Archive for January 5, 2017

Antimicrobial peptide exposure selects for Staphylococcus aureus resistance to human defence peptides

Journal of Antimicrobial & Chemotherapy January 1, 2017 V.72 N.1 P.115-127

Jessica Z. Kubicek-Sutherland, Hava Lofton, Martin Vestergaard, Karin Hjort, Hanne Ingmer, and Dan I. Andersson

1Department of Medical Biochemistry and Microbiology, Uppsala University, Box 582, 75123, Uppsala, Sweden

2Department of Veterinary Disease Biology, University of Copenhagen, Stigbøjlen 4, 1870 Frederiksberg C, Copenhagen, Denmark

Background

The clinical development of antimicrobial peptides (AMPs) is currently under evaluation to combat the rapid increase in MDR bacterial pathogens. However, many AMPs closely resemble components of the human innate immune system and the ramifications of prolonged bacterial exposure to AMPs are not fully understood.

Objectives

We show that in vitro serial passage of a clinical USA300 MRSA strain in a host-mimicking environment containing host-derived AMPs results in the selection of stable AMP resistance.

Methods

Serial passage experiments were conducted using steadily increasing concentrations of LL-37, PR-39 or wheat germ histones. WGS and proteomic analysis by MS were used to identify the molecular mechanism associated with increased tolerance of AMPs. AMP-resistant mutants were characterized by measuring in vitro fitness, AMP and antibiotic susceptibility, and virulence in a mouse model of sepsis.

Results

AMP-resistant Staphylococcus aureus mutants often displayed little to no fitness cost and caused invasive disease in mice. Further, this phenotype coincided with diminished susceptibility to both clinically prescribed antibiotics and human defence peptides.

Conclusions

These findings suggest that therapeutic use of AMPs could select for virulent mutants with cross-resistance to human innate immunity as well as antibiotic therapy. Thus, therapeutic use of AMPs and the implications of cross-resistance need to be carefully monitored and evaluated.

PDF

http://jac.oxfordjournals.org/content/72/1/115.full.pdf+html

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January 5, 2017 at 4:06 pm

Editor’s Choice: Occurrence and characterization of blaNDM-5-positive Klebsiella pneumoniae isolates from dairy cows in Jiangsu, China

Journal of Antimicrobial & Chemotherapy January 1, 2017 V.72 N.1 P.90-94

Tao He, Yang Wang, Lichang Sun, Maoda Pang, Lili Zhang, and Ran Wang

1State Laboratory Cultivation Base – Key Laboratory of Food Safety, Institute of Food Safety, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China

2Beijing Advanced Innovation Centre for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China

Objectives

To investigate the epidemiological characteristics and the surrounding genetic structure of the blaNDM-5 gene in Klebsiella pneumoniae derived from dairy cows in Jiangsu Province, China.

Methods

Ten carbapenem-resistant K. pneumoniae were collected from three dairy farms and were screened for the presence of carbapenemase genes using PCR and sequencing. PFGE and MLST were conducted to analyse the genetic relatedness of the blaNDM-5-harbouring K. pneumoniae isolates. The location of blaNDM-5 was identified by S1 nuclease-PFGE and Southern blotting. The transferability and profiles of blaNDM-5-carrying plasmids were analysed by conjugation experiments, and PCR-based replicon typing and RFLP, respectively. The surrounding genetic structure of the blaNDM-5 gene was obtained using WGS and PCR mapping.

Results

All 10 K. pneumoniae from dairy cows harboured the blaNDM-5 gene, exhibited resistance to multiple antimicrobials and belonged to five STs, of which ST1661 and ST2108 were the most prevalent. The blaNDM-5 gene was located on the ∼46 kb IncX3 plasmid in all isolates and these plasmids could be conjugated to an Escherichia coli recipient with no additional resistance profiles transferred. All blaNDM-5-carrying plasmids shared similar genetic contexts and were nearly identical to that of the human K. pneumoniae plasmid (pNDM-MGR194) previously reported in India.

Conclusions

This was the first case of blaNDM-5-positive K. pneumoniae identified from dairy cows in China. The IncX3 pNDM-MGR194-like plasmid disseminated among cow farms should be highlighted and its potential role in mediating transmission of the blaNDM gene between bacteria from humans and animals requires further monitoring.

PDF

http://jac.oxfordjournals.org/content/72/1/90.full.pdf+html

January 5, 2017 at 4:05 pm

Multicenter Pivotal Clinical Trial of Urine Malaria Test for Rapid Diagnosis of Plasmodium falciparum Malaria

Journal of Clinical Microbiology January 2017 V.55 N.1 P.253-263

Wellington A. Oyibo, Nnenna Ezeigwe, Godwin Ntadom, Oladipo O. Oladosu, Kaitlin Rainwater-Loveth, Wendy O’Meara, Evaezi Okpokoro, and William Brieger

aANDI Centre of Excellence for Malaria Diagnosis, International Malaria Microscopy Training and Rapid Diagnostic Test Quality Assurance Programme, and WHO/TDR/FIND Malaria Specimen Bank Site, College of Medicine, University of Lagos, Lagos, Nigeria

bNational Malaria Elimination Program, Federal Ministry of Health, Abuja, Nigeria

cJohns Hopkins University School of Public Health, Baltimore, Maryland, USA

dDuke University School of Medicine, Durham, North Carolina, USA

eInstitute of Human Virology Nigeria, Abuja, Nigeria

Peter Gilligan, Editor

UNC Health Care System

The need to expand malaria diagnosis capabilities alongside policy requirements for mandatory testing before treatment motivates exploration of noninvasive rapid diagnostic tests (RDTs).

We report the outcome of the first cross-sectional, single-blind clinical performance evaluation of a urine malaria test (UMT) for diagnosis of Plasmodium falciparum malaria in febrile patients.

Matched urine and finger-prick blood samples from participants ≥2 years of age with fever (axillary temperature of ≥37.5°C) or with a history of fever in the preceding 48 h were tested with UMT and microscopy (as the gold standard).

BinaxNOW (Pf and Pan versions) blood RDTs were done to assess relative performance. Urinalysis and rheumatoid factor (RF) tests were conducted to evaluate possible interference.

Diagnostic performance characteristics were computed at 95% confidence intervals (CIs). Of 1,800 participants screened, 1,691 were enrolled; of these 566 (34%) were febrile, and 1,125 (66%) were afebrile.

Among enrolled participants, 341 (20%) tested positive by microscopy, 419 (25%) were positive by UMT, 676 (40%) were positive by BinaxNOW Pf, and 368 (22%) were positive by BinaxNow Pan.

UMT sensitivity among febrile patients (for whom the test was indicated) was 85%, and specificity was 84%. Among febrile children ≤5 years of age, UMT sensitivity was 93%, and specificity was 83%.

The area under the receiver-operator characteristic curve (AUC) of UMT (0.84) was not significantly different from that of BinaxNOW Pf (0.86) or of BinaxNOW Pan (0.87), indicating that the tests do not differ in overall performance.

Gender, seasons, and RF did not impact UMT performance. Leukocytes, hematuria, and urobilinogen concentrations in urine were associated with lower UMT specificities.

UMT performance was comparable to that of the BinaxNOW Pf/Pan tests, making UMT a promising tool to expand malaria testing in public and private health care settings where there are challenges to blood-based malaria diagnosis testing.

PDF

http://jcm.asm.org/content/55/1/253.full.pdf+html

 

January 5, 2017 at 3:59 pm


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