A Bayesian spatiotemporal model for prevalence estimation of a VRE outbreak in a tertiary care hospital.

BACKGROUND: There was a nosocomial outbreak of vancomycin-resistant enterococci (VRE) at the hospital between 1st January 2018 and 31st July 2020. The goals of this study were to describe weekly prevalence, and to identify possible effects of the introduction of selected infection control measures. METHODS: A room-centric analysis of 12 floors (243 rooms) of the main hospital building was undertaken, including data on 37,558 patients over 22,072 person-weeks for the first 2 years of the outbreak (2018-2019). Poisson Bayesian hierarchical models were fitted to estimate prevalence per room and per week, including both spatial and temporal random effects terms. RESULTS: Exploratory data analysis revealed significant variability in prevalence between departments and floors, along with sporadic spatial and temporal clustering during colonization 'flare-ups'. The oncology department experienced slightly higher prevalence over the 104-week study period [adjusted prevalence ratio (aPR) 4.8, 95% confidence interval (CI) 2.6-8.9; P<0.001; compared with general medicine], as did both the cardiac surgery (aPR 3.8, 95% CI 2.0-7.3; P<0.001) and abdominal surgery (aPR 3.7, 95% CI 1.8-7.6; P<0.001) departments. Estimated peak prevalence was reached in July 2018, at which point a number of new infection control measures (including the daily disinfection of rooms and room cleaning with ultraviolet light upon patient discharge) were introduced that resulted in decreasing prevalence (aPR 0.89 per week, 95% CI 0.87-0.91; P<0.001). CONCLUSION: Relatively straightforward but personnel-intensive cleaning with disinfectants and ultraviolet light provided tangible benefits in getting the outbreak under control. Despite additional complexity, Bayesian hierarchical models provide a more flexible platform to study transmission dynamics.

Prevalence and significance of bacterial contamination of autologous stem cell products.

There is limited and conflicting information on the prevalence of contamination of haematopoietic stem and progenitor cell products (HPCPs), and their optimal management remains unclear. The authors reviewed the microbial surveillance data of HPCPs collected between January 2002 and December 2019 for autologous transplantation at the study institution to determine the prevalence of microbial contamination and the potential infectious complications among recipients. Among 3935 HPCPs, 25 (0.6%) were contaminated. Ultimately, 22 patients received contaminated grafts, with pre-emptive antimicrobial therapy initiated in six of these patients. No patients developed subsequent infectious complications. These data suggest that microbial contamination of autologous HPCPs and associated adverse outcomes are rare.

Low Yield of Methicillin-Resistant Staphylococcus aureus Screening in Hemodialysis Patients: 10 Years' Experience.

OBJECTIVE: To determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization in hemodialysis patients and to analyze the cost-effectiveness of our screening approach compared with an alternative strategy. DESIGN Screening study and cost-effectiveness analysis. METHODS: Analysis of twice-yearly MRSA prevalence studies conducted in the hemodialysis unit of a 950-bed tertiary care hospital from January 1, 2004, through December 31, 2013. For this purpose, nasal swab samples were cultured on MRSA screening agar (mannitol-oxacillin biplate). RESULTS: There were 20 mass screenings during the 10-year study period. We identified 415 patients participating in at least 1 screening, with an average of 4.5 screenings per patient. Of 415 screened patients, 15 (3.6%) were found to be MRSA carriers. The first mass screening in 2004 yielded the highest percentage of MRSA (6/101 [6%]). Only 7 subsequent screenings revealed new MRSA carriers, whereas 4 screenings confirmed previously known carriers, and 8 remained negative. None of the carriers developed MRSA bacteremia during the study period. The total cost of our screening approach, that is, screening and isolation costs, was US $93,930. The total cost of an alternative strategy (ie, no mass screening administered) would be equivalent to costs of isolation of index cases and contact tracing was estimated to be US $5,382 (difference, US $88,548). CONCLUSIONS: In an area of low MRSA endemicity (<5%), regular nasal screenings of a high-risk population yielded a low rate of MRSA carriers. Twice-yearly MRSA screening of dialysis patients is unlikely to be cost-effective if MRSA prevalence is low.

Vancomycin resistance has no influence on outcomes of enterococcal bacteriuria.

