An in Vitro Investigation of the Intracellular Bioactivity of Amoxicillin, Clindamycin, and Erythromycin for Staphylococcus aureus

Anderson, Ronald; Jooné, G. K.; Rensburg, C. E. J. Van

doi:10.1093/infdis/153.3.593

Cited by 30 publications

(28 citation statements)

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“…Only a few authors [5,7,9,[30][31][32][33] have used PMNLs from patients with defective respiratory burst, and have found that the intraphagocytic activity of antimicrobial agents was less efficient in these PMNLs.…”

Section: Discussionmentioning

confidence: 99%

Killing of Gram-Negative Bacteria by Ciprofloxacin within both Healthy Human Neutrophils and Neutrophils with Inactivated O<sub>2</sub>-Dependent Bactericidal Mechanisms

et al. 1999

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The intraphagocytic killing of Escherichia coli, Serratia marcescens, Pseudomonas aeruginosa, and Salmonella typhi by ciprofloxacin (0.1, 1 and 5 μg/ml) within human neutrophils with intact and impaired (by phenylbutazone treatment) O₂-dependent killing mechanisms was studied and compared with the extracellular killing in the same medium of the intraphagocytic killing, but omitting neutrophils. The MIC/MBC of ciprofloxacin in vitro (assays performed according to NCCLS specifications) were: 0.015/0.06 for E. coli, 0.12/32 for S. marcescens, 1/16 for P. aeruginosa, and 0.007/0.06 for S. typhi. Ciprofloxacin showed bactericidal activity both extracellular and within phenylbutazone-treated and untreated neutrophils. The minimum concentration of ciprofloxacin to kill 90% of phagocytosed bacteria within neutrophils with normal O₂-dependent killing power after 30 min was: 0.1 μg/ml for E. coli, and S. typhi, 1 μg/ml for P. aeruginosa, and 5 μg/ml for S. marcescens. In contrast, exposure for 60 min was required to reach this percentage within phenylbutazone treated neutrophils. The minimum concentration to kill 90% of extracellular bacteria after 30 min was: 0.1 μg/ml for E. coli, P. aeruginosa and S. typhi, and 5 μg/ml, for S. marcescens. A positive interaction between ciprofloxacin and the O₂-dependent mechanisms of phagocytes was found. The reactive oxygen metabolites produced in the respiratory burst did not affect the intraphagocytic activity of ciprofloxacin. Phenylbutazone treatment of phagocytes would be a good experimental model to study the intraphagocytic killing of drugs in situations such as AIDS and chronic granulomatous disease where inefficient oxidative mechanisms of neutrophils exist.

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Section: Discussionmentioning

confidence: 99%

Killing of Gram-Negative Bacteria by Ciprofloxacin within both Healthy Human Neutrophils and Neutrophils with Inactivated O<sub>2</sub>-Dependent Bactericidal Mechanisms

et al. 1999

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“…A remarkable example is the apoptosis of macrophages induced by pathogens such as Shigella, which both avoid the antibacterial effect of those cells and trigger inflammation (427,428). In some well-characterized examples, bacteria are able to travel from cell to cell without any significant contact with the extracellular milieu (43,273), thus avoiding the immune system as well as contact with antibiotics that do not enter mammalian cells (12,172). This provides the first clue as to how well-characterized virulence phenotypes can be related to antibiotic resistance.…”

Section: Common Mechanisms Involved In Virulence and Resistancementioning

confidence: 99%

“…Mammalian cells are poorly permeable to or easily exclude several families of antibiotics (12,166). Even if the antibiotic enters the mammalian cells, intracellular growth might induce a transient antibiotic-resistant phenotype, a situation that has been described for Legionella pneumophila (35).…”

Section: Common Mechanisms Involved In Virulence and Resistancementioning

confidence: 99%

Interactions among Strategies Associated with Bacterial Infection: Pathogenicity, Epidemicity, and Antibiotic Resistance

2002

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SUMMARY Infections have been the major cause of disease throughout the history of human populations. With the introduction of antibiotics, it was thought that this problem should disappear. However, bacteria have been able to evolve to become antibiotic resistant. Nowadays, a proficient pathogen must be virulent, epidemic, and resistant to antibiotics. Analysis of the interplay among these features of bacterial populations is needed to predict the future of infectious diseases. In this regard, we have reviewed the genetic linkage of antibiotic resistance and bacterial virulence in the same genetic determinants as well as the cross talk between antibiotic resistance and virulence regulatory circuits with the aim of understanding the effect of acquisition of resistance on bacterial virulence. We also discuss the possibility that antibiotic resistance and bacterial virulence might prevail as linked phenotypes in the future. The novel situation brought about by the worldwide use of antibiotics is undoubtedly changing bacterial populations. These changes might alter the properties of not only bacterial pathogens, but also the normal host microbiota. The evolutionary consequences of the release of antibiotics into the environment are largely unknown, but most probably restoration of the microbiota from the preantibiotic era is beyond our current abilities.

