Posts filed under ‘Resistencia bacteriana’
Multicenter Evaluation of MRSASelect II Chromogenic Agar for Identification of Methicillin-Resistant Staphylococcus aureus from Wound and Nasal Specimens
Journal of Clinical Microbiology February 2016 V.54 N.2 P.305-311
Diana R. Hernandez, Duane W. Newton, Nathan A. Ledeboer, Blake Buchan, Carol Young, Andrew E. Clark, Jessica Connoly, and Donna M. Wolk
aGeisinger Health System, Danville, Pennsylvania, USA
bUniversity of Michigan Health System, Ann Arbor, Michigan, USA
cMedical College of Wisconsin, Milwaukee, Wisconsin, USA
dUniversity of Arizona, Tucson, Arizona, USA
Hospitals strive to reduce methicillin-resistant Staphylococcus aureus (MRSA) prevalence via active surveillance of inpatient populations.
Rapid and inexpensive screening methods are utilized when molecular methods are not operationally feasible. In this multisite clinical trial, the utility of Bio-Rad’s MRSASelect II was evaluated for MRSA identification from remnant nares and wound swabs.
The prevalence of MRSA was 11.1% (n = 1,384) from nares samples and 18.1% (n = 842) from wound samples. MRSASelect II had an overall concordance of 95.4% (confidence interval [CI] = 94.5% to 96.2%) compared to a broth-enriched reference standard.
Comparisons between results, stratified by examination times, exhibited a nonsignificant trend toward increased positivity at prolonged incubation times. Cefoxitin screening of colonies directly from MRSASelect II was 96.7% (95.8% to 97.3%) concordant compared to testing of colonies following broth enrichment.
A comparison of MRSASelect and MRSASelect II revealed no statistical differences; however, the latter exhibited earlier positivity, greater selectivity, and more intense indicator staining, which resulted in facilitated differentiation of positive results. MRSASelect II agar is a simple, rapid, and robust method to routinely screen patients for MRSA colonization without the need for additional testing.
Antimicrobial Agents and Chemotherapy December 2015 V.59 N.12 P.7795-7798
Chunhui Chen, Jingyong Sun, Yan Guo, Dongfang Lin, Qinglan Guo, Fupin Hu, Demei Zhu, Xiaogang Xu, and Minggui Wang
aInstitute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China
bKey Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China
cDepartment of Clinical Microbiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
The vanM gene was first found in a vancomycin-resistant Enterococcus faecium (VREm) isolate in Shanghai in 2006.
In this study, we found that, in 70 VREm strains isolated in nine Shanghai hospitals from 2006 to 2014, vanM was more prevalent than the vanA gene (64.3% [45/70] versus 35.7% [25/70]).
The vanM-type isolates showed similar antimicrobial susceptibility patterns with the vanA types. The vanM-type VREm emerged and disseminated in Shanghai.
Antimicrobial Agents and Chemotherapy February 2016 V.60 N.2 P.789-796
Marius Linkevicius, Linus Sandegren, and Dan I. Andersson
Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
Tigecycline is a glycylcycline antibiotic active against multidrug-resistant bacterial pathogens.
The objectives of our study were to examine the potential of the Tet(A), Tet(K), Tet(M), and Tet(X) tetracycline resistance proteins to acquire mutations causing tigecycline resistance and to determine how this affects resistance to earlier classes of tetracyclines.
Mutations in all four tet genes caused a significant increase in the tigecycline MIC in Escherichia coli, and strains expressing mutant Tet(A) and Tet(X) variants reached clinically relevant MICs (2 mg/liter and 3 mg/liter, respectively). Mutations predominantly accumulated in transmembrane domains of the efflux pumps, most likely increasing the accommodation of tigecycline as a substrate.
All selected Tet(M) mutants contained at least one mutation in the functionally most important loop III of domain IV. Deletion of leucine 505 of this loop led to the highest increase of the tigecycline MIC (0.5 mg/liter) among Tet(M) mutants. It also caused collateral sensitivity to earlier classes of tetracyclines. A majority of the Tet(X) mutants showed increased activity against all three classes of tetracylines.
All tested Tet proteins have the potential to acquire mutations leading to increased MICs of tigecycline. As tet genes are widely found in pathogenic bacteria and spread easily by horizontal gene transfer, resistance development by alteration of existing Tet proteins might compromise the future medical use of tigecycline.
