Topical antibiotics to help reduce death and respiratory infections in people in intensive care receiving mechanical ventilation

Review question

We aimed to assess the effect of two topical antibiotic regimens (selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD)) in preventing deaths and respiratory infections in patients receiving mechanical ventilation for at least 48 hours in intensive care units (ICUs). In SDD, non-absorbable antibiotics are applied to the oropharynx (back third of the tongue, the soft palate, the side and back walls of the throat and tonsils), oesophagus, stomach, and intestine. SOD involves the application of non-absorbable antibiotics to the oropharynx only. These regimens may be given alone or in combination with systemic antibiotics.

Background

Infections acquired in ICUs are important complications of treatment with ventilation (invasive mechanical breathing support) in patients with very severe diseases who require such treatment. Some of these people will die because of these infections. One method that has been evaluated to reduce these complications is to use antibiotics as a preventative measure.

Search date

This review is current to 5 February 2020.

Study characteristics:

We included 41 trials involving a total of 11,004 patients mechanically ventilated in ICUs to find out whether giving topical antibiotics, alone or in combination with systemic antibiotics, prevents respiratory tract infections and reduces death. Antibiotics were administered either topically (e.g. antibiotics were applied directly to the oropharynx or to the stomach via a nasogastric tube) or systemically (e.g. intravenously (directly into the patient's vein)).

Study funding sources

Twenty-two studies (52.4%) did not report the funding source; 6 studies (14.3%) were supported by public institutional grants; and 13 studies (30.1%) were totally or partially funded by pharmaceutical companies.

Key results

In patients receiving the combination of topical plus systemic antibiotics, there were fewer deaths (data from 18 studies with 5290 patients) and probably fewer patients with respiratory tract infections (data from 17 studies with 2951 patients) compared to those who received no treatment or placebo, although we cannot exclude the possibility that the systemic component of the treatments contributed to the reduction in deaths. Assuming an illustrative risk of 303 deaths and of 417 cases of respiratory tract infections in 1000 people under mechanical ventilation, we expect 48 fewer death in patients who receive a combination of topical plus systemic antibiotics and 238 fewer cases of respiratory tract infections. When patients who received topical antibiotics only were compared with patients who received no treatment, or when patients who received topical plus systemic antibiotics were compared with patients who received systemic antibiotics alone, the number of deaths was probably similar (data from 22 studies with 4213 patients), although there may be fewer patients with respiratory tract infections in patients who received topical prophylaxis (data from 19 studies; 2698 patients). Adverse events were poorly reported, with limited data.

Certainty of the evidence

We judged the certainty of the evidence as high to moderate for deaths and respiratory tract infections and low to very low for adverse events.

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.

Read the full 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 strategy: 

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.

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