Therapeutics and delivery vehicles for local treatment of osteomyelitis

Osteomyelitis, or the infection of the bone, presents a major complication in orthopedics and may lead to prolonged hospital visits, implant failure, and in more extreme cases, amputation of affected limbs. Typical treatment for this disease involves surgical debridement followed by long-term, systemic antibiotic administration, which contributes to the development of antibiotic-resistant bacteria and has limited ability to eradicate challenging biofilm-forming pathogens including Staphylococcus aureus—the most common cause of osteomyelitis. Local delivery of high doses of antibiotics via traditional bone cement can reduce systemic side effects of an antibiotic. Nonetheless, growing concerns over burst release (then subtherapeutic dose) of antibiotics, along with microbial colonization of the nondegradable cement biomaterial, further exacerbate antibiotic resistance and highlight the need to engineer alternative antimicrobial therapeutics and local delivery vehicles with increased efficacy against, in particular, biofilm-forming, antibiotic-resistant bacteria. Furthermore, limited guidance exists regarding both standardized formulation protocols and validated assays to predict efficacy of a therapeutic against multiple strains of bacteria. Ideally, antimicrobial strategies would be highly specific while exhibiting a broad spectrum of bactericidal activity. With a focus on S. aureus infection, this review addresses the efficacy of novel therapeutics and local delivery vehicles, as alternatives to the traditional antibiotic regimens. The aim of this review is to discuss these components with regards to long bone osteomyelitis and to encourage positive directions for future research efforts.     

Elevated anti-alginate serum titers in patients with acute cholangitis and gallstones imbedded withPseudomonas aeruginosa

Electron microscopy and bacteriological culture revealed viable bacteria covered with a glycocalyx (biofilm) in choledochal stones recovered from two patients with acute cholangitis. On the cut surface of the choledochal stones, the cholesterol stone component was surrounded with a layer of brown pigment stone. In each case, bacterial culture of the choledochal stone recoveredPseudomonas aeruginosa. Since alginate is the main component of the glycocalyx produced byP. aeruginosa, serum IgM, IgG and IgA anti-alginate antibodies were measured in each patient. The present study is the first to demonstrate acute and transient IgM seroconversion to alginate in cases of acute cholangitis. In one case, the elevation of anti-alginate IgM preceded the elevation of anti-alginate IgG. The authors propose that the bacterial glycocalyx may play a significant role in acute cholangitis.     

Implication of biofilm formation in the persistence of urinary tract infection caused by uropathogenic Escherichia coli

Escherichia coli is the most frequent microorganism involved in urinary tract infection (UTI). Acute UTI caused by uropathogenic E. coli (UPEC) can lead to recurrent infection, which can be defined as either re-infection or relapse. E. coli strains causing relapse (n = 27) and re-infection (n = 53) were analysed. In-vitro production of biofilm, yersiniabactin and aerobactin was significantly more frequent among strains causing relapse. Biofilm assays may be helpful in selecting patients who require a therapeutic approach to eradicate persistent biofilm-forming E. coli strains and prevent subsequent relapses.     

Influence of macrolides on mucoid alginate biosynthetic enzyme from Pseudomonas aeruginosa

Objective: The long-term administration of erythromycin (EM), clarithromycin (CAM) or azithromycin (AZM) has generally resulted in a favorable outcome for patients with diffuse panbronchiolitis (DPB) infected with mucoid Pseudomonas aeruginosa. To elucidate the mechanism involved, the influence of macrolides on mucoid alginate production by P. aeruginosa was investigated in vitro.
Methods: The macrolides used in this study were EM with a 14-membered ring, AZM with a 15-membered ring, midecamycin (MDM) with a 16-membered ring, and CP-4305, which has had mycarose removed from MDM, The effects of macrolides on mucoid P. aeruginosa were investigated by quantitative assay of alginate production and inhibition of guanosine diphospho-D-mannose dehydrogenase activity.
Results: After incubation with EM, AZM and CP-4305, the structural material of P. aeruginosa biofilm was distorted, and the enzymatic activity of GDP-D-mannose dehydrogenase, the most important enzyme in mucoid alginate biosynthesis, was inhibited. However, these effects were not observed with the 16-membered macrolide MDM.
Conclusions: The basic mechanism of clinical efficacy seen characteristically in 14- or 15-membered macrolides for patients with airway biofilm disease depends on the ability of such macrolides to inhibit alginate production by P. aeruginosa. Furthermore, this suggests that the inhibitory effect observed with 14-, 15- and 16-membered macrolides may depend on the sugar chain connected with the macrolide ring.     

