Efficacy of oral chlorhexidine in preventing lower respiratory tract infections. Meta-analysis of randomized controlled trials

doi:10.1016/j.jhin.2007.03.025

Journal of Hospital Infection

Volume 66, Issue 3, July 2007, Pages 207-216

https://doi.org/10.1016/j.jhin.2007.03.025 Get rights and content

Summary

Several randomized controlled trials (RCTs) have examined the influence of oral chlorhexidine (CHX) in preventing nosocomial lower respiratory tract infection (LRTI). Most have failed to demonstrate a reduction in the incidence of LRTI. The present meta-analysis summarizes the effect of oral CHX on the development of LRTI. RCTs were identified through searching PubMed, MEDLINE and the Cochrane Central Register of Controlled Trials databases. Those describing the use of chlorhexidine for oral decontamination and reporting the incidence of LRTI as a study outcome were included in the meta-analysis. Seven RCTs met the inclusion criteria; pooling the results from these reveals a reduction in the relative risk (RR) of LRTI in the CHX group [RR_random: 0.58, 95% confidence interval (CI): 0.45–0.74; and RR_fixed: 0.56, CI95: 0.44–0.72, respectively]. Further analyses showed that this result applied only to patients ventilated for up to 48 h (RR_random: 0.58, CI95: 0.45–0.74; and RR_fixed: 0.56, 95% CI: 0.44–0.72). Oral CHX should be included among preventive measures performed to reduce nosocomial LRTI. Whether it has an impact on the development of LRTI in patients requiring mechanical ventilation for a longer period of time remains unresolved.

Introduction

Nosocomial lower respiratory tract infections (LRTIs) are a major problem in intensive care medicine. Nosocomial pneumonia among patients receiving mechanical ventilation (MV), also termed ventilator-associated pneumonia (VAP), is the most important nosocomial infection in intensive care units (ICUs), accounting for eight cases per 1000 ventilation-days in Germany.¹ VAP is leading to lengthening of hospital stay, increased costs and a doubled risk for mortality.²

Numerous factors have been found to increase the risk of developing VAP. Beside MV itself, there are reintubation, aspiration, coma, supine positioning, enteral nutrition, failed subglottic aspiration, antibiotics, and others.3, 4 As the defence mechanisms that usually protect the lung from infection are compromised by patients' underlying disease [chronic obstructive pumonary disease (COPD), acquired respiratory distress syndrome (ARDS)] or MV (local trauma, epithelial damage), the colonization of the upper respiratory tract of ICU patients becomes another important risk factor for VAP.5, 6, 7

Preventive strategies to reduce the colonization of the upper respiratory tract are the selective decontamination of the digestive tract (SDD), oropharyngeal decontamination and combinations of these with or without the use of systemic antibiotics. Oropharyngeal decontamination can be achieved using topical antibiotics, which may increase the risk of antibiotic resistance, or using topical antiseptics. Until recently, oropharyngeal decontamination using the topical application of chlorhexidine (CHX), an antimicrobial cationic compound active against aerobic and anaerobic bacteria, has failed to prove its efficacy in preventing LRTI.8, 9, 10, 11 As the use of antiseptics avoids the problem of antibiotic resistance, it might offer significant advantages over the use of SDD. Therefore, we performed a meta-analysis including recently published studies to determine the efficacy of oral CHX in reducing LRTI.

Section snippets

Data sources

A computerized PubMed literature search of articles published before 15 January 2007, was performed using the key words ‘chlorhexidine’, ‘oropharyngeal’, ‘decontamination’, ‘respiratory’ and ‘pneumonia’ iteratively in different combinations. Truncation was used to identify a range of similar terms. The reference lists of the retrieved articles were reviewed for additional studies, as were review articles on the subject. The search strategy was repeated using MEDLINE and the Cochrane Central

Study selection and characteristics

The initial PubMed search yielded 161 articles. Of these, eight studies were considered for inclusion in the meta-analysis.8, 9, 10, 12, 13, 14, 15, 16 Four of the studies8, 10, 12, 13 had already been included in the meta-analysis published by Pineda et al. in 2006,¹¹ and six of the studies8, 9, 10, 12, 13, 15 in a recent meta-analysis by Chlebicki et al. performed before 15 April 2006.¹⁷ Subsequently, two additional studies were published.14, 16 Reviewing of the reference lists of the

