1. Microb Drug Resist. 2020 Jun;26(6):537-544. doi: 10.1089/mdr.2019.0282. Epub 
2019 Dec 11.

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.

Nguyen TK(1), Argudín MA(2), Deplano A(2), Nhung PH(3), Nguyen HA(4), Tulkens 
PM(1), Dodemont M(2), Van Bambeke F(1).

Author information:
(1)Pharmacologie Cellulaire et Moléculaire, Louvain Drug Research Institute, 
Université Catholique de Louvain (UCLouvain), Brussels, Belgium.
(2)Centre National de Référence des Staphylocoques, Laboratoire Hospitalier 
Universitaire de Bruxelles (LHUB-ULB) Site Anderlecht, Hôpital Erasme-Cliniques 
Universitaires de Bruxelles, Université Libre de Bruxelles, Brussels, Belgium.
(3)Department of Microbiology, Bach Mai Hospital, Hanoi, Vietnam.
(4)The National Center for Drug Information and Adverse Drug Reactions 
Monitoring, Hanoi University of Pharmacy, Hanoi, Vietnam.

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.

DOI: 10.1089/mdr.2019.0282
PMID: 31825276