Considering increasing number of pathogens resistant towards commonly used antibiotics as well as antiseptics, there is a pressing need for antimicrobial approaches that are capable of inactivating pathogens efficiently without the risk of inducing resistances. In this regard, an alternative approach is the antimicrobial photodynamic therapy (aPDT). The antimicrobial effect of aPDT is based on the principle that visible light activates a per se non-toxic molecule, the so-called photosensitizer (PS), resulting in generation of reactive oxygen species that kill bacteria unselectively via an oxidative burst. During the last 10-20 years, there has been extensive in vitro research on novel PS as well as light sources, which is now to be translated into clinics. In this review, we aim to provide an overview about the history of aPDT, its fundamental photochemical and photophysical mechanisms as well as photosensitizers and light sources that are currently applied for aPDT in vitro. Furthermore, the potential of resistances towards aPDT is extensively discussed and implications for proper comparison of in vitro studies regarding aPDT as well as for potential application fields in clinical practice are given. Overall, this review shall provide an outlook on future research directions needed for successful translation of promising in vitro results in aPDT towards clinical practice.

The threat of antibiotic resistance has attracted strong interest during the last two decades, thus stimulating stewardship programs and research on alternative antimicrobial therapies. Conversely, much less attention has been given to the directly related problem of resistance toward antiseptics and biocides. While bacterial resistances toward triclosan or quaternary ammonium compounds have been considered in this context, the bis-biguanide chlorhexidine (CHX) has been put into focus only very recently when its use was associated with emergence of stable resistance to the last-resort antibiotic colistin. The antimicrobial effect of CHX is based on damaging the bacterial cytoplasmic membrane and subsequent leakage of cytoplasmic material. Consequently, mechanisms conferring resistance toward CHX include multidrug efflux pumps and cell membrane changes. For instance, in staphylococci it has been shown that plasmid-borne qac (“quaternary ammonium compound”) genes encode Qac efflux proteins that recognize cationic antiseptics as substrates. In Pseudomonas stutzeri , changes in the outer membrane protein and lipopolysaccharide profiles have been implicated in CHX resistance. However, little is known about the risk of resistance toward CHX in oral bacteria and potential mechanisms conferring this resistance or even cross-resistances toward antibiotics. Interestingly, there is also little awareness about the risk of CHX resistance in the dental community even though CHX has been widely used in dental practice as the gold-standard antiseptic for more than 40 years and is also included in a wide range of oral care consumer products. This review provides an overview of general resistance mechanisms toward CHX and the evidence for CHX resistance in oral bacteria. Furthermore, this work aims to raise awareness among the dental community about the risk of resistance toward CHX and accompanying cross-resistance to antibiotics. We propose new research directions related to the effects of CHX on bacteria in oral biofilms.

With increasing numbers of antibiotic-resistant pathogens all over the world there is a pressing need for strategies that are capable of inactivating biofilm-state pathogens with less potential of developing resistances in pathogens. Antimicrobial strategies of that kind are especially needed in dentistry in order to avoid the usage of antibiotics for treatment of periodontal, endodontic or mucosal topical infections caused by bacterial or yeast biofilms. One possible option could be the antimicrobial photodynamic therapy (aPDT), whereby the lethal effect of aPDT is based on the principle that visible light activates a photosensitizer (PS), leading to the formation of reactive oxygen species, e.g., singlet oxygen, which induce phototoxicity immediately during illumination. Many compounds have been described as potential PS for aPDT against bacterial and yeast biofilms so far, but conflicting results have been reported. Therefore, the aim of the present review is to outline the actual state of the art regarding the potential of aPDT for inactivation of biofilms formed in vitro with a main focus on those formed by oral key pathogens and structured regarding the distinct types of PS.

