Open Access Research Report
In vitro pharmacodynamic study of several antibiotic–antifungal combinations against a bacterial–fungal co-infection in the presence of albumin and / or platelets
Asmaa S. Dhaidan1
, Hussam W. Al-Humadi1,*
1Department of Pharmacology, College of Pharmacy, University of Babylon, Hillah, Iraq
*Corresponding author: Hussam W. Al-Humadi, College of Pharmacy, University of Babylon, Hillah, Iraq; Tel.: +964-(0)7818132556; e-mail: alhumadi2010@gmail.com; phar.hussam.wahab@uobabylon.edu.iq
Published: 04 August 2026; https://doi.org/10.61873/TTLF3475
Abstract
Background: Managing bacterial–fungal co-infections remains clinically challenging due to complex pathogen interactions and host-related factors that can alter antimicrobial activity. Aim: This study aimed to evaluate the influence of albumin and platelets on the pharmacodynamic behavior of combined antibacterial–antifungal therapies against Staphylococcus aureus and Candida albicans. Methodology: Simulation of clinical drug exposures was performed using a dynamic in vitropharmacokinetic/pharmacodynamic (PK/PD) model. Co-infection cultures were treated with combinations of an antibacterial (vancomycin or clindamycin) and an antifungal (caspofungin or amphotericin B) in the presence or absence of albumin, platelets, or both. Antimicrobial efficacy was determined by assessing microbial growth inhibition and calculating corresponding PD parameters. Results: Within this in vitro system, host factors significantly modulated antimicrobial efficacy. Platelets produced the greatest enhancement in growth inhibition, potentially via the release of antimicrobial peptides, while albumin appeared to modulate this platelet effect. Among the tested regimens, the vancomycin-caspofungin combination achieved the highest overall antimicrobial activity across the co-infection models, particularly when combined with platelets. Conversely, vancomycin plus amphotericin B demonstrated lower maximal efficacy. Clindamycin-based combinations showed intermediate activity and were highly sensitive to the presence of host factors. Generally, the co-infection environment reduced overall antimicrobial activity compared to baseline single-pathogen expectations. Conclusion: These in vitro findings suggest that host components, such as platelets and albumin, may play a meaningful role in shaping the PD outcomes of combination therapies. While these laboratory observations highlight the potential impact of the host microenvironment, cautious interpretation is warranted, and further in vivo research is required to validate whether these interactions translate to a clinical setting.
Keywords: polymicrobial co-infection, antibacterial–antifungal combination therapy, PK/PD modelling, host-related factors (albumin and platelets), Emax and AUC analysis
Please cite as:
Dhaidan A. S., Al-Humadi H. W.: In vitro pharmacodynamic study of several antibiotic–antifungal combinations against a bacterial–fungal co-infection in the presence of albumin and / or platelets. Epitheorese Klin. Farmakol. Farmakokinet. 44:11-18 (2026). DOI: 10.61873/TTLF3475
pISSN 1011-6575 • eISSN 2945-1914