Ventilator-associated Infection: The Role for Inhaled Antibiotics

Lucy B. Palmer


Curr Opin Pulm Med. 2015;21(3):239-249. 

In This Article

How Do Aerosolized Antibiotics Affect Emergence of Bacterial Resistance Compared With Systemic Antibiotics?

Increased bacterial resistance in the ICU has been shown to have a direct relationship to the amount of systemic antibiotics used. The relationship between inhaled therapy and emergence of MDRO is limited. The meta-analysis of Ioannidou et al.[37] mentioned previously described a 6.5% (6/46) incidence of new resistance at the end of treatment in the five RCTs included. Table 3 shows recent data on the eradication of pathogens and the emergence of resistance for studies published between 2005 and 2014 mentioned previously. Six trials report data on the emergence of resistance.[28,34,43,46,50] In these trials, no new resistance to drug administered was detected. Included are four RCTs with resistance data. Kofteridis et al.[28] described no new resistance in the group that received aerosol, but there were no data provided for the patients that reviewed only systemic antibiotics. Palmer et al. demonstrated that 8 of the 24 placebo participants acquired resistant organisms during treatment compared with 0 of the 19 aerosolized antibiotic patients (P = 0.0056).[34] In the placebo group receiving only systemic antibiotics, four participants with sensitive bacteria (three P. aeruginosa and one K. pneumoniae) developed resistance on treatment. Two participants acquired a resistant Acinetobacter and two acquired methicillin-resistant Staphylococcus aureus. One of the 19 aerosolized antibiotic participants transiently acquired a resistant organism, a resistant Acinetobacter that resolved during therapy. All patients who acquired resistant organisms received systemic antibiotics. Lu et al.'s[44] randomized trial of i.v. vs. inhaled antibiotics (as exclusive treatment) again showed the emergence of resistance only in the comparator group that received systemic antibiotics.

In another investigation with more chronically ventilated patients, inhaled antibiotics eradicated 26 of the 27 organisms present at randomization compared with 2 of the 23 organisms in the placebo group (P = 0.0001), despite both groups being on similar amounts of appropriate systemic antibiotics. Inhaled antibiotics eradicated the original resistant organism on culture and Gram stain at the end of the treatment in 14 out of the 16 patients compared with 1 of the 11 for placebo (P = 0.001).[50] Resistance to systemic antibiotics significantly increased in the placebo patients receiving only systemic antibiotics (P = 0.03). In chronically intubated critically ill patients, inhaled therapy successfully eradicated existing MDROs and reduced the pressure from systemic agents for new respiratory resistance.

In Lu et al.'s[46] study mentioned previously, which compared systemic therapy given for VAP with β-lactam-susceptible organisms to high-dose nebulized colistin administered to patients with Pseudomonas resistant to β-lactams, the emergence of resistance was described. In patients who had susceptible organism and received i.v. therapy, 75% of the patients who had either not responded or had recurrent VAP acquired resistance to β-lactams. Interestingly, in the patients on nebulized colistin with β-lactam-resistant organisms, 25% of those with recurrent VAP now had organisms susceptible to β-lactams.

These studies all suggest that inhaled therapy may have a beneficial effect decreasing the emergence of resistance supporting our initial hypothesis that very high antibiotic concentrations may eradicate the highly resistant organisms.