First described in 2009 in Japan, the emerging multidrug-resistant fungal pathogen Candida auris is becoming a worldwide public health threat that has been attracting considerable attention due to its rapid and widespread emergence over the past decade. The reasons behind the recent emergence of this fungus remain a mystery to date. Genetic analyses indicate that this fungal pathogen emerged simultaneously in several different continents, where 5 genetically distinct clades of C. auris were isolated from distinct geographical locations. Although C. auris belongs to the CTG clade (its constituent species translate the CTG codon as serine instead of leucine, as in the standard code), C. auris is a haploid fungal species that is more closely related to the haploid and often multidrug-resistant species Candida haemulonii and Candida lusitaniae and is distantly related to the diploid and clinically common fungal pathogens Candida albicans and Candida tropicalis. Infections and outbreaks caused by C. auris in hospitals settings have been rising over the past several years. Difficulty in its identification, multidrug resistance properties, evolution of virulence factors, associated high mortality rates in patients, and long-term survival on surfaces in the environment make C. auris particularly problematic in clinical settings. Here, we review progress made over the past decade on the biological and clinical aspects of C. auris. Future efforts should be directed toward understanding the mechanistic details of its biology, epidemiology, antifungal resistance, and pathogenesis with a goal of developing novel tools and methods for the prevention, diagnosis, and treatment of C. auris infections.

/pdf/candida-auris-epidemiology-biology-antifungal-resistance-and-1w63ujiqzg.pdf

Candida auris: Epidemiology, biology, antifungal resistance, and virulence.

The emerging pathogen Candida auris has been associated with nosocomial outbreaks on five continents. Genetic analysis indicates the simultaneous emergence of separate clades of this organism in different geographical locations. Invasive infection and colonization have been detected predominantly in patients in high-dependency settings and have garnered attention due to variable antifungal resistance profiles and transmission within units instituting a range of infection prevention and control measures. Issues with the identification of C. auris using both phenotypic and molecular techniques have raised concerns about detecting the true scale of the problem. This review considers the literature available on C. auris and highlights the key unknowns, which will provide direction for further work in this field.

Candida auris: a Review of the Literature.

Candida auris is an emerging multidrug-resistant yeast that causes serious invasive infections with high mortality. It was first discovered in 2009, and since then, individual cases or outbreaks have been reported from over 20 countries on five continents. Controlling C. auris is challenging for several reasons: (1) it is resistant to multiple classes of antifungals, (2) it can be misidentified as other yeasts by commonly available identification methods, and (3) because of its ability to colonize patients perhaps indefinitely and persist in the healthcare environment, it can spread between patients in healthcare settings. The transmissibility and high levels of antifungal resistance that are characteristic of C. auris set it apart from most other Candida species. A robust response that involves the laboratory, clinicians, and public health agencies is needed to identify and treat infections and prevent transmission. We review the global emergence, biology, challenges with laboratory identification, drug resistance, clinical manifestations, treatment, risk factors for infection, transmission, and control of C. auris.

Candida auris: The recent emergence of a multidrug-resistant fungal pathogen.

Multidrug-resistant Candida auris has emerged as a cause of insidious hospital outbreaks and complicated infections. We present the analysis of an ongoing C. auris outbreak including the largest published series of C. auris bloodstream infection. All C. auris-positive patients from April-2016 to January-2017 were included. Environmental, clinical and microbiological data were recorded. Definitive isolate identification was performed by ITS-rDNA sequencing, and typing by amplified fragment length polymorphism fingerprinting. One hundred and forty patients were colonised by C. auris during the studied period (68% from surgical intensive care). Although control measures were implemented, we were not able to control the outbreak. Forty-one invasive bloodstream infections (87.8% from surgical intensive care) were included. Clinical management included prompt intravascular catheter removal and antifungal therapy with echinocandins. All isolates were fluconazole- and voriconazole-resistant, but echinocandin- and amphotericin B-susceptible. Thirty-day mortality rate was 41.4%, and severe septic metastasis as spondylodiscitis and endocarditis were observed in 5 patients (12%). C. auris was also recovered from inanimate patient surroundings and medical equipment. Despite antifungal treatment, high mortality and late complication rates were recorded. Molecular typing suggested a clonal outbreak different from those previously published.

