Clinical, economic and societal impact of antibiotic resistance

Barriere, Steven L.

doi:10.1517/14656566.2015.983077

Cited by 113 publications

(91 citation statements)

References 16 publications

(13 reference statements)

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“…In order to cause infection, these pathogens produce a range of virulence factors which in turn, promote host tissue damage and contribute to bacterial evasion from the host’s immune response and their subsequent survival in the bloodstream (Bhatty et al, 2015; Thammavongsa et al, 2015; Theilacker et al, 2015). This scenario coupled with a diminished antibiotic pipeline has lead to serious social and economic complications and it has prompted the search of novel compounds and therapies to combat bacterial infections (Barriere, 2015). …”

Section: Introductionmentioning

confidence: 99%

Cinnamaldehyde Inhibits Staphylococcus aureus Virulence Factors and Protects against Infection in a Galleria mellonella Model

et al. 2016

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Bacterial resistance to the available marketed drugs has prompted the search of novel therapies; especially in regards of anti-virulence strategies that aim to make bacteria less pathogenic and/or decrease their probability to become resistant to therapy. Cinnamaldehyde is widely known for its antibacterial properties through mechanisms that include the interaction of this compound with bacterial cell walls. However, only a handful of studies have addressed its effects on bacterial virulence, especially when tested at sub-inhibitory concentrations. Herein, we show for the first time that cinnamaldehyde is bactericidal against Staphylococcus aureus and Enterococcus faecalis multidrug resistant strains and does not promote bacterial tolerance. Cinnamaldehyde actions were stronger on S. aureus as it was able to inhibit its hemolytic activity on human erythrocytes and reduce its adherence to latex. Furthermore, cinnamaldehyde enhanced the serum-dependent lysis of S. aureus. In vivo testing of cinnamaldehyde in Galleria mellonella larvae infected with S. aureus, showed this compound improves larvae survival whilst diminishing bacterial load in their hemolymph. We suggest that cinnamaldehyde may represent an alternative therapy to control S. aureus-induced bacterial infections as it presents the ability to reduce bacterial virulence/survival without promoting an adaptive phenotype.

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Section: Introductionmentioning

confidence: 99%

Cinnamaldehyde Inhibits Staphylococcus aureus Virulence Factors and Protects against Infection in a Galleria mellonella Model

et al. 2016

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“…The development of antibiotic resistance will obviously impede treatment of several bacterial infections. It will also affect other elements of modern hospital care, e.g., cancer treatment, transplantations and advanced surgery, disciplines that are highly reliant on the use of antibiotics to defeat bacterial infections (Barriere 2015). …”

Section: Antibiotic Resistancementioning

confidence: 99%

Infection control of Staphylococcus aureus : spa typing to elucidate transmission

Mernelius¹

2015

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Staphylococcus aureus is a commensal of the human flora, primarily colonizing the anterior nares and throat, but it may also cause infections ranging from mild skin and soft tissue infections to severe diseases such as endocarditis and septicemia. S. aureus is also a major nosocomial problem increasing with the worldwide dissemination of methicillin-resistant S. aureus (MRSA).The main vector for bacterial cross-transmission in healthcare settings is the hands of healthcare workers (HCWs). No S. aureus was detected in the air in this thesis demonstrating that transmission through air is not important. Despite the fact that good compliance with hand hygiene is essential to prevent cross-transmission the compliance is generally less than 50 %.Gold standard to track bacterial transmission in healthcare settings has for long been pulsedfield gel electrophoresis (PFGE), a method that is labor-intensive, lacks consensus protocol and relies on semi-subjective analysis. Molecular typing by sequencing of the hypervariable part of the S. aureus protein A gene (spa typing) has overcome these problems and has shown promising results in epidemiological investigations.The aims of this thesis were to study bacterial transmission with S. aureus colonization of newborn infants as a model and to evaluate spa typing as a molecular tool. Additionally, the influence of compliance with hygiene guidelines on S. aureus transmission was assessed.Analysis of 280 MRSA isolates by spa typing revealed excellent typeability and epidemiological concordance and satisfactory discriminatory power. Additionally, spa typing was considered superior to PFGE thanks to its accessibility, ease of use and rapidity. Also, spa typing results are registered in a global database, facilitating inter-laboratory comparison.The prevalence of S. aureus ranged from 41 % to 66 % in the populations studied and males had the highest colonization rate. Throat was the premier colonization site for adults and transmission from individuals colonized in the throat only was documented, suggesting that throat cultures should be included in S. aureus screening programs. The umbilicus was the premier colonization site for newborn infants. Incubating the swabs in enrichment broth prior to plating increased the prevalence of S. aureus positive samples by 46 %, resulting in prevalence viii ranging from 51 % to 70 % in the populations studied. Thus enrichment prior to plating is necessary to determine more truthful S. aureus colonization rates. There were no indications of an institutional flora, as the colonization rates, spa type distribution and antibiotic resistance prevalence were similar among parents and HCWs.Direct observations and self-reporting by HCWs were both validated as tools for monitoring compliance with hygiene guidelines. The compliance with hygiene guidelines was significantly higher following a 10-point hygiene intervention as compared to baseline. The compliance was also higher three years after the intervention in three of four participating departm...

