Rifampin Combination Therapy for Nonmycobacterial Infections

Abstract

SUMMARY The increasing emergence of antimicrobial-resistant organisms, especially methicillin-resistant Staphylococcus aureus (MRSA), has resulted in the increased use of rifampin combination therapy. The data supporting rifampin combination therapy in nonmycobacterial infections are limited by a lack of significantly controlled clinical studies. Therefore, its current use is based upon in vitro or in vivo data or retrospective case series, all with major limitations. A prominent observation from this review is that rifampin combination therapy appears to have improved treatment outcomes in cases in which there is a low organism burden, such as biofilm infections, but is less effective when effective surgery to obtain source control is not performed. The clinical data support rifampin combination therapy for the treatment of prosthetic joint infections due to methicillin-sensitive S. aureus (MSSA) after extensive debridement and for the treatment of prosthetic heart valve infections due to coagulase-negative staphylococci. Importantly, rifampin-vancomycin combination therapy has not shown any benefit over vancomycin monotherapy against MRSA infections either clinically or experimentally. Rifampin combination therapy with daptomycin, fusidic acid, and linezolid needs further exploration for these severe MRSA infections. Lastly, an assessment of the risk-benefits is needed before the addition of rifampin to other antimicrobials is considered to avoid drug interactions or other drug toxicities.

Randomized non-inferiority trial to compare trimethoprim/sulfamethoxazole plus rifampicin versus linezolid for the treatment of MRSA infection

“…The combination of rifampicin plus trimethoprim/sulfamethoxazole is a theoretically even more attractive regimen for the treatment of MRSA infections for a number of reasons, including enhanced and intracellular antistaphylococcal activity, excellent bioavailability and favourable pharmacodynamics. 22,23 The combination is widely used in several European countries, especially for osteoarticular infections, although published evidence supporting its use remains sparse. 24,25 Moreover, since these antibiotics are available as generic agents, they offer substantial cost advantages over other agents such as linezolid and daptomycin.…”

Antagonism between Bacteriostatic and Bactericidal Antibiotics Is Prevalent

“…Drug synergy has been demonstrated to result in more-efficient clearance of infections and to achieve clearance at lower drug concentrations (6). Examples of such cases include fusidic acid and rifampin for the treatment of methicillin-resistant Staphylococcus aureus infections and trimethoprim and sulfamethoxazole for the treatment of otitis media (7,8). Furthermore, recent theoretical work indicates that synergistic drugs can prevent treatment failure even when bacteria resistant to one of the drugs are present at the beginning of therapy (9).…”

Using rifapentine – hen egg lipoprotein conjugate as macrophage-targeted drug delivery carrier against intracellularStaphylococcus aureus

“…Staphylococcus aureus could easily invade professional phagocytes and persists in the acidic lysosome compartment for several days (Imbuluzqueta et al, 2010). Rifapentine and rifampin, which show enforced bactericidal activity in acidic conditions, have been applied extensively in combinational antimicrobial therapies against intracellular S. aureus infections (Forrest & Tamura, 2010). The in vitro infection experiments in the current study demonstrated that the incorporation of RPT into heLDL led to a significant reduction of intramacrophage S. aureus.…”