Vancomycin-resistant enterococci (VRE) are important nosocomial pathogens. Invasive VRE infections are difficult to treat since common therapeutic options including ampicillin and glycopeptides often ...fail. In vitro, most VRE remain susceptible to last-resort antibiotics such as linezolid, tigecycline and daptomycin. However, neither tigecycline nor linezolid act in a bactericidal manner, and daptomycin has proven activity only at high dosages licensed for treating enterococcal endocarditis. Despite these pharmacological and therapeutic limitations, reports on resistance to these last-resort drugs in VRE, and enterococci in general, have increased in recent years. In this review, we briefly recapitulate the current knowledge on the mode of action as well as the known and novel mechanisms of resistance and describe surveillance data on resistance to linezolid, tigecycline and daptomycin in enterococci. In addition, we also suggest a common nomenclature for designating enterococci and VRE with resistances to these important last-resort antibiotics.
Background The respiratory tract microbiome is essential for human health and well-being and is determined by genetic, lifestyle, and environmental factors. Patients with Common Variable ...Immunodeficiency (CVID) suffer from respiratory and intestinal tract infections, leading to chronic diseases and increased mortality rates. While CVID patients’ gut microbiota have been analyzed, data on the respiratory microbiome ecosystem are limited. Objective This study aims to analyze the bacterial composition of the oropharynx of adults with CVID and its link with clinical and immunological features and risk for respiratory acute infections. Methods Oropharyngeal samples from 72 CVID adults and 26 controls were collected in a 12-month prospective study. The samples were analyzed by metagenomic bacterial 16S ribosomal RNA sequencing and processed using the Quantitative Insights Into Microbial Ecology (QIME) pipeline. Differentially abundant species were identified and used to build a dysbiosis index. A machine learning model trained on microbial abundance data was used to test the power of microbiome alterations to distinguish between healthy individuals and CVID patients. Results Compared to controls, the oropharyngeal microbiome of CVID patients showed lower alpha- and beta-diversity, with a relatively increased abundance of the order Lactobacillales , including the family Streptococcaceae . Intra-CVID analysis identified age >45 years, COPD, lack of IgA, and low residual IgM as associated with a reduced alpha diversity. Expansion of Haemophilus and Streptococcus genera was observed in patients with undetectable IgA and COPD, independent from recent antibiotic use. Patients receiving azithromycin as antibiotic prophylaxis had a higher dysbiosis score. Expansion of Haemophilus and Anoxybacillus was associated with acute respiratory infections within six months. Conclusions CVID patients showed a perturbed oropharynx microbiota enriched with potentially pathogenic bacteria and decreased protective species. Low residual levels of IgA/IgM, chronic lung damage, anti antibiotic prophylaxis contributed to respiratory dysbiosis.
•PVL toxin could promote haematogenous osteomyelitis (OM) both in children and adults.•Particular lineages such as MSSA ST398 and PVL-positive lineages are associated with OM.•The most frequent ...clones causing OM were the same in healthcare-associated and community-associated infections.
Staphylococcus aureus is the most common causative organism of osteomyelitis (OM). Nevertheless, the molecular epidemiology of S. aureus causing OM remains ill-defined. This study aimed to address the global epidemiology of S. aureus clones from OM patients.
Literature databases were searched for studies reporting the molecular typing of S. aureus involved in OM published between 1 January 2000 and 29 July 2020. Data from 32 articles that fulfilled the inclusion criteria were analysed for year of publication, country of patients, methicillin susceptibility and genotypic characteristics of S. aureus isolates.
Pandemic clones CC5, CC8, CC22, CC30 and CC45 were the most common in OM. The distribution of clones differed greatly among studies owing to the local epidemiology of S. aureus and the MSSA heterogeneity. PVL-positive MRSA clones belonging to ST80/CC80 and ST8/CC8/USA300 were the most common among paediatric patients in Europe and the USA; greater variability was observed in the adult population. In Europe, MRSA belonged to PVL-negative CC5, CC8 and CC22 indicating a nosocomial origin of infections; in Asia PVL-positive ST59/CC59 MRSA was the most frequent. PVL-positive clones were often detected in haematogenous OM in children and adults. Although MSSA were polyclonal, PVL-negative ST398/CC398 MSSA was the most prevalent clone in diabetic foot OM.
All major S. aureus clones circulating both in hospital and community settings appear to be capable of causing OM. Future studies reporting molecular typing and genomic data will provide more insights into the epidemiology and pathobiology of S. aureus clones causing OM.
Identifying healthcare workers (HCW) who have less awareness and knowledge on antibiotic use and resistance represents a challenge for public health, since it might help the development of novel ...educational and training initiatives tailored on specific subgroups of professionals. This work aims to compare knowledge, attitudes and behaviors on antibiotic use and resistance across different groups of Italian HCW.
We used data from the multi-country and multi-professional survey launched by the European Centre for Disease Prevention and Control between 28 January to 4 March 2019 to assess knowledge, attitude and behaviors of HCW on antibiotics, antibiotic use and resistance. We distinguished three clusters of HCW using the Two-Step Cluster analysis, based on their personal and professional characteristics (i.e. profession, role, activity as prescriber, setting, and activity as antibiotic use advisor).
In general, cluster 1 consisted mostly of allied healthcare workers, while clusters 2 and 3 were made up almost completely of pharmacists and medical doctors, respectively. Interestingly, healthcare workers in cluster 3 had the highest knowledge on antibiotic use and resistance. Workers in cluster 1, instead, were those reporting the highest awareness of the importance and role of hand hygiene as an infection prevention and control measure. However, HCW in cluster 2 were those who recognized more their role of advisors on prudent antibiotic use.
