Findings from a study recently published in Cornea assessed the in vitro efficacy of a novel triple-antibiotic combination polymyxin B/trimethoprim (PT) + rifampin on multidrug-resistant (MDR) isolates from patients with bacterial keratitis in India.
Give me some background first.
Bacterial keratitis is the most common form of infectious keratitis, with Staphylococcus (S.) aureus and Pseudomonas (P.) aeruginosa contributing to more than 50% of cases.
Note: P. aeruginosa was previously linked to a multistate outbreak of artificial tear-associated patient cases reported last year.
Go on …
An accelerated rise in drug-resistant bacterial keratitis isolates have rendered fluoroquinolone—the first-line treatment for bacterial keratitis—increasingly ineffective, particularly in India.
This translates to an urgent need for newer, broad-spectrum therapies that can quickly eliminate both gram-positive and gram-negative bacteria that are resistant to antibiotics.
What about this new drug?
Previous studies have shown that PT + rifampin has synergistic, broad-spectrum activity against both laboratory and clinical strains of S. aureus and P. aeruginosa in mouse models.
Past studies by the research team have also evaluated the efficacy of PT + rifampin in 154 and 163 ocular isolates of P. aeruginosa and S. aureus, respectively, from North America and Europe.
They found that it eliminated 100% of organisms, with >90% of the tested isolates showing synergistic/additive effects.
Now talk about the study.
Researchers evaluated the antibiotic resistance of a total of 43 isolates (i.e., samples of bacteria isolated to be studied) using their minimum inhibitory concentration (MIC).
Note: MIC is defined as the lowest concentration of an antibacterial agent under controlled in vitro conditions that can completely prevent the visible growth of a test strain of an organism.
The isolates included:
- 20 S. aureus samples
- 19 P. aeruginosa samples
- 3 P. stutzeri samples
- 1 Acinetobacter baumannii samples
Talk about the antibiotic resistance of the isolate samples.
The research team found that of the S. aureus isolates:
- 100% (20) were resistant to at least one antibiotic class
- 60% (12) were MDR
- 70% (14) were classified as methicillin-resistant
Over 90% of the gram-negative isolates—which are bacteria with an outer membrane that generally make them more resistant to antibiotics—were classified as MDR.
How was the efficacy of the drug measured?
Investigators performed fractional inhibitory concentration index (FICI) testing to measure the antimicrobial impact of the combination of PT + rifampin.
Back up, what is FICI testing?
The fractional inhibitory concentration (FIC) for a drug is found by dividing each drug’s MIC when used in combination by each drug’s MIC when used alone.
As such, the FICI is the sum of the FIC of each drug tested when used in combination, and helps to categorize the interaction and efficacy between drugs being tested.
Findings?
FIC testing revealed that PT + rifampin was effective in completely inhibiting the growth of all isolates, while also displaying additive or synergistic activity in 70% of the strains.
Further, there was a >2-fold reduction in MIC for both PT + rifampin when tested in combination vs. alone, showing the efficacy of the triple-antibiotic combination drug.
Take home.
These findings indicate that PT + rifampin is a promising novel drug to treat bacterial keratitis while also eliminating all tested isolates—even those marked as MDR.
As this drug combination provided wide coverage against virulent and major bacterial keratitis strains, it could potentially become a standard treatment against MDR bacterial keratitis.
Next steps?
Including more isolates and involving a wider range of bacterial keratitis species may further elucidate PT + rifampin’s antibacterial coverage.