Effect of Ampicillin/Sulbactam on Human Polymorphonuclear Leukocyte Function

Pascual, Álvaro; Conejo, M. Carmen; Lopez, Gianluca; Perea, Evelio J.

doi:10.1159/000238876

Cited by 4 publications

(5 citation statements)

References 13 publications

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“…The incubation of the PMN with different concentrations of linezolid did not affect its production of either superoxide or hydrogen peroxidase radicals. A similar effect has been described for some ß-lactams [19], fluoroquinolones [20] and glycopeptides [21].…”

Section: Discussionsupporting

confidence: 77%

Effect of Linezolid on the Phagocytic Functions of Human Polymorphonuclear Leukocytes

Ballesta

Pascual²,

Garcı́a³

et al. 2003

Chemotherapy

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The effect of linezolid on the phagocytic and bactericidal functions of human polymorphonuclear neutrophils (PMN) against gram-positive cocci was evaluated. Preincubation (30 min; 37°C) of PMN with different concentrations of linezolid (2, 10 and 20 mg/l) did not significantly affect the phagocytosis of either Staphylococcus aureus (methicillin susceptible and resistant) or Enterococcus faecalis (vancomycin susceptible and resistant). Overnight exposure of vancomycin-resistant E. faecalis to 1/4 minimum inhibitory concentrations (MIC) of linezolid slightly increased phagocytosis by PMN. Preincubation of the other three strains with 1/4 MIC of linezolid did not affect phagocytosis by these cells. Preincubation of PMN (30 min; 37°C) using different extracellular concentrations of linezolid (2, 10 and 20 mg/l) did not affect their production of either superoxide or hydrogen peroxide radicals. In conclusion, linezolid did not affect the phagocytic and bactericidal functions of human PMN.

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Section: Discussionsupporting

confidence: 77%

Effect of Linezolid on the Phagocytic Functions of Human Polymorphonuclear Leukocytes

Ballesta

Pascual²,

Garcı́a³

et al. 2003

Chemotherapy

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“…Sulbactam is a 1-lactamase inhibitor used in combination with ampicillin and other beta-lactam antibiotics to enhance their spectra (17). It has previously been reported that sulbactam can reverse neutrophil inhibition caused by ampicillin (23) and facilitate bacterial killing (14,20). Our results describe a mechanism(s) by which ampicillin inhibits neutrophil function and offer further insight into the interactions among ampicillin, sulbactam, and host defenses.…”

supporting

confidence: 54%

“…The effects of beta-lactam antibiotics on neutrophil killing have been studied extensively (see Discussion) (25,27). It has previously been reported that sulbactam can also affect neutrophil killing of bacteria (14,20,23). Direct treatment of PMN with sulbactam (2, 5, or 10 ,ug/ml) had no effect upon their ability to kill S. aureus (data not shown).…”

Section: Resultsmentioning

confidence: 69%

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Oxidant-scavenging activities of ampicillin and sulbactam and their effects on neutrophil functions

Gunther

Mao

Cohen

1993

Antimicrob Agents Chemother

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Luminol-enhanced luminescence is a method used to measure formation of reactive oxygen intermediates important in the ability of neutrophils to kill microbes. Several studies have demonstrated that under some conditions of incubation, ampicillin can inhibit neutrophil-derived luminol-enhanced luminescence. We evaluated the mechanism(s) by which ampicillin inhibited the luminescent response of stimulated neutrophils.We also investigated sulbactam, a 13-lactamase inhibitor which has been given in combination with ampicillin and other beta-lactam antibiotics to increase their spectra, for possible similar effects. Both ampicillin and sulbactam attenuated luminol-enhanced luminescence by approximately 40%. Superoxide production was not prevented by added ampicillin, nor was superoxide scavenged by it. Myeloperoxidase reacts with H202 and Clto generate OCl-, which is believed to be the oxidizer of luminol that is primarily responsible for enhancement of neutrophil-derived luminescence. Hydroxyl radicals (HO'), which may also oxidize luminol, resulting in luminescence, can be formed from 02 and H202 via either myeloperoxidase-dependent (involving intermediate OCI-) or myeloperoxidase-independent (through a metal ion catalyst) reactions. Ampicillin scavenged H202 and OCl-and prevented 95% of Fenton reaction-generated HO' from reacting with 5,5-dimethyl-1-pyrroline-N-oxide. Sulbactam was found to scavenge OCl-and HO0, but less avidly than ampicillin did.Neither ampicillin nor sulbactam inhibited myeloperoxidase activity. Sublethal concentrations of sulbactam had no significant effect on neutrophil killing of Staphylococcus aureus and Escherichia coli. Our results demonstrate a mechanism(s) by which ampicillin inhibits luminol-enhanced luminescence from stimulated neutrophils, namely, through scavenging of the oxidant(s) primarily responsible for the generation of luminescence.

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“…A short exposure to vancomycin increased the susceptibility of Enterococcus faecalis to PMNs (Bayer & Tu, 1990). The combination of ampicillan/sulbactam enhanced the suscepbility of Staphylococcus aureus to phagocytosis by PMNs, in contrast, and probably due to low intracellular penetration of /?-lactams, the same combination displayed no significant antimicrobial effect against the bacterium when 'it was intracellularly located, within the PMNs (Pascual et al, 1991). Short exposure of Pseudomonas aeruginosa to supra-MIC concentrations of amikacin increased killing by PMNs even in absence of opsonization (Bayer et al, 1991).…”

mentioning

confidence: 98%