Combination therapy with ampicillin and azithromycin improved outcomes in a mouse model of group B streptococcal sepsis

Kirtikumar Upadhyay, Basu Hiregoudar, Elizabeth Meals, Boyce Keith English, Ajay Talati

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Evidence suggests that β-lactam monotherapy of streptococcal infections may incite stronger inflammation and is inferior to combination therapy with macrolides. We hypothesized that use of macrolides alone or in combination with a β-lactam for group B streptococcal (GBS) sepsis would improve outcomes by reducing inflammation. Methods: TNF-α was measured from supernatants of RAW 264.7 cells stimulated with GBS isolates, in presence of four treatment regimens: ampicillin alone, azithromycin alone, or combination of azithromycin plus ampicillin. Mouse model of GBS sepsis was developed and treated with same four regimens. Clinical sepsis scores were monitored; serum cytokines (TNF-α, IL-6, IL-10) and chemokines (MIP-1α) were measured at the end. Results: GBS isolates exposed to azithromycin or combination (compared to ampicillin alone) stimulated less TNF production in vitro. In the murine sepsis model, mortality was lower along with decreased sepsis scores in mice treated with combination therapy. Mean serum IL-6 was lower in mice treated with azithromycin alone (66±52 pg/ml) or combination of ampicillin plus azithromycin (52±22 pg/ml) compared to ampicillin alone (260±160 pg/ml) (p<0.005). Conclusions: Combination therapy of ampicillin+azithromycin improved outcomes in a murine GBS sepsis model; this therapeutic approach deserves additional study.

Original languageEnglish (US)
Article numbere0182023
JournalPLoS ONE
Volume12
Issue number7
DOIs
StatePublished - Jul 1 2017

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azithromycin
sepsis (infection)
Azithromycin
Ampicillin
ampicillin
Sepsis
animal models
therapeutics
lactams
Lactams
macrolides
Macrolides
mice
interleukin-6
Interleukin-6
Therapeutics
inflammation
Inflammation
Streptococcal Infections
chemokines

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Combination therapy with ampicillin and azithromycin improved outcomes in a mouse model of group B streptococcal sepsis. / Upadhyay, Kirtikumar; Hiregoudar, Basu; Meals, Elizabeth; English, Boyce Keith; Talati, Ajay.

In: PLoS ONE, Vol. 12, No. 7, e0182023, 01.07.2017.

Research output: Contribution to journalArticle

Upadhyay, Kirtikumar ; Hiregoudar, Basu ; Meals, Elizabeth ; English, Boyce Keith ; Talati, Ajay. / Combination therapy with ampicillin and azithromycin improved outcomes in a mouse model of group B streptococcal sepsis. In: PLoS ONE. 2017 ; Vol. 12, No. 7.
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abstract = "Background: Evidence suggests that β-lactam monotherapy of streptococcal infections may incite stronger inflammation and is inferior to combination therapy with macrolides. We hypothesized that use of macrolides alone or in combination with a β-lactam for group B streptococcal (GBS) sepsis would improve outcomes by reducing inflammation. Methods: TNF-α was measured from supernatants of RAW 264.7 cells stimulated with GBS isolates, in presence of four treatment regimens: ampicillin alone, azithromycin alone, or combination of azithromycin plus ampicillin. Mouse model of GBS sepsis was developed and treated with same four regimens. Clinical sepsis scores were monitored; serum cytokines (TNF-α, IL-6, IL-10) and chemokines (MIP-1α) were measured at the end. Results: GBS isolates exposed to azithromycin or combination (compared to ampicillin alone) stimulated less TNF production in vitro. In the murine sepsis model, mortality was lower along with decreased sepsis scores in mice treated with combination therapy. Mean serum IL-6 was lower in mice treated with azithromycin alone (66±52 pg/ml) or combination of ampicillin plus azithromycin (52±22 pg/ml) compared to ampicillin alone (260±160 pg/ml) (p<0.005). Conclusions: Combination therapy of ampicillin+azithromycin improved outcomes in a murine GBS sepsis model; this therapeutic approach deserves additional study.",
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