Archive for January 25, 2017

Carbapenemase-Producing Enterobacteriaceae in Swine Production in the United States: Impact and Opportunities

Antimicrobial Agents & Chemotherapy February 2017 V.61 N.2 e02348-16

Timothy J. Johnson

The discovery of carbapenemase-producing Enterobacteriaceae in U.S. swine production is troubling and underscores a tumultuous period where the outlook on the battle against superbugs is bleak. However, all is not lost. This commentary highlights both the good and the bad that can come from such findings, including those of a recent study published by Mollenkopf et al.



January 25, 2017 at 2:35 pm

In Vitro Tolerance of Drug-Naive Staphylococcus aureus Strain FDA209P to Vancomycin

Antimicrobial Agents & Chemotherapy February 2017 V.61 N.2 e01154-16

Madhuri Singh, Miki Matsuo, Takashi Sasaki, Yuh Morimoto, Tomomi Hishinuma, and Keiichi Hiramatsu

Department of Microbiology, Faculty of Medicine, Juntendo University, Tokyo, Japan

The mechanisms underlying bacterial tolerance to antibiotics are unclear. A possible adaptation strategy was explored by exposure of drug-naive methicillin-susceptible Staphylococcus aureus strain FDA209P to vancomycin in vitro.

Strains surviving vancomycin treatment (vancomycin survivor strains), which appeared after 96 h of exposure, were slow-growing derivatives of the parent strain.

Although the vancomycin MICs for the survivor strains were within the susceptible range, the cytokilling effects of vancomycin at 20-fold the MIC were significantly lower for the survivor strains than for the parent strain.

Whole-genome sequencing demonstrated that ileS, encoding isoleucyl-tRNA synthetase (IleRS), was mutated in two of the three vancomycin survivor strains.

The IleRS Y723H mutation is located close to the isoleucyl-tRNA contact site and potentially affects the affinity of IleRS binding to isoleucyl-tRNA, thereby inhibiting protein synthesis and leading to vancomycin tolerance. Introduction of the mutation encoding IleRS Y723H into FDA209P by allelic replacement successfully transferred the vancomycin tolerance phenotype.

We have identified mutation of ileS to be one of the bona fide genetic events leading to the acquisition of vancomycin tolerance in S. aureus, potentially acting via inhibition of the function of IleRS.


January 25, 2017 at 2:34 pm

Carbapenemase-Producing Enterobacteriaceae Recovered from the Environment of a Swine Farrow-to-Finish Operation in the United States

Dixie F. Mollenkopf, Jason W. Stull, Dimitria A. Mathys, Andrew S. Bowman, Sydnee M. Feicht, Susan V. Grooters, Joshua B. Daniels, and Thomas E. Wittum

aDepartment of Veterinary Preventive Medicine, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA

bDepartment of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA

Carbapenem-resistant Enterobacteriaceae (CRE) present an urgent threat to public health. While use of carbapenem antimicrobials is restricted for food-producing animals, other β-lactams, such as ceftiofur, are used in livestock.

This use may provide selection pressure favoring the amplification of carbapenem resistance, but this relationship has not been established. Previously unreported among U.S. livestock, plasmid-mediated CRE have been reported from livestock in Europe and Asia.

In this study, environmental and fecal samples were collected from a 1,500-sow, U.S. farrow-to-finish operation during 4 visits over a 5-month period in 2015.

Samples were screened using selective media for the presence of CRE, and the resulting carbapenemase-producing isolates were further characterized. Of 30 environmental samples collected from a nursery room on our initial visit, 2 (7%) samples yielded 3 isolates, 2 sequence type 218 (ST 218) Escherichia coli and 1 Proteus mirabilis, carrying the metallo-β-lactamase gene blaIMP-27 on IncQ1 plasmids.

We recovered on our third visit 15 IMP-27-bearing isolates of multiple Enterobacteriaceae species from 11 of 24 (46%) environmental samples from 2 farrowing rooms. These isolates each also carried blaIMP-27 on IncQ1 plasmids.

