The effect of tooth brushing, irrigation, and topical tetracycline administration on the reduction of oral bacteria in mechanically ventilated patients: a preliminary study

Ventilator-associated pneumonia (VAP) is one of the major complications in the intensive care unit (ICU). It is reported that VAP occurs in 8 to 28 % of mechanically ventilated patients [1‐6]. Several risk factors for VAP have been identified, and some methods of prevention have been explored. The main cause of VAP is thought to be due to aspiration of oral bacteria, such as Staphylococcus aureus, Streptococcus pneumonia, or gram-negative rods [7‐10]. Within 48 h of admission to the ICU, oral flora of critically ill patients undergoes a change to predominantly gram-negative flora that includes more virulent organisms [11‐13].

0.12 % chlorhexidine is widely applied in the oral cavity to prevent VAP [14]. However, use of this agent on the mucosal surface is prohibited in Japan due to case reports of anaphylaxis. One of the main causes of VAP is thought to be due to aspiration of oropharyngeal fluid containing pathogenic microorganisms. Many investigators have attempted to reduce VAP by various oral care methods. Although some investigators have attempted to reduce VAP by tooth brushing, the results of three randomized controlled trials (RCTs) [11, 15, 16] showed no beneficial effect of tooth brushing on the prevention of VAP. The oral care methods utilized in these studies included tooth brushing, swabbing of the palate and tongue, and suction, yet irrigation of the oral cavity and oropharynx with water was not performed. Others attempted to reduce VAP by topical administration of various agents, such as tobramycin, amphotericin B, polymyxin E, gentamycin, colistin, and vancomycin, but could not show the effects on the overall survival [12, 17, 18].

There have been no previous studies focused on the number of oral bacteria in patients during intubation. The aims of this study were to examine the quantitative change of oropharyngeal bacteria after tooth brushing, irrigation and topical application of antiseptic or antibiotics.

VAP is an airway infection developing more than 48 h after intubation, which is the leading cause of death among hospital-acquired infections. The Institute for Healthcare Improvement (IHI) proposed four prophylaxis for prevention of VAP (VAP bundle) consisting of head-of-bed elevation, a daily “sedation vacation” and a readiness-to-wean assessment, peptic ulcer disease prophylaxis, and deep vein thrombosis prophylaxis. Additionally, a fifth prophylaxis, oral decontamination with chlorhexidine, was added in 2010 [23]. However, oral hygiene practices of tooth brushing, removal of tongue coating, swabbing of oral mucosa, and irrigation were not included in the VAP bundle.

One of the main causes of VAP is thought to be due to aspiration of oropharyngeal fluid containing pathogenic microorganisms. Many investigators have attempted to reduce VAP by various oral care methods. Mori et al. [24] reported that 1252 mechanically ventilated patients who received oral care consisting of swabbing with povidone iodine gargle, tooth brushing, and irrigation with 300 ml of acidic water showed a significantly lower frequency of VAP compared to the 414 patients who did not receive oral care. Sona et al. [25] also described that the implementation of a simple, low-cost oral care protocol of tooth brushing, rinsing with tap water, and subsequent application of a 0.12 % chlorhexidine gluconate chemical solution led to a significantly decreased risk of acquiring VAP. However, their studies were performed with historically controlled patients and therefore the evidence levels were not high. Munro et al. [11], Pobo et al. [15], and Lorente et al. [16] conducted randomized controlled studies of the effect of tooth brushing on the prevention of VAP and concluded that mechanical tooth brushing did not show any significant efficacy. Some investigators attempted topical antibiotic application for the prevention of VAP, but they were unable to find any effect on the improvement of outcome of mechanically ventilated patients [12, 17, 18]. Hillier et al. stated in a literature review that no consensus has been established yet on best practices for oral hygiene in mechanically ventilated patients, although chlorhexidine was the most popular oral care method [14].

The three RCTs of Munro [11], Pobo [15], and Lorente [16] concluded that mechanical oral care was not effective for preventing VAP, as mentioned above. The current preliminary study also demonstrates that tooth brushing and mucosal cleaning with suction had little effect on reducing the number of bacteria in the oropharyngeal fluid. However, tongue and oropharyngeal bacteria decreased significantly after irrigation with 200 ml tap water in the oral cavity and oropharynx. In their RCTs, 0.12 % chlorhexidine was applied in the oral cavity every eight hours. We used 10 % povidone iodine solution and examined its effect on reducing bacteria on the tongue and in the oropharyngeal fluid, because use of 0.12 % chlorhexidine on mucosal surfaces is prohibited in Japan due to a case report of anaphylaxis. As a result, the increase of oral bacteria was slightly inhibited after topical application of 10 % povidone iodine solution.