An outbreak due to Candida auris with prolonged colonisation and candidaemia in a tertiary care European hospital

Candida auris , first described in 2009, has since emerged as an important, multidrug-resistant, nosocomial agent of candidemia, with large outbreaks reported worldwide and high mortality rates associated with therapeutic failure. The current study employed C. auris isolates from a variety of centers in the United Kingdom to evaluate the pathogenicity of this emerging pathogen compared to that of other common pathogenic yeast species in the invertebrate Galleria mellonella infection model. We showed that C. auris isolates differ in their growth characteristics in vitro , with a proportion of isolates failing to release daughter cells after budding, resulting in the formation of large aggregates of cells that cannot be physically disrupted. Our results also demonstrate strain-specific differences in the behavior of C. auris in G. mellonella , with the aggregate-forming isolates exhibiting significantly less pathogenicity than their nonaggregating counterparts. Importantly, the nonaggregating isolates exhibited pathogenicity comparable to that of C. albicans , which is currently accepted as the most pathogenic member of the genus, despite the fact that C. auris isolates do not produce hyphae and produce only rudimentary pseudohyphae either in vitro or in G. mellonella .

IMPORTANCE The incidence of invasive candidiasis, which includes candidemia and deep tissue infections, continues to rise and is associated with considerable mortality rates. Candida albicans remains the most common cause of invasive candidiasis, although the prevalence of non- albicans species has increased over recent years. Since its first description in 2009, Candida auris has emerged as a serious nosocomial health risk, with widespread outbreaks in numerous hospitals worldwide. However, despite receiving considerable attention, little is known concerning the pathogenicity of this emerging fungal pathogen. Here, using the Galleria mellonella insect systemic infection model, we show strain-specific differences in the virulence of C. auris , with the most virulent isolates exhibiting pathogenicity comparable to that of C. albicans , which is currently accepted as the most pathogenic member of the genus.

Comparative Pathogenicity of United Kingdom Isolates of the Emerging Pathogen Candida auris and Other Key Pathogenic Candida Species

Cytomegalovirus (CMV) infection is the most common viral infection in liver transplant recipients, affecting post-transplant patients and graft survival. Recent advances in diagnosis and management of CMV have led to marked reduction in incidence, severity, and its associated morbidity and mortality. CMV DNA assay is the most commonly used laboratory parameter to diagnose and monitor CMV infection. Current evidence suggests that both pre-emptive and universal prophylaxis approaches are equally justified in liver transplant recipients. Intravenous ganciclovir and oral valganciclovir are the most commonly used drugs for treatment of CMV disease. Most of the centre use valganciclovir prophylaxis for prevention of CMV disease in liver trasplant recipient. The aim of this article is to review the current standard of care for diagnosis and management of CMV disease in liver transplant recipients.

Cytomegalovirus Infection in Liver Transplant Recipients: Current Approach to Diagnosis and Management.

The association between the clinical features of genital chlamydial infection and organism genotype and load was evaluated. Chlamydial DNA was detected and quantified in genital swabs from 233 (7 %) of 3384 consecutive patients attending a genitourinary medicine clinic. The chlamydia-positive subcohort comprised 132 (57 %) females and 101 (43 %) males. Clinical features were present in 33 % women and 72 % men. The chlamydial load was found to be higher in women (median load: 5.6 log) than men (median load: 3.5 log). Single variable analysis failed to show a significant association between chlamydial load and clinical features (P value = 0.3). Owing to the limited amount of clinical material, information on chlamydial genotypes was available for 70 % (n = 162) of chlamydia-positive patients. However, multivariable analysis of these samples did show a significant association between chlamydial load and clinical features (P value = 0.02). This discrepancy is most probably due to the difference in the amount of data analysed by single variable (data from 233 patients) and multivariable (data from 162 patients) analysis. The distribution of chlamydia genotypes was as follows: type E (46 %), F (22 %), D (8 %), K (8 %), G (7 %), J (4 %), I (1 %) and H (0.6 %). No statistically significant association was observed between chlamydial genotype and clinical features in either single variable (P value = 0.6) or multivariable (P value = 0.4) analysis. These findings suggest that chlamydial load and diversity in the ompA gene plays little, if any, role in the pathogenesis of genital chlamydial infection.

