Prospective Cohort Study

Infectious Diseases Society of America.

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

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Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America

The shikimate pathway links metabolism of carbohydrates to biosynthesis of aromatic compounds. In a sequence of seven metabolic steps, phosphoenolpyruvate and erythrose 4-phosphate are converted to chorismate, the precursor of the aromatic amino acids and many aromatic secondary metabolites. All pathway intermediates can also be considered branch point compounds that may serve as substrates for other metabolic pathways. The shikimate pathway is found only in microorganisms and plants, never in animals. All enzymes of this pathway have been obtained in pure form from prokaryotic and eukaryotic sources and their respective DNAs have been characterized from several organisms. The cDNAs of higher plants encode proteins with amino terminal signal sequences for plastid import, suggesting that plastids are the exclusive locale for chorismate biosynthesis. In microorganisms, the shikimate pathway is regulated by feedback inhibition and by repression of the first enzyme. In higher plants, no physiological feedback inhibitor has been identified, suggesting that pathway regulation may occur exclusively at the genetic level. This difference between microorganisms and plants is reflected in the unusually large variation in the primary structures of the respective first enzymes. Several of the pathway enzymes occur in isoenzymic forms whose expression varies with changing environmental conditions and, within the plant, from organ to organ. The penultimate enzyme of the pathway is the sole target for the herbicide glyphosate. Glyphosate-tolerant transgenic plants are at the core of novel weed control systems for several crop plants.

The shikimate pathway.

International study of the prevalence and outcomes of infection in intensive care units

Phagocytosis of tubercle bacilli by antigen-presenting cells in human lung alveoli initiates a complex infection process by Mycobacterium tuberculosis and a potentially protective immune response by the host. M. tuberculosis has devoted a large part of its genome towards functions that allow it to successfully establish latent or progressive infection in the majority of infected individuals. The failure of immune-mediated clearance is due to multiple strategies adopted by M. tuberculosis that blunt the microbicidal mechanisms of infected immune cells and formation of distinct granulomatous lesions that differ in their ability to support or suppress the persistence of viable M. tuberculosis. In this paper, current understanding of various immune processes that lead to the establishment of latent M. tuberculosis infection, bacterial spreading, persistence, reactivation, and waning or elimination of latent infection as well as new diagnostic approaches being used for identification of latently infected individuals for possible control of tuberculosis epidemic are described.

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Pathogenesis, immunology, and diagnosis of latent Mycobacterium tuberculosis infection.

The rapid detection and identification of Candida species in clinical laboratories are extremely important for the management of patients with hematogenous candidiasis. The presently available culture and biochemical methods for detection and species identification of Candida are time-consuming and lack the required sensitivity and specificity. In this study, we have established a seminested PCR (snPCR) using universal and species-specific primers for detection of Candida species in serum specimens. The universal outer primers amplified the 3' end of 5.8S ribosomal DNA (rDNA) and the 5' end of 28S rDNA, including the internally transcribed spacer 2 (ITS2), generating 350- to 410-bp fragments from the four commonly encountered Candida species, viz., C. albicans, C. tropicalis, C. glabrata, and C. parapsilosis. The species-specific primers, complementary to unique sequences within the ITS2 of each test species, amplified species-specific DNA in the reamplification step of the snPCR. The sensitivity of Candida detection by snPCR in spiked serum specimens was close to 1 organism/ml. Evaluation of snPCR for specific identification of Candida species with 76 clinical Candida isolates showed 99% concordant results with the Vitek and/or ID32C yeast identification system. Further evaluation of snPCR for detection of Candida species in sera from culture-proven (n = 12), suspected (n = 16), and superficially colonized (n = 10) patients and healthy subjects (n = 12) showed that snPCR results were consistently negative with sera from healthy individuals and colonized patients. In culture-proven candidemia patients, the snPCR results were in full agreement with blood culture results with respect to both positivity and species identity. In addition, snPCR detected candidemia due to two Candida species in five patients, compared to three by blood culture. In the category of suspected candidemia with negative blood cultures for Candida, nine patients (56%) were positive by snPCR; two of them had dual infection with C. albicans and either C. tropicalis or C. glabrata. In conclusion, the snPCR developed in this study is specific and more sensitive than culture for the detection of Candida species in serum specimens. Moreover, the improved detection of cases of candidemia caused by more than one Candida species is an additional advantage.

