Efficacy of Azithromycin in a Mouse Pneumonia Model against Hospital-Acquired Methicillin-Resistant Staphylococcus aureus

Abstract

The use of macrolides against pneumonia has been reported to improve survival; however, little is known about their efficacy against methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. In this study, we investigated the effect of azithromycin (AZM) and compared it with that of vancomycin (VCM) and daptomycin (DAP) in a murine model of MRSA pneumonia. Mice were infected with MRSA by intratracheal injection and then treated with AZM, VCM, or DAP. The therapeutic effect of AZM, in combination or not with the other drugs, was compared in vivo, whereas the effect of AZM on MRSA growth and toxin mRNA expression was evaluated in vitro. In vivo, the AZM-treated group showed significantly longer survival and fewer bacteria in the lungs 24 h after infection than the untreated group, as well as the other anti-MRSA drug groups. No significant decrease in cytokine levels (interleukin-6 [IL-6] and macrophage inflammatory protein-2 [MIP-2]) in bronchoalveolar lavage fluid or toxin expression levels (α-hemolysin [Hla] and staphylococcal protein A [Spa]) was observed following AZM treatment. In vitro, AZM suppressed the growth of MRSA in late log phase but not in stationary phase. No suppressive effect against toxin production was observed following AZM treatment in vitro. In conclusion, contrary to the situation in vitro, AZM was effective against MRSA growth in vivo in our pneumonia model, substantially improving survival. The suppressive effect on MRSA growth at the initial stage of pneumonia could underlie the potential mechanism of AZM action against MRSA pneumonia.

Novel Tet(L) Efflux Pump Variants Conferring Resistance to Tigecycline and Eravacycline in Staphylococcus Spp.

“…All animal experiments were conducted in accordance with the approved guidelines of the Institutional Animal Care and Use Committee. Seven- to 9-week-old BALB/c female mice weighing 15–18 g served for the sepsis model and SPF level KM female mice for the pneumonia model according to the methods described previously ( 36 , 37 ). They were purchased from Henan Hua Xing Laboratory Animal Co., Ltd. (Zhengzhou, China; HXDW20010004).…”

Pathogenic Effect of Prevotella intermedia on a Mouse Pneumonia Model Due to Methicillin-Resistant Staphylococcus aureus With Up-Regulated α-Hemolysin Expression

“…The following MRSA clinical strains were used in this study: HUYM (saphylococcal cassette chromosome [SCC] mec type III; Yamashita et al, 2019 ), NU1643 (SCC mec type II; TSST+), and NU1516 (SCC mec type IV; PVL+). The HUYM strain was isolated at Hokkaido University School of Medicine; whereas the other two strains were isolated at Nagasaki University Hospital.…”

“…Intratracheal infection was performed as previously described with minor modifications ( Nagaoka et al, 2014a ; Yamashita et al, 2019 ). The MRSA strain was cultured on a sheep blood agar plate (Nissui Pharmaceutical Industrial Co.) for 24 h at 37°C, then scraped and suspended in trypticase soy broth (TSB), and cultured with shaking for 8 h at 37°C and 250 rpm.…”

“…Bronchoalveolar Lavage (BAL) was performed as described previously ( Nagaoka et al, 2014a ; Yamashita et al, 2019 ). Recovered fluid fractions were pooled for each animal.…”

Safety, efficacy, and analysis of key parameters after prophylactic administration of a sustained-release formulation of azithromycin in lung cancer surgery

“…Recently, a single-administration type, sustained-release formulation of AZM, Azithromycin-2 g SR (AZM-SR) has been found to accumulate at high concentrations in the target organs, show broad spectrum for respiratory infection, and ensure simple and secure compliance by single administration (12). Moreover, AZM modulates immune reactions by suppressing inflammatory cytokine release (13)(14)(15)(16)(17). Recently, AZM has been reported to reduce lung inflammation and MUC5B gene expression, which is responsible for encoding a major core protein secreted from the respiratory tract that is correlated with inflammation in the respiratory system (13,15).…”