TABLE 3.

Schematic classification of the phagocytic uptake of antibacterial agents

Drug	Cellular/extracellular concn ratio		Characteristics, location	Intracellular activitya
	PMN	Monocyte/macrophage
Poor accumulation
β-Lactams	<1	<1	Passive diffusion	+/−
Meropenem	2–10	3–12
Imipenem	3–0.3	3.7–0.8	Transient accumulation (hydrolysis?)
Aminoglycosides	<1	2–4	Slow accumulation, pinocytosis (macrophage) (megalin?)	+/−
Daptomycin	0.6
Moderate accumulation			Passive diffusion, lipophilicity
Cyclines	1–3	2–4	Cytoplasm, nucleus	+
Fosfomycin	1.8–2.2			+
Isoniazid	1–1.5	0.6–0.9	Cytosol	+
Ethambutol	1.4–4.8	0.1–9.5	Cytosol	+
Chloramphenicol	2.6–9.6	2–4	Cytosol	+
Sulfamethoxazole	1.7		Cytosol	+
Metronidazole	1	0.5	Cytosol	+
Lincomycin	1.6–3	0.6–2	Cytosol	+
Trimethoprim	6–21	3	Cytosol	+
Quinolones (most)	3–10	4–10	Cytosol, rapid efflux	+
Grepafloxacin	66		?
Pefloxacin	4–10		Active transport system?	+
Ciprofloxacin	4–10		Two active transport systems
Lomefloxacin ofloxacin, norfloxacin (others?)			Two active transport systems
Fusidic acid	2–4
Rifampin, rifabutin	2.4–9.2			+
Strong accumulation			Active mechanisms
Macrolides	>10–100		Active transport (uptake and efflux)	+/−
Erythromycin A derivatives
Dibasic molecules (azithromycin, dirithromycin)	80–>300 (at 180 min)	100–<600	Not saturable over 3 h, granules ++, slow efflux
Monobasic molecules (erythromycin, roxithromycin, clarithromycin)	10–34 (91)c	38–61 (46–190)c	Plateau 30–60 min Fast efflux, granules + cytosol
Ketolides
HMR 3004	>250		Plateau, slow efflux
HMR 3647	250–300		Progressive uptake and efflux
Clindamycin	11–15	8–24	Nucleoside transport system?
Coumermycin	11–17b
Teicoplanin	52 (13)b	41	Membrane associated	+/−
Brodimoprim	74
Rifapentin	88	62
Streptogramins
RP 54476	34 (120 min)d
RP 57669	50 (120 min)

^aIntracellular bioactivity may differ according to bacterial species. 

^bMeasured by bioactivity. 

^cMeasured in cells from smokers. 

^dMeasured in J774 cells.