We predict that Tet(X) might become the most problematic future Tet determinant, since its weak intrinsic tigecycline activity can be mutationally improved to reach clinically relevant levels without collateral loss in activity to other tetracyclines.
Association between Regimen Composition and Treatment Response in Patients with Multidrug-Resistant Tuberculosis: A Prospective Cohort Study
PLOS Medicine December 29, 2015
Courtney M. Yuen, Ekaterina V. Kurbatova, Thelma Tupasi, Janice Campos Caoili, Martie Van Der Walt, Charlotte Kvasnovsky, Martin Yagui, Jaime Bayona, Carmen Contreras, Vaira Leimane, Julia Ershova, Laura E. Via, HeeJin Kim
World Health Organization (WHO) guidelines for the treatment of multidrug-resistant tuberculosis (MDR TB) recommend a regimen consisting of at least four second-line drugs that are likely to be effective as well as pyrazinamide . In the absence of drug susceptibility testing (DST) results for a patient’s isolate, likely effectiveness is determined based on previous exposure to a drug, background resistance levels to that drug in the community, and, in patients who were contacts to other known cases, DST results for an associated case. Furthermore, the guidelines indicate that only marginal benefit has been observed for regimens based directly on the DST results for a patient’s isolate .
A meta-analysis of cohort studies of patients with MDR TB reported that in vitro susceptibility to individual drugs was consistently and statistically significantly associated with higher odds of treatment success compared to in vitro resistance, suggesting clinical utility for DST in regimen design . In addition, the use of baseline DST results to design individualized regimens involving prolonged use of five or more drugs with likely effectiveness has been associated with decreased risks of treatment failure, death, and relapse among patient cohorts in Peru and the Russian Federation [3–5]. Together, this evidence suggests the need to reassess both the role of DST in regimen design as well as the potential benefit of including more drugs in MDR TB regimens….
Critical Care Medicine February 2016 V.44 N.2 P.256-264
Daneman, Nick MD1; Rishu, Asgar H. MBBS2; Xiong, Wei MSc2; Bagshaw, Sean M. MD3; Dodek, Peter MD4; Hall, Richard MD5; Kumar, Anand MD6; Lamontagne, Francois MD7; Lauzier, Francois MD8; Marshall, John MD9; Martin, Claudio M. MD10; McIntyre, Lauralyn MD11; Muscedere, John MD12; Reynolds, Steve MD13; Stelfox, Henry T. MD14; Cook, Deborah J. MD15; Fowler, Robert A. MD16; on behalf of the Canadian Critical Care Trials Group
1Division of Infectious Diseases, Department of Medicine and Clinical Epidemiology, Sunnybrook Health Sciences Centre, University of Toronto and Adjunct Scientist, Institute for Clinical Evaluative Sciences, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
2Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
3Division of Critical Care Medicine, University of Alberta, Edmonton, AB, Canada.
4Division of Critical Care Medicine and Center for Health Evaluation and Outcome Sciences, St. Paul’s Hospital and University of British Columbia, Vancouver, BC, Canada.
5Department of Critical Care Medicine, Dalhousie University and the Capital District, Health Authority, Halifax, NS, Canada.
6Sections of Critical Care Medicine and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada.
7Department of Medicine, Centre de recherche du CHU de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC, Canada.
8Centre de recherche du CHU de Québec, Axe santé des populations et pratiques optimales en santé, Division de soins intensifs adultes, départements de médecine et d’anesthésiologie, Université Laval, Quebec, QC, Canada.
9Departments of Surgery and Critical Care Medicine, St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada.
10Department of Medicine, University of Western Ontario, London, ON, Canada.
11Division of Critical Care, Department of Medicine, The Ottawa Hospital, Ottawa, ON, Canada.
12Department of Medicine, Queen’s University, Kingston, ON, Canada.
13Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
14Department of Critical Care Medicine, University of Calgary, Calgary, AB, Canada.
15Departments of Medicine, Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
16Department of Medicine and Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
The optimum duration of antimicrobial treatment for patients with bacteremia is unknown. Our objectives were to determine duration of antimicrobial treatment provided to patients who have bacteremia in ICUs, to assess pathogen/patient factors related to treatment duration, and to assess the relationship between treatment duration and survival.
Retrospective cohort study.
Fourteen ICUs across Canada.
Patients with bacteremia and were present in the ICU at the time culture reported positive.
Duration of antimicrobial treatment for patients who had bacteremia in ICU.
