Innovative Strategies in Antibiotic Resistance: Expanding the Role of Photodynamic Therapy

Antibiotic resistance is escalating worldwide, with multidrug-resistant Klebsiella pneumoniae presenting an urgent challenge that threatens to outpace current therapies — photodynamic therapy (PDT) emerges from preclinical studies as a novel adjunct to potentially restore antibiotic potency.

As options dwindle against resistant Gram-negative pathogens, integrating photodynamic therapy into antimicrobial regimens offers a path to potentiate bacterial cell death. A recent study demonstrates that combining antibiotics with PDT increases bacterial cell death in resistant isolates, underscoring its potential to shift the treatment paradigm.

Photodynamic therapy operates by activating photosensitizers such as methylene blue with specific wavelengths of light. Upon activation, these agents generate reactive oxygen species that compromise bacterial membranes, proteins and nucleic acids, amplifying the bactericidal effect of co-administered antibiotics.

Translating this mechanism into clinical practice, PDT has demonstrated efficacy against multidrug-resistant Klebsiella pneumoniae. In a 2024 study, researchers achieved a 3.2-log₁₀ reduction in viable bacterial counts (over 99.9% kill; p=0.002) when PDT was integrated with standard antibiotic regimens.

Advances in delivery systems—such as nanocarrier-based photosensitizers and combined photothermal–photodynamic platforms—have further elevated the antimicrobial impact, tackling biofilm-protected communities and limiting resistance development. A 2023 study outlines how dual modalities disrupt bacterial defenses more effectively than either approach alone.

Beyond direct cell kill, PDT disrupts established biofilms and interferes with quorum-sensing pathways that underlie antibiotic tolerance, a reversible state distinct from genetic resistance. Reactive oxygen species weaken biofilm architecture, rendering embedded bacteria more vulnerable to antibiotics.

Incorporating photodynamic therapy into infectious disease protocols offers a complementary approach to conventional antimicrobials. As access to suitable light sources and photosensitizers expands, clinicians can consider PDT for refractory infections, especially those involving device-associated biofilms or isolates with high-level resistance. Further investigation into patient-specific dosing, long-term outcomes and integration with existing stewardship frameworks — as outlined in the IDSA’s 2019 antimicrobial stewardship guidelines — will be essential to optimize this modality.

Key Takeaways:

• Photodynamic therapy (PDT) enhances antibiotic effectiveness against resistant bacteria, notably Klebsiella pneumoniae.
• Photosensitizers like methylene blue play a crucial role by producing reactive oxygen species that damage bacterial structures.
• Advancements in PDT include innovative combinations and delivery systems that address resistance issues.
• Integrating PDT with standard antimicrobial practices offers a promising route to combat the rise of antibiotic-resistant infections.