Use of Antimicrobial Photodynamic Therapy to Inactivate Multidrug-Resistant Klebsiella pneumoniae: Scoping Review

Abstract

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.

Keywords: PRISMA-ScR; multidrug resistance; synergism with antibiotics.

Figure 1

Scheme of the mechanism of action of photodynamic therapy. When the incident light interacts with the PS, it goes from the basal state S0 to an activated S1 or S2 in a singlet state (A). The excited e-spin can be reversed in the excited singlet and derived to an excited triplet state through an intersystem crossing process (B). In this state, the captured energy can be transferred to the nearby molecular oxygen accompanied by an e⁻ (Type I) or alone (Type II), generating OH⁻ or ¹O₂, respectively (C). The OH⁻ and ¹O₂ are reactive oxygen species (ROS) that produce photooxidative stress capable of destroying bacterial structures, causing unspecific death (D). A Gram-negative bacterial envelope’s representation, and interaction with a PS being irradiated by light is observed (E).

Figure 2

PRISMA flowchart showing the results of applying selection criteria to the bibliographic search.

Figure 3

Diversity of PSs against K. pneumoniae aPDT. Pie distribution graphic of the diversity of compounds used as PSs in aPDT found against K. pneumoniae. The most common are Methylene Blue (MB) based (used alone or in combination with other compounds), with 44% of articles using it, followed by cationic-based PSs with 20%. Other PSs include derivatives of PSs and PSs fused to peptides or other compounds.