Health Science Reviews

By Ludwick Hlongwane

The COVID-19 pandemic didn’t just overwhelm ICUs with viral infections; it also opened the floodgates for dangerous secondary bacterial infections. Among the most feared of these is Carbapenem-Resistant Acinetobacter baumannii (CRAB), a multidrug-resistant bacterium that thrives in hospital settings and laughs in the face of our strongest antibiotics.
But what if I told you scientists fought back, not with more antibiotics, but with viruses that kill bacteria? This isn’t science fiction. It’s the real-life story reported in a compelling case series by Wu et al., where phage therapy was successfully used to treat four critically ill COVID-19 patients with A. baumannii infections.
What Was the Study All About?
This study asked three powerful questions:

1. Can personalized, pre-optimized phage therapy work in real-life ICU conditions for patients who don’t respond to antibiotics?
2. Can NEPT Next Evolution Phage Typing predict and prevent resistance to the phages themselves?
3. Is phage therapy safe and effective enough to use in complex, high-risk patients like those in critical care?
   The aim was clear: to assess the feasibility, safety, and effectiveness of using tailor-made bacteriophages to treat CRAB infections in COVID-19 patients who had exhausted all other treatment options.
   Study Design
   This was a modified case series conducted in a COVID-19 ICU in Shanghai, adapted for emergency use during the pandemic. Patients with CRAB infections unresponsive to antibiotics received phage therapy alongside standard care. Outcomes measured included bacterial clearance, ICU discharge, or death.

Methodological Approach

Can Phage Therapy Work in Critical ICU Settings?
Four critically ill male COVID-19 patients (ages 62–81) with drug-resistant CRAB infections were enrolled at a Shanghai ICU after failing standard antibiotic treatment. This real-world emergency setting provided a high-pressure test for personalized phage therapy.

Was It Ethically Sound?
Yes. This emergency-use protocol received approval from the Shanghai Public Health Clinical Centre. Informed consent was obtained from patients or legal surrogates, ensuring adherence to ethical standards under pandemic constraints.

How Were the Right Phages Selected?
Bacterial samples from infection sites (lungs, wounds, blood) were screened against 124 phages. One phage, ɸAb124, showed strong killing power but resistance developed quickly. To stay ahead, researchers turned to NEPT.

Can Resistance Be Predicted Before It Happens?
Using Next Evolution Phage Typing (NEPT), the team simulated future resistance in the lab. This led to the early inclusion of ɸAb121, forming a customized 2-phage cocktail (2ɸ) tailored to each patient’s evolving bacterial profile.

How Was It Delivered, and Was It Safe?
Phages were administered via nebulization for lung infections and topically for wounds. Doses were personalized, and patients were closely monitored. All tolerated treatment well, though one patient experienced a temporary immune flare-up highlighting the need for cytokine tracking.

Interpretation: Did It Work?
Yes and no. All patients showed bacterial load reduction. The dual-phage cocktail especially proved superior, delaying resistance better than a single phage. However, resistance still cropped up in 4 of 6 treatments. Three patients survived: one succumbed to an unrelated infection. A transient cytokine spike in one patient also signalled the immune system’s unpredictable response, a challenge worth noting.

Figure 1: summarizes the clinical profiles and outcomes of four ICU patients treated with phage therapy. Most received a dual-phage cocktail, which reduced CRAB load, though resistance still emerged in some. Three patients recovered; one died during treatment.

What were the Challenges and limitations?
The small sample size (n=4) and lack of a control group limit how far we can generalize these findings. The emergency setting made standardization difficult. One patient experienced a transient spike in IL-6 and IL-8 cytokines after phage inhalation an immune reaction that warrants careful monitoring in future trials. There were also technical challenges in delivering phages consistently to deep lung tissue and infected wounds. And despite using NEPT, resistance still found a way to emerge quickly in some treatments.

My Takeaway
This wasn’t a flawless victory, but it was a scientific breakthrough. The study convincingly shows that personalized phage therapy is feasible and clinically beneficial, especially when guided by predictive tools like NEPT. The integration of real-time phage matching, adaptive dosing, and close clinical monitoring demonstrates how precision medicine can be applied in even the most critical settings. More importantly, this work proves that we no longer have to face antibiotic resistance unarmed. Phages once forgotten are re-emerging as highly targeted, evolving allies. But their success depends on how well we understand resistance mechanisms, immune responses, and patient-specific variables.

Where Do We Go from Here?
To fully unlock the potential of phage therapy, the path forward is clear:
• Larger, controlled clinical trials are essential to validate efficacy and safety.
• Expanding phage libraries and refining NEPT databases will allow for faster, smarter matching.
• Rapid diagnostic and phage-typing tools are needed for real-time bedside application.
• Immune response dynamics must be better understood to avoid adverse reactions.
• Lastly, delivery strategies especially for deep-lung infections must be optimized.

References

Wu, N., Dai, J., Guo, M., Li, J., Zhou, X., Li, F., Gao, Y., Que, H., Lu, H., Jing, J., Li, T., Shi, L. and Zhang, Q., 2021. Pre-optimized phage therapy on secondary Acinetobacter baumannii infection in four critical COVID-19 patients. Temi, 10, pp.1902754. https://doi.org/10.1080/22221751.2021.1902754