Evaluation of linezolid or trimethoprim/sulfamethoxazole in combination with rifampicin as alternative oral treatments based on an in vitro pharmacodynamic model of staphylococcal biofilm

被引：23

作者：

El Haj, Cristina ^{[1
]}

Murillo, Oscar ^{[1
,2
]}

Ribera, Alba ^{[1
]}

Lloberas, Nuria ^{[3
,4
]}

Gomez-Junyent, Joan ^{[1
]}

Tubau, Fe ^{[5
,6
]}

Fontova, Pere ^{[3
,4
]}

Cabellos, Carme ^{[1
,2
]}

Ariza, Javier ^{[1
,2
]}

机构：

[1] Univ Barcelona, Lab Expt Infect, Infect Dis Serv, IDIBELL,Hosp Univ Bellvitge, Feixa Llarga S-N, Barcelona 08907, Spain

[2] Inst Salud Carlos III, Spanish Network Res Infect Dis REIPIRD12 0015, Madrid, Spain

[3] Univ Barcelona, Serv Nephrol, Campus Bellvitge,Feixa Llarga S-N, Barcelona 08907, Spain

[4] Univ Barcelona, Lab Expt Nephrol, Campus Bellvitge,Feixa Llarga S-N, Barcelona 08907, Spain

[5] Hosp Univ Bellvitge, IDIBELL, Dept Microbiol, Barcelona, Spain

[6] ISCIII, CIBERES, Dept Microbiol, Madrid, Spain

来源：

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS | 2018年 / 51卷 / 06期

关键词：

Foreign-body infection; Staphylococcus aureus; Rifampicin combinations; Cotrimoxazole; Trimethoprim/sulfamethoxazole; Biofilm; PROSTHETIC JOINT INFECTIONS; FOREIGN-BODY INFECTION; HIGH-DOSE DAPTOMYCIN; TRIMETHOPRIM-SULFAMETHOXAZOLE; AUREUS; SERUM; TRIAL; BONE; CLARITHROMYCIN; DEBRIDEMENT;

D O I：

10.1016/j.ijantimicag.2018.01.014

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

Combinations of linezolid (LZD) or trimethoprim/sulfamethoxazole (SXT) plus rifampicin (RIF) are alternative oral treatments for staphylococcal prosthetic joint infections (PJIs) when fluoroquinolones are not possible to use, but there is limited evidence regarding their activity. This study evaluated the efficacy of LZD and SXT, alone and in combination with RIF, against Staphylococcus aureus in an in vitro pharmacokinetic/pharmacodynamic biofilm model. Using the CDC Biofilm Reactor (R) system, simulated regimens of LZD (600 mg every 12 h), SXT (160/800 mg every 8 h) and levofloxacin (LVX) (750 mg/day), alone and in combination with RIF (600 mg/day), were evaluated against one methicillin-susceptible S. aureus (MSSA) and one methicillin-resistant S. aureus (MRSA) strain. Antibiotic efficacy was evaluated by the decrease in planktonic bacterial counts from medium and biofilm-embedded bacteria from coupons over 56 h. Resistant strains were screened. In both strains, SXT alone was ineffective and LZD presented low activity, but no resistance emerged. Combinations with RIF significantly increased the antibiofilm efficacy against MSSA (Delta log CFU/mL 56h-0h: SXT + RIF, -2.9 and LZD + RIF, -3.1), but RIF-resistant strains appeared with SXT + RIF. Against MRSA, LZD + RIF (-3.1) protected against the emergence of resistance and was more effective than SXT + RIF (-0.6; P < 0.05), in which RIF-resistant strains were again detected. LVX + RIF confirmed its high efficacy against biofilm-embedded bacteria, this being the most effective therapy (-5.1 against MSSA). The emergence of RIF-resistant strains with SXT + RIF poses serious concerns for its use in clinical practice. Interestingly, LZD + RIF appears to be an appropriate alternative for PJI caused by LVX-resistant S. aureus. (c) 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

引用

页码：854 / 861

页数：8

共 39 条

[1] Executive summary of management of prosthetic joint infections. Clinical practice guidelines by the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) [J].