EDITORIAL – Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses

Clin Infect Dis  Jan 15, 2018 V.64 N.134.

Shawn R. Lockhart  Kizee A. Etienne  Snigdha Vallabhaneni  Joveria Farooqi Anuradha Chowdhary  Nelesh P. Govender  Arnaldo Lopes Colombo  Belinda Calvo Christina A. Cuomo  Christopher A. Desjardins

Background.

Candida auris, a multidrug-resistant yeast that causes invasive infections, was first described in 2009 in Japan and has since been reported from several countries.

Methods.

To understand the global emergence and epidemiology of C. auris, we obtained isolates from 54 patients with C. auris infection from Pakistan, India, South Africa, and Venezuela during 2012–2015 and the type specimen from Japan. Patient information was available for 41 of the isolates. We conducted antifungal susceptibility testing and whole-genome sequencing (WGS).

Results.

Available clinical information revealed that 41% of patients had diabetes mellitus, 51% had undergone recent surgery, 73% had a central venous catheter, and 41% were receiving systemic antifungal therapy when C. auris was isolated. The median time from admission to infection was 19 days (interquartile range, 9–36 days), 61% of patients had bloodstream infection, and 59% died. Using stringent break points, 93% of isolates were resistant to fluconazole, 35% to amphotericin B, and 7% to echinocandins; 41% were resistant to 2 antifungal classes and 4% were resistant to 3 classes. WGS demonstrated that isolates were grouped into unique clades by geographic region. Clades were separated by thousands of single-nucleotide polymorphisms, but within each clade isolates were clonal. Different mutations in ERG11 were associated with azole resistance in each geographic clade.

Conclusions.

  1. auris is an emerging healthcare-associated pathogen associated with high mortality. Treatment options are limited, due to antifungal resistance. WGS analysis suggests nearly simultaneous, and recent, independent emergence of different clonal populations on 3 continents. Risk factors and transmission mechanisms need to be elucidated to guide control measures.

FULL TEXT

https://academic.oup.com/cid/article/64/2/134/2706620

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January 6, 2018 at 12:07 pm

Trends in Antibiotic Susceptibility in Staphylococcus aureus in Boston, Massachusetts, from 2000 to 2014

Journal of Clinical Microbiology January 2018 V.56 N.1

Epidemiology

Sanjat Kanjilal, Mohamad R. Abdul Sater, Maile Thayer, Georgia K. Lagoudas, Soohong Kim, Paul C. Blainey and Yonatan H. Grad

aDivision of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA

bHarvard Medical School, Boston, Massachusetts, USA

cDepartment of Immunology & Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA

dMIT Department of Biological Engineering, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA

eDivision of Infectious Diseases, Brigham and Women’s Hospital, Boston, Massachusetts, USA

The rate of infection by methicillin-resistant Staphylococcus aureus (MRSA) has declined over the past decade, but it is unclear whether this represents a decline in S. aureus infections overall. To evaluate the trends in the annual rates of infection by S. aureus subtypes and mean antibiotic resistance, we conducted a 15-year retrospective observational study at two tertiary care institutions in Boston, MA, of 31,753 adult inpatients with S. aureus isolated from clinical specimens. We inferred the gain and loss of methicillin resistance through genome sequencing of 180 isolates from 2016. The annual rates of infection by S. aureus declined from 2003 to 2014 by 4.2% (2.7% to 5.6%), attributable to an annual decline in MRSA of 10.9% (9.3% to 12.6%). Penicillin-susceptible S. aureus (PSSA) increased by 6.1% (4.2% to 8.1%) annually, and rates of methicillin-susceptible penicillin-resistant S. aureus (MSSA) did not change. Resistance in S. aureus decreased from 2000 to 2014 by 0.8 antibiotics (0.7 to 0.8). Within common MRSA clonal complexes, 3/14 MSSA and 2/21 PSSA isolates arose from the loss of resistance-conferring genes. Overall, in two tertiary care institutions in Boston, MA, a decline in S. aureus infections has been accompanied by a shift toward increased antibiotic susceptibility. The rise in PSSA makes penicillin an increasingly viable treatment option.

