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Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of health-care-associated infections. Controversies regarding the effectiveness of various control strategies have contributed to varying approaches to MRSA control. However, new evidence from large-scale studies has emerged, particularly concerning screening and decolonization. Importantly, implementation and outcomes of control measures in practice are not only influenced by scientific evidence, but also economic, administrative, and political factors, as demonstrated by decreasing MRSA rates in a number of countries after concerted and coordinated efforts at a national level. Flexibility to adapt measures based on local epidemiology and resources is essential for successful MRSA control.

Summary New Delhi metallo-β-lactamase (NDM) gene confers high-level resistance to an array of β-lactams including carbapenems. Short- and long-read sequencing was used to investigate outbreaks of NDM-positive Enterobacterales including a potential horizontal gene transfer (HGT) event of an NDM-positive plasmid between Salmonella enterica and Klebsiella pneumoniae. Genomic analysis demonstrated a high degree of similarity between NDM-carrying plasmids from patient 1 in K. pneumoniae and patient 2 with S. enterica, K. pneumoniae and Klebsiella oxytoca, confirming an inter-species HGT event. The utility of whole-genome sequencing was demonstrated for in-hospital outbreaks, previously undetected using traditional infection-control surveillance.

Antifungal susceptibilities of non-Aspergillus filamentous fungal pathogens cannot always be inferred from their identification. Here we determined, using the Sensititre(®) YeastOne(®) YO10 panel, the in vitro activities of nine antifungal agents against 52 clinical isolates of emergent non-Aspergillus moulds representing 17 fungal groups in Australia. Isolates comprised Mucorales (n = 14), Scedosporium/Lomentospora spp. (n = 18) and a range of hyaline hyphomycetes (n = 9) and other dematiaceous fungi (n = 11). Excluding Verruconis gallopava, echinocandins demonstrated poor activity (MICs generally >8 mg/L) against these moulds. Lomentospora prolificans (n = 4) and Fusarium spp. (n = 6) demonstrated raised MICs to all antifungal drugs tested, with the lowest being to voriconazole and amphotericin B (AmB), respectively (geometric mean MICs of 3.4 mg/L and 2.2 mg/L, respectively). All Scedosporium apiospermum complex isolates (n = 14) were inhibited by voriconazole concentrations of ≤0.25 mg/L, followed by posaconazole and itraconazole at ≤1 mg/L. Posaconazole and AmB were the most active agents against the Mucorales, with MIC90 values of 1 mg/L and 2 mg/L, respectively, for Rhizopus spp. For dematiaceous fungi, all isolates were inhibited by itraconazole and posaconazole concentrations of ≤0.5 mg/L (MIC90, 0.12 mg/L and 0.25 mg/L, respectively), but voriconazole and AmB also had in vitro activity (MIC90, 0.5 mg/L and 1 mg/L, respectively). Differences in antifungal susceptibility within species and between species within genera support the need for testing individual patient isolates to guide therapy. The Sensititre(®) YeastOne(®) offers a practical alternative to the reference methodology for susceptibility testing of moulds.

Mucormycosis is the second most common cause of invasive mould infection and causes disease in diverse hosts, including those who are immuno-competent. We conducted a multicentre retrospective study of proven and probable cases of mucormycosis diagnosed between 2004-2012 to determine the epidemiology and outcome determinants in Australia. Seventy-four cases were identified (63 proven, 11 probable). The majority (54.1%) were caused by Rhizopus spp. Patients who sustained trauma were more likely to have non-Rhizopus infections relative to patients without trauma (OR 9.0, p 0.001, 95% CI 2.1-42.8). Haematological malignancy (48.6%), chemotherapy (42.9%), corticosteroids (52.7%), diabetes mellitus (27%) and trauma (22.9%) were the most common co-morbidities or risk factors. Rheumatological/autoimmune disorders occurred in nine (12.1%) instances. Eight (10.8%) cases had no underlying co-morbidity and were more likely to have associated trauma (7/8; 87.5% versus 10/66; 15.2%; p

We present a case of pseudomembranous cryptococcal laryngotracheobronchitis in an 80-year-old woman with a history of intractable cough with production of long sputum strings and severe dysphonia. Her main risk factor was considered to be the use of high-dose inhaled fluticasone, given for severe mixed asthma/chronic obstructive pulmonary disease (COPD). This is an unusual presentation of pulmonary cryptococcal disease, which commonly presents as parenchymal disease. We also present a review of the published case reports of endobronchial and laryngeal cryptococcal disease.

