In summary, for patients treated with prophylactic antibiotics to protect against respiratory infections and improve mortality in the intensive care setting:

Benefits in NNT

    25% had lower risk of respiratory tract infections with combined topical and systemic antimicrobials

    14% had lower risk of respiratory tract infections with topical antimicrobials alone

    5.5% had lower risk of death with combined topical and systemic antimicrobials
    NNT of 4 for preventing respiratory tract infections with combined topical and systemic antibiotics

    NNT of 7 for preventing respiratory tract infections with topical antibiotics alone

    NNT of 18 for preventing mortality with combined topical and systemic antibiotics

Harms in NNT

    Potential harms of prophylactic antibiotic use was not assessed
    Potential harms of prophylactic antibiotic use was not assessed

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Source: Liberati A, D'Amico R, Pifferi S, Torri V, Brazzi L, Parmelli E. Antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults receiving intensive care. Cochrane Database Syst Rev 2009 OCT 7;(4):CD000022.

Study Population: 6,914 intensive care unit patients across 36 studies. Trials enrolling pre-specified patient groups who required co-interventions that interfered with the main treatment (e.g. elective esophageal resection, cardiac surgery, gastric surgery, acute liver failure, or liver transplant) were excluded. Most of the enrolled patients were intubated.

Efficacy Endpoints: Respiratory infection, death

Harm Endpoints: Not reported

Narrative: Pneumonia is the most common infection in the intensive care unit (ICU) and is directly associated with an increase in mortality, length of ICU stay, and increased hospital costs.1 Given that the ICU setting is highly associated with colonization of the aerodigestive tract, prevention of pneumonia by decontamination of the gastrointestinal or respiratory tract has been the focus of numerous studies in critically ill patients.1, 2, 3, 4

The Cochrane systematic review cited here includes 36 trials with 6,914 ICU patients.2 These studies examined the use of prophylactic antibiotics, administered topically, via a nasogastric tube, or as a combination systemically and topically.

The meta-analysis showed a mortality benefit only with use of the combination of topical and systemic antibiotics.2 Mortality was reduced by 5.5% (Odds ratio [OR], 0.75, 95% CI, 0.65 – 0.87; NNT 18, 95% CI, 12-36). There was also an absolute risk reduction of 25% in respiratory tract infections (OR: 0.28, 95%, CI 0.20 to 0.38; NNT: 4, 95%CI, 3-5). Administration of topical antibiotics alone was not associated with any mortality benefit, but did reduce respiratory tract infections (absolute risk reduction: 14.2%; OR: 0.44, 95%CI 0.31 to 0.63; NNT: 7).

Since the publication of this Cochrane review in 2009, other meta-analyses have confirmed the protective effects of prophylactic antibiotics.1, 3 These studies looked at the incidence of pneumonia with topical digestive decontamination and direct respiratory tract decontamination respectively. Both studies found a significant protective effect in intubated patients, but no mortality benefit. These findings were consistent with the results of the Cochrane review cited here. However, because these reviews are very specific in their intervention we did not use them in calculating the NNTs.

In another meta-analysis published in 2015 a number of protective modalities were evaluated for mortality benefits in ICU patients.4 Selective decontamination of the digestive tract (SDD) with prophylactic antibiotics was the only modality that yielded reduction in mortality with an NNT 27 (Roquilly). They also reported that the mortality benefit was only seen with the SDD regimens that used both topical and systemic antibiotics. This paper looked at multiple different interventions including respiratory circuit methods, oropharyngeal methods and multiple digestive methods. This meta-analysis did not separate topical versus systemic antibiotics treatment and it did not add to the findings reported by the current Cochrane Review.

Caveats: When looking at respiratory infection reduction, all but two of the trials reached statistical significance, although there was significant heterogeneity. Of the 17 articles that reported on mortality, only two were statistically significant for a reduction in mortality.5, 6 These two were the main contributors to the overall mortality benefit. No significant heterogeneity was seen among the trials included in the mortality analysis.

Despite the positive findings of multiple clinical trials and meta-analyses, no specific antibiotic regimen has been identified as superior. In addition, there is no clear data available on the impact of this practice on hospital costs.2

One important concern of prophylactic antibiotic use is the risk for emerging antimicrobial resistance. Among the 36 articles that were studied in this Cochrane review, only one studied the emergence of antibiotic-resistant microorganisms.5 Evaluation of 1000 participants over two years did not suggest any increase in resistance among patients who received both topical and systemic antibiotics. Additionally, a meta-analysis published in 2013 found no relationship between the use of prophylactic antibiotics and the development of antimicrobial resistance.7 Although debate persists regarding the long-term risk of antimicrobial resistance and its cost-effectiveness, evidence of mortality and morbidity benefits supports the use of this intervention in critically ill patients, especially intubated patients at high risk of respiratory infections.

The Cochrane Review additionally pooled the data from studies with different endpoints that used various or undefined methods to diagnose pneumonia. This analysis only examined RTIs as a whole and not ventilator-associated pneumonias (VAPs) versus hospital acquired pneumonias (HAPs). The definition of VAPs have changed considerably over the last 20 years. Objective ventilator changes must be met to qualify for a ventilator associated event (VAE) before an RTI can be qualified as a VAP. Studies going forward may start dividing VAP and HAP which could change these results.

Finally, most of the included patients in this Cochrane review were intubated and no subgroup analysis was done on non-intubated patients making the applicability of these results to all ICU patients debatable.

Conclusion: Due to the recent definition changes, absence of any specific identifiable antibiotic regimen and uncertainty about the long term consequences of using prophylactic antibiotics (including bacterial resistance and costs) we have assigned a color recommendation of yellow (unknown benefit) to this intervention.

Author: Shadi Ghadermarzi, MD

Supervising Editor: Michael Ritchie, MD

Published/Updated: December 21, 2018

  1. The Title Bar

    The title bar is color-coded with our overall recommendation.

    • Green: Benefits outweigh risks.
    • Yellow: Unclear risk/benefit profile.
    • Red: Benefits do not outweigh risks.
    • Black: Obvious harms, no clear benefits.
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