Multi-system Infection with Nocardia farcinica-therapy with linezolid and minocycline

We describe a case of disseminated infection with a multiple-resistant strain of Nocardia farcinica, probably resulting from direct inoculation during a road traffic accident. Initial presentation was with pulmonary symptoms, with subsequent development of cutaneous, renal, soft tissue and cerebral involvement. Precise microbiological diagnosis was delayed. Once sensitivity test results were available, the patient was stabilised on linezolid and minocycline. Premature withdrawal of therapy at one month resulted in recrudescence of infection, requiring re-institution of treatment. Linezolid was discontinued after a total of 4 months, because of evidence of myelosuppression and visual impairment, which subsequently improved. Monotherapy with minocycline was continued for a total of 12 months. The patient now remains well.     

Optimizing therapy for vancomycin-resistant enterococci (VRE)

Enterococci are gram-positive, facultative bacteria with low intrinsic virulence but capable of causing a diverse variety of infections such as bacteremia with or without endocarditis, and intra-abdominal, wound, and genitourinary infection. During the past 2 decades the incidence of hospital-acquired enterococcal infection has significantly risen and is increasingly due to multidrug-resistant strains, primarily to the coacquisition of genetic determinants that encode for the stable expression of high-level beta-lactam, aminoglycoside, and glycopeptide resistance. Because enterococci constitute part of the normal colonizing flora, careful clinical interpretation of cultures that grow enterococci is paramount to avoid unnecessary and potentially deleterious antimicrobial therapy. Traditional antimicrobial treatment for ampicillin- and glycopeptide-susceptible enterococcal infection remains a penicillin-, ampicillin-, semisynthetic penicillin-based regimen, or vancomycin in a penicillin-intolerant individual. The need for a bactericidal combination with a cell-wall active agent combined with an aminoglycoside is most supported for native- or prosthetic valve endocarditis but is unproven for the majority of infections due to enterococci. The emergence of vancomycin-resistant enterococci prompted the clinical development of several novel and modified antimicrobial compounds approved for VRE infection (quinupristin-dalfopristin, linezolid) and several approved for non-VRE indications (daptomycin, tigecycline). There is a paucity of comparative clinical trial data with these new agents, although linezolid, based upon its efficacy and tolerability, appears to be the cornerstone of current treatment approaches. Despite a relatively short period of clinical use, enterococcal resistance has now been described for quinupristin-dalfopristin and linezolid and more recently even for daptomycin and tigecycline. Moreover, the optimal treatment of endocarditis due to VRE strains is unknown because, with the exception of daptomycin, current treatment options only yield bacteriostasis. Nonantimicrobial measures to treat VRE infection, such as foreign body removal and percutaneous or surgical drainage of close-spaced infection, reduce both the need for and the duration of anti-enterococcal treatment and the emergence of resistance to the newer antimicrobials.     

Nocardia asiatica visiting Belgium: nocardiosis in a immunocompetent patient

We report the case of a 57-year-old lady presenting with a Nocardia asiatica infection in Belgium. No predisposing conditions were found except for an underlying asthma. We reviewed the literature and discussed the role of linezolid in the treatment of nocardiosis.     

老年慢性阻塞性肺疾病并肺诺卡菌感染9例临床分析

目的探讨老年慢性阻塞性肺疾病并肺诺卡菌感染患者的临床特征、影像学特点及治疗转归,提高该病的早期诊断及治疗水平。方法回顾性分析我院2014.1-2018.12收治的9例慢性阻塞性肺疾病并肺诺卡菌感染老年患者的临床资料,并进行文献复习。结果9例中男性6例,女性3例,年龄65~83岁,平均年龄73.78±6.14岁;6例长期吸入糖皮质激素,4例合并2型糖尿病;常见症状有发热、咳痰和气短,可伴咯血。常见胸部CT表现为结节、肿块影、支气管扩张、肺实变伴空洞及磨玻璃影。血气分析表现为不同程度的呼吸衰竭,5例患者应用机械通气治疗。经支气管肺泡灌洗液确诊5例,痰培养确诊3例,经皮肺穿刺活检确诊1例。确诊后分别应用磺胺甲噁唑/甲氧苄啶、米诺环素、美罗培南、利奈唑胺、头孢哌酮舒巴坦、莫西沙星、依替米星、伏立康唑等抗菌药物联合治疗,3例患者死亡,6例患者好转出院。结论慢性阻塞性肺疾病合并肺诺卡菌感染在老年患者常为多重复杂混合感染,常见的症状为发热及咳痰,容易合并严重呼吸衰竭,病情进展快,因临床症状不典型,易漏诊及延误诊断,死亡率高。针对肺诺卡菌感染的一线治疗以磺胺甲基异恶唑为主的联合治疗,应尽早足量、足疗程,以改善患者的预后。     

