耐甲氧西林金黄色葡萄球菌(MRSA)感染通常由于其生物膜形成能力和耐药性而难以治疗。我们研究了抗生素的亚最低抑制浓度(MIC)对MRSA生物膜形成的影响。临床MRSA分离株与纳夫西林亚MIC(1/256-1/2×MIC)一起生长,万古霉素,环丙沙星,还有利福平.使用结晶紫染色测量生物膜生物量。在测试的107株MRSA分离物中,63(58.9%)属于序列类型5(ST5),44人(41.1%)属于ST72。纳夫西林的MIC50/MIC90值,万古霉素,环丙沙星,利福平分别为256/512、1/2、64/512和0.008/0.03mg/L,分别。纳夫西林亚中等收入国家,万古霉素,环丙沙星,利福平促进了75例(70.1%)的生物膜形成,49(45.8%),89(83.2%),和89个(83.2%)分离株,分别。在纳夫西林亚中等收入国家,与强生物膜诱导相关的因素是ST5菌株(P=0.001)和agr功能障碍(P=0.005)。对于环丙沙星的亚MIC,相关因素为ST5菌株(P=0.002),葡萄球菌蛋白A型t002株(P<0.001),环丙沙星耐药(P<0.001)。在利福平的次中等收入国家中,只有ST5与强生物膜诱导相关(P=0.006)。因为利福平的亚MIC远低于临床相关浓度,我们进一步测试了在0.03[公式:参见正文]32mg/L利福平中的生物膜诱导能力。在这些浓度下,利福平诱导的生物膜形成在利福平易感MRSA中很少见[1.0%(100个中的1个)],但在利福平耐药MRSA中常见[71.4%(7个中的5个),P<0.001]。在抗生素的亚MIC处诱导生物膜生物量在临床MRSA分离株中很常见,并且受到MRSA菌株和抗生素类别的不同影响。
目的:在给药方案的开始和结束时,细菌可以暴露于亚MIC的抗生素,在剂量之间,或在低剂量治疗期间。越来越多的证据表明,抗微生物剂的亚MIC可以刺激MRSA生物膜形成并改变生物膜基质的组成。大量研究发现,苯唑西林的亚MIC,甲氧西林,和阿莫西林促进一些社区获得性MRSA(CA-MRSA)的生物膜形成。我们评估了44种CA-MRSA和63种医疗保健相关MRSA(HA-MRSA)菌株中四种不同类别抗生素的亚MIC对生物膜的诱导。我们的研究表明,纳夫西林亚MIC,万古霉素,环丙沙星,和利福平经常促进临床MRSA分离株的生物膜诱导。纳夫西林亚MIC中的强生物膜诱导,环丙沙星,利福平在HA-MRSA中比在CA-MRSA中更常见。抗生素诱导的生物膜形成取决于抗生素类别,MRSA菌株,抗生素耐药性。我们的结果强调了维持有效的抗生素杀菌浓度以治疗生物膜相关感染的重要性。
Methicillin-resistant Staphylococcus aureus (MRSA) infections are often difficult to treat because of their biofilm-forming ability and antimicrobial resistance. We investigated the effects of sub-minimal inhibitory concentrations (MICs) of antibiotics on MRSA biofilm formation. Clinical MRSA isolates were grown with sub-MICs (1/256-1/2 × MICs) of
nafcillin, vancomycin, ciprofloxacin, and rifampin. The biofilm biomass was measured using crystal violet staining. Of the 107 MRSA isolates tested, 63 (58.9%) belonged to sequence type 5 (ST5), and 44 (41.1%) belonged to ST72. The MIC50/MIC90 values of
nafcillin, vancomycin, ciprofloxacin, and rifampin were 256/512, 1/2, 64/512, and 0.008/0.03 mg/L, respectively. The sub-MICs of
nafcillin, vancomycin, ciprofloxacin, and rifampin promoted biofilm formation in 75 (70.1%), 49 (45.8%), 89 (83.2%), and 89 (83.2%) isolates, respectively. At sub-MICs of
nafcillin, the factors associated with strong biofilm induction were the ST5 strain (P = 0.001) and agr dysfunction (P = 0.005). For the sub-MICs of ciprofloxacin, the associated factors were the ST5 strain (P = 0.002), staphylococcal protein A type t002 strain (P < 0.001), and ciprofloxacin resistance (P < 0.001). Among the sub-MICs of rifampin, only ST5 was associated with strong biofilm induction (P = 0.006). Because the sub-MICs of rifampin were much lower than clinically relevant concentrations, we further tested the capability of biofilm induction in 0.03[Formula: see text]32 mg/L of rifampin. At these concentrations, rifampin-induced biofilm formation was rare in rifampin-susceptible MRSA [1.0% (1 of 100)] but common in rifampin-resistant MRSA [71.4% (5 of 7), P < 0.001]. Induction of biofilm biomass at sub-MICs of antibiotics is common in clinical MRSA isolates and is differentially affected by the MRSA strain and antibiotic class.
OBJECTIVE: Bacteria can be exposed to sub-MICs of antibiotics at the beginning and end of a dosing regimen, between doses, or during low-dose therapies. Growing evidence suggests that sub-MICs of antimicrobials can stimulate MRSA biofilm formation and alter the composition of the biofilm matrix. Pevious studies have found that sub-MICs of oxacillin, methicillin, and amoxicillin promote biofilm formation in some community-acquired MRSA (CA-MRSA). We evaluated biofilm induction by sub-MICs of four different classes of antibiotics in 44 CA-MRSA and 63 healthcare-associated MRSA (HA-MRSA) strains. Our study indicated that sub-MICs of
nafcillin, vancomycin, ciprofloxacin, and rifampin frequently promote biofilm induction in clinical MRSA isolates. Strong biofilm induction in sub-MICs of nafcillin, ciprofloxacin, and rifampin was more frequent in HA-MRSA than in CA-MRSA. Antibiotic-induced biofilm formation depends on the antibiotic class, MRSA strain, and antibiotic resistance. Our results emphasize the importance of maintaining effective bactericidal concentrations of antibiotics to treat biofilm-related infections.