Semi-mechanistic modeling of resistance development to β-lactam and β-lactamase-inhibitor combinations.

The use of β-lactam (BL) and β-lactamase inhibitor (BLI) combinations, such as piperacillin-tazobactam (PIP-TAZ) is an effective strategy to combat infections by extended-spectrum β-lactamase-producing bacteria. However, in Gram-negative bacteria, resistance (both mutational and adaptive) to BL-BLI combination can still develop through multiple mechanisms. These mechanisms may include increased β-lactamase activity, reduced drug influx, and increased drug efflux.

Longitudinal Study of Dynamic Epidemiology of Extended-Spectrum Beta-Lactamase-Producing Escherichia coli in Pigs and Humans Living and/or Working on Pig Farms.

Extended-spectrum beta-lactamase (ESBL)-producing have been increasingly isolated from pigs, highlighting their potential for transmission to humans living and/or working within pig farms. As longitudinal data on the prevalence and the molecular characteristics of such isolates from the high-risk farming population remain scarce, we performed a long-term study on 39 Dutch pig farms. Fecal samples from pigs, farmers, family members, and employees were collected during four sampling occasions with a 6-month period.

Allele-specific collateral and fitness effects determine the dynamics of fluoroquinolone resistance evolution.

Collateral sensitivity (CS), which arises when resistance to one antibiotic increases sensitivity toward other antibiotics, offers treatment opportunities to constrain or reverse the evolution of antibiotic resistance. The applicability of CS-informed treatments remains uncertain, in part because we lack an understanding of the generality of CS effects for different resistance mutations, singly or in combination. Here, we address this issue in the gram-positive pathogen Streptococcus pneumoniae by measuring collateral and fitness effects of clinically relevant gyrA and parC alleles and their combinations that confer resistance to fluoroquinolones.

Identification of antibiotic collateral sensitivity and resistance interactions in population surveillance data.

Background: Collateral effects of antibiotic resistance occur when resistance to one antibiotic agent leads to increased resistance or increased sensitivity to a second agent, known respectively as collateral resistance (CR) and collateral sensitivity (CS). Collateral effects are relevant to limit impact of antibiotic resistance in design of antibiotic treatments. However, methods to detect antibiotic collateral effects in clinical population surveillance data of antibiotic resistance are lacking.

Design principles of collateral sensitivity-based dosing strategies.

Collateral sensitivity (CS)-based antibiotic treatments, where increased resistance to one antibiotic leads to increased sensitivity to a second antibiotic, may have the potential to limit the emergence of antimicrobial resistance. However, it remains unclear how to best design CS-based treatment schedules. To address this problem, we use mathematical modelling to study the effects of pathogen- and drug-specific characteristics for different treatment designs on bacterial population dynamics and resistance evolution.

Occurrence and Molecular Characteristics of Extended-Spectrum Beta-Lactamase-Producing Enterobacterales Recovered From Chicken, Chicken Meat, and Human Infections in Sao Paulo State, Brazil.

This study aimed to investigate the phylogenetic diversity and epidemiology of extended-spectrum beta-lactamase (ESBL)-producing and from chicken, chicken meat, and human clinical isolates in Sao Paolo, Brazil, and characterize their respective ESBL-encoding plasmids. Three hundred samples from chicken cloaca, chicken meat, and clinical isolates were phenotypically and genotypically assessed for ESBL resistance. Isolates were identified by MALDI TOF-MS and further characterized by MLST analysis and phylogenetic grouping.

Manganese complex [Mn(CO)(tpa-κN)]Br increases antibiotic sensitivity in multidrug resistant Streptococcus pneumoniae.

Objectives: The emergence of multidrug-resistance (MDR) in Streptococcus pneumoniae clones and non-vaccine serotypes necessitate the development of novel treatment strategies. This work aimed to determine the efficacy of the Mn complex [Mn(CO)(tpa-κN)]Br against clinically important MDR strains of S. pneumoniae.

Antibiotic production in is organized by a division of labor through terminal genomic differentiation.