The number of bacteria on the tongue and in the oropharyngeal fluid significantly decreased to the level of before surgery when irrigation was added after tooth brushing. These findings indicate that irrigation is essential to reduce oral bacteria in mechanically ventilated patients. However, oral bacteria increased again only 3 h after irrigation. We think that the procedures described in the above RCTs were not sufficient to decrease oral bacteria due to the lack of irrigation of the oral cavity and prolonged oral care interval. It has been suggested that mechanical oral care requires irrigation and frequent practice: at least every 3 h.

This study demonstrated that topical administration of tetracycline ointment, an approach different from frequent practice, is an alternative method to reduce oral bacteria. After application of tetracycline ointment on the dorsum of tongue, bacteria both on the tongue and oropharyngeal fluid rapidly decreased to 10⁵ cfu/mL or less, and the effects lasted for at least 150 min. We could not clarify how long the effect lasted, because the surgery finished within 150 min. In contrast, topical administration of povidone iodine showed limited effects on reducing oral bacteria.

Some investigators have reported the effects of oral decontamination on the prevention of pneumonia in ventilated patients. Rodriguez-Roldán et al. [17], applied paste containing tobramycin, amphotericin B, and polymyxin E topically in the oral cavity in 13 ventilated patients, and concluded that nosocomial pneumonia could be prevented by local application of nonabsorbable antibiotics to the oropharynx, although the overall mortality was not improved. Abele-Horn et al. [12] reported that 58 patients receiving topical administration of the same paste demonstrated a decreased incidence of pneumonia compared to the 30 control patients; however, the length of the ICU stay and mortality were similar between the groups. Bergmans et al. [18] also reported that the 92 patients who received topical antimicrobial prophylaxis consisting of an Orabase with gentamycin, colistin, and vancomycin had a reduced frequency of developing pneumonia compared to the 153 patients who did not undergo such a procedure, although this was not associated with shorter duration of ventilation or better survival. Because these authors’ studies failed to demonstrate the efficacy of topical antibiotic administration on the mortality of mechanically ventilated patients, this method has not become a standard treatment.

The present results, demonstrated by bacterial count, showed that tooth brushing and mucosal swab were able to reduce bacteria little in the oropharyngeal fluid, but was significantly decreased after irrigation, and that topical administration of tetracycline ointment on the dorsum of the tongue strongly inhibited the growth of bacteria. The reservoir of microorganisms in the oropharyngeal fluid is not clear. We examined the change of the number of bacteria on the buccal mucosa, palate, dorsum of the tongue, and in the oropharyngeal fluid after intubation, and clarified that bacteria increased rapidly on the tongue and in the oropharyngeal fluid, while that on the buccal mucosa and palate did not during intubation [26]. Some investigators have stated that dental plaque is a reservoir of oropharyngeal bacteria and that removal of dental plaque is important for the prevention of pneumonia in ventilated patients [27, 28]. On the other hand, Penel et al. [29] reported that edentulous patients, who are completely plaque-free, develop surgical site infection (SSI) as frequently as those with teeth in head and neck cancers, which indicated that dental plaque was not a main reservoir of oropharyngeal bacteria. We believe that the surface of the dorsum of the tongue may be one of the reservoirs of intraoral bacteria, and that it is necessary to inhibit bacteria growth on the tongue for prevention of VAP. Our report is unique in that it has demonstrated topical administration of tetracycline on the tongue is able to reduce bacteria in the oropharyngeal fluid, as well as on the tongue. However, before clinical application, we think it is necessary to examine the prevalence of species including resistant bacteria after topical administration of tetracycline, especially in case of prolonged intubation.

Oral care with irrigation of the oral cavity and oropharynx followed by topical antibiotic administration may reduce oral bacteria in mechanically ventilated patients.

DI-S, debris index-simplex; IHI, Institute for Healthcare Improvement; OHI-S, oral hygiene index-simplex; RCTs, randomized controlled trials; SSI, surgical site infection; VAP, ventilator-associated pneumonia; ICU, intensive care unit