Exploratory pharmacokinetic/pharmacodynamic range of tigecycline for balancing treatment effect and safety in hospital-acquired pneumonia: a retrospective cohort study

Introduction Tigecycline (TGC) is a core antibiotic for treating hospital-acquired pneumonia (HAP) caused by multidrug-resistant (MDR) bacteria, but the absence of individualized dosing guidance that balances treatment effect and safety frequently results in suboptimal efficacy or coagulation-related adverse events in clinical practice. Methods A single-center retrospective study was conducted, enrolling 100 patients with MDR-HAP who were assigned to a standard-dose group or a high-dose group based on clinical decisions. The efficacy and safety of different TGC dosing regimens were compared between the two groups. Results The trough concentration (C min ), intermediate concentration (C 1/2 ), and peak concentration (C max ), the estimated ratio of the area under the concentration-time curve to the 24h of dosing/minimum inhibitory concentration (eAUIC), pharmacokinetic/pharmacodynamic (PK/PD) target attainment rate, clinical response rate and overall favorable outcome rate in the high-dose group were significantly higher than those in the standard group ( p < 0.05). The incidence of thrombocytopenia was significantly higher in the high-dose group (36.67% vs. 17.14%, p = 0.034), whereas the incidence of hypofibrinogenemia was numerically higher but did not reach statistical significance (40.0% vs. 30.0%, p = 0.330). No significant between-group differences were observed in microbiological eradication rate, median survival time, 30-day all-cause mortality, coagulation parameters, gastrointestinal reactions, or liver function damage. Binary logistic regression analysis revealed that eAUIC [OR = 1.394 (1.135-1.712), p = 0.002] was an influencing predictor associated with clinical treatment effect. The area under the receiver operating characteristic (ROC) curve for eAUIC was 0.813, with a maximum Youden index of 0.557. The corresponding critical value was determined to be 2.915, with a sensitivity of 96.9% and a specificity of 58.8%. Furthermore, eAUIC was independently associated with both hypofibrinogenemia and thrombocytopenia. We identified an exploratory candidate eAUIC range of 2.915 – 3.565 that was associated with both clinical treatment effect and coagulation-related adverse events. Discussion This eAUIC range was derived from retrospective data and should be framed explicitly as a hypothesis to be tested, clinical applicability requires confirmation through prospective studies and external validation. Therapeutic drug monitoring may assist in optimizing therapy, but prospective studies are needed to confirm these observations.