Environmental disinfection with photocatalyst as an adjunctive measure to control transmission of methicillin-resistant Staphylococcus aureus: a prospective cohort study in a high-incidence setting

Multidrug-resistant organisms (MDROs), including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp.(VRE), and multidrug-resistant Acinetobacter baumannii (MRAB), have increased in prevalence in many acute and long-term care facilities [1]. Controlling hospital-acquired infections (HAIs) associated with these organisms has become a major challenge [2, 3].

As patient-to-patient spread is a major route of MDRO transmission, hand hygiene and isolation are pivotal infection control measures [4]. However, compliance with these measures is low [5]. Hospital environments could be source of outbreaks of resistant organisms [6], and experts suggest indirect transmission via the environment to be as likely as direct person-to-person transmission [7]. Although The Society for Healthcare Epidemiology of America recommends environmental cleaning only with moderate strength [4], enhanced environmental cleaning can reduce MDRO transmission [7‐9].

Several technologies have proven antibacterial efficacy and these include hydrogen peroxide vapor [10‐14], ultraviolet (UV) light decontamination [15, 16], and copper- and silver-coated surfaces [17‐19]. However, their use is limited by high cost or high risk of recontamination.

Among currently recognized alternatives are photocatalytic antimicrobial coating. Photocatalysis mainly uses a semiconductor such as titanium dioxide (TiO₂) that can absorb UV wavelength < 400 nm and stimulate reactions on its surface producing highly reactive oxygen species (ROS), contributing to biocidal activity. Presently, further improvements such as composite TiO₂ have enabled activation under visible light, increasing availability in hospital settings [20]. Since this material is stable with respect to self-destruction and responsiveness to light, it is presumed to have durable antimicrobial activity [21]. Furthermore, TiO₂ has better safety data than pure copper- and silver-coated surfaces, especially when exposed in low doses, such as in environmental coating [22‐24].

Although many in vitro studies have presented positive results of photocatalytic antimicrobial action with titania, only little work in real life application has been reported. These works raise numerous issues about applying this material in hospital environment. Inappropriately incorporated binder, which acts as a glue to adhere TiO₂ to the surface, could prevent the action of photocatalyst [25]. Even if properly manufactured, slow action time of photocatalyst makes it act as a supplemental measure to the conventional decontamination procedures at best [26]. Furthermore, others argue that its effect is not significant on already thoroughly cleaned surfaces [27].

Recognizing the significance of these issues, we decided to use metal ion-doped nanoparticle TiO₂, which is firmly attached to the surface, as adjunctive measure of environmental decontamination. Additionally, we recognized high incidence rates of MRSA at this institute (3-year average incidence from 2014 to 2016 was 7.7/1000 patient-days). Taken together, we sought to evaluate the usefulness of a photocatalyst to reduce the risk of MRSA transmission, by comparing MRSA acquisition rate and nosocomial infection rate before and after photocatalyst coating.

Photocatalysts are investigative materials for its efficacy in controlling MDRO in hospital environments. Our study suggests that photocatalysts are effective in controlling MRSA acquisition. However, it has limited efficacy on MRAB. Proper evaluation of its effect on VRE was not possible due to paucity of newly acquired cases.

In Asia Pacific region, MRSA remains a threat, accounting for > 50% of S. aureus infections, and MRSA BSI was reported to be 14.4/10,000 patient-days in 2017 [30]. In such high-prevalence settings, there has been growing interest in the horizontal approach, such as chlorhexidine bathing, hand hygiene, and environmental cleaning instead of isolation. Among these, hand hygiene itself could be cost-effective way of prevention; however, it is often difficult to sustain, especially when monitoring staff is scarce and turnover rate of housekeeping staff is high. One of the reasons for high MRSA prevalence at this institute could be that hand hygiene was practiced at moderate to below average level. Only after temporary closure of wards had been instituted and full decontamination of the departments using photocatalyst was performed did the MRSA acquisition rate reduce.

Stiefel et al. suggested that healthcare workers’ hands were equally contaminated from contact with commonly touched environmental surfaces as from direct contact with colonized patients [31]. Moreover, MRSA can exist on surfaces for as long as 360 days [32, 33], increasing its probability to be transmitted. Our result is promising in that photocatalyst enhanced the effect in combination with regular infection control practices that resulted in lower MRSA acquisition. This result is consistent with previous in vitro evidence, which was conducted in aqueous solution demonstrating positive antimicrobial effect of iron-doped TiO₂ on S. aureus [34].

