•CC17 Enterococcus faecium has emerged as a pandemic clone.•Vancomycin resistance is a critical issue.•Dissemination of CC17 E. faecium in the human–animal–environment interface has been ...documented.•Current epidemiology of vancomycin-resistant E. faecium.•Therapeutic alternatives to vancomycin for vancomycin-resistant CC17 E. faecium.
Enterococcus faecium is a robust opportunistic pathogen that is most commonly found as a commensal of the human and animal gut but can also survive in the environment. Since the introduction and use of antimicrobials, E. faecium has been found to rapidly acquire resistance genes that, when expressed, can effectively circumvent the effects of most antimicrobials. The rapid acquisition of multiple antimicrobial resistances has led to the adaptation of specific E. faecium clones in the hospital environment, collectively known as clonal complex 17 (CC17). CC17 E. faecium are responsible for a significant proportion of hospital-associated infections, which can cause severe morbidity and mortality. Here we review the history of E. faecium from commensal to a significant hospital-associated pathogen, its robust phenotypic characteristics, commonly used laboratory typing schemes, and antimicrobial resistances with a focus on vancomycin and its associated mechanism of resistance. Finally, we review the global epidemiology of vancomycin-resistant E. faecium and potential solutions to problems faced in public health.
In Australia in 2015, Candida auris sternal osteomyelitis was diagnosed in a 65-year-old man with a history of intensive care treatment in Kenya in 2012 and without a history of cardiac surgery. The ...isolate was South Africa clade III. Clinicians should note that C. auris can cause low-grade disease years after colonization.
Production of the Panton-Valentine leukocidin (PVL) by Staphylococcus aureus is mediated via the genes lukS-PV and lukF-PV which are carried on bacteriophage ϕSa2. PVL is associated with S. aureus ...strains that cause serious infections and clones of community-associated methicillin-resistant S. aureus (CA-MRSA) that have additionally disseminated widely. In Western Australia (WA) the original CA-MRSA were PVL negative however, between 2005 and 2008, following the introduction of eight international PVL-positive CA-MRSA, PVL-positive WA CA-MRSA were found. There was concern that PVL bacteriophages from the international clones were transferring into the local clones, therefore a comparative study of PVL-carrying ϕSa2 prophage genomes from historic WA PVL-positive S. aureus and representatives of all PVL-positive CA-MRSA isolated in WA between 2005 and 2008 was performed. The prophages were classified into two genera and three PVL bacteriophage groups and had undergone many recombination events during their evolution. Comparative analysis of mosaic regions of selected bacteriophages using the Alignments of bacteriophage genomes (Alpha) aligner revealed novel recombinations and modules. There was heterogeneity in the chromosomal integration sites, the lysogeny regulation regions, the defence and DNA processing modules, the structural and packaging modules and the lukSF-PV genes. One WA CA-MRSA (WA518751) and one international clone (Korean Clone) have probably acquired PVL-carrying ϕSa2 in WA, however these clones did not disseminate in the community. Genetic heterogeneity made it impossible to trace the source of the PVL prophages in the other WA clones. Against this background of PVL prophage diversity, the sequence of one group, the ϕSa2USA/ϕSa2wa-st93 group, was remarkably stable over at least 20 years and associated with the highly virulent USA300 and ST93-IVa CA-MRSA lineages that have disseminated globally.
The predominant community-associated MRSA strains vary between geographic settings, with ST8-IV USA300 being the commonest clone in North America, and the ST30-IV Southwest Pacific clone established ...as the dominant clone in New Zealand for the past two decades. Moreover, distinct epidemiological risk factors have been described for colonisation and/or infection with CA-MRSA strains, although these associations have not previously been characterized in New Zealand. Based on data from the annual New Zealand MRSA survey, we sought to describe the clinical and molecular epidemiology of MRSA in New Zealand. All non-duplicate clinical MRSA isolates from New Zealand diagnostic laboratories collected as part of the annual MRSA survey were included. Demographic data was collected for all patients, including age, gender, ethnicity, social deprivation index and hospitalization history. MRSA was isolated from clinical specimens from 3,323 patients during the 2005 to 2011 annual surveys. There were marked ethnic differences, with MRSA isolation rates significantly higher in Māori and Pacific Peoples. Over the study period, there was a significant increase in CA-MRSA, and a previously unidentified PVL-negative ST5-IV spa t002 clone replaced the PVL-positive ST30-IV Southwest Pacific clone as the dominant CA-MRSA clone. Of particular concern was the finding of several successful and virulent MRSA clones from other geographic settings, including ST93-IV (Queensland CA-MRSA), ST8-IV (USA300) and ST772-V (Bengal Bay MRSA). Ongoing molecular surveillance is essential to prevent these MRSA strains becoming endemic in the New Zealand healthcare setting.
