Background: Many antibiotics have a high potential for interactions with drugs, as a perpetrator
and/or victim, in critically ill patients, and particularly in sepsis patients.
Methods: The aim of this review is to summarize the pharmacokinetic drug-drug interaction (DDI) of 45 antibiotics
commonly used in sepsis care in China. Literature search was conducted to obtain human pharmacokinetics/
dispositions of the antibiotics, their interactions with drug-metabolizing enzymes or transporters, and their
associated clinical drug interactions. Potential DDI is indicated by a DDI index ≥ 0.1 for inhibition or a treatedcell/
untreated-cell ratio of enzyme activity being ≥ 2 for induction.
Results: The literature-mined information on human pharmacokinetics of the identified antibiotics and their potential
drug interactions is summarized.
Conclusion: Antibiotic-perpetrated drug interactions, involving P450 enzyme inhibition, have been reported
for four lipophilic antibacterials (ciprofloxacin, erythromycin, trimethoprim, and trimethoprim-sulfamethoxazole)
and three antifungals (fluconazole, itraconazole, and voriconazole). In addition, seven hydrophilic antibacterials
(ceftriaxone, cefamandole, piperacillin, penicillin G, amikacin, metronidazole, and linezolid) inhibit drug
transporters in vitro. Despite no clinical PK drug interactions with the transporters, caution is advised in the use
of these antibacterials. Eight hydrophilic antibiotics (all β-lactams; meropenem, cefotaxime, cefazolin, piperacillin,
ticarcillin, penicillin G, ampicillin, and flucloxacillin), are potential victims of drug interactions due to
transporter inhibition. Rifampin is reported to perpetrate drug interactions by inducing CYP3A or inhibiting
OATP1B; it is also reported to be a victim of drug interactions, due to the dual inhibition of CYP3A4 and OATP1B
by indinavir. In addition, three antifungals (caspofungin, itraconazole, and voriconazole) are reported to be
victims of drug interactions because of P450 enzyme induction. Reports for other antibiotics acting as victims
in drug interactions are scarce.