Genital chlamydial infection: association between clinical features, organism genotype and load

Purpose The aim of this study is to evaluate the predisposing risk factors, clinical presentations, laboratory parameters, and treatments taken and outcomes in patients of nocardiosis in the span of 5 years in a tertiary care hospital. Materials and methods The patients whose specimens showed Nocardia like organism in Gram-staining, Kinyoun staining and characteristic colonies in culture were included in the retrospective analysis study. Retrospective analysis of associated risk factors, clinical presentations, and radiological findings was performed. Results Of the thirteen patients, 11 (76.9%) had immunosuppressive pathologies including solid organ transplantation, autoimmune disease, use of steroids, and immunosuppressive drugs as important risk factors. Four types of clinical manifestations were observed, pulmonary (46.1%), cutaneous (23.07%), cerebral (15.3%), and bacteremia (15.3%). The most common presentation was pulmonary with steroid therapy as a significant risk factor. Consolidation and pleural effusion were the common radiological findings in these cases. In eight of the nine patients anti-nocrdial drugs were given. Cotrimoxazole as monotherapy was given in four cases (44.44%), cotrimoxazole in combination with meropenem in two cases (22.22%); minocycline and linezolid were given in one case each. The overall mortality was 36.36% and was seen in patients with pulmonary nocardiosis. Conclusions The study indicates that Nocardial infections are re-emerging on account of an increase in numbers of immunocompromised patients due to increased organ transplants, autoimmune diseases, malignancies, and use of immunosuppressive drugs and steroids. The diagnosis is often missed/not suspected and delayed because of the clinical resemblance to many other infections. Nocardial infection should be suspected and assessed particularly in immunocompromised patients not responding to treatment/improving clinically.

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Clinical manifestations of nocardiosis: Study of risk factors and outcomes in a tertiary care hospital.

Salmonella typhi is a true pathogen, which is capable of causing both intestinal and extraintestinal infections. Unusual presentations of Salmonella should always be kept in mind as this organism can cause disease in almost any organ of the body. S. typhi has been reported to cause the life-threatening infections such as meningitis, endocarditis, myocarditis, empyema, and hepatic abscess. Renal involvement by S. typhi is a relatively rare presentation. We report a case of renal abscess caused by S. typhi in an afebrile, 10-year-old child who did not have any clinical history of enteric fever. To our knowledge, this is the first reported case of isolation of S. typhi from the renal abscess, and interestingly this isolate was found to be resistant to quinolones.

/pdf/renal-abscess-caused-by-salmonella-typhi-y633e55xxy.pdf

Renal Abscess Caused by Salmonella Typhi.

Background: Viruses and atypical pathogens can cause significant respiratory illness in immunocompromised patients. Multiplex polymerase chain reaction (MPCR) has improved the diagnostic yield of pathogens, and it is easier to identify the co-infections also. The present study was done to evaluate the performance of MPCR on bronchoalveolar lavage (BAL) samples in immunocompromised patients. Methods: Atotal of 177 BAL specimens collected over a 19 months period from immunocompromised patients with respiratory illness were analyzed with the MPCR and aerobic culture. Patients were divided into four according to the pathogens. Category V (only viral), Category NV (nonviral, i.e., bacteria and atypical), Category M (mixed, i.e., both viral and nonviral pathogen), and Category UK (unknown etiology). Results: MPCR identified the causative pathogen in 59.3% of patients while culture could identify only in 37.8% of patients. Most frequent etiological agent was Klebsiella pneumoniae (32%), followed by cytomegalovirus (21%), and Pneumocystis jirovecii (10%). Numbers of patients in each category were Category V (9.6%), Category NV (43.5%), Category M (19.8%), and Category UK (27.1%). Mortality was significantly higher in patients of Category M having mixed infections. Conclusion: MPCR is highly sensitive and rapid tool which can be considered in the routine diagnostic algorithm of respiratory illness in immunocompromised patients.

/pdf/respiratory-multiplex-polymerase-chain-reaction-an-important-27hbnmana3.pdf

Respiratory Multiplex Polymerase Chain Reaction: An Important Diagnostic Tool in Immunocompromised Patients

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