Seminested PCR for Diagnosis of Candidemia: Comparison with Culture, Antigen Detection, and Biochemical Methods for Species Identification

To the Editor: Recent reports from Asia (1–4) have highlighted the increasing incidence of the fungus Candida auris as a nosocomial bloodstream pathogen affecting persons of all age groups. We report a case of C. auris candidemia in a 27-year-old woman in Kuwait with a long history of chronic renal failure. On May 9, 2014, the patient was admitted to the intensive care unit with symptoms of septic shock secondary to lobar pneumonia and complicated by acute renal failure. The patient was known to have immotile cilia syndrome (primary ciliary dyskinesia) and bronchiectasis with recurrent episodes of sinusitis. Beginning on day 1, she received treatment with different courses of a wide range of broad-spectrum antimicrobial drugs. However, despite treatment, the patient’s condition continued to deteriorate. On day 12 after admission, a blood culture yielded yeast growth that was identified with 99% probability as C. haemulonii by using the Vitek 2 yeast identification system (bioMerieux, Marcy l’Etoile, France). As part of routine patient care, we sent the isolate (Kw1732/14) to the Mycology Reference Laboratory at Kuwait University for further identification and antifungal susceptibility testing. The isolate was resistant to fluconazole (MIC of >256 μg/mL), but it appeared susceptible to amphotericin B (MIC of 0.064 μg/mL), voriconazole (MIC of 0.38 μg/mL), and caspofungin (MIC of 0.064 μg/mL) by using the Etest (bioMerieux, Marcy l’Etoile, France). The patient was started on liposomal amphotericin B (150 mg/day), but the next day, she died from multiorgan failure.

On MAST ID CHROMagar Candida medium (Mast Group Ltd., Bootle, UK), the isolate formed pink colonies, which grew well at 42°C but not at 45°C. The isolate did not grow on BBL Mycosel Agar (BD, Sparks, MD, USA) containing 0.4 g cycloheximide per liter of medium. As with C. auris isolates from India and South Africa, this isolate assimilated N-acetyl glucosamine (2,5). Because the isolate showed reduced susceptibility to fluconazole, it was further characterized by sequencing of internal transcribed spacer and D1/D2 domains of ribosomal DNA. Genomic sequences for the internal transcribed spacer and D1/D2 regions (EMBL accession nos. {"type":"entrez-nucleotide","attrs":{"text":"LN624638","term_id":"723005175","term_text":"LN624638"}}LN624638 and {"type":"entrez-nucleotide","attrs":{"text":"LN626311","term_id":"725798491","term_text":"LN626311"}}LN626311) shared 99%–100% identity with sequences for corresponding regions of several C. auris strains (identification nos. CBS12874, CBS12875, CBS12876, CBS12880, CBS12882, CBS12886, and CBS12887, and several isolates from India).

C. auris was isolated in 2009 from the ear canal of a woman in Japan (6). The species has attracted attention because of its reduced susceptibility to azoles and amphotericin B (2,5) and its misidentification as C. haemulonii or Rhodotorula glutinis by commercial yeast identification systems (1,4). Because there are no reliable phenotypic methods for the rapid identification of C. auris and because molecular methods are not yet widely available, it is reasonable to infer that C. auris may be a more frequent cause of candidemia than previously recognized, particularly in Asian countries. A recently published multicenter study from India supports this view (7). In that study, a significantly higher occurrence of C. auris candidemia was reported among patients admitted in public sector hospitals compared with those in private hospitals (8.2 vs. 3.9%; p = 0.008) (7). The report reinforces the growing clinical implications of rare Candida spp. in the etiology of candidemia and highlights the role of molecular methods for their unequivocal identification.

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Candida auris candidemia in Kuwait, 2014.

Recent advances in the diagnosis and treatment of multidrug-resistant tuberculosis

The first outbreak of Candida haemulonii fungemia is described. The seven isolates from the blood of four neonates were identified by DNA sequencing of the ribosomal DNA. They were all resistant to amphotericin B, fluconazole, and itraconazole. This report highlights the emergence of C. haemulonii as an opportunistic pathogen in immunocompromised patients.

Suhail Ahmad

Papers

Pathogenesis, immunology, and diagnosis of latent Mycobacterium tuberculosis infection.

Seminested PCR for Diagnosis of Candidemia: Comparison with Culture, Antigen Detection, and Biochemical Methods for Species Identification

Candida auris candidemia in Kuwait, 2014.

Recent advances in the diagnosis and treatment of multidrug-resistant tuberculosis

Outbreak of Fungemia among Neonates Caused by Candida haemulonii Resistant to Amphotericin B, Itraconazole, and Fluconazole