Discussion

The present meta-analysis reveals a significant reduction in the RR of LRTI in patients receiving oral decontamination using CHX (RR_random: 0.58, 95% CI: 0.45–0.74; and RR_fixed: 0.56, 95% CI: 0.44–0.72, respectively). Oropharyngeal colonization of the upper respiratory tract is an important risk factor for the development of nosocomial respiratory tract infection.6, 7 Jacobsen et al. have already demonstrated the association between colonization and infection of the respiratory tract in a study

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Cited by (54)

Control of antibiotic resistance and superinfections as a strategy to manage COVID-19 deaths
2021, Data Science for COVID-19: Volume 2: Societal and Medical Perspectives
According to the World Health Organization (WHO), viral infections continue to emerge and pose severe problems to public health. In mid-December 2019, coronavirus (coronavirus disease 2019 [COVID-19]) infection begun scattering from China. Globally, there are growing worries about community infections, in light of pandemic characterization for the outbreak by the WHO. Some studies have found that 1 out of 7 COVID-19 patients have acquired secondary bacterial infection, and half of the patients who have died had such infections. The challenge of antibiotic resistance could become an enormous force contributing to the rise in illness and death associated with COVID-19, as lower respiratory tract infections are among the leading causes of mortality in critically ill ventilated-patients with COVID-19.
The increasing prevalence of resistance to penicillin and other drugs among pneumococci has considerably complicated the treatment of acquired pneumonia. Resistance to other classes of antibiotics, traditionally used as alternatives in the treatment of pneumococcal infections, has also increased markedly in the recent years. Although the search for new antibiotics remains a top priority, the pipeline for new antibiotics is not encouraging, making it essential to search for other alternative solutions. Researching promising antimicrobial agents that are effective against COVID-19 as well as Streptococcus pneumoniae, which is a major cause of pneumonia, should be encouraged to reduce mortality related to COVID-19 infections. In this chapter, the relation between secondary infections and antibiotic resistance as contributors to high death rate among COVID-19 patients will be traced and highlighted. The possibility of using antimicrobial agents of plant origin, either independently or in combination with nanostructures, as preventive and/or treatment strategies for infections associated with COVID-19 will be reviewed.
Effects of oral hygiene using chlorhexidine on preventing ventilator-associated pneumonia in critical-care settings: A meta-analysis of randomized controlled trials
2013, Journal of Dental Sciences
Citation Excerpt :
The most significant mechanism among those reported is aspiration of oropharyngeal organisms into distal bronchi. Previous meta-analyses aimed at clarifying the effect of oral decontamination with CHX yielded conflicting results.8–11 Results of meta-analyses can be affected by the methodological diversity of the comparative studies included, and can change as additional studies are published and incorporated.
Ventilator-associated pneumonia (VAP) is one of the most frequent causes of morbidity and mortality among mechanically ventilated patients in critical care. Previous meta-analyses demonstrated that oral chlorhexidine (CHX) is beneficial in preventing VAP. Several new studies on oral hygiene as a preventive measure for VAP have been published. Considering all the currently available evidence together, an updated meta-analysis was conducted to evaluate the efficacy of oral CHX in preventing VAP.
A comprehensive literature search was conducted to identify clinical trials comparing oral hygiene care using CHX with conventional care in terms of the incidence of VAP. Two reviewers independently assessed each report to confirm that all reports met the inclusion criteria. The data from each trial were combined using the Mantel–Haenszel fixed-effects model to calculate the pooled relative risk and the corresponding 95% confidence intervals. Funnel plots were used to assess publication bias.
Nine randomized controlled trials met our inclusion criteria. Overall, 1623 patients received oral hygiene with CHX and 1662 received a placebo. The heterogeneity of the data was statistically refuted. Oral hygiene using CHX resulted in a reduced incidence of VAP (relative risk = 0.59; 95% confidence interval, 0.47–0.73; P < 0.001; I² = 27.8%) according to a fixed-effects model. Publication bias was not apparent in the funnel plots.