PDF

http://jcm.asm.org/content/56/1/e01160-17.full.pdf+html

January 5, 2018 at 8:21 am

lytA Quantitative PCR on Sputum and Nasopharyngeal Swab Samples for Detection of Pneumococcal Pneumonia among the Elderly

Journal of Clinical Microbiology January 2018 V.56 N.1

Annika Saukkoriipi, Arto A. Palmu, Thierry Pascal, Vincent Verlant, William P. Hausdorff and Jukka Jokinen

aDepartment of Public Health Solutions, National Institute for Health and Welfare, Oulu, Finland

bDepartment of Public Health Solutions, National Institute for Health and Welfare, Tampere, Finland

cGSK, Wavre, Belgium

dDepartment of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland

Real-time quantitative PCR (qPCR) assay of sputum or nasopharyngeal specimens has shown promising results in the detection of pneumococcal community-acquired pneumonia (PncCAP). We applied qPCR for the autolysin gene (lytA) and compared sputum and nasopharyngeal swab (NPS) pneumococcal loads in elderly patients with community-acquired pneumonia (CAP), and specifically in patients with PncCAP, to those in patient groups with other respiratory diseases. We studied patients aged ≥65 years with radiologically confirmed CAP, clinical CAP not retrospectively radiologically confirmed, other acute respiratory infections, or stable chronic lung disease. Pneumococcal etiology of CAP was ascertained by using a combination of multiple diagnostic methods. We analyzed sputum and NPS specimens by lytA qPCR with 104 pneumococcal genome equivalents (GE)/ml as a cutoff for positivity. Among PncCAP patients, lytA qPCR detected pneumococci in 94% of the sputum samples and in large quantities (mean, 6.82 ± 1.02 log10 GE/ml) but less frequently in NPS (44%) and in smaller quantities (5.55 ± 0.92 log10 GE/ml). In all other patient groups, ≤10% of the sputum samples and <5% of the NPS samples were lytA qPCR positive; but when they were positive, the sputum pneumococcal loads were similar to those in the PncCAP patients, suggesting a pneumococcal etiology in these patients. This was supported by other pneumococcal assay results. Overall, sputum lytA qPCR positivity was more common in PncCAP patients than in the other patient groups, but the quantitative results were mainly similar. NPS lytA qPCR was less sensitive than sputum lytA qPCR in detecting PncCAP.

PDF

http://jcm.asm.org/content/56/1/e01231-17.full.pdf+html

January 5, 2018 at 8:20 am

Comparison of Different Phenotypic Approaches To Screen and Detect mecC-Harboring Methicillin-Resistant Staphylococcus aureus

Journal of Clinical Microbiology January 2018 V.56 N.1

André Kriegeskorte, Evgeny A. Idelevich, Andreas Schlattmann, Franziska Layer, Birgit Strommenger, Olivier Denis, Gavin K. Paterson, Mark A. Holmes, Guido Werner and Karsten Becker

aInstitute of Medical Microbiology, University Hospital Münster, Münster, Germany

bRobert-Koch-Institute, Berlin, Germany

cLaboratoire de Microbiologie, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium

dRoyal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United Kingdom

eDepartment of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom

fRobert-Koch-Institute, Wernigerode Branch, Wernigerode, Germany

Similar to mecA, mecC confers resistance against beta-lactams, leading to the phenotype of methicillin-resistant Staphylococcus aureus (MRSA). However, mecC-harboring MRSA strains pose special difficulties in their detection. The aim of this study was to assess and compare different phenotypic systems for screening, identification, and susceptibility testing of mecC-positive MRSA isolates. A well-characterized collection of mecC-positive S. aureus isolates (n = 111) was used for evaluation. Routinely used approaches were studied to determine their suitability to correctly identify mecC-harboring MRSA, including three (semi)automated antimicrobial susceptibility testing (AST) systems and five selective chromogenic agar plates. Additionally, a cefoxitin disk diffusion test and an oxacillin broth microdilution assay were examined. All mecC-harboring MRSA isolates were able to grow on all chromogenic MRSA screening plates tested. Detection of these isolates in AST systems based on cefoxitin and/or oxacillin testing yielded overall positive agreements with the mecC genotype of 97.3% (MicroScan WalkAway; Siemens), 91.9% (Vitek 2; bioMérieux), and 64.9% (Phoenix, BD). The phenotypic resistance pattern most frequently observed by AST devices was “cefoxitin resistance/oxacillin susceptibility,” ranging from 54.1% (Phoenix) and 83.8% (Vitek 2) to 92.8% (WalkAway). The cefoxitin disk diffusion and oxacillin broth microdilution assays categorized 100% and 61.3% of isolates to be MRSA, respectively. The chromogenic media tested confirmed their suitability to reliably screen for mecC-harboring MRSA. The AST systems showed false-negative results with varying numbers, misidentifying mecC-harboring MRSA as methicillin-susceptible S. aureus. This study underlines cefoxitin’s status as the superior surrogate mecC-positive MRSA marker.