Italian HCW exhibited different knowledge, attitudes, and behaviors on antibiotic use and resistance. These findings raised the need for educational and training interventions targeting specific professional groups.
To estimate the proportion of methicillin-resistant Staphylococcus aureus (MRSA) isolates from humans that were sequence type (ST) 398, we surveyed 24 laboratories in 17 countries in Europe in 2007. ...Livestock-associated MRSA ST398 accounted for only a small proportion of MRSA isolates from humans; most were from the Netherlands, Belgium, Denmark, and Austria.
Daptomycin (DAP) resistance in
is uncommon but there are increasing reports of the emergence of resistance during DAP therapy. Most clinical DAP-resistant
isolates investigated carried mutations in ...the
gene. The aim of this study was to identify mutations between a clinical pair of methicillin-susceptible
(MSSA) isolates (DAP-susceptible and DAP-resistant). Additionally, the activity of genes previously associated with DAP resistance was assessed.
Two MSSA isolates from patient with left-sided endocarditis were analyzed by whole genome sequencing (WGS) and reverse transcription-quantitative real-time PCR (RT-qPCR). The first isolate, DAP-susceptible, was obtained before initiation of treatment and the second isolate, DAP-resistant, was recovered after 4 weeks of DAP therapy.
Comparison of complete genomes of DAP-susceptible and its DAP-resistant variant identified two non-synonymous and one synonymous mutations. The non-synonymous mutations consisted of a S829L substitution in
and a T331I substitution in
. The RT-qPCR experiments revealed an increased expression of
, and
genes in DAP-resistant variant. Strikingly, the expression of
and
genes was significantly downregulated by DAP.
The
and
genes were previously associated with DAP resistance, however, none of the mutations described in this study had been previously identified and linked to DAP resistance. Moreover, we provide a new insight into the DAP action on
, in which the expression of key genes in DAP resistance is decreased by the antibiotic.
Antimicrobial resistance (AMR) is one of the most serious global public health threats in this century. The first World Health Organization (WHO) Global report on surveillance of AMR, published in ...April 2014, collected for the first time data from national and international surveillance networks, showing the extent of this phenomenon in many parts of the world and also the presence of large gaps in the existing surveillance. In this review, we focus on antibacterial resistance (ABR), which represents at the moment the major problem, both for the high rates of resistance observed in bacteria that cause common infections and for the complexity of the consequences of ABR. We describe the health and economic impact of ABR, the principal risk factors for its emergence and, in particular, we illustrate the highlights of four antibiotic-resistant pathogens of global concern - Staphylococcus aureus, Klebsiella pneumoniae, non-typhoidal Salmonella and Mycobacterium tuberculosis - for whom we report resistance data worldwide. Measures to control the emergence and the spread of ABR are presented.
Italy records very alarming levels antimicrobial resistance (AMR), so a National Action Plan on Antimicrobial resistance (PNCAR) was developed, adopting the AMR European Union's recommendations based ...on the results of the ECDC site visit of January 2017. For achieving PNCAR objectives, it is necessary to support and harmonize the implementation of recommendations in all the different healthcare levels (regional authorities and local trusts), so the SPiNCAR project was launched to create a tool for reaching this goal.
We developed a framework based on a scientific literature and national and international guidelines. Firstly, we identified the major intervention areas for tackling AMR, then, for each area, we built a set of standards, both for regional authorities than for local trusts. Every standard is composed by a set of essential and additional criteria, which refer to a minimum or supplemental performance level respectively. The contents were firstly discussed by the project's team during face-to-face kick-off meetings, then confirmed with Delphi methodology and finally validated through a pilot study.
The final framework consists of seven different areas that reflect the PNCAR structure: Governance, Surveillance and Monitoring, Appropriate Use of antimicrobials, Healthcare-associated Infections (HAIs) control and prevention, Education and Training, Alliance among Stakeholders, Implementation. The total number of standards for the regional framework was 34 with 264 criteria and for the local version 36 criteria with 279 standards.
The ongoing use of this tool, developed on international evidences and recommendations that were tailored on the Italian specific context, allows monitoring the improvement achieved over time and plan the next steps.
Staphylococcus aureus is a typical human pathogen. Some animal S. aureus lineages have derived from human strains following profound genetic adaptation determining a change in host specificity. Due ...to the close relationship of animals with the environmental microbiome and resistome, animal staphylococcal strains also represent a source of resistance determinants. Methicillin-resistant S. aureus (MRSA) emerged 50 years ago as a nosocomial pathogen but in the last decade it has also become a frequent cause of infections in the community. The recent finding that MRSA frequently colonizes animals, especially livestock, has been a reason for concern, as it has revealed an expanded reservoir of MRSA. While MRSA strains recovered from companion animals are generally similar to human nosocomial MRSA, MRSA strains recovered from food animals appear to be specific animal-adapted clones. Since 2005, MRSA belonging to ST398 was recognized as a colonizer of pigs and human subjects professionally exposed to pig farming. The "pig" MRSA was also found to colonize other species of farmed animals, including horses, cattle, and poultry and was therefore designated livestock-associated (LA)-MRSA. LA-MRSA ST398 can cause infections in humans in contact with animals, and can infect hospitalized people, although at the moment this occurrence is relatively rare. Other animal-adapted MRSA clones have been detected in livestock, such as ST1 and ST9. Recently, ST130 MRSA isolated from bovine mastitis has been found to carry a novel mecA gene that eludes detection by conventional PCR tests. Similar ST130 strains have been isolated from human infections in UK, Denmark, and Germany at low frequency. It is plausible that the increased attention to animal MRSA will reveal other strains with peculiar characteristics that can pose a risk to human health.
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