Statphylococcus aureus bacteraemia : a major cause of mortaility in Australia and New Zealand

Objective : To document the types of, and mortality from, Staphylococcus aureus bacteraemia in Australia and New Zealand, and determine factors associated with mortality.

Design and setting : Prospective observational study in 27 independent or hospital pathology laboratories in Australia (24) and New Zealand (3), employing a web-based database to prospectively record demographic features, selected risk factors, principal antibiotic treatment and mortality data on all patients with positive blood cultures for S. aureus from June 2007 to May 2008.

Main outcome measure : 30-day all-cause mortality.

Results : 1994 episodes of S. aureus bacteraemia were identified, and complete 30-day follow-up data were available for 1865. Most episodes had their onset in the community (60.8%; 95% CI, 58.7%–63.0%). Methicillin-resistant S. aureus (MRSA) caused 450 episodes (24.1%; 95% CI, 22.2%–25.9%), and 123 of these (27.3%) had a susceptibility profile consistent with community-associated MRSA. All-cause mortality at 30 days was 20.6% (95% CI, 18.8%–22.5%). On univariate analysis, increased mortality was significantly associated with older age, European ethnicity, MRSA infection, infections not originating from a medical device, sepsis syndrome, pneumonia/empyema, and treatment with a glycopeptide or other non-β-lactam antibiotic. On multivariable analysis, independent predictors of mortality were age, sepsis syndrome, pneumonia/empyema, device-associated infection with a secondary focus, left-sided endocarditis, and treatment with a glycopeptide such as vancomycin, but not MRSA infection.

Conclusions : S. aureus bacteraemia is a common infection in both the community and hospitals in Australia and New Zealand, and is associated with appreciable mortality. Invasive MRSA infection may be more life-threatening, partly because of the inferior efficacy of the standard treatment, vancomycin. National web-based surveillance of S. aureus bacteraemia and its outcomes is not only important but also easily achievable.

Occurrence of antibiotic resistance genes in reclaimed water and river water in the Werribee Basin, Australia

The purpose of this study was to investigate the occurrence of antibiotic resistance genes (ARGs) in water used for irrigation in the Werribee River Basin, Australia, including river water and reclaimed effluent water (reclaimed water). Samples of reclaimed water, collected over a one-year period, were screened for the occurrence of ARGs using PCR detection assays. The presence of ARGs in the reclaimed water samples were contrasted with that of water samples taken from the Werribee River Basin, collected over the same time period, from five points selected for varying levels of urban and agricultural impact. Of the 54 river water samples collected, 2 (4%), 2 (4%), 0 and 0 were positive for methicillin, sulfonamide, gentamicin and vancomycin-resistant genes, respectively, while 6 of 11 reclaimed water samples were positive for methicillin (9%) and sulfonamide (45%). The presence/absence of ARGs did not appear to correlate with other measured water quality parameters. The low detection of ARGs in river water indicates that, regardless of its poor quality, the river has not yet been severely contaminated with ARGs. The greater prevalence of ARGs in reclaimed water indicates that this important agricultural water source will need to be monitored into the future.

Australian Enterococcal Sepsis Outcome Programme, 2011

From 1 January to 31 December 2011, 29 institutions around Australia participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2011 was to determine the proportion of enterococcal bacteraemia isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to ampicillin and the glycopeptides, and to characterise the molecular epidemiology of the Enterococcus faecalis and E. faecium isolates. Of the 1,079 unique episodes of bacteraemia investigated, 95.8% were caused by either E. faecalis (61.0%) or E. faecium (34.8%). Ampicillin resistance was detected in 90.4% of E. faecium but not detected in E. faecalis. Using Clinical and Laboratory Standards Institute breakpoints (CLSI), vancomycin non-susceptibility was reported in 0.6% and 31.4% of E. faecalis and E. faecium respectively and was predominately due to the acquisition of the vanB operon. Approximately 1 in 6 vanB E. faecium isolates however, had an minimum inhibitory concentration at or below the CLSI vancomycin susceptible breakpoint of ≤ 4 mg/L. Overall, 37% of E. faecium harboured vanA or vanB genes. Although molecular typing identified 126 E. faecalis pulsed-field gel electrophoresis (PFGE) pulsotypes, more than 50% belonged to 2 pulsotypes that were isolated across Australia. E. faecium consisted of 73 PFGE pulsotypes from which 43 multilocus sequence types were identified. Almost 90% of the E. faecium were identified as clonal complex 17 clones, of which approximately half were characterised as sequence type 203, which was isolated Australia-wide. In conclusion, the AESOP 2011 has shown that although polyclonal, enterococcal bacteraemias in Australia are frequently caused by ampicillin-resistant vanB E. faecium.

Australian Enterococcal Sepsis Outcome Programme annual report, 2013.

From 1 January to 31 December 2013, 26 institutions around Australia participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2013 was to determine the proportion of enterococcal bacteraemia isolates in Australia that are antimicrobial resistant, and to characterise the molecular epidemiology of the Enterococcus faecium isolates. Of the 826 unique episodes of bacteraemia investigated, 94.6% were caused by either E. faecalis (56.1%) or E. faecium (38.5%). Ampicillin resistance was not detected in E. faecalis but was detected in over 90% of E. faecium. Vancomycin non-susceptibility was reported in 0.2% and 40.9% of E. faecalis and E. faecium respectively and was predominately due to the acquisition of the vanB operon. Overall, 41.6% of E. faecium harboured vanA or vanB genes. The percentage of E. faecium bacteraemia isolates resistant to vancomycin in Australia is significantly higher than that seen in most European countries. E. faecium isolates consisted of 81 pulsed-field gel electrophoresis pulsotypes of which 72.3% were classified into 14 major pulsotypes containing five or more isolates. Multilocus sequence typing grouped the 14 major pulsotypes into clonal cluster 17, a major hospital-adapted polyclonal E. faecium cluster. Of the 2 predominant sequence types, ST203 (80 isolates) was identified across Australia and ST555 (40 isolates) was isolated primarily in the western and central regions (Northern Territory, South Australia and Western Australia) respectively. In conclusion, the AESOP 2013 has shown enterococcal bacteraemias in Australia are frequently caused by polyclonal ampicillin-resistant high-level gentamicin resistant vanB E. faecium, which have limited treatment options.

