Enhancing Antibiotic Efficacy Against P. mirabilis Biofilm: The Synergistic Potential of Phage-Antibiotic Combination Therapy

BACKGROUND AND OBJECTIVESProteus mirabilis bacteria are recognized as a significant etiological agent of urinary catheter infections, especially in cases with abnormalities in urinary tracts. This bacterium can form biofilms on both abiotic surfaces, such as urinary catheters, and biotic surfaces. Bacteriophage therapy emerges as a promising alternative approach for treating infections caused by biofilm-forming bacteria. By complementing conventional treatment methods, bacteriophage therapy enhances treatment specificity and mitigates the adverse effects of certain antibiotics. Additionally, it augments the bactericidal activity against pathogenic bacteria while concurrently safeguarding the natural bacterial flora of the patient's body. Co-administration of antibiotics and phages, known as Phage-Antibiotic Synergy (PAS), represents a strategy to amplify therapeutic efficacy. Phages serve as adjuncts to antibiotics by facilitating a decrease in the antibiotic's minimum inhibitory concentration (MIC) when used in conjunction with phages.MATERIALS AND METHODSFirst, the clinical isolates of P. mirabilis were isolated from the urine of patients with urinary tract infections. The antibiogram test was performed by disc diffusion method according to CLSI ۲۰۲۲ protocol, and Multi-Drug Resistance (MDR) strains were identified. In the next step, the measurement MIC for the antibiotic’s cefotaxime and cotrimoxazole were performed by the microdilution broth method (MIC). The Crystal violate microtiter plate assay evaluated the biofilm production of MDR strains. The Checkerboard assay was performed to survey the effect of the combination of Phage and antibiotics. Finally, the effect of phage and antibiotic combination with different concentrations was investigated against the biofilm formation of P. mirabilis bacteria, and to determine the living bacteria, colony count and MTT assay were used.RESULTS AND DISCUSSIONBased on the findings derived from our study, the simultaneous administration of phages along with cotrimoxazole and cefotaxime antibiotics exhibited a notable reduction of one unit in the minimum inhibitory concentration (MIC) for both antibiotics, as compared to their individual usage. Furthermore, this combined treatment approach demonstrated a significant decline in biofilm production by bacteria isolated from clinical samples (P<۰.۰۵).CONCLUSIONOne of the primary concerns within the healthcare system regarding infections attributed to P. mirabilis bacteria is their pronounced propensity for biofilm formation, which poses challenges for individuals utilizing urinary catheters. Moreover, the persistent resistance exhibited by this bacterium towards an assortment of antibiotics in recent years further compounds the issue. Consequently, this alternative therapeutic approach addresses infections induced by biofilm-forming strains of P. mirabilis effectively.

کلیدواژه ها:

Multi-Drug Resistant ، Proteus mirabilis ، Biofilm ، Phage therapy ، Phage-antibiotic synergy (PAS)