诃子水提物对球形马拉色菌及其生物被膜的抑制作用

目的 探究诃子水提物（water extract of Terminalia chebula,TRW）对球形马拉色菌的体外抗菌活性及对生物被膜的抑制作用,并初步探讨其抗菌机制。方法 采用微量稀释法测定TRW对马拉色菌的体外抗菌活性;活菌计数法测定TRW对球形马拉色菌作用的时间-杀菌曲线。通过微板法构建球形马拉色菌生物被膜体外模型,用XTT法测定生物被膜代谢活性;采用活菌计数法和扫描电子显微镜分别检测TRW对球形马拉色菌生物被膜活菌量以及微观形态的影响。采用山梨糖醇保护实验、碘化丙啶（PI）染色分别测定TRW对球形马拉色菌细胞壁和细胞膜的作用影响。结果 TRW对7株马拉色菌的最低抑菌质量浓度为0.90～4.59 mg/mL,其中对TRW敏感性最强的是球形马拉色菌MC14。时间-杀菌曲线结果显示TRW对MC14整个生长周期均有抑制作用。球形马拉色菌MC14生物被膜的初黏附期、聚集期和成熟期分别为0～24 h、24～96 h和96～168 h。TRW可降低MC14各个阶段生物被膜的活菌量,作用效果由强到弱排列为聚集期>黏附期>成熟期;且对MC14各个阶段的生物被膜均有清除作用,可...     

细菌生物被膜耐药屏蔽与相关感染的治疗

综述了细菌生物被膜耐药屏蔽的机制，主要包括生物被膜内细菌的生理状态、细菌生物被膜屏蔽以及其他方面的新进展，并提出了对细菌生物被膜相关感染的治疗方法。     

抗藻酸盐血清对黏液型铜绿假单胞菌生物被膜杀菌活性的影响

目的 :研究抗藻酸盐血清与加替沙星联用对黏液型铜绿假单胞菌生物被膜杀菌活性的影响。方法 :采用MTT方法测定黏液型铜绿假单胞菌生物被膜活菌数 ,用微量稀释法测定抗菌药物最低生物被膜清除浓度(MBEC)。结果 :1∶1抗藻酸盐血清与 1×MIC ,4×MIC和 8×MIC加替沙星联用可以使细菌生物被膜中的活菌数量 (单位为lgcfu·cm-2 )分别从 ( 6 .6 3± 0 .85 ) ,( 6 .48± 1.12 )和 ( 5 .73± 1.10 )显著降低至 ( 5 .76± 0 .90 ) ,( 5 .0 2±0 .93)和 ( 4.70± 0 .6 2 ) ,使加替沙星对铜绿假单胞菌的MBEC从 8μg·mL-1降低至 4μg·mL-1。结论 :抗藻酸盐血清与加替沙星联用后 ,能够增强抗菌药物对黏液型铜绿假单胞菌生物被膜的杀菌活性。     

铜绿假单胞菌生物被膜形成能力与基因型的相关性分析

目的 探讨铜绿假单胞菌（PA）临床分离株的粘附性、生物被膜形成能力及其与基因型的相关性。方法 采用改良的微量平板法对临床分离的48株PA生物被膜的形成进行定量分析；通过肠杆菌基因间重复一致序列-PCR（ERIC—PCR）技术绘制48株PA的指纹图谱，应用计算机软件建立遗传相似性系数矩阵及聚类分析树状图。结果 48株临床分离PA菌株生物被膜的形成能力不同。生物被膜形成能力不同的PA在基因型上表现出多态性，PA在17％遗传相似性系数上分为A、B、C、D、E五个基因型，生物被膜形成能力强的PA大都属于D型，其遗传相似性系数为42％。结论 绝大多数临床分离的PA株具有较强的生物被膜形成能力；生物被膜形成能力不同的PA在基因型上表现出多态性；生物被膜形成能力较强的PA在基因型上表现出一定的相似性。     

老年机械通气患者气管内导管生物被膜形成状况的研究

目的：探讨老年机械通气患者气管内导管生物被膜的形成状况,明确相关性和危险因素.方法：分析22例老年患者的25个气管导管各留置时间段与细菌培养结果.结果：25个气管导管细菌培养阳性22个,占88%,培养阴性的3个,占12%.结论：细菌密度与气管插管时间密切相关,随着插管时间的延长,细菌计量明显增加.