含利奈唑胺化疗方案治疗术后耐多药脊柱结核患者的效果分析

目的 评价含利奈唑胺化疗方案治疗术后耐多药脊柱结核患者的临床疗效及安全性。方法 收集2013年5月至2017年4月北京胸科医院骨科收治的16例耐多药脊柱结核患者,手术后经不含利奈唑胺方案行抗结核药物治疗6个月后无效,后改为含利奈唑胺方案行抗结核药物治疗。通过对比抗结核药物治疗方案调整前后的化疗成功率、植骨融合率、疼痛视觉模拟评分(visual analogue scale, VAS)变化情况,以及与利奈唑胺相关的不良反应发生情况,评价含利奈唑胺方案治疗耐多药脊柱结核的临床疗效及安全性。结果 含利奈唑胺方案抗结核药物治疗的成功率为75.0%(12/16),治疗失败率为25.0%(4/16);植骨融合率为81.3%(13/16);使用含利奈唑胺方案抗结核药物治疗前VAS得分平均为(5.8±1.4)分;使用含利奈唑胺方案后VAS得分平均为(2.3±1.5)分,差异有统计学意义(t=6.546,P=0.000);12例患者椎体感染及椎旁脓肿逐渐吸收。与利奈唑胺相关的不良反应发生率为56.3%(9/16),胃肠道反应的发生率31.3%(5/16),末梢神经炎的发生率43.8%(7/16),贫血的发生率37.5%(6/16),头晕的发生率12.5%(2/16),皮疹的发生率6.3%(1/16)。减少利奈唑胺剂量后,与利奈唑胺相关的药物不良反应严重程度减轻。结论 含利奈唑胺方案治疗耐多药脊柱结核的临床疗效确切,但与利奈唑胺剂量相关的药物不良反应的发生率较高。     

Disseminated Nocardia otitidiscaviarum infection in a woman with sickle cell anemia and end-stage renal disease

Nocardia otitidiscaviarum is an uncommon human pathogen and a rare cause of pulmonary infection and bacteremia. We report a case of N. otitidiscaviarum bacteremia and pulmonary infection in a patient with end-stage renal disease (chronic kidney disease, stage 5) and sickle cell anemia. The epidemiology, pathogenesis, and treatment of Nocardia infections are discussed.     

Pulmonary Nocardia otitidis-caviarum infection in a patient with Cushing's disease]

While Nocardial infections are being diagnosed with increasing frequency, infection with Nocardia otitidiscaviarum remains relatively uncommon. We report a case of pulmonary Nocardia otitidis-caviarum infection in a 35-year-old man with Cushing's disease. This work describes the first case of nocardiosis in Japan caused by Nocardia otitidis-caviarum in Cushing's disease. The patient was admitted to our department because of edema. A diagnosis of Cushing's disease was made on the basis of elevated serum levels of cortisol and adrenocorticotropic hormone (ACTH) and pituitary adenoma was found in a cranial CT scan. One month after admission, chest radiographs showed a large bilateral mass on the lung fields. Nocardia otitidis-caviarum was isolated from the sputum. The patient responded poorly to intravenous PAPM/BP, but later improved after treatment with trimethoprim-sulfamethoxazole, but he died of heart failure and respiratory failure after the initiation of this therapy. This case demonstrated that nocardiosis must be considered in differential diagnosis as an opportunistic infection.     

