TABLE 2

Impact of antibiotics on the respiratory microbiome in CRDs

Antibiotic	Sample analysed	Type of treatment	Impact of antibiotics on diversity of the microbiome	Impact on relative abundance of bacterial taxa	Disease	Reference
Association of different antibiotic class in treatment of CF exacerbation episodes	Sputum	Diverse antibiotic treatments for a course of 8–9 years	↓ α-diversity (inverse Simpson index)	–	CF	[30]
	Sputum	Diverse antibiotics used for the treatment of acute PEx	↑ Species richness through PEx and treatment periods, but return to the baseline state during recovery period	↓ Prevotella melaninogenica and Streptococcus sanguinis ↑ Veillonella parvula during treatment period, but return to baseline state in post-recovery samples	CF	[31]
	Sputum	Diverse antibiotics used for the treatment of acute PEx	Either very little change through exacerbation cycle or return to baseline state on the post-recovery sample	No taxa modification associated with clinical stage, including treatment	CF	[32]
Oral macrolides	Oropharyngeal swab	12 months of twice daily oral doses of 400 mg of erythromycin	No impact on α-diversity measures	Difference between treated and placebo groups: ↓ Actinomyces and Streptococcus ↑ Haemophilus after 48 weeks of treatment	BE	[33]
	Oropharyngeal swab	6 months of 250 mg daily azithromycin for 5 days and then 250 mg 3 times per week	Impact on β-diversity measures	↓ Fusobacteria ↑ Firmicutes during treatment compared with untreated group, but return to pre-treatment state after a 1-month washout period	Severe asthma	[34]
	Sputum	12 months of low-dose azithromycin	↓ Faith's phylogenetic diversity	↓ Gammaproteobacteria (including H. influenzae) after 48 weeks of azithromycin treatment compared with placebo group	Severe asthma	[35]
	Bronchoalveolar lavage of the right upper lung lobe	6 weeks of low-dose azithromycin	↓ Shannon's diversity index	↓ Prevotella, Staphylococcus and Haemophilus ↑ Anaerococcus between pre- and post-treatment state	Moderate and severe asthma	[36]
	Sputum	Low-dose erythromycin	Increase of genus richness between baseline and 48 weeks in treated group but no difference with placebo group	No change in composition of airway microbiome in P. aeruginosa-dominated subgroup ↓ H. influenzae and ↑ P. aeruginosa in non-P. aeruginosa-dominated subgroup	BE	[37]
	Sputum	Treatment of exacerbations exclusively by antibiotics (without addition of corticosteroids) (two treatments azithromycin, one by ofloxacin, one by trimethoprim-sulfamethoxazole)	–	↓ of multiple taxa, mainly Proteobacteria	COPD	[38]
β-lactams	Nasal swabs	Various courses of treatments of several weeks, mostly (71%) β-lactams	↑ Shannon's diversity index	↓ Moraxellaceae ↑ other bacterial families (this increase was verified after more than one antibiotic treatment)	CF	[39]
	Bronchoalveolar lavage, sputum or deep throat swabs	Courses of treatment including β-lactams (25 of 31 involving a single β-lactam molecule) for acute PEx	↓ α-diversity between exacerbation and treatment ↓ α-diversity at therapeutic doses between baseline and treatment ↑ α-diversity at sub-therapeutic doses at the same time points	↓ Haemophilus, Clostridiales and Lachnospiraceae ↑ Fusobacterium and Pseudomonas in the group treated at therapeutic doses between baseline and treatment samples No difference was observed in the sub-therapeutic group at the same time points No difference in the bacterial composition was observed in the two groups between post-recovery and baseline samples, or between exacerbation and treatment samples	CF	[40]
	Sputum	Treatment of exacerbation episodes, 19 of 23 treatments including β-lactams	Minimal impact on global community structure	↓ RA of some low abundance taxa with antibiotic treatment: Gemella, two Pasteurella OTUs, two Streptococcus OTUs, Oribacterium and Neisseria	CF	[41]
	Sputum	Treatment of exacerbation episodes by associations including at least one i.v. β-lactam	↑ Shannon's diversity index in the first 72 h of treatment Return to the baseline state after 8–10 days of treatment	↓ P. aeruginosa ↑ anaerobes (Prevotella and Veillonella), in the first 72 h of treatment but return to the baseline state after 8–10 days of treatment	CF	[42]
	Sputum	Cycle of 28 days of AZLI treatment followed by a 28-day period without treatment	No significant change in Shannon's diversity index or Bray-Curtis β-diversity index in one AZLI cycle ↓ Shannon's diversity index ↓ Bray–Curtis β-diversity with ↑ AZLI cycles	–	CF	[43]
Aminoglycosides	Sputum	A 1-month treatment with TIP	↓ average species richness (Shannon and Simpson diversity indices) after 1 week of therapy Return to baseline state after the end of TIP therapy	Most changes noticed between baseline state and first week of treatment occurring among low abundance taxa, mostly facultative and obligate anaerobes (Neisseria, Megasphaera, Granulicatella, Haemophilus, Streptococcus, Gemella, Rothia, Veillonella, Oribacterium)	CF	[44]
Aminoglycosides	Sputum	TIP or TIS during at least 1 year	No difference in Shannon's diversity index	↓ Parvimonas	CF	[45]

CRD: chronic respiratory disease; CF: cystic fibrosis; PEx: pulmonary exacerbation; BE: bronchiectasis; COPD: chronic obstructive pulmonary disease; RA: relative abundance; OTU: operational taxonomic unit; i.v.: intravenous; AZLI: aztreonam lysine for inhalation; TIP: tobramycin inhaled powder; TIS: tobramycin inhaled solution.