Objectives SARS-CoV-2 is mainly transmitted by inhalation of droplets and aerosols. This puts healthcare professionals from specialties with close patient contact at high risk of nosocomial infections with SARS-CoV-2. In this context, preprocedural mouthrinses with hydrogen peroxide have been recommended before conducting intraoral procedures. Therefore, the aim of this study was to investigate the effects of a 1% hydrogen peroxide mouthrinse on reducing the intraoral SARS-CoV-2 load. Methods Twelve out of 98 initially screened hospitalized SARS-CoV-2-positive patients were included in this study. Intraoral viral load was determined by RT-PCR at baseline, whereupon patients had to gargle mouth and throat with 20 mL of 1% hydrogen peroxide for 30 s. After 30 min, a second examination of intraoral viral load was performed by RT-PCR. Furthermore, virus culture was performed for specimens exhibiting viral load of at least 103 RNA copies/mL at baseline. Results Ten out of the 12 initially included SARS-CoV-2-positive patients completed the study. The hydrogen peroxide mouthrinse led to no significant reduction of intraoral viral load. Replicating virus could only be determined from one baseline specimen. Conclusion A 1% hydrogen peroxide mouthrinse does not reduce the intraoral viral load in SARS-CoV-2-positive subjects. However, virus culture did not yield any indication on the effects of the mouthrinse on the infectivity of the detected RNA copies. Clinical relevance The recommendation of a preprocedural mouthrinse with hydrogen peroxide before intraoral procedures is questionable and thus should not be supported any longer, but strict infection prevention regimens are of paramount importance. Trial registration German Clinical Trials Register (ref. DRKS00022484)

Prevention and control of biofilm-growing microorganisms are serious problems in public health due to increasing resistances of some pathogens against antimicrobial drugs and the potential of these microorganisms to cause severe infections in patients. Therefore, alternative approaches that are capable of killing pathogens are needed to supplement standard treatment modalities. One alternative is the photodynamic inactivation of bacteria (PIB). The lethal effect of PIB is based on the principle that visible light activates a photosensitizer, leading to the formation of reactive oxygen species, e.g., singlet oxygen, which induces phototoxicity immediately during illumination. SAPYR is a new generation of photosensitizers. Based on a 7-perinaphthenone structure, it shows a singlet oxygen quantum yield ΦΔ of 99% and is water soluble and photostable. Moreover, it contains a positive charge for good adherence to cell walls of pathogens. In this study, the PIB properties of SAPYR were investigated against monospecies and polyspecies biofilms formed in vitro by oral key pathogens. SAPYR showed a dual mechanism of action against biofilms: (I) it disrupts the structure of the biofilm even without illumination; (II) when irradiated, it inactivates bacteria in a polymicrobial biofilm after one single treatment with an efficacy of ≥ 99.99%. These results encourage further investigation on the potential of PIB using SAPYR for the treatment of localized infectious diseases.

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Antimicrobial resistance is a serious issue for public health care all over the world. While resistance toward antibiotics has attracted strong interest among researchers and the general public over the last 2 decades, the directly related problem of resistance toward antiseptics and biocides has been somewhat left untended. In the field of dentistry, antiseptics are routinely used in professional care, but they are also included in lots of oral care products such as mouthwashes or dentifrices, which are easily available for consumers over-the-counter. Despite this fact, there is little awareness among the dental community about potential risks of the widespread, unreflected, and potentially even needless use of antiseptics in oral care. Cetylpyridinium chloride (CPC), a quaternary ammonium compound, which was first described in 1939, is one of the most commonly used antiseptics in oral care products and included in a wide range of over-the-counter products such as mouthwashes and dentifrices. The aim of the present review is to summarize the current literature on CPC, particularly focusing on its mechanism of action, its antimicrobial efficacy toward biofilms, and on potential risks of resistance toward this antiseptic as well as underlying mechanisms. Furthermore, this work aims to raise awareness among the dental community about the risk of resistance toward antiseptics in general.

Increasing antibiotic resistances in microorganisms create serious problems in public health. This demands alternative approaches for killing pathogens to supplement standard treatment methods. Photodynamic inactivation of bacteria (PIB) uses light activated photosensitizers (PS) to generate reactive oxygen species immediately upon illumination, inducing lethal phototoxicity. Positively charged phenalen-1-one derivatives are a new generation of PS for light-mediated killing of pathogens with outstanding singlet oxygen quantum yield ΦΔ of >97%. Upon irradiation with a standard photopolymerizer light (bluephase C8, 1260 ± 50 mW/cm(2)) the PS showed high activity against the oral key pathogens Enterococcus faecalis, Actinomyces naeslundii, Streptococcus mutans, and Aggregatibacter actinomycetemcomitans. At a concentration of 10 μM, a maximum efficacy of more than 6 log10 steps (≥ 99.9999%) of bacteria killing is reached in less than 1 min (light dose 50 J/cm(2)) after one single treatment. The pyridinium substituent as positively charged moiety is especially advantageous for antimicrobial action.