Cytomegalovirus (CMV ) 是影响肝移植的结果的普通病毒的病原体。除了 CMV 症候群和织物侵略的疾病的直接效果， CMV 与增加的倾向被联系到尖锐、长期的紧密相联的接枝拒绝，加速的丙肝复发，和另外的机会主义的感染，以及减少了全面耐心、紧密相联的接枝幸存。为 CMV 疾病的风险因素经常被互连，并且包括 CMV D+/R- serostatus，尖锐拒绝，女性，年龄，高剂量的 mycophenolate mofetil 和泼尼松的使用，和免疫的全面的州。除了 CMV 特定的 CD4+ 和 CD8+ T 淋巴细胞的角色，有数据建议天生的免疫系统的功能贡献 CMV 疾病致病。在一研究，有在作为像使用费的受体知道的天生的有免疫力的分子的特定的多型性的肝 transplant 接受者是更可能的开发 CMV 复制和临床的疾病的高水平。因为 CMV 疾病的直接、间接的不利效果，它的预防，是否通过抗病毒的预防或抢先式的治疗，是在改进肝移植的结果的一个必要部件。在 transplant 中心的多数，抗病毒的预防是在为在肝的 CMV-seronegative 接受者的 CMV 疾病的预防的抢先式的治疗上的比较喜欢的策略从 CMV-seropositive 施主(D+/R-) 的紧密相联的接枝。然而，抗病毒的预防的主要缺点是延期发作的出现主要 CMV 疾病。在几未来、回顾的研究，延期发作的发生主要 CMV 疾病从 16% ～ 47% CMV D+/R- 肝 transplant 接受者。当前的数据建议那延期发作 CMV 疾病在肝移植以后与增加的死亡被联系。因此，为预防优化了策略，有行动的唯一的模式的新奇的药被需要。当前，当对在肝的主要 CMV 疾病的预防移植接受者，使随机化的控制临床的试用正在被执行比较 maribavir，新奇苯并咪唑核糖甙，和口头的 ganciclovir 的功效和安全。CMV 疾病的处理由主要组成静脉内(IV ) ganciclovir，并且如果可行，在免疫力的抑制的度的减小。最近的控制临床的试用�

Cytomegalovirus infection after liver transplantation： Current concepts and challenges

Seven mobile oxazolidinone resistance genes, including cfr, cfr(B), cfr(C), cfr(D), cfr(E), optrA, and poxtA, have been identified to date. The cfr genes code for 23S rRNA methylases, which confer a multiresistance phenotype that includes resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A compounds. The optrA and poxtA genes code for ABC-F proteins that protect the bacterial ribosomes from the inhibitory effects of oxazolidinones. The optrA gene confers resistance to oxazolidinones and phenicols, while the poxtA gene confers elevated MICs or resistance to oxazolidinones, phenicols, and tetracycline. These oxazolidinone resistance genes are most frequently found on plasmids, but they are also located on transposons, integrative and conjugative elements (ICEs), genomic islands, and prophages. In these mobile genetic elements (MGEs), insertion sequences (IS) most often flanked the cfr, optrA, and poxtA genes and were able to generate translocatable units (TUs) that comprise the oxazolidinone resistance genes and occasionally also other genes. MGEs and TUs play an important role in the dissemination of oxazolidinone resistance genes across strain, species, and genus boundaries. Most frequently, these MGEs also harbor genes that mediate resistance not only to antimicrobial agents of other classes, but also to metals and biocides. Direct selection pressure by the use of antimicrobial agents to which the oxazolidinone resistance genes confer resistance, but also indirect selection pressure by the use of antimicrobial agents, metals, or biocides (the respective resistance genes against which are colocated on cfr-, optrA-, or poxtA-carrying MGEs) may play a role in the coselection and persistence of oxazolidinone resistance genes.

Mobile Oxazolidinone Resistance Genes in Gram-Positive and Gram-Negative Bacteria.

Background Cytomegalovirus (CMV) colitis is a common manifestation of CMV end-organ disease, which has typically been described in immunocompromised hosts. Recently, it has been noted that this also occurs in immunocompetent patients. To gather relevant data about clinical presentation, prognosis, and risk factors for development of CMV colitis in immunocompetent hosts, we analyzed all cases that occurred during a 19-year period at our institution. Methods A case-control study was performed to identify risk factors for CMV colitis in immunocompetent hosts. Electronic medical records of individuals who were admitted and diagnosed with CMV colitis between January 1995 and February 2014 at a tertiary care university hospital were reviewed. Two non-CMV colitis patients who were age- and sex-matched were selected as controls for each case. Results A total of 51 patients with CMV colitis were included in this study along with 102 control patients. Certain conditions including renal disease on hemodialysis, neurologic disease, rheumatologic disease, intensive care unit admission, and exposure to antibiotics, antacids, steroids, or red blood cell (RBC) transfusions within 1 month of diagnosis of colitis were associated with CMV colitis on univariate analysis. Among these, steroid use and RBC transfusion within 1 month were identified as independent risk factors for developing CMV colitis on multivariate analysis. The 30-day mortality rate was 7.8% without any attributable mortality. Conclusions Steroid use and RBC transfusion within 1 month of the diagnosis of colitis were independent risk factors for development of CMV colitis in immunocompetent hosts.

