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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.

Background Invasive fungal disease (IFD) in liver transplant recipients causes significant morbidity and mortality. We aim to describe institutional epidemiology and risk factors for IFD in the liver transplant population. Methods We conducted a retrospective cohort study of all adult liver transplant recipients in our institution from 2005 to October 2015 to describe the epidemiology of patients with proven and probable IFD according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. To determine risk factors for IFD, a case-control study was also conducted. Cases were defined as liver transplant recipients with proven or probable IFD, and controls were defined as liver transplant recipients without IFD. Each case was matched to two controls by age (±10 years of age), gender, and time of transplant (within one year of the case). Results 28/554 (5.1%) patients developed IFD. Candidiasis (n = 11; 39.3%), Aspergillosis (n = 10; 35.7%), and Cryptococcosis (n = 3; 10.7%) were the most common fungal infections in the proven and probable IFD groups. Mold infections occurred in 13 (46.4%) cases. Reoperation, roux-en-y anastomosis, and massive intraoperative transfusion of ≥40 units of cellular blood products were major risk factors for IFD in the multivariate analysis. Conclusion Candida and Aspergillus are the most common causes of IFD in liver transplantation in our center. There is significant overlap in risk factors for such infections post-transplantation. In our cohort, critically ill patients with complicated perioperative course seem to predispose them to mold infections post-transplantation, but larger studies are required to better delineate risk factors for mold infection as well as determine the efficacy and optimal duration of mold prophylaxis in liver transplantation. With increasing echinocandin use for antifungal prophylaxis, it is also important to monitor for emerging antifungal resistance.

Whole-genome sequencing clustered Australian Candida auris isolates from sporadic cases within clade III. Case isolates were genomically distinct; however, unexpectedly, those from 1 case comprised 2 groups separated by >60 single nucleotide polymorphisms (SNPs) with no isolate being identical, in contrast to outbreaks where isolates from any 1 individual have differed by

Leptomeningitis is a rare central nervous system manifestation of rheumatoid arthritis, generally in patients with established chronic rheumatoid disease. We report a 41-year-old man without previous rheumatoid arthritis or psychiatric disorder who presented with an acute neuropsychiatric disturbance and polyarthralgia. His MR scan of brain showed asymmetric bifrontal leptomeningitis, confirmed on (18F)-fluoro-D-glucose-positron emission tomography. Other investigations showed highly positive serum and cerebrospinal fluid anti-cyclic citrullinated peptide. A leptomeningeal biopsy showed necrotising leptomeningeal inflammation with ill-defined granulomas and lymphoplasmacytic infiltrate without organisms. Prolonged high-dose corticosteroids and then rituximab resulted in recovery. Chronic leptomeningitis can present with an acute neuropsychiatric disorder. We highlight that early rheumatoid disease can, rarely, cause a chronic leptomeningitis, reversible with immunotherapy.

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.

Since the 1960s, methicillin-resistant Staphylococcus aureus (MRSA) has emerged, disseminated globally and become a leading cause of bacterial infections in both health-care and community settings. However, there is marked geographical variation in MRSA burden owing to several factors, including differences in local infection control practices and pathogen-specific characteristics of the circulating clones. Different MRSA clones have resulted from the independent acquisition of staphylococcal cassette chromosome mec (SCCmec), which contains genes encoding proteins that render the bacterium resistant to most beta-lactam antibiotics (such as methicillin), by several S. aureus clones. The success of MRSA is a consequence of the extensive arsenal of virulence factors produced by S. aureus combined with beta-lactam resistance and, for most clones, resistance to other antibiotic classes. Clinical manifestations of MRSA range from asymptomatic colonization of the nasal mucosa to mild skin and soft tissue infections to fulminant invasive disease with high mortality. Although treatment options for MRSA are limited, several new antimicrobials are under development. An understanding of colonization dynamics, routes of transmission, risk factors for progression to infection and conditions that promote the emergence of resistance will enable optimization of strategies to effectively control MRSA. Vaccine candidates are also under development and could become an effective prevention measure.