The analysis showed that oral CHX decontamination significantly reduced the incidence of VAP but not the mortality rate.
Effectiveness of oral care in the prevention of ventilator-associated pneumonia. systematic review and meta-analysis of randomised clinical trials
2011, Enfermeria Clinica
Determinar la efectividad de los cuidados orales en la prevención de neumonía asociada a ventilación mecánica (NAVM).
Búsqueda en CINHAL, Cuiden Plus, Pub Med, EMBASE, ENFISPO, Cochrane, Cuiden, DARE, EBE, JBI, y búsqueda inversa, desde el comienzo de indexación de cada base hasta el 3-5-2010. No se ha restringido el idioma, edad, sexo ni patología de base. Se han incluido ECA que comparan los cuidados orales y se determina su efectividad en la prevención de NAVM. Se han analizado diferentes intervenciones para determinar cuál es más efectiva y protectora. Se ha utilizado Epidat 3.1 para síntesis de datos. Se han revisado 858 artículos, de ellos solo 14 cumplían los criterios de inclusión.
Bajo modelo de efectos aleatorios se ha determinado resultados estadísticamente significativos a favor de la clorhexidina como factor protector frente a NAVM RR = 0,7065; IC 95% [0,5568-0,8963] .La aplicación de clorhexidina 0,12% dos veces al día RR = 0,69; IC 95% [0,53-0,91] y clorhexidina 2% cuatro veces al día RR = 0,53, IC 95% [0,31-0,90] aportan resultados estadísticamente significativos. Clorhexidina 0,12% y 0,2% tres veces al día y cepillado de dientes no aportan resultados estadísticamente significativos.
La aplicación de clorhexidina en los cuidados orales es un factor protector frente a la NAVM. El cepillado de dientes no previene la NAVM: serían necesarios más estudios ECA con esta intervención.
To determine the effectiveness of oral care in preventing pneumonia associated with mechanical ventilation (VAP).
A search was made for randomised clinical trials (RCTs) in CINAHL, Cuiden Plus, Pub Med, EMBASE, ENFISPO, Cochrane, Cuiden, DARE, EBE, JBI, and reverse lookup from the beginning of indexing of each database up to 3 May 2010. There were no restrictions on language, age, sex or underlying disease. RCTs that compared oral care and determined their effectiveness in preventing VAP were included. The different interventions were analysed to determine the most effective and protective. Epidat 3.1 was used for analysing the data. Out of a total of 858 articles reviewed, only 14 met the inclusion criteria.
Using a random effects model statistically significant results were found in favour of chlorhexidine as a protective factor against VAP (RR = 0.7065, 95% CI: 0.5568-0.8963). The application of 0.12% chlorhexidine twice a day gave an RR: 0.69, 95% CI: 0.53 - 0.91 and 0.2% chlorhexidine four times daily: (RR = 0.53, 95% CI: 0.31 to 0.90), being statistically significant. The application of 0.12% and 0.2% chlorhexidine three times a day and brushing did not give statistically significant results.
The use of chlorhexidine in oral care is a protective factor against VAP. Tooth brushing did not prevent VAP. More RCTs using this intervention are needed to confirm these results.
Prevention of ventilator-associated pneumonia with oral antiseptics: A systematic review and meta-analysis
2011, The Lancet Infectious Diseases
Citation Excerpt :
Chan and colleagues37 assessed, besides antiseptics, the effect of oral antibiotics on rates of ventilator-associated pneumonia. Chlebicki and Safdar,38 Kola and Gastmeier,39 and Pineda and colleagues40 focused on oral care with chlorhexidine only. In conclusion, this meta-analysis provides strong evidence of the beneficial effect of oral antiseptics in the prevention of ventilator-associated pneumonia, especially in cardiosurgical patients and with use of 2% chlorhexidine.
We did a systematic review and random effects meta-analysis of randomised trials to assess the effect of oral care with chlorhexidine or povidone-iodine on the prevalence of ventilator-associated pneumonia versus oral care without these antiseptics in adults.
Studies were identified through PubMed, CINAHL, Web of Science, CENTRAL, and complementary manual searches. Eligible studies were randomised trials of mechanically ventilated adult patients receiving oral care with chlorhexidine or povidone-iodine. Relative risks (RR) and 95% CIs were calculated with the Mantel-Haenszel model and heterogeneity was assessed with the I² test.
