Table 3.

Schematic classification of the phagocytic uptake of antibacterial agents

DrugCellular/extracellular concn ratioCharacteristics, locationIntracellular activitya
PMNMonocyte/macrophage
Poor accumulation
 β-Lactams<1<1Passive diffusion+/−
  Meropenem2–103–12
  Imipenem3–0.33.7–0.8Transient accumulation (hydrolysis?)
 Aminoglycosides<12–4Slow accumulation, pinocytosis (macrophage) (megalin?)+/−
 Daptomycin0.6
Moderate accumulationPassive diffusion, lipophilicity
 Cyclines1–32–4Cytoplasm, nucleus+
 Fosfomycin1.8–2.2+
 Isoniazid1–1.50.6–0.9Cytosol+
 Ethambutol1.4–4.80.1–9.5Cytosol+
 Chloramphenicol2.6–9.62–4Cytosol+
 Sulfamethoxazole1.7Cytosol+
 Metronidazole10.5Cytosol+
 Lincomycin1.6–30.6–2Cytosol+
 Trimethoprim6–213Cytosol+
 Quinolones (most)3–104–10Cytosol, rapid efflux+
 Grepafloxacin66?
 Pefloxacin4–10Active transport system?+
 Ciprofloxacin4–10Two active transport systems
 Lomefloxacin ofloxacin, norfloxacin (others?)Two active transport systems
 Fusidic acid2–4
 Rifampin, rifabutin2.4–9.2+
Strong accumulationActive mechanisms
 Macrolides>10–100Active transport (uptake and efflux)+/−
 Erythromycin A derivatives
  Dibasic molecules (azithromycin, dirithromycin)80–>300 (at 180 min)100–<600Not saturable over 3 h, granules ++, slow efflux
  Monobasic molecules (erythromycin, roxithromycin, clarithromycin)10–34 (91)c38–61 (46–190)cPlateau 30–60 min Fast efflux, granules + cytosol
 Ketolides
  HMR 3004>250Plateau, slow efflux
  HMR 3647250–300Progressive uptake and efflux
 Clindamycin11–158–24Nucleoside transport system?
 Coumermycin11–17b
 Teicoplanin52 (13)b41Membrane associated+/−
 Brodimoprim74
 Rifapentin8862
 Streptogramins
  RP 54476 34 (120 min)d
  RP 57669 50 (120 min)
  • a Intracellular bioactivity may differ according to bacterial species.

  • b Measured by bioactivity.

  • c Measured in cells from smokers.

  • d Measured in J774 cells.