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. 2024 Jun 13;13(6):553.
doi: 10.3390/antibiotics13060553.

Optimizing Antibiotic Therapy for Stenotrophomonas maltophilia Infections in Critically Ill Patients: A Pharmacokinetic/Pharmacodynamic Approach

Helena Barrasa  1   2 , Miguel Angel Morán  2   3 , Leire Fernández-Ciriza  4 , Arantxa Isla  2   5 , María Ángeles Solinís  2   5 , Andrés Canut-Blasco  2   6 , Alicia Rodríguez-Gascón  2   5
Affiliations

Optimizing Antibiotic Therapy for Stenotrophomonas maltophilia Infections in Critically Ill Patients: A Pharmacokinetic/Pharmacodynamic Approach

Helena Barrasa et al. Antibiotics (Basel). .

Abstract

Stenotrophomonas maltophilia is an opportunistic, multidrug-resistant non-fermentative Gram-negative bacillus, posing a significant challenge in clinical treatment due to its numerous intrinsic and acquired resistance mechanisms. This study aimed to evaluate the adequacy of antibiotics used for the treatment of S. maltophilia infections in critically ill patients using a pharmacokinetic/pharmacodynamic (PK/PD) approach. The antibiotics studied included cotrimoxazole, levofloxacin, minocycline, tigecycline, cefiderocol, and the new combination aztreonam/avibactam, which is not yet approved. By Monte Carlo simulations, the probability of target attainment (PTA), the PK/PD breakpoints, and the cumulative fraction of response (CFR) were estimated. PK parameters and MIC distributions were sourced from the literature, the European Committee on Antimicrobial Susceptibility Testing (EUCAST), and the SENTRY Antimicrobial Surveillance Program collection. Cefiderocol 2 g q8h, minocycline 200 mg q12h, tigecycline 100 mg q12h, and aztreonam/avibactam 1500/500 mg q6h were the best options to treat empirically infections due to S. maltophilia. Cotrimoxazole provided a higher probability of treatment success for the U.S. isolates than for European isolates. For all antibiotics, discrepancies between the PK/PD breakpoints and the clinical breakpoints defined by EUCAST (or the ECOFF) and CLSI were detected.

Keywords: PK/PD; Stenotrophomonas maltophilia; aztreonam/avibactam; cefiderocol; cotrimoxazole; levofloxacin; minocycline; tigecycline.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Probability of target attainment (PTA) and MIC distribution of S. maltophilia against cotrimoxazole, levofloxacin, minocycline, tigecycline, cefiderocol, and aztreonam/avibactam. For aztreonam/avibactam, PTA corresponds to the joint PTA (target of aztreonam and target for avibactam achieved simultaneously). For cotrimoxazole, the PTA refers to trimethoprim.
Figure 2
Figure 2
Relationship between fAUC24/MIC and MIC for different dosing regimens of cotrimoxazole (trimethoprim component). PK/PD target (horizontal line): 67.4.
Figure 3
Figure 3
Relationship between fAUC24/MIC and MIC for different dosing regimens of levofloxacin. PK/PD target (horizontal line): 62.
Figure 4
Figure 4
Relationship between fAUC24/MIC and MIC for different dosing regimens of minocycline. PK/PD target (horizontal line): 8.75.
Figure 5
Figure 5
Relationship between fAUC24/MIC and MIC for different dosing regimens of tigecycline. PK/PD target (horizontal line).
Figure 6
Figure 6
Relationship between fAUC24/MIC and MIC for cefiderocol. PK/PD target (horizontal line): 75%.
Figure 7
Figure 7
Relationship between %fT>MIC and MIC for aztreonam/avibactam. PK/PD target (horizontal line): 60%.
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