Abstract
Limited therapeutic options are available for multidrug-resistant Acinetobacter baumannii (MDR-AB), and the development of effective treatments is urgently needed. The efficacy of four aerosolized antibiotics (gentamicin, amikacin, imipenem, and meropenem) on three different MDR-AB strains was evaluated using hypertonic saline (HS, 7 g/100 mL) as the aerosol carrier. HS aerosol effectively hindered biofilm formation by specific MDR-AB strains. It could also interrupt the swarming dynamics of MDR-AB and the production of extracellular polymeric substances, which are essential for biofilm progression. Biofilms protect the microorganisms from antibiotics. The use of HS aerosol as a carrier resulted in a decreased tolerance to gentamicin and amikacin in the biofilm-rich MDR-AB. Moreover, we tested the aerosol characteristics of antibiotics mixed with HS and saline, and results showed that HS enhanced the inhaled delivery dose with a smaller particle size distribution of the four antibiotics. Our findings demonstrate the potential of using “old” antibiotics with our “new” aerosol carrier, and potentiate an alternative therapeutic strategy to eliminate MDR-AB infections from a biofilm-disruption perspective.
Highlights
Hospital-acquired pneumonia is most commonly caused by multidrug resistant Gramnegative bacteria, such as Acinetobacter baumannii, P. aeruginosa, and K. pneumonia
We speculated that the delivery of aerosolized hypertonic saline (950 mM sodium chloride) can modulate the ionic concentration of the bacterial microenvironment, and we explored the potency of hypertonic saline for multidrug-resistant A. baumannii (MDR-AB) therapy
A previous study showed that the stickiness of extracellular polymeric substances (EPSs) of Sagutula can be altered by ionic strength in the surrounding microenvironment [20]
Summary
Hospital-acquired pneumonia is most commonly caused by multidrug resistant Gramnegative bacteria, such as Acinetobacter baumannii, P. aeruginosa, and K. pneumonia. A. baumannii is one of the most common causative pathogens [1]. A. baumannii, a Gram-negative coccobacillus, is a leading cause of severe nosocomial infections in the current health system [2]. A. baumannii is the primary agent associated with pneumonia, septicemia, endocarditis, meningitis, and urinary tract infections [3]. A. baumannii can be intrinsically resistant to many commonly used antibiotics, such as aminopenicillins, first-generation and second-generation cephalosporins. The increasing prevalence of multidrug-resistant A. baumannii (MDR-AB) infection has emerged worldwide due to prolonged hospital stays [4,5]. With the high prevalence of MDR-AB, combination therapy is frequently used to decrease the risk of resistance and improve patient outcomes [6]
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