Nebulized antibiotics in mechanically ventilated patients: roadmap and challenges

Abstract

Nebulized antibiotics use has become common practice in the therapeutics of pneumonia in cystic fibrosis patients. There is an increasing interest in their use for respiratory infections in mechanically ventilated (MV) patients in order to a) overcome pharmacokinetic issues in the lung compartment with traditional systemic antibiotic use and b) prevent the emergence of multi-drug-resistant (MDR) pathogens. Areas covered: The beneficial effects of antibiotic nebulization in MV patients e.g. increasing efficacy, reduced toxicity and prevention of resistance are described. Physicochemical parameters of optimal lung deposition, characteristics of currently available nebulizers, practical aspects of the procedure, including drug preparation and adjustments of ventilator and circuit parameter are presented. Antibiotics used in nebulized route, along with efficacy in various clinical indications and safety issues are reviewed. Expert commentary: The safety of nebulization of antibiotics has been proven in numerous studies; efficacy as adjunctive treatment to intravenous regimens or as monotherapy has been demonstrated in ventilator-associated pneumonia or ventilator-associated tracheobronchitis due to MDR or susceptible pathogens. However, due to the heterogeneity of studies, multiple meta-analyses fail to demonstrate a clear effect. Clarification of indications, standardization of technique and implementation of clinical practice guidelines, based on new large-scale trials will lead to the optimal use of nebulized antibiotics.

Pharmacokinetic/Pharmacodynamics-Optimized Antimicrobial Therapy in Patients with Hospital-Acquired Pneumonia/Ventilator-Associated Pneumonia

“…Several antibiotics have been studied as nebulized agents, including polymyxins, vancomycin, aztreonam, aminoglycosides (i.e., tobramycin, gentamicin, and amikacin), fosfomycin, cephalosporins (i.e., ceftazidime), carbapenems (i.e., imipenem), and penicillins (i.e., ampicillin sulbactam). 164,165 Direct lung delivery has the potential for reducing systemic toxicity compared with parenteral administration, as the amount of drug absorbed from the lungs into the systemic circulation is minimized. Moreover, supranormal concentrations of antibiotics that may exceed MIC breakpoints by more than 100-fold can be achieved in lung tissues, which may allow the use of those antibiotics even when they test resistant in vitro.…”

“…There are currently three types of nebulizing device used in delivering antibiotics, namely, jet, ultrasonic, and vibrating mesh nebulizers. 164 Jet nebulizer is relatively inexpensive and easy to use, but the drug delivery rarely exceeds 15% of the nominal antibiotic dose due to various issues including impaction of the particles onto the delivery limb system. 23,164 Ultrasonic nebulizers are expensive and may have undesirable heating during nebulization, which may damage the antibiotic.…”

“…164 Jet nebulizer is relatively inexpensive and easy to use, but the drug delivery rarely exceeds 15% of the nominal antibiotic dose due to various issues including impaction of the particles onto the delivery limb system. 23,164 Ultrasonic nebulizers are expensive and may have undesirable heating during nebulization, which may damage the antibiotic. 23,164,170 Vibrating mesh nebulizers are also more expensive but are more efficient.…”

Study of the disposition of nebulized tobramycin

“…Although there are a number of delivery devices available, VMN is recommended for nebulized antibiotic therapy in mechanically ventilated patients [192,193]. We As recommended by expert consensus, humidification was turned off for the experiments [194].…”

“…Tobramycin 500 mg/5 ml (Tobra-day®, Phebra, Australia) yielding a concentration of 100 mg/ml. Recent guidelines support the use of a vibrating mesh nebulizer (VMN) for aerosolised antibiotic therapy with MV [19,193]. Accordingly, disposable VMNs (Aeroneb pro, Aerogen Inc., Galway, Ireland) were employed for the study.…”