PDF

http://jcm.asm.org/content/56/1/e00826-17.full.pdf+html

January 5, 2018 at 8:19 am

mecC-Harboring Methicillin-Resistant Staphylococcus aureus: Hiding in Plain Sight

Journal of Clinical Microbiology January 2018 V.56 N.1

Commentaries

Bradley A. Ford

aDepartment of Pathology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA

Previously there was scant data on the performance of laboratory testing to detect mecC-mediated beta-lactam resistance in Staphylococcus aureus. Kriegeskorte and colleagues (J Clin Microbiol 56:e00826-17, 2018, https://doi.org/10.1128/JCM.00826-17) report the performance of various clinical tests for the detection of mecC-harboring methicillin-resistant S. aureus (MRSA), which failed to identify from 0 to 41% of tested mecC-harboring MRSA isolates. Changes in practice and new test development are necessary to address the challenge of mecC-harboring MRSA.

PDF

http://jcm.asm.org/content/56/1/e01549-17.full.pdf+html

January 5, 2018 at 8:18 am

Using Treponemal Assay Signal Strength Cutoff Ratios To Predict Syphilis Infection

Journal of Clinical Microbiology January 2018 V.56 N.1

Commentaries

Claire C. Bristow and Jeffrey D. Klausner

aDivision of Infectious Diseases & Global Public Health, Department of Medicine, University of California—San Diego, La Jolla, California, USA

bDepartment of Epidemiology, Fielding School of Public Health, University of California—Los Angeles, Los Angeles, California, USA

cDivision of Infectious Diseases, Department of Medicine, University of California—Los Angeles, Los Angeles, California, USA

Syphilis screening with the reverse algorithm, a treponemal test for screening followed by a nontreponemal test if reactive, is increasingly being used. That algorithm has several advantages, including use of an automated screening test, saving on laboratory time and costs, as well as detection of very early syphilis infection. However, under that algorithm, in situations where the treponemal result is positive and the nontreponemal result is nonreactive a second treponemal test must be performed, which may actually lead to inefficiencies in the laboratory. In this issue of the Journal of Clinical Microbiology, Y. F. Fakile et al. (J Clin Microbiol 56:e01165-17, 2017, https://doi.org/10.1128/JCM.01165-17) report the results of their study, which demonstrates the capability of signal strength ratio cutoffs for automated treponemal immunoassays to predict the outcome of repeat treponemal testing. Their findings suggest that anti-treponemal signal strength ratio values above a cutoff value can be used in lieu of repeat treponemal tests.

PDF

http://jcm.asm.org/content/56/1/e01555-17.full.pdf+html

January 5, 2018 at 8:17 am

In Vitro Antibacterial Properties of Cefiderocol, a Novel Siderophore Cephalosporin, against Gram-Negative Bacteria

Antimicrobial Agents and Chemotherapy January 2018 V.62 N.1

Akinobu Ito, Takafumi Sato, Merime Ota, Miki Takemura, Toru Nishikawa, Shinsuke Toba, Naoki Kohira, Satoshi Miyagawa, Naoki Ishibashi, Shuhei Matsumoto, Rio Nakamura, Masakatsu Tsuji and Yoshinori Yamano

aShionogi & Co., Ltd., Toyonaka, Osaka, Japan

Cefiderocol (CFDC; S-649266), a novel parenteral siderophore cephalosporin conjugated with a catechol moiety, has a characteristic antibacterial spectrum with a potent activity against a broad range of aerobic Gram-negative bacterial species, including carbapenem-resistant strains of Enterobacteriaceae and nonfermenting bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii.

Cefiderocol has affinity mainly for penicillin-binding protein 3 (PBP3) of Enterobacteriaceae and nonfermenting bacteria similar to that of ceftazidime.

A deficiency of the iron transporter PiuA in P. aeruginosa or both CirA and Fiu in Escherichia coli caused 16-fold increases in cefiderocol MICs, suggesting that these iron transporters contribute to the permeation of cefiderocol across the outer membrane.

The deficiency of OmpK35/36 in Klebsiella pneumoniae and the overproduction of efflux pump MexA-MexB-OprM in P. aeruginosa showed no significant impact on the activity of cefiderocol.

PDF

http://aac.asm.org/content/62/1/e01454-17.full.pdf+html

December 25, 2017 at 12:21 pm

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