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Prophylactic Post-Lung Transplant Bacteriophage Therapy against XDR Pseudomonas aeruginosa in Cystic Fibrosis: a case report

This case report describes the first use of personalized prophylactic bacteriophage therapy to successfully suppress extensively drug-resistant Pseudomonas aeruginosa in a cystic fibrosis patient following lung retransplantation, although the patient ultimately died from unrelated multiorgan failure.

Original authors: Jules Milesi, Sophie Alexandra Baron, Carole Eldin, Fanny Mathias, Florence Peyron, Katlyn Jumel, Alexandre Bleibtreu, Giovanni Bousquet, David Boulate, Xavier-Benoit D’journo, Sami Hraiech, Benjamin

Published 2026-07-06

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CC BY 4.0

Original authors: Jules Milesi, Sophie Alexandra Baron, Carole Eldin, Fanny Mathias, Florence Peyron, Katlyn Jumel, Alexandre Bleibtreu, Giovanni Bousquet, David Boulate, Xavier-Benoit D’journo, Sami Hraiech, Benjamin Coiffard

Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). ✨ This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer

The Big Picture: A High-Stakes Rescue Mission

Imagine a patient with Cystic Fibrosis (a disease that makes lungs very sticky and prone to infection) who has already had one lung transplant. Unfortunately, her new lungs are failing, and she needs a second transplant (retransplantation).

The problem? Her lungs are colonized by a "superbug" bacteria called Pseudomonas aeruginosa. This isn't just any bacteria; it is XDR (Extensively Drug-Resistant). Think of this bacteria as a fortress with impenetrable walls. Almost every antibiotic (the standard weapons doctors use) bounces right off it, leaving doctors with very few options to stop it from killing the patient during the surgery.

The New Weapon: Bacteriophage Therapy

The medical team decided to try a "last resort" strategy called Bacteriophage Therapy (BT).

The Analogy: If antibiotics are like a carpet bomb that tries to kill all bacteria (good and bad) but often misses the super-resistant ones, bacteriophages are like sniper drones.
What are they? Bacteriophages (or "phages") are tiny viruses that only hunt bacteria. They don't hurt humans. They latch onto a specific type of bacteria, inject their DNA, and turn the bacteria into a factory that explodes, killing the bacteria from the inside out.
The Plan: Since the patient's specific superbug was known, the team found four specific "sniper drones" (phages) that were known to hunt that exact strain. They mixed them into a "cocktail."

The Strategy: Prophylactic (Preventative) Attack

Usually, doctors wait until a patient gets sick before using these phages. But this team did something very rare: they used them prophylactically (as a shield before the infection could take hold).

The Setup: The patient underwent a massive double-lung transplant. The surgery was difficult, requiring a heart-lung machine (ECMO) and lots of blood transfusions.
The Attack: Immediately after the surgery, while the new lungs were still being checked, the team started the treatment.
- IV Drip: They pumped the phage cocktail directly into her bloodstream (like sending drones into the air).
- Direct Spray: They used a bronchoscope (a camera tube down the throat) to spray the phages directly into the new lungs (like dropping drones right onto the target).
The Duration: They did this for three weeks.

The Results: A Mixed Bag

The Good News (The Microbiology):
The treatment worked exactly as the "sniper drones" were designed to. Within one week, the new lungs were completely clear of the XDR superbug. The bacteria that had been living there for years vanished. The paper claims this is one of the first times this "preventative shield" strategy has been successfully used in a lung transplant to clear the lungs of a superbug.

The Bad News (The Outcome):
Even though the lungs were clean of the specific superbug, the patient did not survive.

Why? The patient was extremely frail from the surgery and the previous illness.
New Problems: She developed a different, unrelated infection in her abdomen (a different strain of the same bacteria that had mutated and was now resistant to the phages). She also developed severe fungal infections and pneumonia from other bacteria.
The Failure: Her body went into multiorgan failure (her heart, kidneys, and liver stopped working) due to these other complications, not the original lung superbug. She passed away 88 days after the transplant.

The Conclusion: What Did We Learn?

The paper concludes with two main points:

It Worked for the Target: The phage therapy successfully wiped out the specific superbug in the lungs. It proved that you can use these "sniper drones" to protect a new lung transplant from a known super-infection.
It's Not a Magic Cure-All: While the lungs were saved from the superbug, the patient was too weak to survive the other complications of such a massive surgery. The team notes that the bacteria found in her abdomen later was a different strain that the phages couldn't catch, proving that these viruses are very specific (they only hunt one type of target).