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Clinical Presentation and Risk Factors for Cytomegalovirus Colitis in Immunocompetent Adult Patients

Symptomatic cytomegalovirus (CMV) disease has been the standard endpoint for clinical trials in organ transplant recipients. Viral load may be a more relevant endpoint due to low frequency of disease. We performed a meta-analysis and systematic review of the literature. We found several lines of evidence to support the validity of viral load as an appropriate surrogate end-point, including the following: (1) viral loads in CMV disease are significantly greater than in asymptomatic viremia (odds ratio, 9.3 95% confidence interval, 4.6-19.3); (2) kinetics of viral replication are strongly associated with progression to disease; (3) pooled incidence of CMV viremia and disease is significantly lower during prophylaxis compared with the full patient follow-up period (viremia incidence: 3.2% vs 34.3%; P < .001) (disease incidence: 1.1% vs 13.0%; P < .001); (4) treatment of viremia prevented disease; and (5) viral load decline correlated with symptom resolution. Based on the analysis, we conclude that CMV load is an appropriate surrogate endpoint for CMV trials in organ transplant recipients.

/pdf/use-of-viral-load-as-a-surrogate-marker-in-clinical-studies-4mbsc5eyud.pdf

Use of Viral Load as a Surrogate Marker in Clinical Studies of Cytomegalovirus in Solid Organ Transplantation: A Systematic Review and Meta-analysis.

Bacterial enteric infections resulting in diarrhea, dysentery, or enteric fever constitute a huge public health problem, with more than a billion episodes of disease annually in developing and developed countries. In this study, the deadly agent of hemorrhagic diarrhea and hemolytic uremic syndrome, Escherichia coli O157:H7 was investigated with extensive computational approaches aimed at identifying novel and broad-spectrum antibiotic targets. A systematic in silico workflow consisting of comparative genomics, metabolic pathways analysis, and additional drug prioritizing parameters was used to identify novel drug targets that were essential for the pathogen's survival but absent in its human host. Comparative genomic analysis of Kyoto Encyclopedia of Genes and Genomes annotated metabolic pathways identified 350 putative target proteins in E. coli O157:H7 which showed no similarity to human proteins. Further bio-informatic approaches including prediction of subcellular localization, calculation of molecular weight, and web-based investigation of 3D structural characteristics greatly aided in filtering the potential drug targets from 350 to 120. Ultimately, 44 non-homologous essential proteins of E. coli O157:H7 were prioritized and proved to have the eligibility to become novel broad-spectrum antibiotic targets and DNA polymerase III alpha (dnaE) was the top-ranked among these targets. Moreover, druggability of each of the identified drug targets was evaluated by the DrugBank database. In addition, 3D structure of the dnaE was modeled and explored further for in silico docking with ligands having potential druggability. Finally, we confirmed that the compounds N-coeleneterazine and N-(1,4-dihydro-5H-tetrazol-5-ylidene)-9-oxo-9H-xanthene-2-sulfon-amide were the most suitable ligands of dnaE and hence proposed as the potential inhibitors of this target protein. The results of this study could facilitate the discovery and release of new and effective drugs against E. coli O157:H7 and other deadly human bacterial pathogens.

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Identification of potential drug targets by subtractive genome analysis of Escherichia coli O157:H7: an in silico approach

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/lt.23540

Cytomegalovirus infection: its incidence and management in cytomegalovirus-seropositive living related liver transplant recipients: a single-center experience.

Case Report Yokenella regensburgei infection in India mimicking enteric fever

Coagulase-negative Staphylococci (CoNS) have emerged as a major causative agent of blood-stream infections (BSI). Linezolid (LZD) is currently used for treating glycopeptide and methicillin-resistant staphylococci. It is important to understand the resistance mechanism and probable transmission of LZD resistant (LR) CoNS within the hospital. Clinically significant LRCoNS from patients with BSI were characterized using MALDI-TOF and 16S rRNA gene sequence analysis. Antimicrobial susceptibility and MIC of vancomycin and LZD were determined. LZD resistance mechanisms using PCR for the cfr gene and mutation in the V domain of the 23S rRNA gene were studied. The MIC of LZD ranged from 8 to 32 μg/ml. LR was observed in three different CoNS species from diverse locations within the hospital. The cfr gene was identified in all the isolates. Sequence analysis of V domain region of 23S rRNA gene confirmed mutation in single copy among 12/15 isolates with novel mutations: G2614 T and C2384T. All infections were nosocomially acquired and LZD resistance was emerging in the absence of prior LZD use. Horizontal spread of resistant isolates and cfr gene among diverse species were the probable mechanisms of transmission. The study highlights the novel mutations associated with LRCoNS and the importance of surveillance & transmission pathway within the hospital. It also systematically discusses the published information on LRCoNS.

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Linezolid resistant coagulase negative staphylococci (LRCoNS) with novel mutations causing blood stream infections (BSI) in India

Escherichia vulneris is an opportunistic human pathogen. It has been primarily reported in adult patients and invasive infections have been observed in immune-suppressed individuals. This is the first report of E. vulneris causing complicated diarrhoea and sepsis in an infant.

Two month old sick infant, born full-term, was admitted to the paediatrics department with loose motions and refusal to feed for four days. E. vulneris was isolated from blood in pure culture. The isolate was characterized for diarrhoeal virulence markers: heat labile and heat stable toxins (LT, ST) and hemolysin (hlyA) by PCR. The presence of LT enterotoxin and hemolysin provides strong evidence of the diarrhoeagenic potential of E. vulneris, further leading to the invasive infection triggering sepsis.

As E. vulneris can lead to serious complications, an attempt should be made in clinical laboratories to identify and further characterize this new Escherichia species.

Reetika Dawar

Papers

Cytomegalovirus infection: its incidence and management in cytomegalovirus-seropositive living related liver transplant recipients: a single-center experience.

Case Report Yokenella regensburgei infection in India mimicking enteric fever

Linezolid resistant coagulase negative staphylococci (LRCoNS) with novel mutations causing blood stream infections (BSI) in India

Escherichia vulneris: an unusual cause of complicated diarrhoea and sepsis in an infant. A case report and review of literature

Corynebacterium striatum: An emerging nosocomial pathogen in a case of laryngeal carcinoma