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Evaluation of High-Dose Daptomycin Versus Vancomycin Alone or Combined with Clarithromycin or Rifampin Against Staphylococcus aureus and S. epidermidis in a Novel In Vitro PK/PD Model of Bacterial Biofilm.

Hall Snyder AD, Vidaillac C, Rose W, McRoberts JP, Rybak MJ - Infect Dis Ther (2014)

Bottom Line: Of interest, CLA did not appear to enhance DAP or VAN killing activities, and the addition of RIF prevented the emergence of resistance to DAP or VAN in all organisms.Using an in vitro bacterial biofilm model containing three common prosthetic device materials, DAP + RIF and VAN + RIF were the most effective regimens.DAP + RIF displayed the greatest activity and represents a promising combination to evaluate for treatment of biofilm-associated staphylococcal infections.

View Article: PubMed Central - PubMed

Affiliation: Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Ave., Detroit, MI, 48201, USA.

ABSTRACT

Introduction: Medical device infections are associated with significant morbidity and mortality. These difficult-to-treat infections often result in antibiotic failure and resistance. Combination therapy is often required, however, the most optimal combination is unknown. We evaluated the in vitro activity of daptomycin (DAP) or vancomycin (VAN) alone and in combination with rifampin (RIF) or clarithromycin (CLA) against strains of Staphylococcus aureus and S. epidermidis grown in biofilm on 3 prosthetic device materials.

Methods: One methicillin-resistant S. aureus (MRSA R5266), one heteroresistant vancomycin-intermediate S. aureus (hVISA R3640), and one methicillin-resistant S. epidermidis (MRSE R461) strain was evaluated in a CDC biofilm reactor with titanium, Teflon(®), and steel coupons. Regimens simulated included DAP 10 mg/kg/day, and VAN 1 g q12h alone or in combination with RIF 600 mg q24h or CLA 250 mg q12h. Additional regimens including DAP 12 mg/kg/day or VAN ± RIF 450 mg q12h were evaluated against the hVISA strain.

Results: DAP + RIF or VAN + RIF demonstrated enhanced activity against R3640 in embedded biofilm (EB) cells in all materials versus DAP or VAN alone (P ≤ 0.040). Only DAP + RIF demonstrated sustained bactericidal activity (≥3.80 log10 CFU/cm(2) reduction from baseline) against EB and planktonic cells of R5266 and EB cells of R461 in all 3 materials. Of interest, CLA did not appear to enhance DAP or VAN killing activities, and the addition of RIF prevented the emergence of resistance to DAP or VAN in all organisms.

Conclusion: Using an in vitro bacterial biofilm model containing three common prosthetic device materials, DAP + RIF and VAN + RIF were the most effective regimens. DAP + RIF displayed the greatest activity and represents a promising combination to evaluate for treatment of biofilm-associated staphylococcal infections.

No MeSH data available.


Related in: MedlinePlus

MRSE 461 embedded biofilm a Teflon coupon prior to antibiotic exposure; b after 72 h of DAP + RIF exposure. SEM images are at 1000× magnification. DAP daptomycin, MRSE methicillin-resistant Staphylococcus epidermidis, RIF rifampin, SEM scanning electron microscopy
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Fig2: MRSE 461 embedded biofilm a Teflon coupon prior to antibiotic exposure; b after 72 h of DAP + RIF exposure. SEM images are at 1000× magnification. DAP daptomycin, MRSE methicillin-resistant Staphylococcus epidermidis, RIF rifampin, SEM scanning electron microscopy

Mentions: Against MRSA 5266 and MRSE 461 (Fig. 1a, b), only DAP combined with RIF demonstrated therapeutic enhancement, even reaching bactericidal activity and exceeding 4 log10 CFU/cm2 kill (range 4.13–4.38) when using TT, TE and ST. Reduction in the colony counts from baseline (T0) to 72 h were significantly greater on TT and ST coupons from baseline (T0) to 72 h (Δ0 to 72, P ≤ 0.032, P ≤ 0.024, respectively) than all other regimens (Fig. 1; Table 2). These reductions were visible on SEM for MRSE 461 displaying fewer cells on TE coupons after therapy with DAP and RIF at 72 h (Fig. 2a). Although the combination of VAN + RIF did not display significant enhancement against MRSA 5266 versus VAN alone, a >3 log10 CFU/cm2 reduction (range 3.2–3.82) was noted for this combination against MRSE 461 for TT, TE and ST (P ≤ 0.044). Regrowth at 48 h was correlated with the emergence of resistance to RIF (RIF MIC >32 mg/L) for DAP-containing regimen against MRSE 461. Resistance to RIF was noted in the VAN + RIF for 5266, however, it was not correlated with regrowth. Against platonic bacteria (PB) of both MRSE 461 and MRSA 5266, DAP alone or combined with CLA or RIF, and VAN displayed bactericidal activity, however, only the combinations with RIF had sustained activity over 72 h (data not shown). The addition of CLA to VAN or DAP did not improve killing activity compared to either agent alone against PB (data not shown) or EB of MRSA 5266.Fig. 1


Evaluation of High-Dose Daptomycin Versus Vancomycin Alone or Combined with Clarithromycin or Rifampin Against Staphylococcus aureus and S. epidermidis in a Novel In Vitro PK/PD Model of Bacterial Biofilm.

