RT Journal Article
SR Electronic
T1 The role of suboptimal concentrations of nebulized tobramycin in driving antimicrobial resistance in <em>Pseudomonas aeruginosa</em> isolates in cystic fibrosis - an <em>in vitro</em> study
JF Respiratory Care
FD American Association for Respiratory Care
SP respcare.08671
DO 10.4187/respcare.08671
A1 Moore, John E.
A1 Millar, B. Cherie
A1 Ollman-Selinger, Marika
A1 Cambridge, Lisa
YR 2021
UL http://rc.rcjournal.com/content/early/2021/05/24/respcare.08671.abstract
AB BACKGROUND: Antimicrobial resistance in Pseudomonas aeruginosa (PA) may be driven by exposure to suboptimal concentrations of tobramycin antibiotic delivered by less efficient nebulizers.METHODS: PA isolates (N=114; 32 first+82 chronic) were challenged in vitro employing extrapolated peak and trough concentrations of tobramycin inhalation solution (TIS), corresponding to three nebulizers, PARI LC PLUS, Sidestream12NEB400 and MistyNeb2035G . Bacterial persistence and antibiotic susceptibility to tobramycin was determined following four TIS cycles:- (i) 28d ON, (ii) 28d ON+28d OFF (iii) 2x28d ON and (iv) 28d ON+28d ON+28d OFF.RESULTS: All first isolates were eradicated at peak and trough concentrations except for the trough concentration for Sidestream 12NEB400 (bactericidal activity 87%). For chronic isolates, peak concentrations eradicated 88%, 90% &amp; 92% and trough concentrations eradicated 43%, 62% &amp; 85%, with Sidestream 12NEB400, MistyNeb2035G and PARI LC PLUS, respectively. A statistically significant increase in antibiotic resistance (MIC) with sensitive, intermediate and resistant PA was noted following cycles (i)-(iv), at trough concentrations with Sidestream 12NEB400 and MistyNeb2035G. There was a significant reduction in tobramycin resistance following a 28d OFF cycle and no difference, following 1x28d ON versus 2x28d ON cycles.CONCLUSION: This in vitro study showed that suboptimal tobramycin concentrations drove antibiotic resistance, emulating standard ON/OFF cycles. This was evident at extrapolated tobramycin concentrations at trough levels with less efficient nebulizers, by (i). initially allowing for the survival of intermediate and resistant organisms, because nebuliser performance did not achieve critical MIC concentrations sufficient to eradicate the organism, (ii). allowing the development of resistance in those cells that were able to survive the initial tobramycin challenge. Transferred to clinical practice, this means for CF individuals on TIS treatment, it is important that clinicians employ an efficient nebulizer that helps mitigate an upward drift in antibiotic resistance, thereby protecting the continued clinical value of TIS within CF care.