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“…In vitro, the elution of the macrolides out of the phagocytes is very rapid (within minutes) once the extracellular drug is removed (13). Several investigators have shown that 14-membered macrolides can significantly impair oxidative metabolism of the neutrophils in vitro, as assessed by luminolenhanced chemiluminescence, superoxide generation, H202 and OH-production, and myeloperoxidase-mediated iodination of proteins (1,3,11,18,21). Inhibition occurred at fairly high concentrations (50 mg/liter for roxithromycin and erythromycin) and was reversible by washing the cells (18).…”

mentioning

confidence: 99%

In vitro and in vivo intraleukocytic accumulation of azithromycin (CP-62, 993) and its influence on ex vivo leukocyte chemiluminescence

Bonnet

Auwera

1992

Antimicrob Agents Chemother

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The accumulation of azithromycin in phagocytic cells was studied both in vitro by using a radiolabelled drug and a bioassay and in vivo for 12 volunteers receiving 1.5 g (total dose) orally within 3 days. In vitro, neutrophils and unfractionated blood leukocytes accumulated azithromycin up to 160-fold the extracellular concentration within 1 h at 37°C but less than 3-fold at 4°C. Dead cells accumulated up to 30-fold azithromycin, whereas NaF-treated celis accumulated up to 60-fold arithromycin. The mean efflux from preloaded cells was at most 31.0%O ± 10.6% (standard error of the mean) of the cell-associated concentration within 4 h of incubation at 37°C in drug-free buffer. In vivo, the azithromycin concentration was 45.2 + 6.1 mg/liter of intracellular fluid at 2 h after the third dose and 36.6 ± 8.3 mg/liter at 1 week thereafter. The corresponding concentrations in serum were 0.2 ± 0.1 (2 h) and <0.05 (1 week). The luminol-enhanced chemiluminescence response induced by phorbol myristate acetate, opsonized zymosan, and two opsonized strains ofHaemophilus influenzae (a type b capsulated strain and a noncapsulated strain) was also studied ex vivo by using the blood leukocytes from the 12 test volunteers and 4 control volunteers at 2 and 6 h after the third oral dose of azithromycin and at 2, 4, and 7 days thereafter. Azithromycin did not influence this response despite high levels of cellular accumulation.Azithromycin (CP-62, 993; XZ-450) is a new 15-membered macrolide with high tissue penetration (9) and in vitro activity against intracellular pathogens such as Legionella pneumophila and Chlamydia trachomatis (8,32). Macrolides are highly accumulated by phagocytic cells through at least two mechanisms: an energy-independent mechanism, which occurs even in dead cells or at 4°C and probably depends on pH and liposolubility (23), and an energy-dependent mechanism associated with the nucleoside transport system (22). Most of the intracellular drug is located in the cytoplasm (6). In vitro, the elution of the macrolides out of the phagocytes is very rapid (within minutes) once the extracellular drug is removed (13). Several investigators have shown that 14-membered macrolides can significantly impair oxidative metabolism of the neutrophils in vitro, as assessed by luminolenhanced chemiluminescence, superoxide generation, H202 and OH-production, and myeloperoxidase-mediated iodination of proteins (1,3,11,18,21). Inhibition occurred at fairly high concentrations (50 mg/liter for roxithromycin and erythromycin) and was reversible by washing the cells (18). Other antimicrobial agents have been shown to impair the oxidative metabolism of human polymorphonuclear leukocytes (PMN) investigated in vitro (11,21,31). Very few studies have questioned the in vivo relevance of these findings. Labro et al. (17) showed the opposite results when testing roxithromycin ex vivo (enhancing of oxidative mechanisms) by comparison with their in vitro studies (16,18). The mechanism of ex vivo enhancement of oxidative functions might be due...

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An in Vitro Investigation of the Intracellular Bioactivity of Amoxicillin, Clindamycin, and Erythromycin for Staphylococcus aureus

Cited by 30 publications

References 20 publications

Killing of Gram-Negative Bacteria by Ciprofloxacin within both Healthy Human Neutrophils and Neutrophils with Inactivated O<sub>2</sub>-Dependent Bactericidal Mechanisms

Killing of Gram-Negative Bacteria by Ciprofloxacin within both Healthy Human Neutrophils and Neutrophils with Inactivated O<sub>2</sub>-Dependent Bactericidal Mechanisms

Interactions among Strategies Associated with Bacterial Infection: Pathogenicity, Epidemicity, and Antibiotic Resistance

In vitro and in vivo intraleukocytic accumulation of azithromycin (CP-62, 993) and its influence on ex vivo leukocyte chemiluminescence

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