A case of liver nocardiosis associated with Crohn's disease while treating infliximab

A 23-year-old man, complaining of chronic diarrhea, was given a diagnosis of Crohn's disease. He responded well to steroid therapy and infliximab administration. However, high fever appeared on the 28th day of hospitalization, and CT scan revealed multiple liver abscesses. Gram-positive branched rods were harvested by ultrasonography guided puncture examination. As Nocardia infection was suspected, sulfamethoxazole-trimethoprim was started immediately, and his clinical course improved dramatically. Afterwards, Nocardia farcinica was isolated from the culture of the liver abscess. This case is the first report of liver nocardiosis associated with Crohn's disease. Generally, Nocardia infection can be successfully treated by sulfamethoxazole-trimethoprim therapy. Liver nocardiosis is very rare but could be an important complication for patients with Crohn's disease.     

Disseminated nocardiosis due to Nocardia otitidiscaviarum:A case report and literature review

Rationale: Disseminated nocardiosis due to Nocardia otitidiscaviarum is rarely reported in immunocompetent hosts.Patient concerns: A 59 year old male patient complained of painful soft tissue swellings and fever for two days.Diagnosis: Disseminated nocardiosis due to Nocardia otitidiscaviarum. Interventions: Initial antimicrobial therapy with imipenem and trimethoprim/sulfamethoxazole was switched to 6 weeks of trimethoprim/sulfamethoxazole, linezolid and tigecycline after sensitivity test results were available. Thereafter, the patient was switched to maintenance trimethoprim/sulfamethoxazole and moxifloxacin. Prednisolone was gradually tapered.Outcomes: Soft tissue swelling and pain disappeared and the patient was discharged uneventfully.Lessons: Disseminated nocardiosis due to Nocardia otitidiscaviarum should be suspected in immunocompetent hosts with risk factors such as medication with prednisolone. Early identification of the causative species and susceptibility results is crucial given the diverse resistance patterns amongst various Nocardia species.     

糖尿病合并原发性肝癌患者介入术后感染发生状况及其影响因素分析

目的分析糖尿病合并原发性肝癌患者介入治疗后发生感染的影响因素,以期指导未来临床该疾病介入治疗后防治感染方案的制定。方法回顾性分析,搜集2019年2月至2020年10月期间入院行介入治疗后发生感染的42例糖尿病合并原发性肝癌患者的临床资料,将其纳入感染组;另搜集同时间入院行介入治疗后未发生感染的40例糖尿病合并原发性肝癌患者的临床资料,将其纳入未感染组。记录并对比两组基线资料,找出可能导致糖尿病合并原发性肝癌患者介入治疗后发生感染的高危因素。结果将糖尿病合并原发性肝癌患者介入治疗后发生感染的情况作为因变量(1=发生,2=未发生),经Logistic回归分析显示,糖尿病病程、原发性肝癌病程、放化疗、Child-Pugh分级、围术期侵入性操作、贫血、胰岛素抵抗指数均可能是糖尿病合并原发性肝癌患者介入治疗后发生感染的影响因素(OR=73.667、85.500、61.667、380.00、74.000、218.667、68.889,P<0.05)。结论糖尿病病程(≥1年)、原发性肝癌病程(≥1年)、放化疗(是)、Child-Pugh分级、围术期侵入性操作(≥3次)、贫血(是)、胰岛素抵抗指数均可能是糖尿病合并原发性肝癌患者介入治疗后发生感染的影响因素,临床针对合并上述高危因素的患者,给予针对性干预治疗,对提高糖尿病合并原发性肝癌患者介入治疗效果,促进良性结局具有关键意义。     

Remission of severe aplastic anemia associated with hepatitis B virus infection after viral clearance: potential role of lamivudine

Although viral hepatitis infection is known to be associated with aplastic anemia, a causal link between viral hepatitis and aplastic anemia has not been convincingly demonstrated. A case of hepatitis B-associated severe aplastic anemia is described which only partially responded to conventional immunosuppressive treatment but went into complete clinical remission after clearance of the hepatitis B virus. Disappearance of the hepatitis B virus occurred during lamivudine treatment and coincided with immune activation secondary to discontinuation of immunosuppressive therapy. This case was somewhat atypical in that a history of acute hepatitis preceding the aplastic anemia was absent. The observation made in this case report supports a cause-effect relationship between hepatitis B virus infection and aplastic anemia.     