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

Summary There is concern of global resurgence of invasive group A Streptococcus (iGAS) infections. We compared the clinical and molecular epidemiology of patients admitted with iGAS over two time periods, 2008 and 2010, in Western Sydney, Australia. The annual incidence was 19 cases per 100,000 admissions in 2008, compared to 33 per 100,000 in 2010. An increasing proportion of patients died (0% versus 13%), had an APACHE II score ≥30 (0% versus 19%), and had no known risk-factors (12% versus 25%). A potential skin source was identified as a trigger in fewer cases in 2010 (36% versus 11%). In total, there were 27 different emm types and 11 different emm clusters. There were some new emm types/clusters in 2010 that were not present in 2008. However, the study was not adequately powered to detect statistically significant differences in the distribution of emm types ( p = 0.06) and emm clusters ( p = 0.16) between the two years. There were also no clear associations between emm types/clusters and severity and clinical manifestations of iGAS infections. Although the proposed 30-valent M protein vaccine encompasses only 47% of our isolates, it will likely provide coverage for at least 71% of iGAS infections due to cross-opsonisation.

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.

IntroductionWe report a case of an isolated acute neuropsychiatric presentation due to rheumatoid meningitis (RM), successfully treated with steroids and rituximab.CaseA 41 year old man with a chronic headache and acute neuropsychiatric disturbance including impulsivity, grandiose delusions and agitation on a background of no known psychiatric history. Incidentally, he reported migratory palindromic, large and small joint polyarthritis over the preceding 18 months accompanied by headache, symptomatically treated with indomethacin. He had no prior diagnosis of rheumatoid arthritis (RA) or other connective tissue disorder. Serum and cerebrospinal fluid (CSF) cyclic citrullinated peptide antibodies were strongly positive, with a normal serum rheumatoid factor. An interferon-gamma release assay was positive, suggestive of prior tuberculosis (TB) exposure. CSF examination was unremarkable with an MRI brain demonstrating asymmetric features of leptomeningeal thickening and enhancement over both cerebral cortices, suggesting an inflammatory or infiltrative leptomeningitis. Lymphoma, IgG4–related disease, granulomatous diseases such as TB, granulomatosis with polyangiitis, neurosarcoidosis, neurosyphilis and meningeal metastasis were considered as differential diagnoses. A leptomeningeal and brain biopsy showed necrotising inflammation with ill-defined granulomas and a dense lymphoplasmacytic infiltrate. No organisms were identified. Mycobacterial polymerase chain reaction and cultures over three months were negative. RM was the favoured histological diagnosis. Empirical treatment for prior TB exposure was commenced in conjunction with steroids. Subsequent addition of iv rituximab resulted in sustained improvement of neuropsychiatric and joint symptoms.ConclusionThis report illustrates for the first time isolated acute neuropsychiatric disturbances attributable to RM without a prior history of RA that was responsive to rituximab. Clinicians should consider infiltrative and inflammatory leptomeningeal causes, particularly with asymmetric meningeal thickening and enchantment on MRI and should commit to a tissue biopsy when no other systemic connective tissue, infective or neoplastic causes are identified.

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.

Objective To evaluate the relative efficacy of the World Health Organization 2005 campaign (WHO-5) and other interventions to promote hand hygiene among healthcare workers in hospital settings and to summarize associated information on use of resources. Design Systematic review and network meta-analysis. Data sources Medline, Embase, CINAHL, NHS Economic Evaluation Database, NHS Centre for Reviews and Dissemination, Cochrane Library, and the EPOC register (December 2009 to February 2014); studies selected by the same search terms in previous systematic reviews (1980-2009). Review methods Included studies were randomised controlled trials, non-randomised trials, controlled before-after trials, and interrupted time series studies implementing an intervention to improve compliance with hand hygiene among healthcare workers in hospital settings and measuring compliance or appropriate proxies that met predefined quality inclusion criteria. When studies had not used appropriate analytical methods, primary data were re-analysed. Random effects and network meta-analyses were performed on studies reporting directly observed compliance with hand hygiene when they were considered sufficiently homogeneous with regard to interventions and participants. Information on resources required for interventions was extracted and graded into three levels. Results Of 3639 studies retrieved, 41 met the inclusion criteria (six randomised controlled trials, 32 interrupted time series, one non-randomised trial, and two controlled before-after studies). Meta-analysis of two randomised controlled trials showed the addition of goal setting to WHO-5 was associated with improved compliance (pooled odds ratio 1.35, 95% confidence interval 1.04 to 1.76; I 2 =81%). Of 22 pairwise comparisons from interrupted time series, 18 showed stepwise increases in compliance with hand hygiene, and all but four showed a trend for increasing compliance after the intervention. Network meta-analysis indicated considerable uncertainty in the relative effectiveness of interventions, but nonetheless provided evidence that WHO-5 is effective and that compliance can be further improved by adding interventions including goal setting, reward incentives, and accountability. Nineteen studies reported clinical outcomes; data from these were consistent with clinically important reductions in rates of infection resulting from improved hand hygiene for some but not all important hospital pathogens. Reported costs of interventions ranged from $225 to $4669 (£146-£3035; €204-€4229) per 1000 bed days. Conclusion Promotion of hand hygiene with WHO-5 is effective at increasing compliance in healthcare workers. Addition of goal setting, reward incentives, and accountability strategies can lead to further improvements. Reporting of resources required for such interventions remains inadequate.