One of the hallmark behaviors of social groups is division of labor, where different group members become specialized to carry out complementary tasks. By dividing labor, cooperative groups increase efficiency, thereby raising group fitness even if these behaviors reduce individual fitness. We find that antibiotic production in colonies of is coordinated by a division of labor.

Occurrence and characterization of extended-spectrum cephalosporin-resistant Enterobacteriaceae in healthy household dogs in Greece.

Extended-spectrum cephalosporin- and/or carbapenem-resistant (ESC and/or Carb) Enterobacteriaceae constitute a public health hazard because of limited treatment options and are endemic among humans in Greece. Recently, ESC and CarbEnterobacteriaceae have been increasingly isolated from companion animals, stressing their potential role as a reservoir for humans. However, the presence of ESC bacteria in companion animals within Greek households has not been determined yet.

Genomic and functional characterisation of IncX3 plasmids encoding bla in Escherichia coli from human and animal origin.

The bla β-lactamase gene is one of the most prevalent genes conferring resistance to extended-spectrum β-lactams in Enterobacteriaceae disseminating within and between reservoirs, mostly via plasmid-mediated horizontal gene transfer. Yet, studies regarding the biology of plasmids encoding bla are very limited. In this study, we revealed the emergence of IncX3 plasmids alongside IncI1α/γ in bla in animal-related Escherichia coli isolates.

High Prevalence of Intra-Familial Co-colonization by Extended-Spectrum Cephalosporin Resistant in Preschool Children and Their Parents in Dutch Households.

Extended-spectrum cephalosporin-resistant (ESC) pose a serious infection control challenge for public health. The emergence of the ESC phenotype is mostly facilitated by plasmid-mediated horizontal extended-spectrum β-lactamases (ESBLs) and AmpC gene transfer within . Current data regarding the plasmid contribution to this emergence within the Dutch human population is limited.

Molecular relatedness of ESBL/AmpC-producing Escherichia coli from humans, animals, food and the environment: a pooled analysis.

Background: In recent years, ESBL/AmpC-producing Escherichia coli (ESBL/AmpC-EC) have been isolated with increasing frequency from animals, food, environmental sources and humans. With incomplete and scattered evidence, the contribution to the human carriage burden from these reservoirs remains unclear.

Objectives: To quantify molecular similarities between different reservoirs as a first step towards risk attribution.

Emergence and nosocomial spread of carbapenem-resistant OXA-232-producing Klebsiella pneumoniae in Brunei Darussalam.

Objectives: Carbapenem-resistant Enterobacteriaceae (CRE) are identified as a major global health concern. The success of CRE is facilitated by the emergence, acquisition and spread of successful clones carrying plasmid-encoded resistance genes. In this study, an outbreak of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in patients hospitalised in Brunei Darussalam was investigated.

A Review of SHV Extended-Spectrum β-Lactamases: Neglected Yet Ubiquitous.

β-lactamases are the primary cause of resistance to β-lactams among members of the family Enterobacteriaceae. SHV enzymes have emerged in Enterobacteriaceae causing infections in health care in the last decades of the Twentieth century, and they are now observed in isolates in different epidemiological settings both in human, animal and the environment. Likely originated from a chromosomal penicillinase of Klebsiella pneumoniae, SHV β-lactamases currently encompass a large number of allelic variants including extended-spectrum β-lactamases (ESBL), non-ESBL and several not classified variants.

Molecular Characterization of Extended-Spectrum-Cephalosporin-Resistant Enterobacteriaceae from Wild Kelp Gulls in South America.

Extended-spectrum-cephalosporin-resistant Enterobacteriaceae are a public health concern due to limited treatment options. Here, we report on the occurrence and the molecular characteristics of extended-spectrum-cephalosporin-resistant Enterobacteriaceae recovered from wild birds (kelp gulls). Our results revealed kelp gulls as a reservoir of various extended-spectrum cephalosporinase genes associated with different genetic platforms.