Pulmonary nocardiosis re-visited: experience of 35 patients at diagnosis

Pulmonary infection by Nocardia is an uncommon opportunistic infection in humans. Thirty-five patients with pulmonary nocardiosis were identified in two tertiary referral hospitals. A retrospective review of the patient characteristics, clinical and laboratory features including antimicrobial susceptibility at diagnosis was carried out. Radiological features derived from chest radiographs and CT scans were also documented. In our population, the predominant risk factors were immuno-compromised state, corticosteroid therapy, and underlying pulmonary pathology. The presenting features were similar to those previously described but disseminated infection was not common. The radiological changes were diverse and non-specific. Nocardia asteroides was the commonest species. Most Nocardia isolates were susceptible to imipenem, ceftriaxone, amikacin, and cotrimoxazole. Co-existing microbial agents are common and reflect the underlying complex disorders.     

Isolation of Nocardia species in patients with cystic fibrosis

The isolation of Nocardia species from the respiratory secretions of patients with cystic fibrosis presents problems with important clinical implications. From the sputum culture of a total of 387 patients with cystic fibrosis, Nocardia species was isolated in 9 cases (2%; 8 females and 1 male) with a mean (SD) age of 17 (7) years. Sixty-seven percent of the patients were asymptomatic and no relevant radiographic or analytical changes were detected. In only 3 patients was of Nocardia species isolated again in successive samples. Two patients were not treated, 7 were treated with cotrimoxazole and 3 with minocycline; in 2 cases therapy was intravenous. After a mean follow-up of 48 (33) months, all patients had improved. Isolation of Nocardia species from the secretions of patients with cystic fibrosis does not necessarily imply infection and the need for treatment should be assessed on an individual basis.     

诺卡菌感染患者44例的临床特征及其预后

目的:了解诺卡菌感染患者的临床特征及预后。方法:回顾性分析2013年1月至2019年7月于上海复旦大学附属华山医院感染科诊治的44例诺卡菌感染患者的临床资料,包括一般临床表现、基础疾病、使用糖皮质激素情况、实验室检查指标(包括血常规、降钙素原、C反应蛋白、淋巴细胞亚群等)、影像学改变、菌种鉴定、治疗与转归。根据感染类型分为单纯肺部感染组、肺外单个器官感染组和播散性感染组。两组间比较采用曼-惠特尼U检验,多组间比较采用Kruskal-Wallis H检验。结果:44例诺卡菌感染患者中,14例为单纯肺部感染,17例为肺外单个器官感染(其中中枢神经系统感染9例,皮肤软组织感染6例,腹腔脓肿1例,尿路感染1例),13例为播散性感染(其中血流感染4例,中枢神经系统合并肺部或皮肤软组织感染6例,肺部合并皮肤软组织感染3例)。34例患者合并基础疾病,27例患者正在使用糖皮质激素或免疫抑制剂。11例单纯肺部感染患者的主要表现为咳嗽、咳痰;肺外单个器官感染和播散性感染患者的主要表现为发热。诺卡菌菌种以巴西、星形、鼻疽诺卡菌为主。白细胞计数和中性粒细胞比例正常或轻度升高42例,血小板计数正常或轻度下降41例,红细胞沉降率升高19例,降钙素原升高21例,C反应蛋白升高34例,铁蛋白升高18例。34例患者检测了淋巴细胞亚群,其中15例CD4+T淋巴细胞下降,14例CD8+T淋巴细胞升高,7例B淋巴细胞升高,7例B淋巴细胞下降,8例自然杀伤细胞下降。单纯肺部诺卡菌感染患者血红蛋白高于肺外单个器官感染患者,差异有统计学意义(U=0.095,P=0.025)。影像学表现以脓肿、炎症渗出为主。治愈或好转40例,1例仍在治疗,死亡3例。结论:累及各部位的诺卡菌病的临床表现无特异性,经过规范治疗可降低诺卡菌病的病死率。     

