Klebsiella pneumoniae is a Gram-negative bacillus responsible for a wide variety of potentially fatal infections and, in turn, constitutes a critical agent of healthcare-associated infections. Moreover, K. pneumoniae is characterized by multi-drug-resistant (MDR) bacteria, such as extended-spectrum beta-lactamases (ESBL) and carbapenemase (KPC) producer strains, representing a significant health problem. Because resistances make it difficult to eradicate using antibiotics, antimicrobial photodynamic therapy (aPDT) promises to be a favorable approach to complementing conventional therapy against MDR bacteria. This study aims to provide relevant bibliographic information on the state of the art of application of aPDT against K. pneumoniae and MDR K. pneumoniae. Our methodology follows a protocol using the PRISMA extension for scoping reviews (PRISMA-ScR) guidelines, and the search consults the PubMed (MESH), Google Scholar, and Scopus databases from January 2012 to September 2024. The eligibility criteria were (1) original articles after 2012 referring to antimicrobial photodynamic activity in K. pneumoniae in vitro and in vivo: clinical applications and synergism with antibiotics, other antimicrobial drugs, or PS coupled to other particles, (2) articles in English, and (3) articles peer-reviewed. Results. Following two independent searches in databases, 298 records were found. After applying eligibility criteria and various filters, such as removing duplicates, 25 studies were included in this review. The evidence demonstrates the effectiveness of aPDT in vitro in eradicating sensitive or MDR-K. pneumoniae strains, including strains producing biofilms, ESBL, and KPC. Finally, it is concluded that aPDT is a recommended antimicrobial therapy, but more research in vivo is needed to support studies in humans.

One of the most urgent threats to public health worldwide is the ongoing rise of multidrug-resistant (MDR) bacterial strains. Among the most critical pathogens are MDR-Klebsiella pneumoniae strains. The lack of new antibiotics has led to an increased need for non-antibiotic antimicrobial therapies. Photodynamic therapy (PDT) has become increasingly significant in treating MDR bacteria. PDT uses photosensitizer compounds (PS) that generate reactive oxygen species (ROS) when activated by light. These ROS produce localized oxidative stress, damaging the bacterial envelope. A downside of PDT is the limited bioavailability of PSs in vivo, which can be enhanced by conjugating them with carriers like nanoparticles (NPs). Zinc nanoparticles possess antibacterial properties, decreasing the adherence and viability of microorganisms on surfaces. The additive or synergistic effect of the combined NP-PS could improve phototherapeutic action. Therefore, this study evaluated the effectiveness of the copper(I)-based PS CuC1 compound in combination with Zinc Oxide NP, ZnONP, to inhibit the growth of both MDR and sensitive K. pneumoniae strains. The reduction in bacterial viability after exposure to a PS/NP mixture activated by 61.2 J/cm² of blue light photodynamic treatment was assessed. The optimal PS/NP ratio was determined at 2 µg/mL of CuC1 combined with 64 µg/mL of ZnONP as the minimum effective concentration (MEC). The bacterial gene response aligned with a mechanism of photooxidative stress induced by the treatment, which damages the bacterial cell envelope. Additionally, we found that the PS/NP mixture is not harmful to mammalian cells, such as Hep-G2 and HEK-293. In conclusion, the CuC1/ZnONP combination could effectively aid in enhancing the antimicrobial treatment of infections caused by MDR bacteria.

Background/Objectives: Multidrug-resistant (MDR) Enterobacter spp. are critical pathogens within the ESKAPE group, frequently exhibiting resistance to carbapenems. Antimicrobial photodynamic therapy (aPDT) represents a promising non-antibiotic strategy to circumvent these resistance mechanisms. This scoping review aims to map the current evidence regarding the efficacy of aPDT in inactivating Enterobacter spp., identifying the most effective photosensitizers (PS), light parameters, and existing research gaps. Methods: A systematic search was performed across PubMed, Scopus, and Google Scholar (2013–2025) following PRISMA-ScR guidelines and registered on OSF. Studies were included if they evaluated aPDT against Enterobacter spp. (in vitro or in vivo) and provided quantitative data on microbial reduction. Data was extracted using a standardized charting form covering bacterial strains, PS type, light source, and viability reduction. The results from the eligible sources of evidence were synthesized narratively to address the review objectives. Results: Despite the clinical priority of Enterobacter, only seven studies met the eligibility criteria. Methylene Blue remains the most frequently studied PS, achieving reductions of 3–8 log₁₀. Emerging evidence highlights the synergistic efficacy of monocationic chlorins and graphene-based nanomaterials in enhancing the bactericidal effect of light-based treatments. Notably, aPDT demonstrated the ability to inactivate carbapenemases, the bacterial enzymes responsible for carbapenem resistance. However, only two studies evaluated in vivo applications, primarily within dental settings. Conclusions: aPDT is a promising method against MDR Enterobacter spp. and bypasses traditional resistance mechanisms. However, the limited number of studies indicates a significant knowledge gap. Future research should focus on standardized in vivo protocols and the synergy between aPDT and conventional antibiotics to support clinical translation.