Effective Photodynamic Therapy with Ir(III) for Virulent Clinical Isolates of Extended-Spectrum Beta-Lactamase Klebsiella pneumoniae

The extended-spectrum beta-lactamase (ESBL) is one of the leading causes of health-associated infections (HAIs), whose antibiotic treatments have been severely reduced. Moreover, HAI bacteria may harbor pathogenic factors such as siderophores, enzymes, or capsules, which increase the virulence of th...

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Published in:Pharmaceutics 2021-04, Vol.13 (5), p.603
Main Authors: Núñez, Constanza, Palavecino, Annegrett, González, Iván A, Dreyse, Paulina, Palavecino, Christian Erick
Format: Article
Language:English
Subjects:
antibiotic resistance
Antibiotics
Antimicrobial agents
Bacteria
Drug resistance
Genes
Infections
Klebsiella pneumoniae
Laboratories
Phenols
photodynamic therapy
Urogenital system
Virulence
virulence factors
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Summary:The extended-spectrum beta-lactamase (ESBL) is one of the leading causes of health-associated infections (HAIs), whose antibiotic treatments have been severely reduced. Moreover, HAI bacteria may harbor pathogenic factors such as siderophores, enzymes, or capsules, which increase the virulence of these strains. Thus, new therapies, such as antimicrobial photodynamic inactivation (aPDI), are needed. A collection of 118 clinical isolates of was characterized by susceptibility and virulence through the determination of the minimum inhibitory concentration (MIC) of amikacin (Amk), cefotaxime (Cfx), ceftazidime (Cfz), imipenem (Imp), meropenem (Mer), and piperacillin-tazobactam (Pip-Taz); and, by PCR, the frequency of the virulence genes K2, magA, rmpA, entB, ybtS, and allS. Susceptibility to innate immunity, such as human serum, macrophages, and polymorphonuclear cells, was tested. All the strains were tested for sensitivity to the photosensitizer PSIR-3 (4 µg/mL) in a 17 µW/cm for 30 min aPDI. A significantly higher frequency of virulence genes in ESBL than non-ESBL bacteria was observed. The isolates of the genotype K2+, ybtS+, and allS+ display enhanced virulence, since they showed higher resistance to human serum, as well as to phagocytosis. All strains are susceptible to the aPDI with PSIR-3 decreasing viability in 3log10. The combined treatment with Cfx improved the aPDI to 6log10 for the ESBL strains. The combined treatment is synergistic, as it showed a fractional inhibitory concentration (FIC) index value of 0.15. The aPDI effectively inhibits clinical isolates of , including the riskier strains of ESBL-producing bacteria and the K2+, ybtS+, and allS+ genotype. The aPDI with PSIR-3 is synergistic with Cfx.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics13050603