1例盖尔森基兴诺卡菌血流感染病原学诊断报告

目的 加强对诺卡菌病的认识,以提升其临床诊疗水平。方法 回顾分析乐山市人民医院肾病内科的1例盖尔森基兴诺卡菌血流感染的临床资料,包括临床表现、实验室检查、影像学检查、诊疗情况等。结果 此病人的临床表现及影像学检查缺乏特异性,检验人员镜检发现其革兰氏染色涂片结果为革兰阳性、分枝状长杆菌,细菌的16S rRNA测序分析证实为盖尔森基兴诺卡菌。结论 诺卡菌病多发生于机体免疫受损及合并慢性基础疾病的人群,临床表现和影像学缺乏特异性,诊断需依赖于病原学检查,合格标本的采集和革兰氏染色对诺卡菌病是早期诊断及正确治疗的重要步骤。     

Efficacy of linezolid in the treatment of mediastinitis due to methicillin-resistant Staphylococcus aureus: an experimental study.

INTRODUCTION: The treatment of postoperative mediastinitis is very important because of its high morbidity, mortality, and increased hospital stay and hospital costs. The aims of our research were to investigate whether linezolid alone can be an effective treatment agent for methicillin-resistant Staphylococcus aureus (MRSA) mediastinitis, and to determine whether linezolid can provide synergistic activity when given in combination with rifampin. METHODS: A partial upper median sternotomy was performed on 70 rats. The animals were divided into seven groups: an uncontaminated control group; an untreated contaminated group; three contaminated groups that received antibiotic therapy with either 25 or 50 mg/kg linezolid twice a day, or rifampin 5 mg/kg twice a day; and two contaminated groups that received a combination therapy consisting of 25 or 50 mg/kg linezolid and rifampin 5 mg/kg twice a day. The antibiotic treatment lasted 7 days. Tissue samples from the upper ends of the sternum and swab specimens of the upper mediastinum were obtained and evaluated microbiologically. RESULTS: The 25-mg/kg dose of linezolid, either alone or combined with rifampin, was not effective in reducing the bacterial counts in mediastinum and sternum. Quantitative bacterial cultures of mediastinum and sternum were significantly lower in the groups receiving 50 mg/kg linezolid alone or in combination with rifampin compared with the control. Adding of rifampin to linezolid therapy did not result in a significant change in bacterial counts versus linezolid alone. CONCLUSION: A high dose of linezolid should be considered as a possible therapeutic agent for the treatment of post-sternotomy infection caused by MRSA.     

Nocardiasis in patients with HIV infection

The frequency of Nocardia infection in HIV-infected patients has increased during the past few years from 0.3% in 1985 to 1.8% in 1989. Although it is not of great concern as an AIDS-associated infection, the nonspecific clinical presentation in these patients might be confused with other lung infections such as tuberculosis (TB). The mortality rate can be as high as 60%. The authors diagnosed three homosexual men with nocardiasis among 1060 HIV-infected patients (0.2%) in a tertiary care center in Mexico City from 1981 to 1997. The mean age was 32 years. The CD4 count was less than 260 cells/mm3 in all these individuals. The clinical presentations were subacute sinusitis, chronic localized abdominal abscess, and acute disseminated nocardiasis. The respective associated infections were none; TB and cytomegalovirus (CMV); and candidiasis, TB, CMV, Isospora belli, and disseminated Mycobacterium avium complex (MAC). Trimethoprim/sulfamethoxazole (TMP/SMX) was the treatment in all the cases; at the time of this writing, two patients were living and one had died during the acute episode. A literature search uncovered 130 cases of Nocardia infection in HIV patients since 1982. According to the published data and our results, nocardiasis should be suspected in those HIV-infected patients who (1) do not respond to appropriate antituberculous treatment; (2) are intravenous drug users; and (3) develop a characteristic pericardial infection. Finally, adequate surgical or percutaneous drainage of abscesses are extremely valuable for diagnosis and therapy.     