OBJECTIVETo describe the transmission dynamics of the emergence and persistence of vanA vancomycin-resistant enterococcus (VRE) in an intensive care unit (ICU) using whole-genome sequencing of patient and environmental isolates.DESIGNRetrospective cohort study.SETTINGICU in a tertiary referral center.PARTICIPANTSPatients admitted to the ICU over an 11-month period.METHODSVanA VRE isolated from patients (n=31) were sequenced using the Illumina MiSeq platform. Environmental samples from bed spaces, equipment, and waste rooms were collected. All vanA VRE-positive environmental samples (n=14) were also sequenced. Data were collected regarding patient ward and bed movements.RESULTSThe 31 patient vanA VRE isolates were from screening (n=19), urine (n=4), bloodstream (n=3), skin/wound (n=3), and intra-abdominal (n=2) sources. The phylogeny from sequencing data confirmed several VRE clusters, with 1 group accounting for 38 of 45 isolates (84%). Within this cluster, cross-transmission was extensive and complex across the ICU. Directionality indicated that colonized patients contaminated environmental sites. Similarly, environmental sources not only led to patient colonization but also to infection. Notably, shared equipment acted as a conduit for transmission between different ICU areas. Infected patients, however, were not linked to further VRE transmission.CONCLUSIONSGenomic sequencing confirmed a predominantly clonal outbreak of VRE with complex transmission dynamics. The environmental reservoir, particularly from shared equipment, played a key role in ongoing VRE spread. This study provides evidence to support the use of multifaceted strategies, with an emphasis on measures to reduce bacterial burden in the environment, for successful VRE control.Infect Control Hosp Epidemiol 2018;39:668–675

Objectives: sasX is a colonization-virulence factor that potentially underlies the success of methicillin-resistant Staphylococcus aureus (MRSA) sequence type (ST) 239 in Asia. We aimed to study the spread of sasX and the population structure of MRSA in two geographically distinct regions, Europe and India. Methods: MRSA (n = 128) from screening and clinical samples from tertiary care patients in 12 European countries (n = 119), and from India (n = 9) were multilocus-sequence-typed and screened for sasX and its carrier phi SP beta-like prophage by PCR. Whole genome sequencing was performed on sasX-harbouring strains from India (n = 5) and Europe (n = 2) and on a selection non-harbouring sasX (n = 36) (2 x 150 bp, Miseq, Illumina). Reads were mapped to the ST239 reference strain, TW20. Results: sasX and sesI, a sasX homologue native to Staphylococcus epidermidis, were detected in five of the nine Indian MRSA belonging to ST239 and to other sequence types of CC8. In contrast, sasX was restricted to two ST239 strains in Europe. The intact sasX and sesI carrier phi SP beta-like prophages were similar to 80 kb and similar to 118 kb, and integrated in the yeeE gene. We identified 'novel' ST239 clades in India and Serbia that showed significant differences in base substitution frequencies (0.130 and 0.007, respectively, Tamura-Nei model) (p

The authors regret that the author name Silvano Esposito was published incorrectly. The authors would like to apologise for any inconvenience caused.

Background VRE are prevalent among patients in ICUs. Non-typeable vanA VRE, due to loss of one of the genes used for MLST (pstS), have increased in Australia, suggestive of a new, hospital-acquired lineage. Objectives To understand the significance of this lineage and its transmission using WGS of strains isolated from patients in ICUs across New South Wales, Australia. Methods A total of 240 Enterococcus faecium isolates collected between February and May 2016, and identified by conventional PCR as vanA positive, were sequenced. Isolates originated from 12 ICUs in New South Wales, grouped according to six local health districts, and represented both rectal screening swab (n = 229) and clinical (n = 11) isolates. Results ST analysis revealed the absence of the pstS gene in 84.2% (202 of 240) of vanA isolates. Two different non-typeable STs were present based on different allelic backbone patterns. Loss of the pstS gene appeared to be the result of multiple recombination events across this region. Evidence for pstS-negative lineage spread across all six local health districts was observed suggestive of inter-hospital transmission. In addition, multiple outbreaks were detected, some of which were protracted and lasted for the duration of the study. Conclusions These findings confirmed the evolution, emergence and dissemination of non-typeable vanA E. faecium. This study has highlighted the utility of WGS when attempting to describe accurately the hospital-based pathogen epidemiology, which in turn will continue to inform optimal infection control measures necessary to halt the spread of this important nosocomial organism.