Synthesis and evaluation of cationic norbornanes as peptidomimetic antibacterial agents

A series of structurally amphiphilic biscationic norbornanes have been synthesised as rigidified, low molecular weight peptidomimetics of cationic antimicrobial peptides. A variety of charged hydrophilic functionalities were attached to the norbornane scaffold including aminium, guanidinium, imidazolium and pyridinium moieties. Additionally, a range of hydrophobic groups of differing sizes were incorporated through an acetal linkage. The compounds were evaluated for antibacterial activity against both Gram-negative and Gram-positive bacteria. Activity was observed across the series; the most potent of which exhibited an MIC's ≤ 1 μg mL(-1) against Streptococcus pneumoniae, Enterococcus faecalis and several strains of Staphylococcus aureus, including multi-resistant methicillin resistant (mMRSA), glycopeptide-intermediate (GISA) and vancomycin-intermediate (VISA) S. aureus.

Norbornene-based anion receptors as D-alanine binders

Vancomycin is currently used as last-line therapy against many Gram-positive bacterial pathogens. Herein, we report a series of peptidomimetic norbornene-based anion receptors that were designed as simple vancomycin mimics New hosts were evaluated for their affinity to both acetate and acetyl D-Ala by 1H NMR titration. Modest binding to both anions was observed in DMSO-d6 (Log Ka 1-2 for TBA Acetyl D-Alanine) in the anticipated 1:1 mode of binding.

Clinical MRSA isolates from skin and soft tissue infections show increased in vitro production of phenol soluble modulins

BACKGROUND: Phenol-soluble modulins (PSMs) are amphipathic, pro-inflammatory proteins secreted by most Staphylococcus aureus isolates. This study tested the hypothesis that in vitro PSM production levels are associated with specific clinical phenotypes. METHODS: 177 methicillin-resistant S. aureus (MRSA) isolates from infective endocarditis (IE), skin and soft tissue infection (SSTI), and hospital-acquired/ventilator-associated pneumonia (HAP) were matched by geographic origin, then genotyped using spa-typing. In vitro PSM production was measured by high performance liquid chromatography/mass spectrometry. Statistical analysis was performed using Chi-squared or Kruskal-Wallis tests as appropriate. RESULTS: Spa type 1 was significantly more common in SSTI isolates (62.7% SSTI; 1.7% IE; 16.9% HAP; p < 0.0001) while HAP and IE isolates were more commonly spa type 2 (0% SSTI; 37.3% IE; 40.7% HAP; p < 0.0001). USA300 isolates produced the highest levels of PSMs in vitro. SSTI isolates produced significantly higher quantities of PSMα1-4, PSMβ1, and δ-toxin than other isolates (p < 0.001). These findings persisted when USA300 isolates were excluded from analysis. CONCLUSIONS: Increased in vitro production of PSMs is associated with an SSTI clinical source. This significant association persisted after exclusion of USA300 genotype isolates from analysis, suggesting that PSMs play a particularly important role in the pathogenesis of SSTI as compared to other infection types.

Australasian Society of Infectious Diseases updated guidelines for the management of Clostridium difficile infection in adults and children in Australia and New Zealand

The incidence of Clostridium difficile infection (CDI) continues to rise, whilst treatment remains problematic due to recurrent, refractory and potentially severe nature of disease. The treatment of C. difficile is a challenge for community and hospital-based clinicians. With the advent of an expanding therapeutic arsenal against C. difficile since the last published Australasian guidelines, an update on CDI treatment recommendations for Australasian clinicians was required. On behalf of the Australasian Society of Infectious Diseases, we present the updated guidelines for the management of CDI in adults and children.

Selection and characterization of probiotic culture of Streptococcus thermophilus from dahi

For the isolation of probiotic cultures of Streptococcus thermophilus from dahi, we collected 120 samples from the southern regions of Punjab, Pakistan. Eleven isolates were obtained, and six were scrutinized for antibacterial activities against food-borne pathogens. The carbohydrate fermentation profile of these six strains was determined by the API50 CHL system. Additionally, these strains were amplified for their 16S rRNA regions to confirm their genotypic relationship. Furthermore, phenotypic characteristics among these strains were established by S-layer protein analysis of their cell walls by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and by plasmid profiling. The outer cell wall layers of these strains have 6-14 different sizes of protein bands of 27, 34, 37, 40, 45 and 60 kDa molecular weight. Similarly, except S02FT, all strains have a single prominent plasmid of 23 kbp, whereas S02FT has an additional plasmid of 9 kbp. On the basis of this unique feature and a wide spectrum of killing patterns against pathogenic bacteria, S. thermophilus S02FT was further characterized. This culture showed an optimum antibacterial activity of 800 AU/ml at pH 5.0-5.5 and a temperature of 30-37°C. It grows well in in vitro acidic conditions and tolerates bile salt up to 2% concentration. It was resistant to nalidixic acid, ciprofloxacin, gentamicin and sulphamethoxazol, but showed intermediate behaviour to vancomycin and erythromycin.