BACKGROUND: Predictive models to identify unknown methicillin-resistant Staphylococcus aureus (MRSA) carriage on admission may optimise targeted MRSA screening and efficient use of resources. However, common approaches to model selection can result in overconfident estimates and poor predictive performance. We aimed to compare the performance of various models to predict previously unknown MRSA carriage on admission to surgical wards. METHODS: The study analysed data collected during a prospective cohort study which enrolled consecutive adult patients admitted to 13 surgical wards in 4 European hospitals. The participating hospitals were located in Athens (Greece), Barcelona (Spain), Cremona (Italy) and Paris (France). Universal admission MRSA screening was performed in the surgical wards. Data regarding demographic characteristics and potential risk factors for MRSA carriage were prospectively collected during the study period. Four logistic regression models were used to predict probabilities of unknown MRSA carriage using risk factor data: 'Stepwise' (variables selected by backward elimination); 'Best BMA' (model with highest posterior probability using Bayesian model averaging which accounts for uncertainty in model choice); 'BMA' (average of all models selected with BMA); and 'Simple' (model including variables selected >50% of the time by both Stepwise and BMA approaches applied to repeated random sub-samples of 50% of the data). To assess model performance, cross-validation against data not used for model fitting was conducted and net reclassification improvement (NRI) was calculated. RESULTS: Of 2,901 patients enrolled, 111 (3.8%) were newly identified MRSA carriers. Recent hospitalisation and presence of a wound/ulcer were significantly associated with MRSA carriage in all models. While all models demonstrated limited predictive ability (mean c-statistics

We recently diagnosed rickettsial spotted fever in four patients from the south-eastern coastal region of South Australia near Adelaide, an area not known to be endemic for this infection. All infections were acquired within the geographic range of Aponomma hydrosauri, the tick vector of Rickettsia honei. Infection by R. honei was confirmed in two patients. This extension of the known geographic range of R. honei infection may be explained, in part, by alterations in host-parasite ecology.

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.

Background Allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients are at high risk of invasive pneumococcal disease (IPD). We investigated the incidence and risk factors of IPD in alloHSCT recipients from 4 regional transplant centers over an 11-year period. This study aimed to inform future improvements in post-transplant care. Methods We conducted a retrospective nested 1:2 case–control study in patients aged ≥18 years who underwent alloHSCT between 2001 and 2011 in 4 major allogeneic transplant centers. Controls were matched with IPD cases on the basis of conditioning intensity and donor relationship (related or unrelated). Demographics and clinical characteristics of cases and controls were summarized. Univariate analysis of risk factors in matched case–control sets, and multivariate conditional logistic regression to control for confounding, were performed. Results In 23 alloHSCT recipients, 26 IPD episodes were identified. The cumulative incidence over 11 years was 2.3% (95% confidence interval [CI] 1.45–3.15) and the incidence density 956 per 100,000 transplant years of follow-up (95% CI 580–1321). Multivariate risk factor analysis and backwards elimination showed a significant positive association between mycophenolate mofetil (MMF), hyposplenism/asplenia, and IPD, whereas trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis for Pneumocystis jirovecii pneumonia (PJP) was associated with lower odds of IPD cases. Of alloHSCT recipients with IPD, 38.5% required intensive care, and, of deaths documented in cases over the period of review, 30% were attributable to IPD. Serotypes causing IPD matched currently available vaccines in 15/22 (68.1%) episodes. Conclusions The incidence of IPD in alloHSCT recipients is an important cause of morbidity and mortality, with rates of disease being many fold higher than the general population. Patients with evidence of hyposplenism/asplenia define a high-risk group in the alloHSCT population for IPD, and the independent association with IPD and MMF in the adjusted model from this study requires further evaluation. The occurrence of post-transplant IPD may be reduced by measures such as vaccination with both 13-valent and 23-valent pneumococcal vaccines. TMP/SMX prophylaxis for the prevention of PJP may offer incidental protection against IPD in alloHSCT recipients.

BMJ open 3(9), e003126 (2013). doi:10.1136/bmjopen-2013-003126, Published by BMJ Publ., London