The aim of this study was to evaluate the epidemiology and characteristics and to identify modifiable risk factors for community-associated (CA) MRSA colonisation in a region with high prevalence. A large patient population (n=2280) from two tertiary care centres in Athens (Greece) was evaluated. Demographics and potential risk factors for CA-MRSA colonisation were recorded prospectively. Presence of the Panton-Valentine Leukocidin (PVL) toxin and mecA gene was determined in all MRSA isolates. Two definitions for CA-MRSA were applied. Univariate and multivariate analyses to identify predictors of previously unknown CA-MRSA colonisation were performed. In total, 120 (5.3%) MRSA carriers were identified; in 67 the isolates were classified as CA-MRSA using criteria based on the CDC definition, compared with 35 based on a definition including PVL toxin positivity. Factors significantly associated with previously unknown CA-MRSA carriage (CDC definition) included being a child or adolescent (OR=3.6, 95% CI 1.5-8.6), belonging to the family of an index case (OR=2.4, 95% CI 1.2-4.8), and presence of any co-morbidity (OR=1.7, 95% CI 1.04-2.8) or chronic skin disease (OR=3.6, 95% CI=2.2-6.1). In multivariate analysis, presence of any co-morbidity was the only significant predictor (OR=4.9, 95% CI 1.07-22.5; P=0.04). No easily modifiable risk factor for previously unknown CA-MRSA colonisation was identified. The CDC-based epidemiological definition for CA-MRSA appears to be more sensitive in detection of CA-MRSA colonisation than a purely molecular definition based on presence of the PVL gene.

Earlier targeted therapy for bacteraemia optimizes patient outcomes and reduces broad spectrum antibiotic use. Standardized susceptibility testing results are available at 36–48 h. Direct disc susceptibility testing from blood culture broth reduces time to results but the inoculum is not standardized. No studies have looked at the clinical utility of direct susceptibility results. This retrospective cohort study aimed to assess the correlation between direct and formal testing methods as well as the clinical utility of direct susceptibility results. 160 episodes of bacteraemia with paired direct and formal susceptibility testing were studied. Direct disc testing was performed on blood culture broth. Formal testing was performed on isolates, using automated broth microdilution or Etests. The rate of error was 9.0 % (95 % CI 7.0–11.6 %). In 10 cases (6.3 %, 95 % CI 3.0–11.2 %), inappropriate antibiotics were used due to direct susceptibility results, including two cases with ineffective (as opposed to too broad) antibiotics being used. Antibiotics were changed in 28.1 % of cases once direct susceptibility data was available. There was a decreased time to effective antibiotics in 9.3 % (95 % CI 5.3–15.0 %), and a decreased time to a targeted antibiotics in 14.3 % (95 % CI 9.3–20.8 %) of cases. Despite the error rate, the advantages of earlier times to effective and targeted antibiotics justifies continuing direct testing in bacteraemia episodes with Gram-negative rods. In the Gram-positive group, given the contamination rate, the availability of adjunctive PCR, and the fact that early identification of the isolate could equally influence antibiotic choices, direct susceptibility testing may no longer be warranted.

Twenty-three hospital laboratories from Europe and Israel participated in an external quality assessment (EQA) of the culture-based detection of methicillin-resistant Staphylococcus aureus (MRSA). Participants also reported the MRSA prevalence in clinical cultures and patient screening specimens, as well as the MRSA screening practices employed at their hospitals. An EQA panel of 18 samples consisting of two MRSA harbouring SCCmec IV and I, and one strain each of methicillin-resistant coagulase-negative S. epidermidis, methicillin-sensitive S. aureus and Escherichia coli as pure strains or in mixtures at 1071 cfu absolute loads was analysed by the 23 participants. Seventeen (74%) participants identified 17 or more samples correctly. Of these, 15 (88%) utilised a chromogenic medium alone (ChromID, bioMérieux; BBL CHROMagar, BD Diagnostics; MRSA Select, Bio-Rad Laboratories) or combined with a conventional medium and up to three confirmatory tests. Proportions of MRSA among S. aureus isolated from clinical cultures varied widely, even among hospitals within countries, ranging from 1120% to 6170%. MRSA carriage rates were less variable (020%) between countries. Almost all participants (n = 22, 96%) screened patients for MRSA carriage during 20092010, of which 15 (68%) screened intensive care unit (ICU) patients alone or combined with other targeted high-risk groups, and 10 (45%) combined nasal screening with another body site.

