In this episode, I’ll discuss adjunctive inhaled antibiotics for ICU patients with pneumonia and invasive ventilation.
A theoretical benefit of using adjunctive inhaled antibiotics to treat ICU patients with pneumonia and invasive ventilation is that it allows for high concentrations at the site of the infection and the potential for reduced systemic exposure and therefore reduced toxicity.
Several studies have examined this approach and recently in the journal Critical Care a group of authors published a systematic review and meta-analysis to examine the benefits of this technique.
11 randomized controlled trials representing nearly 1500 patients were analyzed. The primary outcome was the rate of microbiological eradication after treatment. Secondary outcomes were the rate of clinical recovery, the incidence of drug-related adverse events, ICU and hospital mortality.
In all cases, the inhaled antibiotics were given in addition to systemic antibiotics, and compared vs systemic antibiotics alone.
Compared with systemic antibiotics alone, adjunctive inhaled antibiotics resulted in a greater rate of microbiological eradication with an OR of 2.63. This finding was confirmed when the authors applied trial sequential analysis.
However, patients who received inhaled antibiotics had an increased risk of bronchospasm with an OR of 3.15. Additionally, there were no differences between groups in rates of nephrotoxicity, clinical recovery, ICU and hospital survival.
When the authors looked only at patients with multi drug resistant bacteria, there was still no survival benefit for adjunctive inhaled antibiotics.
When discussing publication bias, the authors did note that:
…studies with some concerns of risk of bias showed a greater rate of microbiological eradication in the inhaled group, while studies at low risk of bias showed no differences between subgroups…
However a subsequent meta-analysis published in Critical Care Medicine looked at a VAP-only subset of patients and came to a different conclusion. Dozens of studies were analyzed, and in the VAP-only patients, inhaled antibiotics had a statistically significant benefit on both clinical cure and all-cause mortality, with relative risk ratios of 1.29 and 0.77, respectively. When the authors applied meta-regression they confirmed the VAP-only population as a significant effect modifier.
Taking these two meta-analyses into consideration, clinicians might target patients with confirmed VAP for inhaled antibiotics rather than broadly applying them to all ICU patients with pneumonia and respiratory failure.
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