In Vitro Activity of Rifampin, Rifabutin, Rifapentine, and Rifaximin against Planktonic and Biofilm States of Staphylococci Isolated from Periprosthetic Joint Infection

Abstract

The in vitro activities of rifampin, rifabutin, rifapentine, and rifaximin were tested against 200 periprosthetic joint infection (PJI)-associated staphylococci. Seven rifampin-resistant isolates had MICs of ≥4 μg/ml. Three isolates had rifampin MICs of 0.25 to 1 μg/ml and harbored an Asp471Gly RpoB variant, suggesting that the CLSI rifampin-susceptible staphylococcal breakpoint of ≤1 μg/ml may be too high. The remaining isolates had rifampin MICs of ≤0.016 μg/ml, and the rifampin, rifabutin, rifapentine, and rifaximin minimum biofilm bactericidal concentrations (MBBC) for ≥50% of isolates were 8, 1, 2, and 4 μg/ml (for S. aureus) and 2, 0.06, 0.25, and 0.5 μg/ml (for S. epidermidis), respectively, for rifampin-susceptible isolates. Nonrifampin rifamycins have promising staphylococcal activity, including antibiofilm activity.

Controversy about the Role of Rifampin in Biofilm Infections: Is It Justified?

“…However, the interaction of rifampin and other antibiotics in vitro is difficult to interpret, because synergism/antagonism in vitro does not correlate with the effect in vivo [48]. Based on experimental data, the antibiofilm effect seems to be a class effect of all rifamycin derivatives [26,49,50]. First clinical data suggest that rifabutin is a valuable alternative to rifampin with less adverse events and less drug-drug interactions [51].…”

Liposomes as a Nanoplatform to Improve the Delivery of Antibiotics into Staphylococcus aureus Biofilms

“…Three antibiotics were chosen for an initial screening, regarding susceptibility tests and incorporation in liposomes. The selected antibiotics were the fluoroquinolone, levofloxacin (LEV), usually recommended for the treatment of S. aureus bone and joint infections [ 24 ], the glycopeptide vancomycin (VCM), the gold standard antibiotic in clinical practice against S. aureus infections [ 12 , 25 ], and the rifamycin, rifabutin (RFB), a broad-spectrum antibiotic covering S. aureus strains [ 26 ]. To achieve our goal, the design and characterization of liposomes with different lipid compositions for each antibiotic were accomplished and the susceptibility of a S. aureus methicillin-susceptible strain (MSSA), both in planktonic and biofilm forms, was assessed.…”

Peer Review #1 of "Biofilm released cells can easily be obtained in a fed-batch system using ica+ but not with ica- isolates (v0.1)"

“…S. epidermidis infections are more likely to happen upon invasive procedures involving indwelling medical devices, in which the physiological barriers are compromised, since this bacterium is a ubiquitous inhabitant of the skin and mucosae in humans (Ziebuhr et al, 2006) and has a strong ability to form biofilms on the surface of medical devices (Cerca et al, 2005;Laverty et al, 2013). Bacteria within biofilms are undoubtedly more resistant to antibiotics (Albano et al, 2019;Cerca et al, 2005a;Dias et al, 2018) and to the host immune defense (Cerca et al, 2006;Gray et al, 1984;Yao et al, 2005), contributing to the persistence and recurrence of infections (Mah, 2012;Schommer et al, 2011;Singh and Ray, 2014). For all these reasons, biofilms have been a major research target and extensive studies allowed to characterize the biofilm lifecycle and divide it into three main stages: attachment, maturation and disassembly (as reviewed in (Boles and Horswill, 2011;Otto, 2013)).…”