In short: The doctors successfully used a custom-made viral shield to clear a superbug from a new lung, but the patient ultimately succumbed to other severe complications unrelated to that specific bug. The paper suggests that while this method is promising and feasible, more studies are needed to see if it can save lives in the long run.

Technical Summary: Prophylactic Post-Lung Transplant Bacteriophage Therapy against XDR Pseudomonas aeruginosa in Cystic Fibrosis

Problem Statement
Lung transplant recipients (LTRs) with cystic fibrosis (CF) face high risks of peri-transplant morbidity and mortality due to colonization by multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens, particularly Pseudomonas aeruginosa (PA). While bacteriophage therapy (BT) has demonstrated efficacy in treating established MDR infections, its application as a prophylactic strategy in the immediate post-transplant period remains unreported. The clinical challenge involves preventing the recurrence of XDR PA colonization in a retransplanted lung, a scenario where conventional antimicrobials often fail due to resistance profiles.

Methodology
This case report details the management of a 46-year-old female CF patient undergoing retransplantation in 2024 for chronic lung allograft dysfunction. The patient was chronically colonized with an XDR PA strain (resistant to most beta-lactams, aminoglycosides, and fluoroquinolones, but susceptible to colistin) and Aspergillus spp.

Phage Selection: Pre-transplant PA isolates underwent Phage Susceptibility Testing (PST). The strain was found susceptible to four Good Manufacturing Practice (GMP)-grade phages: PP1450, PP1777, PP1792, and PP1797.
Therapeutic Protocol: Following institutional and regulatory approval, a personalized prophylactic BT cocktail was initiated immediately post-transplant. The regimen included:
- Intravenous (IV) Administration: 10 mL per dose (containing 1 mL of each of the four phages at $10^{10}$ PFU/mL, diluted in 0.9% NaCl) administered twice daily for 7 days.
- Endobronchial Instillation: 10 mL per main bronchus (same cocktail) administered via bronchoscopy on postoperative days 1, 3, 7, 14, and 21.
Concomitant Therapy: The patient received standard peri-transplant prophylaxis (ceftolozane/tazobactam, colistin, amoxicillin/clavulanic acid, liposomal amphotericin B) and immunosuppression.
Monitoring: Pulmonary surveillance was conducted via bronchoalveolar lavage (BAL) and multiplex PCR.

Key Results

Microbiological Efficacy: Despite an initial detection of $10^5$ copies of PA in BAL on postoperative day 1, all subsequent pulmonary cultures performed within one week were negative for PA. The bacterium remained undetected in pulmonary samples for the duration of the BT protocol (21 days) and beyond.
Genomic Analysis: Sequencing of PA strains revealed that the pre-transplant pulmonary strain (ST654) was genetically distinct from a later XDR PA strain isolated from blood and peritoneal fluid (ST5036) during a separate intra-abdominal infection. This confirmed that the pulmonary clearance was specific to the original colonizing strain and that the later extrapulmonary infection was not a recurrence of the lung strain.
Resistance Development: A new PST performed on the extrapulmonary strain showed resistance to all available anti-Pseudomonas phages. However, because this strain was genetically distinct from the original pulmonary isolate, the authors concluded that the prophylactic BT did not induce resistance in the original colonizing XDR PA.
Clinical Outcome: While the lungs achieved complete microbiological clearance of XDR PA, the patient developed invasive pulmonary aspergillosis, ventilator-associated pneumonia (VAP) with Enterococcus faecium and Corynebacterium tuberculostearicum, and subsequent multiorgan failure. The patient died 88 days post-transplant. The authors attribute the mortality to these unrelated complications rather than the failure of BT against PA.

Significance and Claims
The paper positions this report as one of the first documented cases of prophylactic bacteriophage therapy in lung transplantation. The primary significance lies in demonstrating the feasibility and microbiological efficacy of using a personalized phage cocktail to achieve complete pulmonary clearance of XDR PA in a high-risk retransplant setting.

The authors claim that the combination of BT and conventional antimicrobials likely facilitated the eradication of PA from the lungs within one week—a result they suggest would be unlikely with conventional antimicrobials alone given the resistance profile. They explicitly state that while the patient's death was determined by other complications, the observed microbiological success supports the potential of prophylactic BT to reduce infection-related morbidity in high-risk candidates. The paper concludes that prospective studies are necessary to define the optimal administration, safety, and impact on clinical outcomes, maintaining a modest stance that this single case cannot establish definitive efficacy but provides a proof-of-concept for further investigation.