Special phage therapy saved the patient from resistant infection

(ORDO NEWS) — After 700 days of antibiotic treatment, the infection in the 30-year-old victim of the attack was still raging.

Tragically, the patient suffered life-threatening injuries during the attacks at Brussels airport on March 22, 2016. Over the next three years, she faced numerous medical complications as her fracture wound became infected with drug-resistant bacteria, or, as we colloquially call them, superbugs.

Faced with little progress, doctors decided to resort to a combination of antibiotics and specialized bacteriophage therapy, a new treatment that uses specialized viruses to infect and kill bacteria. Her unique and successful case was described in the journal Nature Communications.

Superbug infections are a growing public health problem, and phage therapy is one of the most promising new tools in our arsenal.

Typically, phages infect a subset of bacterial strains belonging to a single bacterial species, however, clinicians are working on personalized forms of phage therapy where phages from a prepared bank are selected by analyzing bacterial strains isolated from a patient’s bacterial infection.

Given sufficient time and resources, clinicians may select “preadapted” phage mutants that have an increased ability to infect a particular bacterial species in a patient or may have a reduced ability to induce bacterial resistance. The last decade has seen a surge in research into this type of phage therapy.

Clinicians who have studied this patient’s case explain that most phage preparations developed in Western countries are generalized “cocktails” that do not take into account the evolutionary struggle between bacteria and phages that often makes them so specific to each other.

“In recent randomized controlled trials, these static phage cocktails have shown disappointing results, which contrast with the growing number of case studies using phages as adjuvant therapy or pre-adapted (or even engineered) phages that are more effective against infecting bacteria,” adds authors.

In this particular case, the patient’s drug-resistant infection was caused by resistant Klebsiella pneumoniae, a particularly nasty superbug that forms resistant biofilms that allow it to recover from multiple antibiotic treatments.

“Biofilms are structures created by bacterial communities attached to the surface of implants or avascular tissue fragments. Within biofilms, persistent cells form a subpopulation of metabolically dormant cells that play an important role in the ability of biofilms to survive and recover from antibiotic treatment,” the authors explain.

Currently, there is still a lack of data on the overall effectiveness of phage therapy for the treatment of resistant bacterial infections, as well as on the possibility of any side effects that may occur in patients.

Because of this, doctors took the precaution of applying the phages locally to the infected areas rather than intravenously. In addition, a short course of treatment with phages – only six days – was chosen to minimize the likelihood of a negative reaction of the patient’s immune system.

However, three months after treatment with phages, the patient’s condition improved dramatically, and the bacterial infection was finally defeated.

The authors believe that the combination of individualized phage treatment followed by the use of a longer course of antibiotics formed a kind of “one-two punch” when the phages were able to destroy the protective biofilms, leaving antibiotics a clear path to the final destruction of the bacterial infection.

“In vitro data indicate that the combination of phages and antibiotics was more effective in reducing the number of K. pneumoniae bacteria in mature biofilms than antibiotics or phages alone.”

Fortunately, no adverse effects associated with the use of phages were observed in the patient. Three months after the start of phage antibiotic therapy, the woman’s condition improved dramatically in all respects, and her wound finally healed properly.

Finally, 798 days after the injury, doctors were able to stop antibiotic treatment; thereafter, there was no sign of recurrence of the infection, and the patient was able to slowly regain her mobility.

“This study may open a new perspective on phage therapy: the use of individually tailored combinations of phages and antibiotics,” the authors write.


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