Table 1.

Aerosol studies with tobramycin, amikacin, and gentamicin

Reference	Drug	Subjects	Production system	Result	Dosage	LFTs	Major adverse effects
Ramsey et al27	Tobramycin	663 patients Mean age 21 years	PARI LC Plus and Pulmo-Aide	↑FEV1, decreased sputum PA density, fewer hospitalizations	300 mg inhaled tobramycin or placebo, 24 weeks	FEV1	Tinnitus, voice alteration and pneumothorax
Stelmach et al73	Tobramycin	6–18 years	–	Improved body mass index, reduced FEV1 decline over 2 years, delayed X-ray disease progression	300 mg inhaled tobramycin 28 days on and 28 days off drug, 2 years	FEV1	No major adverse effects reported
Murphy et al30	Tobramycin	184 patients recruited and 63 completed the 56-week evaluation	PARI LC Plus and Pulmo-Aide DeVilbiss	Increased FEF25–75 by8%, weight increase in both groups, fewer adverse events on aerosol tobramycin, fewer concomitant antibiotics	300 mg inhaled tobramycin<br/>28 days on and 28 days off drug, 56 weeks	FEV1, FVC, FEF25–75 SaO2	Cough, sore throat, sneeze, dizziness, pharyngitis, tinnitus, conjunctival hyperemia
McCoy et al37	Tobramycin Aztreonam lysinate	≥6 years First step, 246 enrolled Second step, 21 1 enrolled Mean age 26.2 years	PARI LC Plus and eFlow nebulizer system	CFQ-R and FEV1 increase after AZLI and delayed time to inhaled or intravenous antibiotic administration after AZLI	300 mg twice daily, 28 days<br/>75 mg twice or three times daily, 28 days	FEV,	6 patients, > 15% FEV1 reduction
Hodson et al43	Tobramycin Colistin	≥6 years, 115 patients	PARI LC Plus and Ventstream	FEV1 increase in the TOBI Group, and GRCQ improvement in TOBI group	TOBI 300 mg twice daily<br/>Colistin 80 mg twice daily 1 month plus an additional 4 weeks of follow-up	FEV1	Pharyngitis, 17 patients, ≥ 10% decrease after aerosol administration
Geller et al26	Tobramycin	523 patients, >6 years, Mean age 21 years	PARI LC Plus and Pulmo-Aide DeVilbiss	Efficient deposition, low plasma concentration, increased sputum MIC	300 mg twice daily<br/>28 days, 24 weeks	FEV1, FVC, FEV1/FVC ratio	–
Moss et al28,25	Tobramycin	128 patients	PARI LC Plus and Pulmo-Ade DeVilbiss	Increase in FEV1 correlated with reduction in sputum PA density	300 mg, 96 weeks	FEV1	–
Briesacher et al74	Tobramycin	804 patients	–	Decreased days of hospitalization with more than four cycles of administration	2001–2006 data	–	–
Geller et al49	Tobramycin, both aerosol and dry powder	90 randomized	PARI LC PLUS and Pulmo-Aide DeVilbiss and T-326 DPI	Efficient pharmacokinetic evaluation of dry powder	300 mg aerosol and four capsules =112 mg equivalent to 300 mg of aerosol tobramycin	FEV1	Cough, dysgeusia, decline of FEV, after both aerosol and dry powder administration
Konstan et al; EVOLVE trial75	Tobramycin dry powder	102 patients	T-326 DPI	Increase in FEV1 reduction in sputum PA density	Four capsules = 112 mg	FEV1	Cough, sore throat, pyrexia
Konstan et al; EAGER Trial50	Aerosol tobramycin versus light-porous particle, dry powder	≥6 years, 553 randomized	PARI LC Plus and Pulmo-Aide DeVilbiss and T-326 DPI	Equal increase in FEV1, higher reduction in sputum PA density in TIP, higher treatment satisfaction in TIP group, TSQM	300 mg aerosol and four capsules =112 mg × 2 equivalent to 300 mg aerosol tobramycin 3 × 28 days	FEV1	Cough, dysphonia, dysgeusia, bronchospasm, equal in both groups, 5.2% TIP and 5.3% TIS
Bhavsar et al76	Human lysozyme, tobramycin	PA	Misty-Ox Nebulizer	Three groups: 60 mg rhLZ, 5 μg ΤBΜΝ, 60 mg rhLZ	Reduced PA density and inflammatory index	–	–
Parkins et al62	TOBI dry powder	Review	Review	Review	Review	Review	Review
Geller et al26	TOBI dry powder	Review	Review	Review	Review	Review	Review
Trapnell et al56	Fosfomycin/tobramycin	162 CF patients screened 121 completed ≥ 18 years, mean 32 years	eFlow nebulizer system (PARI)	↑FEV1, ↑CFQ-R, fewer symptoms with 80/20 mg	160/40 mg or 80/20 mg placebo, 28 days, twice daily	FEV1	Cough, dyspnea, wheezing less common with 80/20 mg
Newman et al116	Gentamicin	Eight nebulizers from each brand	Bird Micronebuliser DeVilbiss 646 Bard Inspiron Mini-Neb, Medic-Aid Upmist	The higher the flow rate the smaller the MMAD and shorter the nebulization time	–	–	–
Safdar et al82	Amikacin	9 patients Case series	Jet nebulizer	8 of 9 patients were efficiently treated	Amikacin 100 mg per 3 mL (intravenously) twice daily	–	Throat irritation, bitter taste, hoarseness of voice
Aquino et al78	Gentamicin dry powder	CuFi-1	Single-stage glass impinge and Turbospin®	Efficient manufacturing of gentamicin capsules	Storage stability	–	–
Ghannam et al77	Gentamicin, amikacin, Colistin, tobramycin	VAP pneumonia	Jet nebulizer	Efficient VAP pneumonia resolution in 81% aerosol versus 31%	Amikacin (100 mg/3 mL) Colistin (75 mg/4 mL) Gentamicin (40 mg/mL) Tobramycin (30 mg/5 mL)	–	–
Alhanout et al108	ASD and tobramycin	PA and SA	PARI LC Plus eFlow	For ASD, MIC remained the same after mucin addition MMAD <5 μm	ASD 2–10 mg/mL	–	–
Meers et al53	Liposomal amikacin	Animal	12-port nose-only inhalation chamber, PAI LC Star	Sustained release of liposomal amikacin based on supernatants	20 mg/mL	–	–

Abbreviations: FEV₁, forced expiratory volume in one second; FVC, forced vital capacity; FEF_25–75, forced expiratory flow during middle half of forced vital capacity; SaO₂, oxygen saturation; CFQ-R, Cystic Fibrosis Questionnaire-Revised; TOBI, inhaled tobramycin solution; AZLI, aztreonam lysinate; PA, Pseudomonas aeruginosa; TIP, inhaled tobramycin powder; TIS, inhaled tobramycin solution; TSQM, Treatment Satisfaction Questionnaire for Medication; DPI, dry powder; MMAD, mass median aerodynamic diameter; CuFi-1, human airway epithelial (HAE) cell line; SA, Staphylococcus aureus; VAP, ventilation-associated pneumonia; ASD, aminosterol derivative; MIC, minimum inhibitory concentration; LFTs, lung function tests.