High frequency of thrombocytopenia in patients with acute-on-chronic liver failure treated with linezolid

BACKGROUND:Linezolid is an effective antibiotic reagent for Gram-positive bacterial infection;its most common side effect is thrombocytopenia.However,the incidence of thrombocytopenia in patients with acute-on-chronic liver failure(ACLF)who underwent linezolid therapy was unclear.The present study was to evaluate the incidence of thrombocytopenia in ACLF and non-ACLF patients treated with linezolid and the risk factors of thrombocytopenia in these patients.METHODS:Thirty-five patients with ACLF who had been subjected to intravenous administration of 600 mg linezolid every 12 hours for more than 7 days were categorized as a ACLF treatment(ACLF-T)group,72 patients without ACLF treated with the same dosage of linezolid were recruited as a non-ACLF treatment(NACLF-T)group,and 70 patients with ACLF without linezolid treatment served as an ACLF control(ACLF-C)group.The incidences of thrombocytopenia in different groups were compared at day 14.Risk factors were investigated using logistic regression analysis.RESULTS:The incidence of thrombocytopenia at day 14 was significantly higher in the ACLF-T group than in the ACLF-C group(20/35 vs 24/70,P=0.025)and in the NACLF-T group(20/35 vs 9/72,P0.001).Multivariate analysis showed that the ratio of platelet count(day 7/day 0)1(OR=10.021;P=0.012) and the baseline platelet count(OR=0.985;P=0.036)were independent risk factors of thrombocytopenia at day 14 of linezolid therapy.CONCLUSIONS:The benefits of linezolid treatment should outweigh the risk of thrombocytopenia in patients with ACLF Moreover,it is necessary to closely monitor the platelet count during linezolid therapy especially in the patients with de creased platelet count at day 7 of linezolid therapy.     

Nocardia infection in heart-lung transplant recipients at Alfred Hospital, Melbourne, Australia, 1989-1998.

Nocardia infections are uncommon in recipients of heart, lung, or heart-lung transplants, but such infections are well described. Frequent episodes of rejection, high-dose prednisolone treatment, renal impairment, and prolonged respiratory support have all been shown to increase the risk of Nocardia infection in this group. In this retrospective review of 540 recipients of heart, lung, or heart-lung transplants, 10 patients developed Nocardia infection (frequency, 1.85%). Infection occurred at a mean +/- standard deviation of 13+/-14.5 months after transplantation. All patients had pulmonary disease with no evidence of extrapulmonary disease. The Nocardia infection did not contribute directly to patient deaths. Coinfection with other pathogens was present in 6 patients, and 2 patients had sequential infections. Radiological findings varied. All isolates were susceptible to trimethoprim-sulfamethoxazole, amikacin, and imipenem. Treatment regimens varied. Two (30%) of 6 patients treated with trimethoprim-sulfamethoxazole developed adverse reactions, which necessitated a change in antibiotic therapy. The optimal treatment regimen, which comprises both the antimicrobial agent and the length of treatment, is unclear.     

利奈唑胺治疗革兰阳性菌呼吸机相关性肺炎的疗效观察

目的探讨利奈唑胺治疗革兰阳性（G^＋）菌呼吸机相关性肺炎（VAP）的疗效和安全性。方法分析2007年6月-2010年7月在我院住院的52例G^＋菌感染的VAP患者临床资料,分为治疗组25例和对照组27例。所有患者下呼吸道标本中3次以上培养出G^＋菌。两组分别给予利奈唑胺注射液和万古霉素注射液,治疗疗程为7-14 d。按卫生部颁发的抗菌药物临床研究指导原则判定疗效。结果治疗组有效率高于对照组（52.0%vs 37.0%）;病死率低于对照组（28.0%vs 44.4%）;G^＋菌清除率高于对照组（72.0%vs 55.6%）;使用机械通气时间明显短于对照组,差异均有统计学意义（P〈0.05）。治疗组和对照组的不良反应发生率（16.0%vs 29.6%）,差异有统计学意义（P〈0.05）。结论利奈唑胺治疗G^＋的VAP疗效显著,安全性好。