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. 2024 Nov 8:18:5073-5086.
doi: 10.2147/DDDT.S474470. eCollection 2024.

Population Pharmacokinetic/Pharmacodynamic Study of Linezolid in Hospital-Acquired Pneumonia Patients with Renal Insufficiency

Jinhui Xu #  1 , Xianglong Chen #  1 , Qian Zhang #  1 , Zhiwei Zhuang  2 , Yunlong Yuan  3 , Lufen Duan  1 , Lu Shi  1 , Chenqi Zhu  1 , JingJing Li  1 , Jian Lu  4 , Yanxia Yu  1 , Lian Tang  1   5
Affiliations

Population Pharmacokinetic/Pharmacodynamic Study of Linezolid in Hospital-Acquired Pneumonia Patients with Renal Insufficiency

Jinhui Xu et al. Drug Des Devel Ther. .

Abstract

Purpose: The optimal treatment strategy in patients with hospital-acquired pneumonia (HAP) due to Gram-positive bacteria and renal insufficiency remains challenging. The objective of this study was to compare the outcomes of linezolid versus teicoplanin in HAP patients with renal insufficiency and to explore optimal dosage strategy for linezolid.

Methods: The retrospective study enrolled adult patients treated with intravenous linezolid or teicoplanin at Suzhou Municipal Hospital between July 2018 and August 2023. For the comparative pharmacodynamic study, effectiveness, safety and target attainment of trough concentration (Cmin) for teicoplanin versus linezolid treatment in HAP patients with document Gram-positive bacteria and renal insufficiency were compared. For the population pharmacokinetics (PPK) analyses, linezolid concentrations collected exclusively from HAP patients with renal insufficiency were used and the optimal dosage strategy was investigated using Monte Carlo simulations.

Results: Linezolid-treated patients had a higher bacterial eradication rate than teicoplanin-treated patients (88.5% vs 63.4%, P < 0.001). A higher proportion of patients in the linezolid group experienced at least one adverse reaction (42.0% vs 25.0%, P = 0.025). Significantly more supratherapeutic Cmin, less therapeutic Cmin were achieved in the linezolid group (adjusted P < 0.05). A total of 207 linezolid concentrations from 166 patients with renal insufficiency were available for the PPK analysis. Age and creatinine clearance (CrCL) were identified as significant covariates that influenced clearance. Simulations show that 300 mg q12h provide the optimal exposure in patients with a CrCL of 60 or 45 mL/min, and 200 mg q12h was recommended for patients with a CrCL of 30 or 15 mL/min.

Conclusion: Linezolid-treated patients with HAP and renal insufficiency had higher bacterial eradication rates, supratherapeutic exposure and adverse reactions than teicoplanin-treated patients. Linezolid dose reduction in patients with renal insufficiency improved the probability of achieving optimal exposure.

Keywords: hospital-acquired pneumonia; linezolid; pharmacodynamic; population pharmacokinetic; renal insufficiency.

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Conflict of interest statement

We declare that there are no conflicts of interest related to the research.

Figures

Figure 1
Figure 1
Target attainment of trough concentration (Cmin) in patients with renal insufficiency receiving linezolid and teicoplanin therapy.
Figure 2
Figure 2
Goodness-of-fit plots for the basic model.
Figure 3
Figure 3
Goodness-of-fit plots for the final model.
Figure 4
Figure 4
Prediction corrected-visual predictive check of the final model.
See this image and copyright information in PMC

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References

    1. Magill SS, O’Leary E, Janelle SJ, et al. Changes in Prevalence of Health Care–Associated Infections in U.S. Hospitals. N Engl J Med. 2018;379(18):1732–1744. doi:10.1056/NEJMoa1801550 - DOI - PMC - PubMed
    1. Torres A, Niederman MS, Chastre J, et al. International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociacion Latinoamericana del Torax (ALAT). Eur Respir J. 2017;50(3). doi:10.1183/13993003.00582-2017 - DOI - PubMed
    1. Gales AC, Sader HS, Ribeiro J, Zoccoli C, Barth A, Pignatari AC. Antimicrobial susceptibility of gram-positive bacteria isolated in Brazilian hospitals participating in the SENTRY Program (2005-2008). Braz J Infect Dis. 2009;13(2):90–98. doi:10.1590/s1413-86702009000200004 - DOI - PubMed
    1. Antonelli A, Giani T, Coppi M, et al. Staphylococcus aureus from hospital-acquired pneumonia from an Italian nationwide survey: activity of ceftobiprole and other anti-staphylococcal agents, and molecular epidemiology of methicillin-resistant isolates. J Antimicrob Chemother. 2019;74(12):3453–3461. doi:10.1093/jac/dkz371 - DOI - PubMed
    1. Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63(5):e61–e111. doi:10.1093/cid/ciw353 - DOI - PMC - PubMed

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