Hall Snyder AD, Vidaillac C, Rose W, McRoberts JP, Rybak MJ - Infect Dis Ther (2014)

MRSE 461 embedded biofilm a Teflon coupon prior to antibiotic exposure; b after 72 h of DAP + RIF exposure. SEM images are at 1000× magnification. DAP daptomycin, MRSE methicillin-resistant Staphylococcus epidermidis, RIF rifampin, SEM scanning electron microscopy
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Related In: Results  -  Collection

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Fig2: MRSE 461 embedded biofilm a Teflon coupon prior to antibiotic exposure; b after 72 h of DAP + RIF exposure. SEM images are at 1000× magnification. DAP daptomycin, MRSE methicillin-resistant Staphylococcus epidermidis, RIF rifampin, SEM scanning electron microscopy
Mentions: Against MRSA 5266 and MRSE 461 (Fig. 1a, b), only DAP combined with RIF demonstrated therapeutic enhancement, even reaching bactericidal activity and exceeding 4 log10 CFU/cm2 kill (range 4.13–4.38) when using TT, TE and ST. Reduction in the colony counts from baseline (T0) to 72 h were significantly greater on TT and ST coupons from baseline (T0) to 72 h (Δ0 to 72, P ≤ 0.032, P ≤ 0.024, respectively) than all other regimens (Fig. 1; Table 2). These reductions were visible on SEM for MRSE 461 displaying fewer cells on TE coupons after therapy with DAP and RIF at 72 h (Fig. 2a). Although the combination of VAN + RIF did not display significant enhancement against MRSA 5266 versus VAN alone, a >3 log10 CFU/cm2 reduction (range 3.2–3.82) was noted for this combination against MRSE 461 for TT, TE and ST (P ≤ 0.044). Regrowth at 48 h was correlated with the emergence of resistance to RIF (RIF MIC >32 mg/L) for DAP-containing regimen against MRSE 461. Resistance to RIF was noted in the VAN + RIF for 5266, however, it was not correlated with regrowth. Against platonic bacteria (PB) of both MRSE 461 and MRSA 5266, DAP alone or combined with CLA or RIF, and VAN displayed bactericidal activity, however, only the combinations with RIF had sustained activity over 72 h (data not shown). The addition of CLA to VAN or DAP did not improve killing activity compared to either agent alone against PB (data not shown) or EB of MRSA 5266.Fig. 1

Bottom Line: Of interest, CLA did not appear to enhance DAP or VAN killing activities, and the addition of RIF prevented the emergence of resistance to DAP or VAN in all organisms.Using an in vitro bacterial biofilm model containing three common prosthetic device materials, DAP + RIF and VAN + RIF were the most effective regimens.DAP + RIF displayed the greatest activity and represents a promising combination to evaluate for treatment of biofilm-associated staphylococcal infections.

View Article: PubMed Central - PubMed

Affiliation: Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Ave., Detroit, MI, 48201, USA.

ABSTRACT

Introduction: Medical device infections are associated with significant morbidity and mortality. These difficult-to-treat infections often result in antibiotic failure and resistance. Combination therapy is often required, however, the most optimal combination is unknown. We evaluated the in vitro activity of daptomycin (DAP) or vancomycin (VAN) alone and in combination with rifampin (RIF) or clarithromycin (CLA) against strains of Staphylococcus aureus and S. epidermidis grown in biofilm on 3 prosthetic device materials.

Methods: One methicillin-resistant S. aureus (MRSA R5266), one heteroresistant vancomycin-intermediate S. aureus (hVISA R3640), and one methicillin-resistant S. epidermidis (MRSE R461) strain was evaluated in a CDC biofilm reactor with titanium, Teflon(®), and steel coupons. Regimens simulated included DAP 10 mg/kg/day, and VAN 1 g q12h alone or in combination with RIF 600 mg q24h or CLA 250 mg q12h. Additional regimens including DAP 12 mg/kg/day or VAN ± RIF 450 mg q12h were evaluated against the hVISA strain.

Results: DAP + RIF or VAN + RIF demonstrated enhanced activity against R3640 in embedded biofilm (EB) cells in all materials versus DAP or VAN alone (P ≤ 0.040). Only DAP + RIF demonstrated sustained bactericidal activity (≥3.80 log10 CFU/cm(2) reduction from baseline) against EB and planktonic cells of R5266 and EB cells of R461 in all 3 materials. Of interest, CLA did not appear to enhance DAP or VAN killing activities, and the addition of RIF prevented the emergence of resistance to DAP or VAN in all organisms.

Conclusion: Using an in vitro bacterial biofilm model containing three common prosthetic device materials, DAP + RIF and VAN + RIF were the most effective regimens. DAP + RIF displayed the greatest activity and represents a promising combination to evaluate for treatment of biofilm-associated staphylococcal infections.

No MeSH data available.


Related in: MedlinePlus