Introduction
Ventilator-associated pneumonia (VAP) is a common and serious infection in ICU patients who undergo invasive mechanical ventilation for more than 48 hours. It is caused by various microorganisms, including Gram-negative bacteria (Klebsiella spp., E. coli, Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus, including MRSA). Advances in molecular diagnostics have also identified organisms such as Mycoplasma, broadening the understanding of VAP microbiology and guiding future therapeutic strategies. Endotracheal intubation further increases risk by impairing airway defenses and allowing bacterial secretions to enter the lower respiratory tract.
Empirical antibiotics remain central to VAP management but their side effects and rising resistance highlight the need for alternative approaches. Oral hygiene has emerged as a preventive strategy since dental plaque is a reservoir for respiratory pathogens. Studies show that higher plaque scores correlate with higher VAP risk, and that pathogens in the lungs often match those found in the oral cavity. Agents like chlorhexidine and povidone-iodine are commonly used, while hydrogen peroxide, sodium bicarbonate, octenidine, and herbal formulations are under investigation for their antimicrobial potential in ICU settings.
International guidelines, including those from the CDC and AARC, recommend strict oral hygiene to reduce VAP risk in mechanically ventilated patients. Early and consistent oral care can limit plaque accumulation, enhance local immunity, and lower infection risk. However, further research is needed to standardize oral health practices and develop evidence-based, personalized oral hygiene protocols for critically ill patients. Further research is needed to standardize oral health practices and develop evidence-based protocols for critically ill patients, as illustrated in Figure 1 (oral hygiene agents) and Figure 2 (methods to prevent VAP).
Figure 1. The pathogenic mechanism of VAP.
Figure 2. Various suggested methods to avoid VAP.
Method
We conducted a PubMed search for articles published between January 1964 and April 2024 using the terms “VAP,” “ICU care,” “oral care,” “oral medication and formulation,” “antibiotics,” “chlorhexidine,” “octenidine,” “povidone iodine,” “sodium bicarbonate,” and “H2O2.” Guidelines from the CDC and AARC were also reviewed, along with articles from authors’ personal files and references cited in retrieved studies. Publications in English, Japanese, and Portuguese that met predefined inclusion criteria were considered.
Results and discussions
Antibiotics for VAP Prevention
Antibiotic prophylaxis refers to the preventive use of antibiotics in mechanically ventilated patients to reduce the incidence of VAP. The goal is to lower infection risk in high-risk populations rather than directly impact mortality. Studies show that prophylactic antibiotics, especially via nebulization, significantly reduce VAP rates compared with control groups. Unlike empirical treatment, the focus here is on preventing colonization rather than treating established infections.
Prophylaxis can be delivered through systemic antibiotics, nebulized/inhaled antibiotics, or selective oropharyngeal decontamination (SOD). Systemic antibiotics such as intravenous ampicillin–sulbactam have reduced VAP incidence but show little effect on mortality or ICU stay. Nebulized antibiotics, particularly tobramycin and aminoglycosides, are more effective and not linked to higher mortality or adverse events, making them promising options. SOD, which uses topical antibiotics to limit oropharyngeal colonization, has potential but requires further comparative evidence.
A major limitation of prophylactic antibiotic use is antimicrobial resistance (AMR). Prolonged or widespread use, even topically, can disrupt microbial balance and promote resistant strains. Resistance develops through mechanisms such as antibiotic inactivation or efflux pumps that reduce drug activity. In addition, antibiotics may cause adverse reactions including diarrhea, nausea, vomiting, and allergies. Therefore, while antibiotics are valuable in reducing VAP incidence, their use must be carefully balanced against side effects and the risk of resistance.
Oral care medications currently used in ICU
Chlorhexidine
Chlorhexidine is a widely used ICU antiseptic effective against Gram-positive and Gram-negative bacteria linked to VAP. It is available in 0.12%–2% solutions or gels and is recommended by global critical care societies. Studies show it lowers VAP incidence, especially in cardiac surgery and critically ill patients, with meta-analyses reporting about a 37% risk reduction.