Gentamicin-susceptible methicillin-resistant Staphylococcus aureus (GS-MRSA) clones have gradually replaced gentamicin-resistant MRSA (GR-MRSA) clones in many European countries. We studied molecular and epidemiological aspects of MRSA strain replacement in individual patients. All patients from whom at least 2 MRSA strains showing different gentamicin susceptibility patterns were isolated between 1996 and 2008 were retrospectively identified. Staphylococcal cassette chromosome mec (SCC mec ) type and clonality between isolates were determined using molecular methods. Risk factors for individual GR-MRSA SCC mec I (prevalent clone) strain replacement with GS-MRSA non-SCC mec I types were studied in a nested case-crossover study ( n = 55 patients). MRSA strain replacement was observed in 127 patients, 85 (67%) of whom were initially colonized with GR-MRSA replaced subsequently by GS-MRSA. Most GS-MRSA replacement strains (50; 59%) possessed SCC mec IV. All MRSA isolate pairs from the same patient that consisted of different gentamicin susceptibility and SCC mec types were also genotypically different. Exposure to domiciliary nursing assistance (odds ratio [OR], 8.1; 95% confidence interval [CI], 1.2 to 53.7) and high Charlson scores (OR, 7.1; 95% CI, 1.1 to 46.8) were associated with individual strain replacement. In individual patients, exogenous acquisition of a different MRSA strain was responsible for strain replacement in most cases. Domiciliary nursing assistance could be a target for specific control measures to prevent transmission of GS-MRSA in our setting.

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of health care-associated infections worldwide. Controversies with regard to the effectiveness of various MRSA control strategies have contributed to varying approaches to the control of this pathogen in different settings. However, new evidence from large-scale studies has emerged, particularly with regards to MRSA screening and decolonization strategies, which will inform future control practices. The implementation as well as outcomes of control measures in the real world is not only influenced by scientific evidence but also depends on economic, administrative, governmental, and political influences.

Topical mupirocin is widely used for the decolonization of methicillin-resistant Staphylococcus aureus (MRSA) carriers. We evaluated the capacity of various MRSA clonotypes to develop mutations in the ileS gene associated with low-level mupirocin resistance. Twenty-four mupirocin-sensitive MRSA isolates from a variety of genotypes (determined by a multilocus variable-number tandem-repeat assay) were selected. Mupirocin MICs were determined by Etest. The isolates were then incubated in subinhibitory concentrations of mupirocin for 7 to 14 days. Repeat MIC determinations and sequencing of the ileS gene were then performed. Doubling times of isolates exposed to mupirocin and of unexposed isolates were compared. We found that exposure to mupirocin led to rapid induction of low-level resistance (MICs of 8 to 24 μg/ml) in 11 of 24 (46%) MRSA isolates. This phenomenon was observed in strains with diverse genetic backgrounds. Various mutations were detected in 18 of 24 (75%) MRSA isolates. Acquisition of mutations appeared to be a stepwise process during prolonged incubation with the drug. Among the five isolates exhibiting low-level resistance and the highest MICs, four tested sensitive after incubation in the absence of mupirocin but there was no reversion to the susceptible wild-type primary sequence. Resistance was not associated with significant fitness cost, suggesting that MRSA strains with low-level mupirocin resistance may have a selective advantage in facilities where mupirocin is commonly used. Our findings emphasize the importance of the judicious use of this topical agent and the need to closely monitor for the emergence of resistance.

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of nosocomial infections worldwide. Different approaches to the control of this pathogen have met with varying degrees of success in different health care settings. Controversies exist with regards to various MRSA control strategies. The implementation and outcomes of control measures depend on several factors, including scientific, economic, administrative, governmental, and political influences. It is clear that flexibility to adapt and institute these measures in the context of local epidemiology and resources is required.

