Studies on the Antibacterial Effects of Statins - In Vitro and In Vivo

Abstract

BackgroundStatin treatment has been associated with a beneficial outcome on respiratory tract infections. In addition, previous in vitro and in vivo experiments have indicated favorable effects of statins in bacterial infections.AimThe aim of the present study was to elucidate possible antibacterial effects of statins against primary pathogens of the respiratory tract.MethodsMIC-values for simvastatin, fluvastatin and pravastatin against S. pneumoniae, M. catarrhalis and H. influenzae were determined by traditional antibacterial assays. A BioScreen instrument was used to monitor effects of statins on bacterial growth and to assess possible synergistic effects with penicillin. Bacterial growth in whole blood and serum from healthy volunteers before and after a single dose of simvastatin, fluvastatin and penicillin (positive control) was determined using a blood culture system (BactAlert).FindingsThe MIC-value for simvastatin against S pneumoniae and M catarrhalis was 15 µg/mL (36 mmol/L). Fluvastatin and Pravastatin showed no antibacterial effect in concentrations up to 100 µg/mL (230 µmol/L). Statins did not affect growth or viability of H influenzae. Single doses of statins given to healthy volunteers did not affect growth of pneumococci, whereas penicillin efficiently killed all bacteria.ConclusionsSimvastatin at high concentrations 15 µg/mL (36 µmol/L) rapidly kills S pneumoniae and M catarrhalis. However, these concentrations by far exceed the concentrations detected in human blood during simvastatin therapy (1–15 nmol/L) and single doses of statins given to healthy volunteers did not improve antibacterial effects of whole blood. Thus, a direct bactericidal effect of statins in vivo is probably not the mechanism behind the observed beneficial effect of statins against various infections.

Is There Potential for Repurposing Statins as Novel Antimicrobials?

“…Simvastatin and lovastatin (10 mg/liter) are also reportedly bactericidal against the spirochete Borrelia burgdorferi (the causative agent of Lyme disease) (45), and atorvastatin, rosuvastatin, and simvastatin were found to inhibit the growth of Escherichia coli, a prominent cause of gastroenteritis and urinary tract infections (38). In contrast, however, Bergman et al, using a maximum concentration of 250 mg/liter, observed that simvastatin did not inhibit the growth of H. influenzae (43), while Graziano et al found that simvastatin, atorvastatin, and pravastatin at concentrations up to 250 mg/liter did not inhibit the growth of P. aeruginosa, E. coli, or Enterococcus faecalis (42). Furthermore, a study by Thangamani et al (41) indicated that, while the growth of Gram- (41,42), it is worth noting that the E. coli ATCC 3218 assays were performed on solid agar while the other studies were performed using the broth microdilution method, perhaps explaining the apparent differences in activity.…”

“…Taken together, the data suggest that the antibacterial activity of statins may be statin specific and/or strain/species specific or both. Simvastatin and atorvastatin generally appear to be more effective against S. aureus, S. pneumoniae, and enterococci than other statins (37)(38)(39)43), while three distinct simvastatin MICs were reported against S. aureus clinical isolates from the United Kingdom and Jordan as well as against typed reference strains (Table 1) (37,38,41,42). It is also noteworthy that, while the MICs of statins varied according to the statin and pathogen tested, the in vitro MICs ranged from circa 15 to 400 mg/liter, far exceeding the range of typical peak plasma concentrations of patients on oral statins, which generally range from circa 10 to 300 g/liter.…”

“…Current information on the synergistic relationship between statins and antibiotics is limited and conflicting (Table 3). A significant synergistic effect resulting in increased bacterial lysis has been reported with sublethal doses of penicillin and simvastatin (7.8 mg/liter) against pneumococcal growth in vitro (43), while atorvastatin and simvastatin (0.2 M) treatment increased the efficacy of rifampin against M. tuberculosis and M. leprae infection in vitro by approximately 50% (54). In addition, in vivo mouse studies showed that atorvastatin (80 mg/kg/day) treatment increased the efficacy of rifampin against M. leprae infection (P Ͻ 0.05) (54) and that simvastatin (25 mg/kg) treatment increased the in vivo activity of first-line anti-TB antibiotics, reducing the lung bacillary burden by Ͼ1 log 10 (P Ͻ 0.01) (82).…”

Perioperative Statin Therapy Is Not Associated With Reduced Risk of Anastomotic Leakage After Colorectal Resection

“…30,31 these mechanisms could support a hypothetical effect of statins for prevention of al after colorectal surgery; however, most of the published studies on the pleiotropic effects was conducted in experimental settings other than intestinal anastomosis. therefore, results should be interpreted with caution in relation to al.…”

Is there a role for statins in fungal infections?

“…Thus, both pravastatin and pitavastatin are interesting candidates for clinical studies of synergy between statins and traditional antifungal drugs. At therapeutic doses, the mean concentrations of statins in human serum are in the nanomolar range [18][19][20][21][22] as shown in TABLE 1.…”