Effect of low intraphagolysosomal pH on antimicrobial activity of antibiotics against ingested staphylococci

The ability of aminoglycoside antibiotics and rifampicin to kill Staphylococcus aureus that had been ingested by blood polymorphonuclear leukocytes (PMNs) in vitro was investigated. Gentamicin and streptomycin failed to kill intracellular staphylococci, possibly because they could not penetrate PMNs or were inactivated by the low intraphagolysosomal pH. Rifampicin accumulated within the leukocytes in a form that killed staphylococci in a cell-free medium, but the bactericidal activity of intracellular rifampicin against ingested staphylococci was much less than that in a cell-free system. Investigations with granules isolated from PMNs, at various pH-values, revealed that the impairment of rifampicin activity was a result of limitation of the staphylococcal growth rate by a low pH. These observations indicate that the inhibition of intraphagocytic bacterial growth by the low intraphagolysosomal pH and other phagolysosomal bacteristatic factors determines the antimicrobial activity of accumulated antibiotics.