Abstract
Enterococcus faecium and Enterococcus faecalis are opportunistic pathogens that can cause a vast variety of nosocomial infections. Moreover, E. faecium belongs to the group of ESKAPE microbes, which are the main cause of hospital-acquired infections and are especially difficult to treat because of their resistance to many antibiotics. Antimicrobial photodynamic inactivation (aPDI) represents an alternative to overcome multidrug resistance problems. This process requires the simultaneous presence of oxygen, visible light, and photosensitizing compounds. In this work, aPDI was used to resensitize Enterococcus spp. isolates to antibiotics. Antibiotic susceptibility testing according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations was combined with synergy testing methods recommended by the American Society for Microbiology. Two clinical isolates, E. faecalis and E. faecium, were treated with a combination of aPDI utilizing rose bengal (RB) or fullerene (FL) derivative as photosensitizers, antimicrobial blue light (aBL), and 10 recommended antibiotics. aPDI appeared to significantly impact the survival rate of both isolates, while aBL had no significant effect. The synergy testing results differed between strains and utilized methods. Synergy was observed for RB aPDI in combination with gentamycin, ciprofloxacin and daptomycin against E. faecalis. For E. faecium, synergy was observed between RB aPDI and gentamycin or ciprofloxacin, while for RB aPDI with vancomycin or daptomycin, antagonism was observed. A combination of FL aPDI gives a synergistic effect against E. faecalis only with imipenem. Postantibiotic effect tests for E. faecium demonstrated that this isolate exposed to aPDI in combination with gentamycin, streptomycin, tigecycline, doxycycline, or daptomycin exhibits delayed growth in comparison to untreated bacteria. The results of synergy testing confirmed the effectiveness of aPDI in resensitization of the bacteria to antibiotics, which presents great potential in the treatment of infections caused by multidrug-resistant strains.
Highlights
1980, and to date, this resistance has spread massively among E. faecium isolates. This urgent problem of resistance is associated with an increasing number of nosocomial infections linked with VAN-resistant E. faecium. These reasons explain why this organism belongs to the group of ESKAPE microbes, which are the main cause of hospital-acquired infections and are especially difficult to treat because of their resistance to many antibiotics [3]
When Antimicrobial photodynamic inactivation (aPDI) (RB) was applied, the most severe damage to the cell membrane was observed under this condition (Figure 7); we are convinced that the increased permeabilization may be the most important reason for the observed synergistic effect between antimicrobials and aPDI as it may result in increased antibiotic uptake
It is worth mentioning here that E. faecalis is commonly detected in persistent infections after failed endodontic treatments, and E. faecium is mainly associated with infections caused by the use of indwelling medical devices, e.g., central venous and urinary catheters [15,16]
Summary
1980, and to date, this resistance has spread massively among E. faecium isolates This urgent problem of resistance is associated with an increasing number of nosocomial infections linked with VAN-resistant E. faecium. These reasons explain why this organism belongs to the group of ESKAPE microbes, which are the main cause of hospital-acquired infections and are especially difficult to treat because of their resistance to many antibiotics [3]. Absorption of photons by photosensitizing agents leads to the formation of excited states of such compounds, which through further photochemical reactions lead to the production of highly toxic reactive oxygen species (ROS) or singlet oxygen [9,10].
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