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

Lam, Charles; Mathison, G. E.

doi:10.1099/00222615-16-3-309

Cited by 28 publications

(20 citation statements)

References 22 publications

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“…As for facultative intracellular bacteria, aminoglycosides are usually considered poorly effective compared to their activities in axenic medium, such as for Salmonella spp. (98), Legionella pneumophila (58), and S. aureus (102,117). A more significant intracellular activity of aminoglycosides was shown against Mycobacterium spp.…”

Section: In Vitro Activities Of Aminoglycosides Against Intracellularmentioning

confidence: 96%

“…Experimental data on intracellular pharmacokinetic properties of aminoglycosides obviously do not correlate well with their poor activity against many intracellular pathogens, especially those residing within lysosomes, such as Staphylococcus aureus (102,117) or Coxiella burnetii (137). It has been hypothesized that, among antibiotics capable of intracellular penetration and concentration, a reduced activity may result from the deleterious action of the intracellular milieu (183).…”

Section: Intracellular Pharmacokinetic and Pharmacodynamic Propertiesmentioning

confidence: 99%

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Use of Aminoglycosides in Treatment of Infections Due to Intracellular Bacteria

Maurin

Raoult

2001

Antimicrob Agents Chemother

113

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Section: In Vitro Activities Of Aminoglycosides Against Intracellularmentioning

confidence: 96%

Section: Intracellular Pharmacokinetic and Pharmacodynamic Propertiesmentioning

confidence: 99%

Use of Aminoglycosides in Treatment of Infections Due to Intracellular Bacteria

Maurin

Raoult

2001

Antimicrob Agents Chemother

113

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“…This intracellular location may afford the microbe protection from the effects of the antibiotic (5,8). Some of the reasons suggested for this protection are intracellular inactivation of the antibiotic (10,14,15), lack of penetration of the antibiotic into the phagocyte (10,20), and resistance of the ingested bacteria to the action of antibiotic (10).…”

mentioning

confidence: 99%

Evaluation of antibacterial agents in a high-volume bovine polymorphonuclear neutrophil Staphylococcus aureus intracellular killing assay

Sanchez¹,

Ford²,

Yancey³

1986

Antimicrob Agents Chemother

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A bovine polymorphonuclear leukocyte (PMN) monolayer system was used to determine the ability of different antibiotics to kill surviving intracellular Staphylococcus aureus. The following classes of antimicrobial agents were tested in this high-volume assay procedure: aminocyclitol, I(-lactam, coumarin, lincosaminide, macrolide, naphthalenic ansamycin, paulomycin, peptide, quinolone, and tetracycline. The activities of these compounds were compared with those of positive (rifampin), negative (cloxacillin), and non-antibiotic-treated controls. Only oxytetracycline, the ansamycins (rifampin, rifamycin SV, streptovaricin A, C, and D), paulomycin, and paldimycin caused a significant reduction in the viable count of intracellular S. aureus. Of these, however, the intracellular killing by the streptovaricins was directly related to the cytotoxicity (as determined by trypan blue exclusion) of these compounds for the PMNs. Although the paulomycins were cytotoxic for the PMNs, the cytotoxic and the intracellular killing activity of these new compounds could be distinguished. The relevance of these results to the therapeutic effectiveness of these antibiotics in the treatment of bovine staphylococcal mastitis is discussed.

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“…Mackaness (11) reported no effect of streptomycin on S. aureus phagocytosed by peritoneal macrophages, but Brown and Percival (4) reported intracellular activity of streptomycin and gentamicin against S. aureus in peritoneal macrophages, albeit lower than that against extracellular bacteria. Several investigators have studied the intracellular activity of aminoglycosides on S. aureus ingested by granulocytes (2,6,7,8,12,21,22). Some of them (2,6,12,21,22) found no activity, and others (7,8) found a lower level of intracellular than of extracellular activity.…”

Section: Discussionmentioning

confidence: 99%

“…Several investigators have studied the intracellular activity of aminoglycosides on S. aureus ingested by granulocytes (2,6,7,8,12,21,22). Some of them (2,6,12,21,22) found no activity, and others (7,8) found a lower level of intracellular than of extracellular activity. In the present study, both kanamycin and gentamicin had a distinct effect on S. aureus phagocytosed by human monocytes.…”

Section: Discussionmentioning

confidence: 99%

Influence of human monocytes on the antibacterial activity of kanamycin and gentamicin for Staphylococcus aureus

Broek¹,

Buys²,

Barselaar³

et al. 1986

Antimicrob Agents Chemother

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The present study was performed to compare the antibacterial activities of kanamycin and gentamicin on Staphylococcus aureus phagocytosed by human monocytes and on nonphagocytosed S. aureus. The method used permitted the measurement of the effect of antibiotics on intracellular bacteria independent of phagocytosis and intracellular killing by the monocytes. A morphological assay with lysostaphin established the intracellular localization of about 70% of the cell-associated S, aureus in the monocyte-bacterium suspension. After 1 h of incubation, the antibacterial activity of both aminoglycosides was greater against intracellular than against nonphagocytosed S. aureus, but after 3 h, the reverse was true. The maximal effect on phagocytosed S. aureus, i.e., killing of about 98% of the bacteria, was reached in the first hour of incubation at kanamycin and gentamicin concentrations of 5 and 1 ,uglml, respectively. A cell-free medium in which monocytes had been incubated increased the antibacterial activity of kanamycin, indicating that monocytes secrete a factor that enhances the antibacterial activity of aminoglycosides.Host defense mechanisms and antimicrobial therapy together determine the outcome of an infection. A well-known, albeit negative, example of this is the diminished efficacy of aminoglycosides in granulocytopenic patients (3, 17). Interactions, whether negative or positive, between antimicrobial drugs and the host defense system, in which phagocytic cells play an important role, may be of great clinical importance. For the sake of brevity, the extensive literature on the interactions between aminoglycosides and phagocytic cells will not be discussed here.Recently, we showed that human monocytes enhance the antibacterial effect of penicillins on extracellular Staphylococcus aureus (18) and presented evidence that penicillins are active against S. aureus phagocytosed by monocytes (17a). These observations raised the question of whether the same was the case for aminoglycosides, and the present study was performed to investigate the influence of human monocytes on the antibacterial activity of aminoglycosides against S. aureus. The assay used permitted the measurement of the effect of aminoglycosides on intracellular S. aureus independent of phagocytosis and intracellular killing by the monocytes (20 was considered to be active if 99.5% of the bacteria were killed during this incubation.Serum. Blood from healthy type-AB blood donors was allowed to clot at room temperature, after which serum was prepared by centrifugation for 20 min at 1,100 x g. Serum was stored at -70°C.S. aureus. A kanamycin-and gentamicin-susceptible strain of S. aureus (type 42D) and a kanamycin-arnd gentamicinresistant strain of S. aureus (clinical isolate obtained from

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

Cited by 28 publications

References 22 publications

Use of Aminoglycosides in Treatment of Infections Due to Intracellular Bacteria

Use of Aminoglycosides in Treatment of Infections Due to Intracellular Bacteria

Evaluation of antibacterial agents in a high-volume bovine polymorphonuclear neutrophil Staphylococcus aureus intracellular killing assay

Influence of human monocytes on the antibacterial activity of kanamycin and gentamicin for Staphylococcus aureus

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