The clinical importance of low-level mupirocin resistance and genotypic chlorhexidine resistance remains unclear. We aimed to determine whether resistance to these agents increases the risk of persistent methicillin-resistant Staphylococcus aureus (MRSA) carriage after their use for topical decolonization therapy.A nested case-control study was conducted of MRSA carriers who received decolonization therapy from 2001 through 2008. Cases, patients who remained colonized, were matched by year to controls, those in whom MRSA was eradicated (follow-up, 2 years). Baseline MRSA isolates were tested for mupirocin resistance by Etest and chlorhexidine resistance by qacA/B polymerase chain reaction. MRSA carriers with high-level mupirocin resistance were excluded. The effect of the primary exposure of interest, low-level mupirocin and genotypic chlorhexidine resistance, was evaluated with multivariate conditional logistic regression analysis.The 75 case patients and 75 control patients were similar except that those persistently colonized were older (P = .007) with longer lengths of hospital stay (P = .001). After multivariate analysis, carriage of combined low-level mupirocin and genotypic chlorhexidine resistance before decolonization independently predicted persistent MRSA carriage (odds ratio [OR], 3.4 [95% confidence interval {CI}, 1.5-7.8]). Other risk factors were older age (OR, 1.04 [95% CI, 1.02-1.1]), previous hospitalization (OR, 2.4 [95% CI, 1.1-5.7]), presence of a skin wound (OR, 5.7 [95% CI, 1.8-17.6]), recent antibiotic use (OR, 3.1 [95% CI, 1.3-7.2]), and central venous catheterization (OR, 5.7 [95% CI, 1.4-23.9]).Combined low-level mupirocin and genotypic chlorhexidine resistance significantly increases the risk of persistent MRSA carriage after decolonization therapy. Institutions with widespread use of these agents should monitor for resistance and loss of clinical effectiveness.

Non-tuberculous mycobacteria (NTM) causing clinical disease have become increasingly common and more diverse. A new reverse line probe assay, GenoType Mycobacterium CM/AS (Hain Lifescience), was evaluated for identification of a broad range of NTM. It was compared with phenotypic (HPLC) and molecular (DNA probes, in-house real-time multiplex species-specific PCR, 16S rRNA gene PCR and sequencing) identification techniques, which together provided the reference ‘gold standard’. A total of 131 clinical isolates belonging to 31 Mycobacterium species and 19 controls, including 5 non-Mycobacterium species, was used. Concordant results between the GenoType Mycobacterium assay and the reference identification were obtained in 119/131 clinical isolates (90.8 %). Identification of Mycobacterium abscessus and Mycobacterium lentiflavum by the assay was problematic. The GenoType Mycobacterium assay enables rapid identification of a broad range of potentially clinically significant Mycobacterium species, but some species require further testing to differentiate or confirm ambiguous results.

We compared the impacts of direct plating on a chromogenic medium and of plating after enrichment (4 h and overnight) on the detection of methicillin-resistant Staphylococcus aureus (MRSA) from 52 patient screening samples. MRSA colony counts for approximate to 70% of samples after overnight pre-enrichment were >20-fold higher than the counts after the other two treatments. The qualitative differences (sample was MRSA positive/negative) between the results of the direct plating and 4-h pre-enrichment treatments were not significant, indicating no advantage of the latter; however, the number of samples positive for MRSA increased significantly after an overnight sample pre-enrichment (P < 0.005). L.V.H. and this work are supported by funding from the European Community (MOSAR network contract LSHP-CT-2007-037941 and TheraEDGE network contract FP7-216027). S.M.-K. is funded by the Research Foundation-Flanders (FWO-V), Belgium. G.M., M.A., and J.C.A. gratefully acknowledge support from FWO-V, research grant G.0151.05, and Belgian IUAP/PAI network P6/03, Statistical Techniques and Modeling for Complex Substantive Questions with Complex Data of the Belgian Government (Belgian Science Policy).

The epidemiology of invasive fungal disease (IFD) due to filamentous fungi other than Aspergillus may be changing. We analysed clinical, microbiological and outcome data in Australian patients to determine the predisposing factors and identify determinants of mortality. Proven and probable non-Aspergillus mould infections (defined according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria) from 2004 to 2012 were evaluated in a multicentre study. Variables associated with infection and mortality were determined. Of 162 episodes of non-Aspergillus IFD, 145 (89.5%) were proven infections and 17 (10.5%) were probable infections. The pathogens included 29 fungal species/species complexes; mucormycetes (45.7%) and Scedosporium species (33.3%) were most common. The commonest comorbidities were haematological malignancies (HMs) (46.3%) diabetes mellitus (23.5%), and chronic pulmonary disease (16%); antecedent trauma was present in 21% of cases. Twenty-five (15.4%) patients had no immunocompromised status or comorbidity, and were more likely to have acquired infection following major trauma (p

Controversies regarding control of endemic methicillin-resistant Staphylococcus aureus (MRSA) stem in part from the paucity of data available on the actual costs of implementing MRSA control strategies.