Antimicrobial treatment concepts for orthopaedic device-related infection

Successful management of orthopaedic device-related infections requires combined surgical and antimicrobial therapy. Because of the heterogeneity of clinical situations, controlled trials are lacking. Although rational concepts for surgical treatment have been published, many aspects of antimicrobial therapy are still not well documented. In this review, some of these knowledge gaps are discussed, and rational arguments for initial parenteral treatment are presented. In addition, the interpretation of data regarding bone penetration is discussed. Whereas rifampin is now a standard combination partner in the treatment of staphylococcal infections, its role against other microorganisms is still unclear. Finally, in view of the increasing prevalence of methicillin-resistant staphylococci and their decreasing susceptibility to vancomycin, data are provided on linezolid and daptomycin, which can potentially be used in bone and joint infections.     

Treatment of prosthetic osteoarticular infections

Introduction: Despite being relatively infrequent, prosthetic joint infections are a devastating medical complication. However, recent advances in surgical techniques, new antibiotics, and knowledge about pathogenic mechanisms have improved the outcome for affected patients.

Areas covered: We have analyzed recent advances in pathogenesis, medical and surgical therapy of prosthetic joint infections, with special focus on new antibiotics useful for this disease. Recent studies focused on the important role of biofilms and intracellular bacteria in the pathogenesis of biomaterial-related infections. These advances must guide the management of the patients. Together with more classical antibiotics, linezolid and daptomycin have shown their usefulness for the treatment of these infections. Recently developed lipoglycopeptides have the potential to be used for these infections. In this sense, the possibility of treating patients with oral antibiotics without lack of efficacy is of great interest.

Expert opinion: Individualized therapies that take into account the microbial etiology, pathogenesis of the disease, antimicrobial susceptibility, and efficacy of antibiotics against biofilms and intracellular organisms make it possible to treat even those infections caused by multidrug-resistant organisms. A multidisciplinary approach (including a surgeon, infectious diseases specialist and microbiologist) provides the best possible management of patients.     

Current treatment for nocardia infections

Introduction: Nocardiosis is an infectious actinomycetic disease with a variable clinical spectrum that makes it difficult to diagnose. It mainly affects immunosuppressed individuals. Advances in molecular genomic technology have helped in identifying new pathogenic Nocardia species. This has made identification of their specific antimicrobial sensitivity possible.

Areas covered: It is important to know the taxonomy, clinical features, diagnosis and precise species identification because of the multitude of pathogenic species involved and the different antibiotic susceptibility patterns. The authors review sulfonamides, aminoglycosides, penicillin derivatives, tetracyclines, glycylcyclines, oxazolidinones, carbapenems and the association of other potential drugs, the therapeutic effectiveness of traditional antimicrobials and new monotherapy and combined treatment alternatives. New oxazolidinones and the benzothiazinones are compounds that have been found effective in vitro and in experimental models.

Expert opinion: Clinicians should be aware of nocardiosis in patients with different forms of immunosuppression. The identification of organisms, their patterns of antibiotic susceptibility and the adverse effects related to these drugs must be considered. Treatments can vary from traditional schemes with trimethoprim–sulfamethoxazole to other combination therapies and new antibiotics and treatment modalities depending on the organ or site involved, the severity of infection and the presence of comorbidities.     

高效液相色谱法测定人血清、脑脊液和胰液中利奈唑胺浓度

 目的 建立同时测定人血清、脑脊液、胰液中利奈唑胺药物浓度的HPLC测定方法。方法 以利培酮为内标物,在0.1 mol·L^-1NaOH碱性条件下甲基叔丁基醚-正丙醇=90∶10(V/V)液液提取,Shima-pack CLC-ODS-C₁₈(6.0 mm×150 mm,5 μm)色谱柱分离,流动相为甲醇-乙腈-磷酸缓冲溶液(0.02 mol·L^-1KH₂PO₄,H₃PO₄调pH 3.5)=20∶16∶64(V/V/V),流速1.0 mL·min^-1,柱温35 ℃,检测波长254 nm条件下测定。结果 血清中利奈唑胺在0.25~40.0 mg·L^-1内线性良好(r=0.999 9),3个浓度质控样本(0.8、8.0、25.0 mg·L^-1)的批内、批间变异(RSD)分别为1.64%~2.38%(n=5)、4.53%~6.34%(n=5),方法学和提取回收率分别为93.781%~97.393%(n=5)、72.318%~73.442%(n=5);脑脊液中在0.1~20.0 mg·L^-1内线性良好(r=0.999 3),3个浓度质控样本(0.2、2.0、15.0 mg·L^-1)的批内、批间变异(RSD)分别为3.84%~4.83%(n=5)、6.04%~8.16%(n=5),方法学和提取回收率分别为106.910%~110.971%(n=5)、73.226%~80.603%(n=5);胰液中在0.1~20.0 mg·L^-1内线性良好(r=0.999 4),3个浓度质控样本(0.2、2.0、15.0 mg·L^-1)的批内、批间变异(RSD)分别为2.96%~5.30%(n=5)、4.68%~6.40%(n=5),方法学和提取回收率分别为97.178%~105.072%(n=5)、73.333%~76.010%(n=5)。内标提取回收率＞87%。结论 本方法灵敏度高,准确性好,简便快捷,应用液液提取处理样本去除更多杂峰干扰,更广泛适用于临床,尤其适用于合并用药患者生物标本中利奈唑胺药物浓度的测定。     

