Posts filed under ‘Resistencia bacteriana’

Interaction of Avibactam with Class B Metallo-β-Lactamases

Antimicrobial Agents and Chemotherapy October 2016 V.60 N.10 P.5655-5662

Martine I. Abboud, Christian Damblon, Jürgen Brem, Nicolas Smargiasso, Paola Mercuri, Bernard Gilbert, Anna M. Rydzik, Timothy D. W. Claridge, Christopher J. Schofield, and Jean-Marie Frère

aDepartment of Chemistry, University of Oxford, Oxford, United Kingdom

bLaboratoire de Chimie Biologique Structurale (CBS), Département de Chimie, Université de Liège, Liège, Belgium

cLaboratory of Mass Spectrometry, GIGA-R-CART, Université de Liège, Liège, Belgium

dCentre d’Ingénierie des Protéines, Université de Liège, Liège, Belgium

eChimie Analytique Inorganique, Département de Chimie, Université de Liège, Liège, Belgium

β-Lactamases are the most important mechanisms of resistance to the β-lactam antibacterials.

There are two mechanistic classes of β-lactamases: the serine β-lactamases (SBLs) and the zinc-dependent metallo-β-lactamases (MBLs). Avibactam, the first clinically useful non-β-lactam β-lactamase inhibitor, is a broad-spectrum SBL inhibitor, which is used in combination with a cephalosporin antibiotic (ceftazidime).

There are multiple reports on the interaction of avibactam with SBLs but few such studies with MBLs.

We report biochemical and biophysical studies on the binding and reactivity of avibactam with representatives from all 3 MBL subfamilies (B1, B2, and B3).

Avibactam has only limited or no activity versus MBL-mediated resistance in pathogens.

Avibactam does not inhibit MBLs and binds only weakly to most of the MBLs tested; in some cases, avibactam undergoes slow hydrolysis of one of its urea N-CO bonds followed by loss of CO2, in a process different from that observed with the SBLs studied.

The results suggest that while the evolution of MBLs that more efficiently catalyze avibactam hydrolysis should be anticipated, pursuing the development of dual-action SBL and MBL inhibitors based on the diazabicyclooctane core of avibactam may be productive.


October 23, 2016 at 6:23 pm

Cefazolin and Ertapenem, a Synergistic Combination Used To Clear Persistent Staphylococcus aureus Bacteremia

Antimicrob. Agents Chemother. November 1, 2016 V.60 N.11 P.6609-6618

George Sakoulas, Joshua Olson, Juwon Yim, Niedita B. Singh, Monika Kumaraswamy, Diana T. Quach, 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

cEugene Appelbaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA

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

eSkaggs School of Pharmacy, University of California San Diego, La Jolla, California, USA

Ertapenem and cefazolin were used in combination to successfully clear refractory methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia.

In addition, recent work has demonstrated activity of combination therapy with beta-lactams from different classes against methicillin-resistant S. aureus (MRSA).

The ertapenem-plus-cefazolin combination was evaluated for synergy in vitro and in vivo in a murine skin infection model using an index MSSA bloodstream isolate from a patient in whom persistent bacteremia was cleared with this combination and against a cadre of well-described research strains and clinical strains of MSSA and MRSA.

Against the index MSSA bloodstream isolate, ertapenem and cefazolin showed synergy using both checkerboard (fractional inhibitory concentration [FIC] index = 0.375) and time-kill assays.

Using a disk diffusion ertapenem potentiation assay, the MSSA isolate showed a cefazolin disk zone increased from 34 to 40 mm. In vitro pharmacokinetic/pharmacodynamic modeling at clinically relevant drug concentrations demonstrated bactericidal activity (>3 log10-CFU/ml reduction) of the combination but bacteriostatic activity of ether drug alone at 48 h.

A disk diffusion potentiation assay showed that ertapenem increased the cefazolin zone of inhibition by >3 mm for 34/35 (97%) MSSA and 10/15 (67%) MRSA strains.

A murine skin infection model of MSSA showed enhanced activity of cefazolin plus ertapenem compared to monotherapy with these agents. After successful use in clearance of MSSA bacteremia, the combination of ertapenem and cefazolin showed synergy against MSSA in vitro and in vivo.

This combination may warrant consideration for future clinical study in MSSA bacteremia.


