Aerosolized Amikacin as Adjunctive Therapy of Ventilator-associated Pneumonia Caused by Multidrug-resistant
Chang Liu1, Yu-Ting Zhang1, Zhi-Yong Peng1
1Department of Intensive Care Unit, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.
Background:
Aerosolized amikacin (AA) is a current option for the management of ventilator-associated pneumonia (VAP) caused by multidrug-resistant Gram-negative bacteria (MDR-GNB), as it is reported that AA could increase the alveolar level of the drug without increasing systemic toxicity. This study aimed to evaluate the efficacy and safety of AA as an adjunctive therapy for VAP caused by MDR-GNB.
Methods:
In this single-center, double-blind study conducted in a 36-bed general Intensive Care Unit (ICU) in a tertiary hospital from June 2014 to June 2016, 52 ICU patients with confirmed MDR-GNB VAP were randomized to two groups (AA group, n = 27 and placebo group, n = 25). Amikacin (400 mg, q8h) or saline placebo (4 ml, q8h) was aerosolized for 7 days. The attending physician determined the administration of systemic antibiotics for VAP. Patients were followed up for 28 days. Bacteriological eradication, clinical pulmonary infection score (CPIS), and serum creatinine were assessed on day 7 of therapy. New resistance to amikacin, cure rate of VAP, weaning rate, and mortality were assessed on day 28.
Results:
The baseline characteristics of patients in both groups were similar. At the end of the treatment, 13 of the 32 initially detected bacterial isolates were eradicated in AA group, compared to 4 of 28 in placebo group (41% vs. 14%, P= 0.024). As for patients, 11 of 27 patients treated with AA and 4 of 25 patients treated with placebo have eradication (41% vs. 16%, P= 0.049). The adjunction of AA reduced CPIS (4.2 ± 1.6 vs. 5.8 ± 2.1, P= 0.007). New drug resistance to amikacin and the change in serum creatinine were not detected in AA group. No significant differences in the clinical cure rate in survivors (48% vs. 35%, P= 0.444), weaning rate (48% vs. 32%, P= 0.236), and mortality (22% vs. 32%, P= 0.427) were detected between the two groups on day 28.
Conclusions:
As an adjunctive therapy of MDR-GNB VAP, AA successfully eradicated existing MDR organisms without inducing new resistance to amikacin or change in serum creatinine. However, the improvement of mortality was not found.
Insights
Aerosolized amikacin (AA) effectively eradicated multidrug-resistant Gram-negative bacteria in ventilator-associated pneumonia (VAP) without increasing resistance or toxicity. However, AA did not significantly improve mortality rates in this study.
Area of Science:
- Critical Care Medicine
- Infectious Diseases
- Pulmonology
Background:
- Ventilator-associated pneumonia (VAP) caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) presents a significant treatment challenge.
- Aerosolized amikacin (AA) is explored for VAP management due to potential for high alveolar drug concentrations and reduced systemic toxicity.
Purpose of the Study:
- To evaluate the efficacy and safety of aerosolized amikacin as an adjunctive therapy for VAP caused by MDR-GNB.
Main Methods:
- A single-center, double-blind study randomized 52 ICU patients with confirmed MDR-GNB VAP to receive either aerosolized amikacin (400 mg, q8h) or saline placebo for 7 days.
- Outcomes assessed included bacteriological eradication, clinical pulmonary infection score (CPIS), serum creatinine, development of new amikacin resistance, VAP cure rate, weaning rate, and mortality over 28 days.
Main Results:
- Aerosolized amikacin demonstrated a significantly higher rate of bacteriological eradication compared to placebo (41% vs. 14% for isolates, P=0.024; 41% vs. 16% for patients, P=0.049).
- AA significantly reduced the clinical pulmonary infection score (CPIS) (4.2 ± 1.6 vs. 5.8 ± 2.1, P=0.007).
- No new amikacin resistance or significant changes in serum creatinine were observed. No significant differences were found in clinical cure rates, weaning rates, or mortality between groups.
Conclusions:
- Adjunctive aerosolized amikacin effectively eradicated existing MDR organisms in VAP without inducing new resistance or nephrotoxicity.
- While AA improved microbiological and clinical markers, it did not translate to a significant improvement in mortality rates for MDR-GNB VAP.
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