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“…Overlooked for many years due to associated nephro-and neurotoxicity (25,26), colistin is increasingly used to treat life-threatening infections (24) and as an inhaled therapy in CF to prevent establishment of infection by MDR bacteria (25). While resistance to colistin remains low (27), the emergence of colistin-resistant strains heralds fears of a postantibiotic era (28).…”

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confidence: 99%

A Low-Molecular-Weight Alginate Oligosaccharide Disrupts Pseudomonal Microcolony Formation and Enhances Antibiotic Effectiveness

Pritchard

Powell

Jack

et al. 2017

Antimicrob Agents Chemother

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In chronic respiratory disease, the formation of dense, 3-dimensional "microcolonies" by Pseudomonas aeruginosa within the airway plays an important role in contributing to resistance to treatment. An in vitro biofilm model of pseudomonal microcolony formation using artificial-sputum (AS) medium was established to study the effects of low-molecular-weight alginate oligomers (OligoG CF-5/20) on pseudomonal growth, microcolony formation, and the efficacy of colistin. The studies employed clinical cystic fibrosis (CF) isolates (n ϭ 3) and reference nonmucoid and mucoid multidrug-resistant (MDR) CF isolates (n ϭ 7). Bacterial growth and biofilm development and disruption were studied using cell viability assays and image analysis with scanning electron and confocal laser scanning microscopy. Pseudomonal growth in AS medium was associated with increased ATP production (P Ͻ 0.05) and the formation (at 48 h) of discrete (Ͼ10-m) microcolonies. In conventional growth medium, colistin retained an ability to inhibit growth of planktonic bacteria, although the MIC was increased (0.1 to 0.4 g/ml) in AS medium compared to Mueller-Hinton (MH) medium. In contrast, in an established-biofilm model in AS medium, the efficacy of colistin was decreased. OligoG CF-5/20 (Ն2%) treatment, however, induced dose-dependent biofilm disruption (P Ͻ 0.05) and led to colistin retaining its antimicrobial activity (P Ͻ 0.05). While circular dichroism indicated that OligoG CF-5/20 did not change the orientation of the alginate carboxyl groups, mass spectrometry demonstrated that the oligomers induced dose-dependent (Ͼ0.2%; P Ͻ 0.05) reductions in pseudomonal quorum-sensing signaling. These findings reinforce the potential clinical significance of microcolony formation in the CF lung and highlight a novel approach to treat MDR pseudomonal infections.

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Clinical, economic and societal impact of antibiotic resistance

Cited by 113 publications

References 16 publications

Cinnamaldehyde Inhibits Staphylococcus aureus Virulence Factors and Protects against Infection in a Galleria mellonella Model

Cinnamaldehyde Inhibits Staphylococcus aureus Virulence Factors and Protects against Infection in a Galleria mellonella Model

Infection control of Staphylococcus aureus : spa typing to elucidate transmission

A Low-Molecular-Weight Alginate Oligosaccharide Disrupts Pseudomonal Microcolony Formation and Enhances Antibiotic Effectiveness

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