October 23, 2016 at 6:22 pm

Results from the Canadian Nosocomial Infection Surveillance Program on Carbapenemase-Producing Enterobacteriaceae, 2010 to 2014

Antimicrob. Agents Chemother. November 1, 2016  V.60 N.11 P.6787-6794

Laura F. Mataseje, Kahina Abdesselam, Julie Vachon, Robyn Mitchel, Elizabeth Bryce, Diane Roscoe, David A. Boyd, Joanne Embree, Kevin Katz, Pamela Kibsey, Andrew E. Simor, Geoffrey Taylor, Nathalie Turgeon, Joanne Langley, Denise Gravel, Kanchana Amaratunga, and Michael R. Mulvey , on behalf of the Canadian Nosocomial Infection Surveillance Program

aAntimicrobial Resistance and Nosocomial Infections, Public Health Agency of Canada, Winnipeg, MB, Canada

bCenter for Communicable Diseases and Infection Control, Public Health Agency of Canada, Ottawa, ON, Canada

cDepartment of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, BC, Canada

dDepartment of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada

eDepartment of Infection Prevention and Control, North York General Hospital, Toronto, ON, Canada

fDepartment of Laboratory Medicine, Victoria General Hospital, Victoria, BC, Canada

gDepartment of Infectious Diseases, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

hDepartment of Infectious Diseases, University of Alberta Hospital, Edmonton, AB, Canada

iDepartment of Medical Microbiology, Hotel-Dieu de Quebec du CHUQ, QC, Canada

jDepartment of Pediatrics, IWK Health Centre, Halifax, NS, Canada

Carbapenemase-producing Enterobacteriaceae (CPE) are increasing globally; here we report on the investigation of CPE in Canada over a 5-year period. Participating acute care facilities across Canada submitted carbapenem-nonsusceptible Enterobacteriaceae from 1 January 2010 to 31 December 2014 to the National Microbiology Laboratory.

All CPE were characterized by antimicrobial susceptibilities, pulsed-field gel electrophoresis, multilocus sequence typing, and plasmid restriction fragment length polymorphism analysis and had patient data collected using a standard questionnaire. The 5-year incidence rate of CPE was 0.09 per 10,000 patient days and 0.07 per 1,000 admissions.

There were a total of 261 CPE isolated from 238 patients in 58 hospitals during the study period. blaKPC-3 (64.8%) and blaNDM-1 (17.6%) represented the highest proportion of carbapenemase genes detected in Canadian isolates. Patients who had a history of medical attention during international travel accounted for 21% of CPE cases.

The hospital 30-day all-cause mortality rate for the 5-year surveillance period was 17.1 per 100 CPE cases. No significant increase in the occurrence of CPE was observed from 2010 to 2014. Nosocomial transmission of CPE, as well as international health care, is driving its persistence within Canada.



October 23, 2016 at 6:20 pm

Duration of treatment of antibiotics in community acquired pneumonia.

Rev Chilena Infectol. 2016 Apr;33(2):177-86.

[Article in Spanish]

Bernal-Vargas MA, Cortés JA.


Community acquired pneumonia (CAP) is an important cause of morbidity and mortality around the world, with high treatment costs due to hospitalization and complications (adverse events due to medications, antibiotic resistance, healthcare associated infections, etc.). It has been proposed administration of short courses and early switch of intravenous administration to oral therapy to avoid costs and complications. There are recommendations about these topics in national and intemational guidelines, based on clinical trials which do not demónstrate diffe-rences in mortality and complications when there is an early change from intravenous administration to the oral route. There are no statistically significant differences in safety and resolution of the disease when short and long treatment schemes were compared. In this review we present the most important guidelines and clinical studies, taking into account the pharmacological differences between different medications. It is considered that early switch from intravenous to oral administration route and use of short cycles in CAP is safe and brings benefits to patients and institutions.


October 21, 2016 at 1:41 pm

Colangitis Aguda – Revisión de aspectos fundamentales

Rev. Medicina y Humanidades. Vol. III N°1-2, 2011

Dr. Humberto Flisfisch F.1  Ana Heredia C.2

1 Prof. Dpto. de Cirugía Sur. Facultad de Medicina Universidad de Chile.

2 Interno del Dpto. de Cirugía Sur. Facultad de Medicina Universidad de Chile.

La Colangitis Aguda ha sido una patología de gran morbimortalidad a través de la historia. En los años ’70 tenía una mortalidad habitual de un 50%, la que cae en los años ´80 a un 7% gracias al avance de las unidades de cuidado intensivo, advenimiento de nuevos antibióticos y técnicas de drenaje biliar. Sin embargo, durante los ´90 se reportaron tasas de mortalidad de 11 a 27%, y sigue siendo una enfermedad letal en ausencia de un tratamiento oportuno adecuado….


October 21, 2016 at 1:38 pm

Mycoplasma pneumoniae: Current Knowledge on Macrolide Resistance and Treatment.

Front Microbiol. 2016 Jun 22;7:974.

