Topical antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults receiving mechanical ventilation

Abstract

Background: Patients treated with mechanical ventilation in intensive care units (ICUs) have a high risk of developing respiratory tract infections (RTIs). Ventilator-associated pneumonia (VAP) has been estimated to affect 5% to 40% of patients treated with mechanical ventilation for at least 48 hours. The attributable mortality rate of VAP has been estimated at about 9%. Selective digestive decontamination (SDD), which consists of the topical application of non-absorbable antimicrobial agents to the oropharynx and gastroenteric tract during the whole period of mechanical ventilation, is often used to reduce the risk of VAP. A related treatment is selective oropharyngeal decontamination (SOD), in which topical antibiotics are applied to the oropharynx only. This is an update of a review first published in 1997 and updated in 2002, 2004, and 2009.

Objectives: To assess the effect of topical antibiotic regimens (SDD and SOD), given alone or in combination with systemic antibiotics, to prevent mortality and respiratory infections in patients receiving mechanical ventilation for at least 48 hours in ICUs.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections (ARI) Group's Specialised Register, PubMed, and Embase on 5 February 2020. We also searched the WHO ICTRP and ClinicalTrials.gov for ongoing and unpublished studies on 5 February 2020. All searches included non-English language literature. We handsearched references of topic-related systematic reviews and the included studies.

Selection criteria: Randomised controlled trials (RCTs) and cluster-RCTs assessing the efficacy and safety of topical prophylactic antibiotic regimens in adults receiving intensive care and mechanical ventilation. The included studies compared topical plus systemic antibiotics versus placebo or no treatment; topical antibiotics versus no treatment; and topical plus systemic antibiotics versus systemic antibiotics.

Data collection and analysis: We used standard methodological procedures expected by Cochrane.

Main results: We included a total of 41 trials involving 11,004 participants (five new studies were added in this update). The minimum duration of mechanical ventilation ranged from 2 (19 studies) to 6 days (one study). Thirteen studies reported the mean length of ICU stay, ranging from 11 to 33 days. The percentage of immunocompromised patients ranged from 0% (10 studies) to 22% (1 study). The reporting quality of the majority of included studies was very poor, so we judged more than 40% of the studies as at unclear risk of selection bias. We judged all studies to be at low risk of performance bias, though 47.6% were open-label, because hospitals usually have standardised infection control programmes, and possible subjective decisions on who should be tested for the presence or absence of RTIs are unlikely in an ICU setting. Regarding detection bias, we judged all included studies as at low risk for the outcome mortality. For the outcome RTIs, we judged all double-blind studies as at low risk of detection bias. We judged five open-label studies as at high risk of detection bias, as the diagnosis of RTI was not based on microbiological exams; we judged the remaining open-label studies as at low risk of detection bias, as a standardised set of diagnostic criteria, including results of microbiological exams, were used. Topical plus systemic antibiotic prophylaxis reduces overall mortality compared with placebo or no treatment (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.73 to 0.96; 18 studies; 5290 participants; high-certainty evidence). Based on an illustrative risk of 303 deaths in 1000 people this equates to 48 (95% CI 15 to 79) fewer deaths with topical plus systemic antibiotic prophylaxis. Topical plus systemic antibiotic prophylaxis probably reduces RTIs (RR 0.43, 95% CI 0.35 to 0.53; 17 studies; 2951 participants; moderate-certainty evidence). Based on an illustrative risk of 417 RTIs in 1000 people this equates to 238 (95% CI 196 to 271) fewer RTIs with topical plus systemic antibiotic prophylaxis. Topical antibiotic prophylaxis probably reduces overall mortality compared with no topical antibiotic prophylaxis (RR 0.96, 95% CI 0.87 to 1.05; 22 studies, 4213 participants; moderate-certainty evidence). Based on an illustrative risk of 290 deaths in 1000 people this equates to 19 (95% CI 37 fewer to 15 more) fewer deaths with topical antibiotic prophylaxis. Topical antibiotic prophylaxis may reduce RTIs (RR 0.57, 95% CI 0.44 to 0.74; 19 studies, 2698 participants; low-certainty evidence). Based on an illustrative risk of 318 RTIs in 1000 people this equates to 137 (95% CI 83 to 178) fewer RTIs with topical antibiotic prophylaxis. Sixteen studies reported adverse events and dropouts due to adverse events, which were poorly reported with sparse data. The certainty of the evidence ranged from low to very low.

Authors' conclusions: Treatments based on topical prophylaxis probably reduce respiratory infections, but not mortality, in adult patients receiving mechanical ventilation for at least 48 hours, whereas a combination of topical and systemic prophylactic antibiotics reduces both overall mortality and RTIs. However, we cannot rule out that the systemic component of the combined treatment provides a relevant contribution in the observed reduction of mortality. No conclusion can be drawn about adverse events as they were poorly reported with sparse data.