Long-term use, however, may promote resistance in organisms like Enterobacter, Pseudomonas, Proteus, Providencia, and Enterococcus faecalis, as well as multidrug-resistant Klebsiella pneumoniae.
Adverse effects include dry mouth, altered taste, tooth staining, calculus formation, and tongue pigmentation. Rarely, serious reactions such as anaphylaxis have been reported, leading to restrictions in some countries. In vitro studies also suggest potential cytotoxicity, so risks must be carefully weighed.
Povidone-iodine
Povidone-iodine is another broad-spectrum antiseptic that also prevents biofilm formation. In countries like Japan, where chlorhexidine is restricted due to allergy risks, it is widely used. Clinical trials show it suppresses bacterial growth, maintains oral balance, and reduces VAP incidence in ventilated patients, including those with traumatic brain injury.
Evidence, however, is mixed. Some studies found no preventive benefit and even linked it to a higher risk of acute respiratory distress syndrome in brain injury cases. More research is needed to confirm its safety and role in ICU oral care.
Other oral care medications with potential applications used in ICU
Hydrogen Peroxide
Hydrogen peroxide (H2O2) has been used in dentistry since the early 20th century and is FDA-approved as a 3% oral debridement agent. Studies show that H2O2 mouthwash significantly reduces VAP risk, with some reporting up to a 2.6-fold decrease compared to saline. It has been successfully incorporated into comprehensive VAP prevention protocols. However, concerns exist about its genotoxic effects and the potential for precancerous lesions with prolonged use. Therefore, H2O2 should be applied cautiously and only as part of a broader prevention strategy.
Sodium Bicarbonate
Sodium bicarbonate is a safe, inexpensive, and patient-friendly option for oral hygiene in the ICU. Its bactericidal and neutralizing properties help reduce oral bacterial load, disrupt plaque formation, and improve oral health. Toothpaste containing sodium bicarbonate has shown superior plaque removal compared to other formulations, maintaining lower plaque levels with regular brushing. While generally safe, individuals with hypertension or low-sodium diets should use it cautiously. More research is needed to determine optimal concentrations and long-term safety in ICU patients.
Octenidine
Octenidine (OCT) is a broad-spectrum antiseptic with lower systemic toxicity than chlorhexidine. At 0.1%, OCT has demonstrated strong antiplaque effects, reducing plaque formation by up to 93%, with benefits lasting for several days. It also inhibits colonization and biofilm formation by pathogens like Staphylococcus aureus and Pseudomonas aeruginosa on tracheotomy tubes, showing promise in VAP prevention. While generally safe, some evidence suggests it may penetrate wounds or skin and cause chronic inflammation, though further studies are needed to confirm these risks.
Advice and recommendation for future studies on VAP oral care
To improve patient outcomes in ventilator-associated pneumonia (VAP), focus should be placed on better diagnostics and therapies. More precise methods are needed to guide antimicrobial selection, while further study of antibiotic resistance and oral microorganisms could help tackle multidrug resistance and improve treatment effectiveness.
For diagnosis, point-of-care tests (POCT) enable faster detection and timely adjustment of therapy. Emerging methods like multiplex PCR, exhaled breath analysis, and chromogenic tests are advancing VAP diagnostics, allowing quicker and more targeted interventions.
On the therapy side, multidrug-resistant bacteria remain a major challenge. Nanocarrier systems offer promise, as their small size and engineered surfaces improve bacterial targeting and overcome resistance mechanisms. Still, new drug development is complex, requiring rigorous research, clinical trials, and regulatory approval before reaching patients.
Conclusion
Oral bacteria play an important role in the development of pneumonia, yet the best approach to maintaining oral health in critical care remains debated. While current oral hygiene drugs help prevent VAP, they also have limitations.
Some new drug options show promise as alternatives to empirical antibiotics, but translating microbiology research into clinical practice is still a long journey. Promising technologies need further validation before wide adoption.
More research is required to standardize oral health assessments and develop evidence-based, personalized oral hygiene strategies for ICU patients. This review aims to support progress in ICU oral care and VAP prevention.