Measurements and Main Results
Among 1,202 ICU patients with bacteremia, the median duration of treatment was 14 days, but with wide variability (interquartile range, 9–17.5). Most patient characteristics were not associated with treatment duration. Coagulase-negative staphylococci were the only pathogens associated with shorter treatment (odds ratio, 2.82; 95% CI, 1.51–5.26). The urinary tract was the only source of infection associated with a trend toward lower likelihood of shorter treatment (odds ratio, 0.67; 95% CI, 0.42–1.08); an unknown source of infection was associated with a greater likelihood of shorter treatment (odds ratio, 2.14; 95% CI, 1.17–3.91). The association of treatment duration and survival was unstable when analyzed based on timing of death.
Critically ill patients who have bacteremia typically receive long courses of antimicrobials. Most patient/pathogen characteristics are not associated with treatment duration; survivor bias precludes a valid assessment of the association between treatment duration and survival. A definitive randomized controlled trial is needed to compare shorter versus longer antimicrobial treatment in patients who have bacteremia.
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SOS System Induction Inhibits the Assembly of Chemoreceptor Signaling Clusters in Salmonella enterica
Plos One January 19, 2016
Oihane Irazoki, Albert Mayola, Susana Campoy, Jordi Barbé
Swarming, a flagellar-driven multicellular form of motility, is associated with bacterial virulence and increased antibiotic resistance.
In this work we demonstrate that activation of the SOS response reversibly inhibits swarming motility by preventing the assembly of chemoreceptor-signaling polar arrays. We also show that an increase in the concentration of the RecA protein, generated by SOS system activation, rather than another function of this genetic network impairs chemoreceptor polar cluster formation.
Our data provide evidence that the molecular balance between RecA and CheW proteins is crucial to allow polar cluster formation in Salmonella enterica cells.
Thus, activation of the SOS response by the presence of a DNA-injuring compound increases the RecA concentration, thereby disturbing the equilibrium between RecA and CheW and resulting in the cessation of swarming.
Nevertheless, when the DNA-damage decreases and the SOS response is no longer activated, basal RecA levels and thus polar cluster assembly are reestablished.
These results clearly show that bacterial populations moving over surfaces make use of specific mechanisms to avoid contact with DNA-damaging compounds.
Distinctive Binding of Avibactam to Penicillin-Binding Proteins of Gram-Negative and Gram-Positive Bacteria
Antimicrobial Agents and Chemotherapy February 2016 V.60 N.2 P.752-756;
Abdelhamid Asli, Eric Brouillette, Kevin M. Krause, Wright W. Nichols, and François Malouin
aCentre d’Étude et de Valorisation de la Diversité Microbienne (CEVDM), Département de biologie, Faculté des sciences, Université de Sherbrooke, Sherbrooke, QC, Canada
bCerexa, Inc., Oakland, California, USA
cAstraZeneca Pharmaceuticals, Waltham, Massachusetts, USA
Avibactam is a novel non-β-lactam β-lactamase inhibitor that covalently acylates a variety of β-lactamases, causing inhibition. Although avibactam presents limited antibacterial activity, its acylation ability toward bacterial penicillin-binding proteins (PBPs) was investigated.
Staphylococcus aureus was of particular interest due to the reported β-lactamase activity of PBP4.
The binding of avibactam to PBPs was measured by adding increasing concentrations to membrane preparations of a variety of Gram-positive and Gram-negative bacteria prior to addition of the fluorescent reagent Bocillin FL.
Relative binding (measured here as the 50% inhibitory concentration [IC50]) to PBPs was estimated by quantification of fluorescence after gel electrophoresis. Avibactam was found to selectively bind to some PBPs.
In Escherichia coli, Pseudomonas aeruginosa, Haemophilus influenzae, and S. aureus, avibactam primarily bound to PBP2, with IC50s of 0.92, 1.1, 3.0, and 51 μg/ml, respectively, whereas binding to PBP3 was observed in Streptococcus pneumoniae (IC50, 8.1 μg/ml).
Interestingly, avibactam was able to significantly enhance labeling of S. aureus PBP4 by Bocillin FL. In PBP competition assays with S. aureus, where avibactam was used at a fixed concentration in combination with varied amounts of ceftazidime, the apparent IC50 of ceftazidime was found to be very similar to that determined for ceftazidime when used alone.
In conclusion, avibactam is able to covalently bind to some bacterial PBPs.
Identification of those PBP targets may allow the development of new diazabicyclooctane derivatives with improved affinity for PBPs or new combination therapies that act on multiple PBP targets