14 studies were included (2481 patients), 12 investigating the effect of chlorhexidine (2341 patients) and two of povidone-iodine (140 patients). Overall, antiseptic use resulted in a significant risk reduction of ventilator-associated pneumonia (RR 0.67; 95% CI 0.50–0.88; p=0.004). Chlorhexidine application was shown to be effective (RR 0.72; 95% CI 0.55–0.94; p=0.02), whereas the effect resulting from povidone-iodine remains unclear (RR 0.39; 95% CI 0.11–1.36; p=0.14). Heterogeneity was moderate (I²=29%; p=0.16) for the trials using chlorhexidine and high (I²=67%; p=0.08) for those assessing povidone-iodine use. Favourable effects were more pronounced in subgroup analyses for 2% chlorhexidine (RR 0.53, 95% CI 0.31–0.91), and in cardiosurgical studies (RR 0.41, 95% CI 0.17–0.98).
This analysis showed a beneficial effect of oral antiseptic use in prevention of ventilator-associated pneumonia. Clinicians should take these findings into account when providing oral care to intubated patients.
None.
Hospital-acquired lower respiratory tract infections among high risk hospitalized patients in a tertiary care teaching hospital in China: An economic burden analysis
2018, Journal of Infection and Public Health
Citation Excerpt :
These infections expose patients to potential risks and complications such as antibiotic resistance and flora imbalance. This would lead to poor clinical and economic outcomes in the long term, including increasing costs, longer hospital length of stay (LOS), and increased morbidity and mortality [7–9]. Studies about economic burden of hospital-acquired LRTI have been performed in the United States, England and Germany [10–12].
Data on the economic burden of hospital-acquired lower respiratory tract infection (LRTI) among high risk hospitalized patients are lacking in China. This study aims to fill this knowledge gap.
We used a prospective matched cohort design, comparing patients with LRTIs and 1:1 matched patients without LRTIs. Study period was from January 2013 to December 2015 analyzing inpatients from high risk wards – intensive care unit (ICU), dialysis, hematology, etc. – in a tertiary hospital. Hospital information system and hospital infection surveillance system were applied to extract necessary information. The primary outcome was incidence of hospital-acquired LRTIs, and the secondary was economic burden outcomes, including incremental medical costs and prolonged length of stay (LOS). Wilcoxon’s signed rank test was used to explore the differences in the economic burden.
Among 5990 hospital visitors over the period of time, 895 (14.94%) had hospital-acquired LRTIs. We analyzed 340 patients with LRTIs and 340 respective controls without infections. The median hospital costs for patients with ICU-acquired LRTIs were significantly higher than those without LRTIs in other wards ($12,301.17 vs. $4674.64, P < 0.01). The average attributable cost per patient was $2853.93 ($6916.48 vs. $4062.55, P < 0.01). Patients from hematology department had the longest LOS, at 15 days (25 days vs. 10 days, P < 0.01). An LRTI led to an attributable increase in LOS by 8 days on average (P < 0.01). Western medicine, treatment and laboratory test were the dominant contributors to the growth in overall medical costs in hospital-acquired LRTIs.
Hospital-acquired LRTI imposed considerable economic burden on patients hospitalized in high risk wards in China. This study provides the first data for economic evaluation of LRTI, highlighting the urgent need to establish targeted preventive strategies to minimize the occurrence of this complication to reduce economic burden.
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ReviewEfficacy of oral chlorhexidine in preventing lower respiratory tract infections. Meta-analysis of randomized controlled trials

Summary

Introduction

Section snippets

Data sources

Study selection and characteristics

Discussion

J Hosp Infect

Heart Lung

Chest

Clinical and economic consequences of ventilator-associated pneumonia: a systematic review

Crit Care Med

Risk factors for ICU-acquired pneumonia

J Am Med Assoc

Prevention of ventilator-associated pneumonia: an evidence-based systematic review

Ann Intern Med

Risk factors for pneumonia, and colonization of respiratory tract and stomach in mechanically ventilated ICU patients

Am J Respir Crit Care Med

Colonization of dental plaque: a source of nosocomial infections in intensive care unit patients

Crit Care Med

Oropharyngeal or gastric colonization and nosocomial pneumonia in adult intensive care unit patients. A prospective study based on genomic DNA analysis

Am J Respir Crit Care Med

Effectiveness of 0.12% chlorhexidine gluconate oral rinse in reducing prevalence of nosocomial pneumonia in patients undergoing heart surgery

Am J Crit Care

Review
Efficacy of oral chlorhexidine in preventing lower respiratory tract infections. Meta-analysis of randomized controlled trials