Pereyre S1, Goret J1, Bébéar C1.

Author information

1USC EA 3671 Mycoplasmal and Chlamydial Infections in Humans, Univ. BordeauxBordeaux, France; USC EA 3671 Mycoplasmal and Chlamydial Infections in Humans, INRABordeaux, France; Laboratoire de Bactériologie, Centre Hospitalier Universitaire de BordeauxBordeaux, France.


Mycoplasma pneumoniae causes community-acquired respiratory tract infections, particularly in school-aged children and young adults.

These infections occur both endemically and epidemically worldwide. M. pneumoniae lacks cell wall and is subsequently resistant to beta-lactams and to all antimicrobials targeting the cell wall.

This mycoplasma is intrinsically susceptible to macrolides and related antibiotics, to tetracyclines and to fluoroquinolones.

Macrolides and related antibiotics are the first-line treatment of M. pneumoniae respiratory tract infections mainly because of their low MIC against the bacteria, their low toxicity and the absence of contraindication in young children.

The newer macrolides are now the preferred agents with a 7-to-14 day course of oral clarithromycin or a 5-day course of oral azithromycin for treatment of community-acquired pneumonia due to M. pneumoniae, according to the different guidelines worldwide.

However, macrolide resistance has been spreading for 15 years worldwide, with prevalence now ranging between 0 and 15% in Europe and the USA, approximately 30% in Israel and up to 90-100% in Asia.

This resistance is associated with point mutations in the peptidyl-transferase loop of the 23S rRNA and leads to high-level resistance to macrolides.

Macrolide resistance-associated mutations can be detected using several molecular methods applicable directly from respiratory specimens.

Because this resistance has clinical outcomes such as longer duration of fever, cough and hospital stay, alternative antibiotic treatment can be required, including tetracyclines such as doxycycline and minocycline or fluoroquinolones, primarily levofloxacin, during 7-14 days, even though fluoroquinolones and tetracyclines are contraindicated in all children and in children < 8 year-old, respectively.

Acquired resistance to tetracyclines and fluoroquinolones has never been reported in M. pneumoniae clinical isolates but reduced susceptibility was reported in in vitro selected mutants.

This article focuses on M. pneumoniae antibiotic susceptibility and on the development and the evolution of acquired resistance. Molecular detection of resistant mutants and therapeutic options in case of macrolide resistance will also be assessed.


October 20, 2016 at 3:28 pm

Staphylococcus aureus Toxins and Diabetic Foot Ulcers: Role in Pathogenesis and Interest in Diagnosis.

Toxins (Basel). 2016 Jul 7;8(7).

Dunyach-Remy C1,2, Ngba Essebe C3, Sotto A4,5, Lavigne JP6,7.

Author information

1Institut National de la Santé Et de la Recherche Médicale U1047, Université de Montpellier, UFR de Médecine, Nîmes 30908, France.

2Service de Microbiologie, Centre Hospitalo-Universitaire Carémeau, Nîmes 30029, France.

3Institut National de la Santé Et de la Recherche Médicale U1047, Université de Montpellier, UFR de Médecine, Nîmes 30908, France.

4Institut National de la Santé Et de la Recherche Médicale U1047, Université de Montpellier, UFR de Médecine, Nîmes 30908, France.

5Service des Maladies Infectieuses et Tropicales, Centre Hospitalo-Universitaire Carémeau, Nîmes 30029, France.

6Institut National de la Santé Et de la Recherche Médicale U1047, Université de Montpellier, UFR de Médecine, Nîmes 30908, France.

7Service de Microbiologie, Centre Hospitalo-Universitaire Carémeau, Nîmes 30029, France.


Infection of foot ulcers is a common, often severe and costly complication in diabetes.

Diabetic foot infections (DFI) are mainly polymicrobial, and Staphylococcus aureus is the most frequent pathogen isolated.

The numerous virulence factors and toxins produced by S. aureus during an infection are well characterized. However, some particular features could be observed in DFI.

The aim of this review is to describe the role of S. aureus in DFI and the implication of its toxins in the establishment of the infection.

Studies on this issue have helped to distinguish two S. aureus populations in DFI: toxinogenic S. aureus strains (harboring exfoliatin-, EDIN-, PVL- or TSST-encoding genes) and non-toxinogenic strains.

Toxinogenic strains are often present in infections with a more severe grade and systemic impact, whereas non-toxinogenic strains seem to remain localized in deep structures and bone involving diabetic foot osteomyelitis.

Testing the virulence profile of bacteria seems to be a promising way to predict the behavior of S. aureus in the chronic wounds.


October 20, 2016 at 3:25 pm

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