Antibiotic Resistance, Biofilm Formation, and Intracellular Survival As Possible Determinants of Persistent or Recurrent Infections by Staphylococcus aureus in a Vietnamese Tertiary Hospital: Focus on Bacterial Response to Moxifloxacin.

Abstract

Resistance is notoriously high in Asia but may not entirely explain therapeutic failures. Specific modes of bacterial life, such as biofilm or intracellular survival, may also contribute to the persistent and/or recurrent character of infections. Most Staphylococcus aureus isolates form biofilm and many survive and even thrive intracellularly. We collected 36 nonduplicate S. aureus isolates (including 18 methicillin-resistant S. aureus) from patients with clinical evidence of persistent or recurrent infections in a large tertiary Vietnamese hospital. We examined their antibiotic resistance profile (minimal inhibitory concentration determination) and clonal relatedness (spa and agr typing, pulsed field gel electrophoresis profiles). We then assessed the activity of moxifloxacin in both biofilms and infected phagocytes (moxifloxacin previously proved to be one of the most active antibiotics against reference strains in these models). spa-types t189 and t437 and agr group I were the most frequent. Among the 36 isolates, 30 were multidrug resistant but 30 were recovered from patients having received an active drug. All tested isolates produced biofilm and survived inside phagocytes. At its human Cmax, moxifloxacin was inactive on biofilms made by moxifloxacin-susceptible as well as moxifloxacin-resistant isolates. It caused only a modest intracellular colony-forming unit decrease against moxifloxacin-susceptible isolates and was inactive against those resistant to moxifloxacin. While our data confirm for this collection the high resistance levels and prevalence of endemic spa- or agr- types in Asia, they show that tolerance in both biofilm and phagocytes are correlated and markedly limit moxifloxacin activity, which goes in line with the suggested role of these modes of life in persistence or recurrence of infections.