It is meaningful to note that MRSA acquisition rate remained low throughout intervention period. Although pure TiO₂ is considered indefinitely active, very few real-time studies concerning durability of TiO₂ coating have been reported. Instead, laboratory-stimulated endurance test is performed as a substitute for real-time study [35]. The TiO₂ coating we used was checked for its durability with weather-O-meter test (Testing system for weathering performances CI5000, ATLAS). Nevertheless, existing real-time studies of composite TiO₂ coating provide positive results in terms of durability. Silver-doped TiO₂ produced in Japan under the name of MVX reported to remain active after 2 years of lab test, according to data provided by the manufacturer [27]. Furthermore, decontamination with zinc containing TiO₂ in a long-term care facility reduced HAIs even after 17 months [36]. Their result was consistent with our result on MRSA. The effect was greater among patients who stayed longer than 7 days in ICU. It is possible that 72% reduction of MRSA acquisition was attributed to this durable antimicrobial activity of photocatalyst. Notwithstanding other environmental cleaning methods such as hydrogen peroxide, ultraviolet light, and copper-coated surfaces that proved effective in controlling MRSA [15, 37, 38], photocatalysts still have the advantage of easy application and durability. However, there is concern that the effect is less prominent in stringently cleaned settings. A study from the Netherlands conducted in an ICU, where strict cleaning is a priority, found no microbiological benefit of photocatalyst [27]. However, that study was conducted over a short period and further study is needed to verify its efficacy in low-incidence settings.

We found no beneficial effect of photocatalyst on MRAB. The photocatalysts we used lacked well-established data of its antibiotic efficacy on MRAB. Although visible light-activated composite TiO₂ is generally expected to have enhanced antimicrobial activity compared to pure TiO₂, only a limited number of organisms had been tested in laboratory settings. Most of the studies used E.coli as representative of gram-negative organism, and S.auerus as representative of gram-positive organism [39]. It is not reliable to conclude that these materials are capable of inactivating various kinds of microorganism beyond the scope of organisms tested in laboratory settings. MRAB has different structural properties in terms of outer membrane and number of porins, compared to E.coli [40]. Since affinity of ROS to outer membrane determines its antibacterial property, different organisms can have different sensitivity to photocatalyst [41]. Although we did not conduct active surveillance and only counted incidental isolates of MRAB, this questionable characteristic can partly explain why MRAB incidence did not decrease. Notwithstanding, we admit that the number of cultured MRAB was small. Further study using larger number of patients for longer period of time is warranted.

We did not observe any trend on clinical endpoints of VRE due to low rate of these endpoints. Our study was underpowered to detect clinically significant differences in these endpoints because average length of ICU stay of our study population was relatively short.

Reduced incidence of hospital-acquired pneumonia was noted, while BSI and UTI were not significantly reduced. Slightly higher percentage of cases of pneumonia was caused by MRSA than by other infections. Only two cases of BSI were caused by MRSA, while 5/29 cases of culture-proven pneumonia were thought to be related to MRSA. We cautiously concluded that reduced MRSA acquisition partly explained decreased incidence of hospital-acquired pneumonia. Additionally, considering more than 50% of isolated organisms were gram-negative bacteria, undetected benefits of photocatalyst may have led to positive result. However, this hypothesis is not robust due to the lack of data supporting it, and study period was relatively short for reduced colonization translated into reduced infection. Moreover, incidence of pneumonia could have been affected by various unquantifiable factors, such as skill level of medical personnel.

We acknowledge several limitations in our study. First, general deep cleaning which was conducted generally at the end of the year could act as confounding. We cannot exclude that previous deep cleaning reduce MRSA acquisition, and photocatalyst coating may serve as a mean to maintain low level of environmental contamination. Second, active surveillance was conducted only during ICU stay, underestimating incidence rate of MRSA from patients who were discharged ICU within 48 h. Third, incidence rate of organisms on which active surveillance had not been conducted could have been under- or overestimated. Finally, efforts to enhance hand hygiene and following effect of this strategy had not been performed. Further study comparing the efficacy of photocatalyst coating with that of enhanced hand hygiene is warranted.

In conclusion, this study is the first prospective cohort study to evaluate the efficacy of photocatalyst in a practical setting and to provide evidence that photocatalyst disinfection can be an adjunctive measure to control MRSA acquisition in high-incidence settings.