chest scan showed partial consolidation in both lower lobes, and clinicians began treating suspected pulmonary and central nervous system infections with intravenous piperacillin-tazobactam at 4.5 g every eight hours.

Four days after treatment began, liver abnormalities appeared, raising the possibility of either infection-associated liver injury or DILI. ALT rose to 151.1 U/L on 14 May, with AST at 176.9 U/L, ALP at 143.31 U/L and gamma-glutamyl transferase (GGT) at 133.54 U/L. The patient also received acyclovir for persistent fever after cerebrospinal fluid culture was negative and brain magnetic resonance imaging showed mild cerebral swelling and leptomeningeal enhancement. His aminotransferases subsequently declined, but ALP and GGT remained elevated. By 31 May, he had developed cutaneous and scleral jaundice, abdominal tenderness, ALT of 410.7 U/L, AST of 502.3 U/L, ALP of 638.21 U/L and total bilirubin of 141.13 μmol/L. Imaging found no biliary obstruction, and testing did not identify viral, autoimmune or parasitic causes.

The treating team stopped piperacillin-tazobactam and acyclovir on 31 May and continued supportive treatment with agents including polyene phosphatidylcholine and magnesium isoglycyrrhizinate. This first withdrawal was followed by a decrease in AST and ALT, although ALP, GGT and total bilirubin continued to rise for several days. The patient was transferred to the gastroenterology department on 2 June with persistent biochemical abnormalities. On 3 June, fever returned to 39 °C, accompanied by cough and sputum production. Although the measured procalcitonin concentration was 0.3 ng/mL, above the cited reference range of 0 to 0.077 ng/mL, clinicians suspected inadequately controlled pulmonary bacterial infection and restarted piperacillin-tazobactam. The drug was the only one of the two suspect agents to be reintroduced.

Following the restart, the patient’s liver profile deteriorated rapidly. By 6 June, ALT had risen to 654.2 U/L and AST to 894.2 U/L, while total bilirubin reached 377.0 μmol/L and marked jaundice persisted. Double plasma molecular adsorption system therapy was initiated, but the patient’s condition worsened further on 7 June. ALT reached 1,263.9 U/L and AST 1,746.1 U/L; the INR rose to 1.95 and then 1.97 on 8 June. The R value, a ratio derived from ALT and ALP relative to their upper limits of normal, was 1.61 on 31 May, consistent with a cholestatic biochemical pattern, and increased to 5.23 by 7 June, indicating a shift toward hepatocellular injury. The case met stated biochemical criteria for acute DILI and was classified as grade 3, or severe, acute DILI.

A clinical pharmacist assessed causality and recommended stopping piperacillin-tazobactam again on 7 June. Its last administration was 8 June, after which it was not used again. Additional double plasma molecular adsorption system sessions were performed on 8, 10, 11 and 13 June alongside continued pharmacological support. AST and ALT subsequently fell markedly, and the INR declined. For example, ALT decreased from 1,310.2 U/L on 8 June to 224.5 U/L on 11 June and 88.4 U/L by 15 June, while AST fell from 1,263.3 to 26.7 U/L over the same period. In contrast, cholestatic measures remained abnormal: on the day of discharge, ALP was 234.6 U/L, GGT 311.1 U/L and total bilirubin 352.9 μmol/L. Thus, the hepatocellular and coagulation abnormalities improved substantially after the second withdrawal, whereas cholestasis had not resolved.

The investigators used the Roussel Uclaf Causality Assessment Method, or RUCAM, to evaluate the suspected adverse reaction and obtained a score of 3, which was interpreted as a possible association between piperacillin-tazobactam and acute liver injury. A Naranjo score of 7 indicated a probable drug-related reaction and supported the RUCAM assessment. These scores were based on the clinical timeline rather than a specific laboratory marker, since no diagnostic biomarker for DILI was available. Other evidence included normal liver tests at admission, onset of abnormalities four days after the antibiotic was started, improvement in aminotransferases after withdrawal and renewed injury after re-exposure. Negative tests reduced support for viral, autoimmune and obstructive alternatives, although infection-associated liver injury could not be excluded completely.

The interpretation carries important limitations. This was a single-patient case report rather than a controlled epidemiological study, and it cannot determine whether piperacillin-tazobactam caused the liver injury with certainty. Other medicines were given during the initial exposure period, including acyclovir, although the fact that only piperacillin-tazobactam was reintroduced during the severe recurrence made acyclovir a less likely explanation for the second episode. Some tests were unavailable, including anti-hepatitis B core IgM, hepatitis B virus DNA, hepatitis C virus RNA, anti-hepatitis E IgM and hepatitis E virus RNA. Cerebrospinal fluid cultures and a sputum culture were negative, and the Sequential Organ Failure Assessment score was below 2. Although sepsis was considered unlikely, infection-associated liver injury could not be completely excluded. No laboratory follow-up was available after discharge on 15 June, leaving the duration and completeness of recovery unknown.

Piperacillin-tazobactam is a widely used antipseudomonal penicillin and beta-lactamase inhibitor combination. The article cites a reported DILI frequency of approximately 0.097% among hospitalized patients receiving it, while previous reports have described predominantly cholestatic or mixed biochemical patterns and a latency of about two weeks. In this patient, the first abnormalities appeared after four days and the second episode produced a different biochemical trajectory: aminotransferases and INR improved after each withdrawal, while ALP, GGT and bilirubin remained elevated or continued to rise. The authors said this contrast may indicate heterogeneity in liver-injury mechanisms between people receiving the same drug, but one case cannot establish a general pattern. The clinical takeaway is observational rather than a controlled efficacy result: suspected DILI warrants a clearly documented exposure timeline, and information about suspected adverse reactions should be transferred explicitly when care changes hands.

Subject of Research: Single-patient case report of possible severe drug-induced liver injury after piperacillin-tazobactam re-exposure

Article Title: Possible severe piperacillin-tazobactam–associated drug-induced liver injury after re-exposure: a case report

Article References: Ren, J., Yu, W., & Dai, Y. (2026). Possible severe piperacillin-tazobactam–associated drug-induced liver injury after re-exposure: a case report. Frontiers in Medicine, 13, Article 1977830. https://doi.org/10.3389/fmed.2026.1977830

Image Credits: AI Generated

DOI: 10.3389/fmed.2026.1977830

Keywords: piperacillin-tazobactam, drug-induced liver injury, antibiotic re-exposure, hepatotoxicity, cholestasis, liver enzymes, adverse drug reaction, case report, clinical pharmacy, Possible, severe, associated