No CRE isolates were recovered from fecal swabs or samples in this study. As is common in U.S. swine production, piglets on this farm receive ceftiofur at birth, with males receiving a second dose at castration (≈day 6). This selection pressure may favor the dissemination of blaIMP-27-bearing Enterobacteriaceae in this farrowing barn.

The absence of this selection pressure in the nursery and finisher barns likely resulted in the loss of the ecological niche needed for maintenance of this carbapenem resistance gene.


January 25, 2017 at 2:32 pm

Classical β-Lactamase Inhibitors Potentiate the Activity of Daptomycin against Methicillin-Resistant Staphylococcus aureus and Colistin against Acinetobacter baumannii

Antimicrobial Agents & Chemotherapy February 2017 V.61 N.2 e01745-16

George Sakoulas, Warren Rose, Andrew Berti, Joshua Olson, Jason Munguia, Poochit Nonejuie, Eleanna Sakoulas, Michael J. Rybak, Joseph Pogliano, and Victor Nizet

aUniversity of California—San Diego School of Medicine, La Jolla, California, USA

bSharp Healthcare System, San Diego, California, USA

cUniversity of Wisconsin—Madison School of Pharmacy, Madison, Wisconsin, USA

dDepartment of Biological Sciences, University of California—San Diego, La Jolla, California, USA

eEugene Appelbaum College of Pharmacy, Wayne State University, Detroit, Michigan, USA

fSkaggs School of Pharmacy, University of California—San Diego, La Jolla, California, USA

We asked whether beta-lactamase inhibitors (BLIs) increased the activity of daptomycin (DAP) against methicillin-resistant Staphylococcus aureus (MRSA), the peptide antibiotic colistin (COL) against the emerging Gram-negative nosocomial pathogen Acinetobacter baumannii, and the human host defense peptide cathelicidin LL37 against either pathogen. DAP and LL37 kill curves were performed with or without BLIs against MRSA, vancomycin-intermediate S. aureus (VISA), and heterogeneous VISA (hVISA). COL and LL37 kill curves were performed against A. baumannii.

Boron-dipyrromethene (BODIPY)-labeled DAP binding to MRSA grown with the BLI tazobactam (TAZ) was assessed microscopically.

The combination of COL plus TAZ was studied in a murine model of A. baumannii pneumonia.

TAZ alone lacked in vitro activity against MRSA or A. baumannii. The addition of TAZ to DAP resulted in a 2- to 5-log10 reduction in recoverable MRSA CFU at 24 h compared to the recoverable CFU with DAP alone.

TAZ plus COL showed synergy by kill curves for 4 of 5 strains of A. baumannii tested. Growth with 20 mg/liter TAZ resulted in 2- to 2.5-fold increases in the intensity of BODIPY-DAP binding to MRSA and hVISA strains.

TAZ significantly increased the killing of MRSA and A. baumannii by LL37 in vitro. TAZ increased the activity of COL in a murine model of A. baumannii pneumonia. Classical BLIs demonstrate synergy with peptide antibiotics.

Since BLIs have scant antimicrobial activity on their own and are thus not expected to increase selective pressure toward antibiotic resistance, their use in combination with peptide antibiotics warrants further study.


January 25, 2017 at 2:31 pm

Inhibition of Plasmodium Liver Infection by Ivermectin

Antimicrobial Agents & Chemotherapy February 2017 V.61 N.2 e02005-16

António M. Mendes, Inês S. Albuquerque, Marta Machado, Joana Pissarra, Patrícia Meireles, and Miguel Prudêncio

Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal

Avermectins are powerful endectocides with an established potential to reduce the incidence of vector-borne diseases. Here, we show that several avermectins inhibit the hepatic stage of Plasmodium infection in vitro. Notably, ivermectin potently inhibits liver infection in vivo by impairing parasite development inside hepatocytes. This impairment has a clear impact on the ensuing blood stage parasitemia, reducing disease severity and enhancing host survival. Ivermectin has been proposed as a tool to control malaria transmission because of its effects on the mosquito vector. Our study extends the effect of ivermectin to the early stages of mammalian host infection and supports the inclusion of this multipurpose drug in malaria control strategies.


January 25, 2017 at 2:29 pm


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