Invited Commentary 

December 18, 2023

Daily Toothbrushing to Prevent Hospital-Acquired Pneumonia—Brushing Away the Risk

Rupak Datta

JAMA Intern Med. Published online December 18, 2023. doi:10.1001/jamainternmed.2023.6807

Often overlooked and understudied, oral care is critical to health, quality of life, and prevention of infection such as hospital-acquired pneumonia (HAP). HAP is classified into ventilator-associated pneumonia (VAP) and nonventilator HAP (NV-HAP), with both leading to poor outcomes.^1-3 HAP is largely due to aspiration of microflora from the oral microbiome, a complex and highly diverse ecosystem with an estimated 700 species of bacteria, fungi, viruses, and protozoa.⁴ Extensive data from epidemiological, microbiological, and molecular studies have established a link between the oral microbiome, oral health, dental plaques, and periodontal disease and the development of pneumonia. Accordingly, rigorous oral care is recommended to prevent HAP.⁵ However, the precise components of oral care remain unclear due in large part to conflicting studies with respect to oral chlorhexidine. Chlorhexidine gluconate is a cationic antiseptic with broad-spectrum activity against bacteria, fungi, and enveloped viruses that alters cell membrane permeability and prevents biofilm formation. Historically, chlorhexidine gluconate oral rinses were included in VAP prevention bundles based on a meta-analysis demonstrating a 30% to 40% decrease in VAP.⁶ However, a subsequent systematic review and meta-analysis of randomized clinical trials from general intensive care unit (ICU) settings found that chlorhexidine was associated with increased mortality (odds ratio, 1.25; 95% CI, 1.05-1.50).⁷ These conflicting studies left the field with a lack of clarity on strategies to prevent HAP.

In this issue of JAMA Internal Medicine, Ehrenzeller and Klompas attempt to address this knowledge gap and circumvent the controversy around chlorhexidine by focusing on a simple and seemingly innocuous strategy to prevent HAP: toothbrushing.⁸ In a well-designed systematic review and meta-analysis of randomized clinical trials of hospitalized adults, the authors sought to determine whether daily toothbrushing was associated with lower rates of HAP. Secondary outcomes included mortality, length of stay, duration of mechanical ventilation, and antibiotic use. All studies were screened independently by the authors to ensure that trials evaluated toothbrushing vs no toothbrushing and included at least 1 outcome of interest. No date or language restrictions were applied. However, inclusion of 2 trials with participants 16 years and older is debatable, given the stated focus on hospitalized adults and population distribution of HAP, which is skewed toward older adults. Both of these studies came from Asia, where the cutoff for pediatric vs adult populations differs from the US. Furthermore, subgroup analyses focused on ventilation status (ventilated vs nonventilated), toothbrushing personnel (dental professional vs nursing staff), toothbrushing frequency (twice vs ≥3 times daily), toothbrushing type (electronical vs mechanical), and potential for bias (low risk vs high risk). Examining the effect of this prevention strategy in high-risk populations would have been meaningful to inform practice.

Overall, 15 studies met inclusion criteria, with an effective sample size of 2786 patients.⁸ Fourteen studies were conducted in the ICU, 13 involved ventilated patients, and 11 applied chlorhexidine gluconate in both the toothbrushing and control arms. Techniques and frequency differed in each study, but generally, toothbrushing was performed with a soft toothbrush between 2 and 4 times daily. Unfortunately, only 7 studies were considered low risk of bias, and none were truly double blinded given the impossibility of concealing toothbrushing. Nevertheless, when examining studies that included data on HAP, including both NV-HAP and VAP, randomization to toothbrushing was associated with a statistically significant lower rate of HAP with a risk ratio (RR) of 0.67 (95% CI, 0.56-0.81) and low heterogeneity (I² = 0%). However, this effect appears to be driven by the influence of toothbrushing on VAP. On meta-analysis of the 2 studies with NV-HAP data (n = 813), no difference was observed (RR, 0.32; 95% CI, 0.05-2.02; I² = 0%). Among studies reporting data on secondary outcomes, outcomes were statistically significant. Toothbrushing was associated with lower ICU mortality (RR, 0.81; 95% CI, 0.69-0.95; I² = 0%), shorter time to extubation (mean difference, 1.24 days; 95% CI, −2.42 to −0.06 days), and shorter ICU length of stay (mean difference, −1.78 days; 95% CI, −2.85 to −0.70 days; I² = 0%). Each of these findings persisted when restricting to studies with low risk of bias. Toothbrushing had no association with recorded metrics of antibiotic use, and brushing 3 or more times daily was found to confer no additional benefit over brushing twice daily.

Collectively, this study represents an exciting contribution to infection prevention and reinforces the notion that routine toothbrushing is an essential component of standard of care in ventilated patients. However, there is still uncertainty regarding NV-HAP. The investigators could only identify 2 studies with nonventilated patients that met inclusion criteria.⁸ Among these, the effect estimate suggested toothbrushing could prevent NV-HAP, but the sample size was small and the confidence interval was large, underscoring the need for more data on NV-HAP. Several nuances, albeit minor, are also worth noting. First, there is minimal evidence from the US. Studies were primarily from Asia (n = 9), South America (n = 3), and Europe (n = 2), where hospital settings, nursing protocols, and adjunctive measures may vary. None of the studies among ventilated patients were performed in the US, where prevention bundles differ. Second, follow-up periods were highly variable, ranging from 5 to 28 days vs nonspecific intervals based on extubation or discharge (from ICU or hospital). Shorter follow-up periods may introduce ascertainment bias, particularly given the lack of blinding. Third, it is unclear what expertise is required to provide oral care in ventilated patients. Two studies had toothbrushing performed by dental professionals, whereas nondental nursing staff performed oral care in all others. The technique differed among studies included, suggesting the need for studies that help standardize this practice. Finally, toothbrushing may serve as a marker to examine the oral cavity and for the implementation of additional infection-prevention measures. This suggests a potential advantage, as health care personnel may identify other factors, such as dysphagia, dental plaque, or periodontal disease, contributing to the risk of infection.

Limitations notwithstanding, Ehrenzeller and Klompas⁸ present compelling data that toothbrushing is an effective strategy to prevent VAP and should be emphasized in VAP prevention bundles. Future trials on toothbrushing to prevent NV-HAP are needed. As the literature on HAP continues to evolve, oral hygiene could assume an indispensable role akin to hand hygiene in the prevention and control of health care–associated infections.