ArticleApplied microbiology and biotechnology2026
In vitro and in vivo synergistic effects of cyclizine and piroxicam in combination with linezolid against methicillin-resistant Staphylococcus aureus.
Article in Applied microbiology and biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundLinezolid (LNZ) is considered one of the last-resort antimicrobial agents reserved for treating methicillin resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Staphylococcus aureus (VRSA). The development of resistance against linezolid necessitates the exploration of novel therapies. Aim: This study aims to investigate the synergistic activity of various combinations of linezolid with non-antibiotic through in vitro and in vivo approaches. METHODS AND
resultsIn our research, 44 S. aureus isolates were obtained from various clinical sources. S. aureus isolates presented high levels of resistance to β-lactams and moderate resistance to doxycycline and erythromycin. Among the isolates, 43 (97.73%) were MRSA, 10 (22.73%) were linezolid resistant S. aureus (LRSA), and 17 (38.64%) were classified as VRSA. A total of 97.73% of the isolates presented the mecA gene (MRSA), whereas the optrA gene was detected in 9.09% of the isolates (LRSA). The synergistic activity of nine compounds with linezolid was assessed in vitro against LRSA isolates using broth microdilution and checkerboard microdilution methods. Linezolid/cyclizine and linezolid/piroxicam combinations showed fractional inhibitory concentration indexes (FICIs) ranging from 0.28 to 0.5 against LRSA isolates. Time-kill curves were used to confirm their bactericidal activity. Promising combinations (linezolid/cyclizine and linezolid/piroxicam) were further evaluated in vivo LRSA-induced lung infection murine animal model. Compared with monotherapy, combination therapies significantly enhance bacterial eradication and increase sensitivity to linezolid, resulting in superior bacterial eradication. Linezolid/cyclizine and linezolid/piroxicam combinations provided complete protection (100% survival), improved lung pathology, and enhanced clinical scores.
conclusionThis study presents two novel combination therapies (linezolid/cyclizine and linezolid/piroxicam) with promising applications in treating severe LRSA infections. KEY POINTS: optrA gene was detected in four linezolid S. aureus-resistant isolates (LRSA) Linezolid/cyclizine and linezolid/piroxicam synergism was detected against LRSA. Combinations revealed complete lung protection in lung-infected LRSA murine model.
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