Predicting clinical phage therapy outcomes in vitro: results using mixed versus single isolates from an MRSA case...

Area of Science:

• Microbiology
• Infectious Diseases
• Bacteriophage Therapy

Background:

• Phage therapy is a promising alternative for treating bacterial infections, especially those caused by antibiotic-resistant strains.
• Current in vitro testing methods (phagograms) often use limited bacterial isolates, potentially not reflecting the complexity of in vivo infections.
• Bacterial populations can exhibit diverse susceptibility to phages and antibiotics, influencing treatment response.

Purpose of the Study:

• To evaluate if in vitro testing of mixed bacterial isolates with phages provides more accurate predictions of clinical outcomes than single isolates.
• To compare in vitro phage susceptibility results with clinical observations from a patient with methicillin-resistant Staphylococcus aureus (MRSA) infection.

Main Methods:

• A previously published clinical case study of MRSA treated with phage therapy and antibiotics was used as a reference.
• In vitro experiments tested phage efficacy against single and mixed isolates of the infecting MRSA strains.
• Results were compared between in vitro findings and clinical outcomes in different infection sites (blood vs. lungs).

Main Results:

• In vitro, mixed bacterial isolates were more likely to persist when treated with phages compared to single isolates.
• This persistence of mixed isolates in vitro more closely mirrored the slower bacterial clearance observed in the patient's lung infections.
• However, in vitro results did not as accurately represent the rapid clearance seen in the patient's blood cultures.

Conclusions:

• The choice of using single versus mixed bacterial isolates significantly impacts in vitro phage therapy predictions.
• The predictive accuracy of in vitro models depends on the specific site of infection and the genetic diversity of the bacteria in vivo.
• These findings highlight the importance of considering bacterial population heterogeneity in developing personalized phage therapy strategies.