In vitro activity and pharmacodynamic/pharmacokinetic parameters of clarithromycin and azithromycin: why they matter in the treatment of respiratory tract infections

Figures & data

Table 1 In vitro susceptibilities of azithromycin and clarithromycin against selected pathogens

Organism	MIC90 (μg/mL)			Sources (references)
	Erythromycin	Azithromycin	Clarithromycin
Gram-positive aerobes
Streptococcus pyogenes	0.03–0.2	0.05–0.4	0.01–0.2	^Citation53^–^Citation55, ^Citation60
Streptococcus pneumoniae				^Citation53, ^Citation54, ^Citation59, ^Citation60
Penicillin-susceptible	0.02–0.1	0.12–0.16	0.015–0.06	^Citation53, ^Citation54, ^Citation59
Penicillin-intermediate	0.06–>32	0.125–16	0.03–8.0	^Citation53, ^Citation54, ^Citation59
Penicillin-resistant	0.12–>64	0.12–>64	0.06–>64	^Citation53, ^Citation54, ^Citation59
Streptococcus agalactiae	0.03–0.06	0.06–0.1	0.06	^Citation54
Gram-negative aerobes
Haemophilus influenzae	4.0–8.0	0.5–2.0	4.0–16.0	^Citation53^–^Citation55, ^Citation60
Moraxella catarrhalis	0.25–0.5	0.06–0.16	0.25	^Citation53, ^Citation55, ^Citation60
Legionella pneumophila	0.25–2.0	0.50–2.0	0.25–0.50	^Citation53^–^Citation55
Bordetella pertussis	0.03	0.06	0.03	^Citation55
Other pathogens
Chlamydophila pneumoniae	0.06–0.12	0.1–0.5	0.01–0.10	^Citation53
Mycoplasma pneumoniae	0.004–0.01	<0.01	0.008–0.5	^Citation53, ^Citation55
Helicobacter pylori	0.25	0.25	0.03	^Citation55

Notes: Data derived from these studies.53–55,59,60.

Abbreviation: MIC, minimum inhibitory concentration.

Table 2 Pharmacokinetics of clarithromycin and azithromycin in plasma. (Derived from data published in references.^75–78,80)

Parameter	Azithromycin	Clarithromycin	14-Hydroxy-clarithromycin
Bioavailability (%)	37	55	35
Cmax (μg/mL)	0.4	2.1–2.4	0.6–1.0
tmax (hours)	2	2	1.8
Half-life (hours)	40–68	4.3–4.9	5.5–7.2
AUC (μg/mL × hour)	3.4	12–18.9	6.0
Protein binding (%)	7–50	60–75	ND

Abbreviations: AUC, area under the plasma concentration–time curve; C_max, maximum plasma concentration; ND, not determined; t_max, time to reach maximum plasma concentration.

Figure 1 Differential effects of randomized, open-label macrolide assignment on the prevalence of macrolide-resistant strains in the oral flora of children.

Notes: One week after treatment, ~90% of patients treated with azithromycin, clarithromycin, erythromycin, roxithromycin, or josamycin harbored resistant strains. By 6 weeks posttreatment, the percentage of resistant organisms had decreased to 17% for clarithromycin but for azithromycin the prevalence of resistant organisms remained very high (85%) and was associated with a substantial re-infection rate (11.6%). (Derived from data published in reference.⁸²)

Figure 2 Comparison of achieved concentrations of azithromycin (500 mg on day 1 then 250 mg/day for 4 days) and clarithromycin (500 mg twice daily for 9 days) in (A) plasma, (B) epithelial lining fluid (ELF), and (C) alveolar macrophages of healthy adult volunteers at 4 and 24 hours after last drug administration.

Notes: All comparisons P<0.05 vs azithromycin except ELF at 24 hours. The mean ratio of clarithromycin to 14-HC in plasma was 4.7:1 at 4 hours and decreased to 1.2:1 at 24 hours (data not shown). (Derived from data published in reference.⁷⁷)

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