Providencia stuartii Isolates from Greece: Co-Carriage of Cephalosporin (blaSHV-5, blaVEB-1), Carbapenem (blaVIM-1), and Aminoglycoside (rmtB) Resistance Determinants by a Multidrug-Resistant Outbreak Clone.

Providencia stuartii has emerged as an important nosocomial pathogen. We describe an outbreak due to a multidrug-resistant strain over a 4-month period in a critical care unit in Athens. Molecular typing revealed each of the isolates to be clonally related with coresistance to cephalosporins, carbapenems, aminoglycosides, and quinolones.

Extended-Spectrum Cephalosporin-Resistant Salmonella enterica serovar Heidelberg Strains, the Netherlands(1).

Extended-spectrum cephalosporin-resistant Salmonella enterica serovar Heidelberg strains (JF6X01.0022/XbaI.0251, JF6X01.

Reduction of extended-spectrum-β-lactamase- and AmpC-β-lactamase-producing Escherichia coli through processing in two broiler chicken slaughterhouses.

Whilst broilers are recognised as a reservoir of extended-spectrum-β-lactamase (ESBL)- and AmpC-β-lactamase (AmpC)-producing Escherichia coli, there is currently limited knowledge on the effect of slaughtering on its concentrations on poultry meat. The aim of this study was to establish the concentration of ESBL/AmpC producing E. coli on broiler chicken carcasses through processing.

Dissemination of Methicillin-Susceptible CC398 Staphylococcus aureus strains in a rural Greek area.

A large collection of Staphylococcus aureus including a. 745 clinically significant isolates that were consecutively recovered from human infections during 2012-2013, b. 19 methicillin-susceptible (MSSA), randomly selected between 2006-2011 from our Staphylococcal Collection, c.

Identification and characterization of genetic structures coding for carbapenemases in Enterobacteria from Central Greece.

The dissemination of carbapenemases among different species of Enterobacteriaceae was investigated in the University Hospital of Larissa, Central Greece. The presence of the isoform (Tn4401a) of the transponson carrying blaKPC-2 and 5 divergent blaVIM-carrying class I integrons, including a novel structure, suggests interspecies transfer of these mobile elements and underscores their ongoing evolution.

Coagulase-negative staphylococcal bloodstream and prosthetic-device-associated infections: the role of biofilm formation and distribution of adhesin and toxin genes.

Coagulase-negative staphylococci (CNS), especially Staphylococcus epidermidis and Staphylococcus haemolyticus, have emerged as opportunistic pathogens in immunocompromised patients and those with indwelling medical devices. In this study, CNS recovered from patients with bloodstream infections (BSIs) or prosthetic-device-associated infections (PDAIs) were compared in terms of biofilm formation, antimicrobial resistance, clonal distribution, and carriage of adhesin and toxin genes. A total of 226 CNS isolates (168 S.

Factors influencing linezolid-nonsusceptible coagulase-negative staphylococci dissemination among patients in the intensive care unit: a retrospective cohort study.

Background: The aim of the present study was to identify risk factors for linezolid-nonsusceptible coagulase-negative staphylococci (CNS) dissemination in the intensive care unit.

Methods: Among the 246 patients included, 33 revealed a linezolid-nonsusceptible CNS-positive culture specimen, 68 were positive for linezolid-susceptible CNS and 145 served as controls. Isolates were characterized by phenotypic and genotypic methods to species level, susceptibility to antistaphylococcal agents and clones.

Successful control of a neonatal outbreak caused mainly by ST20 multidrug-resistant SHV-5-producing Klebsiella pneumoniae, Greece.

Background: Extended spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-Kp) infection can cause significant morbidity and mortality in neonates. We investigated a nosocomial ESBL-Kp outbreak in a neonatal intensive care unit (NICU) of the University Hospital of Larissa (UHL), Central Greece.

Methods: A total of sixty-four ESBL-Kp were studied; twenty six isolates were recovered from the NICU and were compared with thirty-eight randomly selected isolates from different wards of the hospital during the period March- December 2012.