•Daptomycin non-susceptible S. aureus causing disease in Australia was polyclonal.•Approximately 40% of daptomycin non-susceptible isolates were MRSA or multidrug-resistant, which is a public health ...concern.•ST22 was the predominant sequence type.•Daptomycin non-susceptibility was primarily due to mutations in MprF. Although novel mutations were identified, most mutations were of amino acid residues previously reported to be associated with daptomycin non-susceptibility.•No previously reported mutations were identified in candidate loci other than MprF.
Daptomycin is one of the few last-line antimicrobials available for the treatment of multidrug-resistant Staphylococcus aureus infections. An increasing number of daptomycin non-susceptible S. aureus infections has been reported worldwide, including Australia. Resistance to daptomycin is multifactorial and involves chromosomal mutations in genes encoding proteins involved in cell membrane and cell wall synthesis.
In this study, we performed broth microdilution (BMD) to determine the daptomycin minimum inhibitory concentration (MIC) of 66 clinical isolates of S. aureus previously reported as daptomycin non-susceptible by the VITEKⓇ 2. We used whole-genome sequencing to characterise the isolates and screened the genomes for mutations associated with daptomycin non-susceptibility.
Only 56 of the 66 isolates had a daptomycin MIC >1 mg/L by BMD. Although the 66 isolates were polyclonal, ST22 was the predominant sequence type and one-third of the isolates were multidrug resistant. Daptomycin non-susceptibility was primarily associated with MprF mutations—at least one MprF mutation was identified in the 66 isolates. Twelve previously reported MprF mutations associated with daptomycin non-susceptibility were identified in 83% of the isolates. Novel MprF mutations identified included P314A, P314F, P314T, S337T, L341V, F349del, and T423R.
Daptomycin non-susceptible S. aureus causing infections in Australia are polyclonal and harbour MprF mutation(s). The identification of multidrug-resistant daptomycin non-susceptible S. aureus is a public health concern.
This work investigated the molecular epidemiology and antimicrobial resistance of methicillin-resistant Staphylococcus aureus (MRSA) isolated from veterinarians in Australia in 2009. The collection ...(n = 44) was subjected to extensive molecular typing (MLST, spa, SCCmec, dru, PFGE, virulence and antimicrobial resistance genotyping) and antimicrobial resistance phenotyping by disk diffusion. MRSA was isolated from Australian veterinarians representing various occupational emphases. The isolate collection was dominated by MRSA strains belonging to clonal complex (CC) 8 and multilocus sequence type (ST) 22. CC8 MRSA (ST8-IV 2B, spa t064; and ST612-IV 2B, spa variable,) were strongly associated with equine practice veterinarians (OR = 17.5, 95% CI = 3.3-92.5, P < 0.001) and were often resistant to gentamicin and rifampicin. ST22-IV 2B, spa variable, were strongly associated with companion animal practice veterinarians (OR = 52.5, 95% CI = 5.2-532.7, P < 0.001) and were resistant to ciprofloxacin. A single pig practice veterinarian carried ST398-V 5C2, spa t1451. Equine practice and companion animal practice veterinarians frequently carried multiresistant-CC8 and ST22 MRSA, respectively, whereas only a single swine specialist carried MRSA ST398. The presence of these strains in veterinarians may be associated with specific antimicrobial administration practices in each animal species.
The spread of multidrug resistance among bacterial pathogens poses a serious threat to public health worldwide. Recent approaches towards combating antimicrobial resistance include repurposing old ...compounds with known safety and development pathways as new antibacterial classes with novel mechanisms of action. Here we show that an analog of the anticoccidial drug robenidine (4,6-bis(2-((E)-4-methylbenzylidene)hydrazinyl)pyrimidin-2-amine; NCL195) displays potent bactericidal activity against Streptococcus pneumoniae and Staphylococcus aureus by disrupting the cell membrane potential. NCL195 was less cytotoxic to mammalian cell lines than the parent compound, showed low metabolic degradation rates by human and mouse liver microsomes, and exhibited high plasma concentration and low plasma clearance rates in mice. NCL195 was bactericidal against Acinetobacter spp and Neisseria meningitidis and also demonstrated potent activity against A. baumannii, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and Enterobacter spp. in the presence of sub-inhibitory concentrations of ethylenediaminetetraacetic acid (EDTA) and polymyxin B. These findings demonstrate that NCL195 represents a new chemical lead for further medicinal chemistry and pharmaceutical development to enhance potency, solubility and selectivity against serious bacterial pathogens.
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