Bacteriophage-enhanced doxycycline activity against Escherichia coli in chronic bacterial prostatitis

Abstract

Objectives: Prostatitis caused by antibiotic-resistant Escherichia coli poses a significant treatment challenge, and phage therapy is emerging as a promising antibacterial strategy. Here we report the case of a patient with prostatitis caused by an extended spectrum β-lactamase-producing E. coli successfully treated with oral doxycycline and two phage cocktails. The use of doxycycline was supported by the detection of Mycoplasma spp. in the patient's urine. We also tested the same phage-antibiotic combination against a panel of different E. coli strains in vitro.

Methods: A patient received oral SES and PYO phage cocktails alongside oral doxycycline for 30 days. The MIC values of doxycycline and phages alone and in combination were evaluated by checkboard assay versus five E. coli isolates, including the patient's strain. Synergy was assessed using a modified fractional inhibitory concentration index. Data were analysed by synogram and an interaction plot based on the percentage reduction of the absorbance values (OD₅₇₀) between untreated control and treated samples. Growth curves were performed over 24 h to monitor bacterial replication in the presence/absence of phage and/or antibiotic.

Results: After treatment microbiological cultures were negative and symptoms remitted. A synergistic/additive effect between doxycycline and the phages was observed in vitro in three out of five E. coli isolates. Synogram analysis showed a synergistic effect versus one strain, while an additive effect was observed for the other four isolates. Growth curve analysis demonstrated enhanced bacterial growth inhibition for up to 12 h with the combined treatment compared with either therapy alone.

Conclusions: Although the E. coli strain was resistant to doxycycline, the antibiotic was administered specifically to target the Mycoplasma infection. Interestingly, the enhanced in vitro activity observed when the antibiotic was combined with phages versus E. coli suggests that this combination may be effective at eradicating chronic prostatitis caused by extended spectrum β-lactamase-producing E. coli.

Keywords: Bacteriophages; Doxycycline; Escherichia coli; Phage therapy; Phage-antibiotic synergism; Prostatitis; Urinary tract infections.