2株利奈唑胺中介粪肠球菌23S rRNA V区基因变异检测

目的研究粪肠球菌对利奈唑胺（LNZ）的耐药情况和耐药机制,为临床合理用药提供依据。 方法收集2012年1月-2013年1月深圳市南山区人民医院接受LNZ治疗患者痰液标本分离的粪肠球菌12株,采用琼脂稀释法测定抗菌药物的最低抑菌浓度(MIC),聚合酶链反应（PCR）扩增23S rRNA V区基因,并进行测序分析。结果12株菌中,2株为中介株（菌株编号分别为3和6）,10株为敏感株。2株中介株均检测到G2576U突变,其中1株（编号6）还同时存在C2424U突变;10株敏感株未检测到变异。C2424U和G2576U突变分别发生在23S rRNA V区基因的R1区和R4区。结论粪肠球菌LNZ中介株中发现23S rRNA V区基因变异,提示临床应密切关注LNZ的MIC变化。     

2743株革兰阳性菌的临床分离及耐药性分析

目的探讨我院2013年革兰阳性菌的临床分离及耐药情况。方法常规方法培养、分离革兰阳性菌,用纸片扩散法、Etest法或全自动细菌分析仪测定细菌对不同抗菌药物的敏感性,采用2013年版CLSI标准判读结果。结果共分离2 743株革兰阳性菌,葡萄球菌属占43.3%,肠球菌属占35.6%,链球菌属占15.2%。金黄色葡萄球菌、表皮葡萄球菌和溶血葡萄球菌对苯唑西林耐药率分别为46.9%,81.4%和94.2%,未发现万古霉素和利奈唑胺耐药葡萄球菌。屎肠球菌对利奈唑胺和万古霉素耐药率分别为0.4%和0.5%,粪肠球菌对利奈唑胺耐药率为0.3%,未发现万古霉素耐药粪肠球菌。结论万古霉素、利奈唑胺和替考拉宁对葡萄球菌、肠球菌和链球菌仍有很高抗菌活性,甲氧西林耐药葡萄球菌比率较高。     

Predictors of Clinical Success Among a National Veterans Affairs Cohort With Methicillin-Resistant Staphylococcus aureus Pneumonia

Background

The treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is exceedingly complicated, which is concerning because of the high mortality rate associated with the infection. Identification of independent predictors of clinical success can optimize patient care by assisting clinicians in treatment decisions.

Objectives

Our goal was to identify independent predictors of clinical success in a national Veterans Affairs (VA) cohort of patients with MRSA pneumonia.

Methods

A nested case-control study was conducted among a cohort of VA patients with MRSA pneumonia receiving linezolid or vancomycin between January 2002 and September 2010. Cases included those demonstrating clinical success, defined as discharge from the hospital or intensive care unit by day 14 after treatment initiation, in the absence of death, therapy change, or intubation by day 14. Control subjects represented nonsuccess, defined as therapy change, intubation, intensive care unit admission, readmission, or death between treatment initiation and day 14. The potential predictors assessed included treatment, patient demographic and admission characteristics, previous health care and medication exposures, comorbidities, and medical history. Odds ratios (ORs) and 95% CIs were calculated from logistic regression.

Results

Our study included 2442 cases of clinical success and 1290 control subjects. Demographic characteristics varied between the clinical success and nonsuccess groups, including age, race, and region of facility. A current diagnosis of chronic respiratory disease (46% vs 42%) and diagnosis of pneumonia in the year before the MRSA pneumonia admission (37% vs 32%) were both more common in the clinical success group. Despite these significant differences, only 2 predictors of clinical success were identified in our study: previous complication of an implant or graft, including mechanical complications and infections, in the year before the MRSA pneumonia admission (adjusted OR, 1.55 [95% CI, 1.17–2.06]) and treatment with linezolid (adjusted OR, 1.53 [95% CI, 1.12–2.10]). Predictors of nonsuccess (adjusted OR [95% CI) included diagnosis of concomitant urinary tract infection (0.82 [0.70–0.96]), intravenous line (0.76 [0.66–0.89]), previous coagulopathy (0.74 [0.56–0.96]), previous amputation procedure (0.72 [0.53–0.98]), current coagulopathy diagnosis (0.71 [0.53–0.96]), dialysis (0.54 [0.38–0.76]), multiple inpatient procedures (0.53 [0.45–0.62]), inpatient surgery (0.48 [0.41–0.57]), and previous endocarditis (0.24 [0.07–0.81]).

Conclusions

MRSA pneumonia tends to affect patients with complex care, and identification of the predictors of clinical success is useful when considering different therapeutic approaches. In this national cohort of VA patients with MRSA pneumonia, treatment was the only modifiable variable predicting clinical success.