Objectives: Albeit the prevalence of macrolide resistance in Streptococcus pyogenes reported by several countries has significantly increased, these alarming in vitro results not always demonstrate a relationship with an in vivo negative impact on clinical efficacy, since the standard susceptibility testing methods do not take into account several host's defense mechanisms, that play a key role during infection in preventing the triggering and spreading of a bacterial infection process. In order to evaluate the potential immunomodulatory activity of erythromycin upon the binomial antibiotic-resistant bacterium/host, the PMN phagocytic and bactericidal activities against streptococcal strains Ery-S and Ery-R belonging to different phenotypes were assessed in the presence of the macrolide. Methods: The erythromycin-resistance phenotypes of S.pyogenes were determined by the triple-disk diffusion testing. Polymorphonuclear cells (PMNs) were separated from lithium heparinized venous blood pooled from healthy donors, negative for the presence of microbial diseases, by using Ficoll–Paque. The effects of erythromycin on either the phagocytosis of radiolabelled S. pyogenes [3H-uracil (specific activity: 1.27 TBq/mmol; NEN Products, Milan, Italy)] or intracellular bacterial killing by PMNs were investigated by incubating the bacteria and the phagocytes (bacterium:PMN ratio was 10:1) at 37 °C for various periods in the presence of the MIC of the drug. Erythromycin-free controls were also included. Results: Our results showed that when erythromycin, PMNs and streptococci, both Ery-S and Ery-R (cMLSB, M, iMLSB-A,-B-C phenotypes), were present in the culture medium, the phagocytic activity of PMNs overlapped that of controls without drug. In contrast, the results emphasized a significant high increase of intracellular killing by PMNs in the presence of erythromycin for Ery-S and Ery-R S. pyogenes, with high (cMLSB, iMLSB-A and iMLSB-B phenotypes) and moderate (M and iMLSB-C phenotypes) level of Ery-resistance compared to controls without drug. Conclusion: These results indicate that erythromycin has a significant immunomodulating activity on host-bacterium interaction being able to determine a significant increase of microbicidal activity in human PMNs against all S. pyogenes strains, either Ery-S or Ery-R, with high and moderate resistant level, confirming that the antibiotic resistance detected in vitro does not always imply a failure of antimicrobial treatment.

Different erythromycin-resistant phenotypes of Streptococcus pyogenes do not prevent human polymorphonuclear cells from their antibacterial activity

BANCHE, Giuliana;TULLIO, Viviana Cristina;ALLIZOND, VALERIA;MANDRAS, Narcisa;ROANA, Janira;SCALAS, Daniela;CARLONE, Nicola;CUFFINI, Annamaria
2010-01-01

Abstract

Objectives: Albeit the prevalence of macrolide resistance in Streptococcus pyogenes reported by several countries has significantly increased, these alarming in vitro results not always demonstrate a relationship with an in vivo negative impact on clinical efficacy, since the standard susceptibility testing methods do not take into account several host's defense mechanisms, that play a key role during infection in preventing the triggering and spreading of a bacterial infection process. In order to evaluate the potential immunomodulatory activity of erythromycin upon the binomial antibiotic-resistant bacterium/host, the PMN phagocytic and bactericidal activities against streptococcal strains Ery-S and Ery-R belonging to different phenotypes were assessed in the presence of the macrolide. Methods: The erythromycin-resistance phenotypes of S.pyogenes were determined by the triple-disk diffusion testing. Polymorphonuclear cells (PMNs) were separated from lithium heparinized venous blood pooled from healthy donors, negative for the presence of microbial diseases, by using Ficoll–Paque. The effects of erythromycin on either the phagocytosis of radiolabelled S. pyogenes [3H-uracil (specific activity: 1.27 TBq/mmol; NEN Products, Milan, Italy)] or intracellular bacterial killing by PMNs were investigated by incubating the bacteria and the phagocytes (bacterium:PMN ratio was 10:1) at 37 °C for various periods in the presence of the MIC of the drug. Erythromycin-free controls were also included. Results: Our results showed that when erythromycin, PMNs and streptococci, both Ery-S and Ery-R (cMLSB, M, iMLSB-A,-B-C phenotypes), were present in the culture medium, the phagocytic activity of PMNs overlapped that of controls without drug. In contrast, the results emphasized a significant high increase of intracellular killing by PMNs in the presence of erythromycin for Ery-S and Ery-R S. pyogenes, with high (cMLSB, iMLSB-A and iMLSB-B phenotypes) and moderate (M and iMLSB-C phenotypes) level of Ery-resistance compared to controls without drug. Conclusion: These results indicate that erythromycin has a significant immunomodulating activity on host-bacterium interaction being able to determine a significant increase of microbicidal activity in human PMNs against all S. pyogenes strains, either Ery-S or Ery-R, with high and moderate resistant level, confirming that the antibiotic resistance detected in vitro does not always imply a failure of antimicrobial treatment.
2010
20th European Congress of Clinical Microbiology and Infectious Diseases
Vienna
10-13 april 2010
Abstract ot the 20th ECCMID
ESCMID
16 (s2)
s717
s717
Banche G; Tullio V; Allizond V; Mandras N; Roana J; Scalas D; El Fassi F; D’Antico S; Carlone N; Cuffini AM
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/72247
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