BACKGROUND: Infections with vancomycin-resistant enterococci (VRE) are a growing concern in hospitals. The impact of vancomycin resistance in enterococcal urinary tract infection is not well-defined. AIM: To describe the epidemiology of enterococcal bacteriuria in a hospital and compare the clinical picture and patient outcomes depending on vancomycin resistance. METHODS: This was a 6-month prospective cohort study of hospital patients who were admitted with or who developed enterococcal bacteriuria in a 1250-bed tertiary care hospital. We examined clinical presentation, diagnostic work-up, management, and outcomes. FINDINGS: We included 254 patients with enterococcal bacteriuria; 160 (63%) were female and median age was 65 years (range: 17-96). A total of 116 (46%) bacteriurias were hospital-acquired and 145 (57%) catheter-associated. Most patients presented with asymptomatic bacteriuria (ASB) (119; 47%) or pyelonephritis (64; 25%); 51 (20%) had unclassifiable bacteriuria and 20 (8%) had cystitis. Secondary bloodstream infection was detected in 8 (3%) patients. Seventy of 119 (59%) with ASB received antibiotics (mostly vancomycin). There were 74 (29%) VRE bacteriurias. VRE and vancomycin-susceptible enterococci (VSE) produced similar rates of pyelonephritis [19 (25%) vs 45 (25%); P = 0.2], cystitis, and ASB. Outcomes such as ICU transfer [10 (14%) VRE vs 17 (9%) VSE; P = 0.3], hospital length of stay (6.8 vs 5.0 days; P = 0.08), and mortality [10 (14%) vs 13 (7%); P = 0.1] did not vary with vancomycin susceptibility. CONCLUSIONS: Vancomycin resistance did not affect the clinical presentation nor did it impact patient outcomes in this cohort of inpatients with enterococcal bacteriuria. Almost half of our cohort had enterococcal ASB; more than 50% of these asymptomatic patients received unnecessary antibiotics. Antimicrobial stewardship efforts should address overtreatment of enterococcal bacteriurias.

MEK/Erk-based negative feedback mechanism involved in control of Steel Factor-triggered production of Krüppel-like factor 2 in mast cells.

The receptor tyrosine kinase, c-kit (Steel Factor (SF) receptor) controls survival, proliferation, chemotaxis, and secretion of proinflammatory cytokines in mast cells (MCs). Activation of c-kit results, amongst others, in induction of the PI3K and MEK/Erk pathways. Comparison of two MEK inhibitors, the specific, widely used U0126 and the more selective PD0325901, in different MC models revealed severe differences on SF-induced expression of proinflammatory cytokines IL-6 and TNF-α as well as the transcription factor Krüppel-like factor 2 (KLF2). Expression of the latter in MCs was not investigated so far. Whereas SF-induced expression of IL-6, TNF-α, and KLF2 was unaltered by U0126, it was significantly augmented by PD0325901. The effect of PD0325901 was corroborated by a second selective MEK inhibitor, PD184352 (Cl-1040), indicating the presence of MEK/Erk-based negative feedback mechanism(s) downstream of c-kit activation. Further analysis of KLF2 production revealed a positive function of PI3K. Depending on additional stimuli (e.g. antigen, IGF-1, LPS, thapsigargin), SF-triggered KLF2 expression was differentially modified, most likely controlled by the respective ratio between MEK/Erk and PI3K pathway activation. Moreover, the statin, simvastatin, was demonstrated to upregulate expression of KLF2 in MCs. In conclusion, data obtained by solely using the MEK inhibitor U0126 have to be carefully corroborated by using more selective inhibitors, such as PD0325901 or PD184352. SF-induced expression of the transcription factor KLF2 and its regulation by the MEK/Erk and PI3K pathways could impact on physiological as well as pathophysiological MC functions.

Locust ion transport peptide (ITP): primary structure, cDNA and expression in a baculovirus system.

Ion transport peptide (ITP) purified from locust nervous corpus cardiacum (CC) has previously been shown to stimulate salt and water reabsorption and inhibit acid secretion in the ileum of Schistocerca gregaria. We used the partial amino acid sequence of purified ITP to derive degenerate primers. These were used to amplify a cDNA from brain RNA using reverse transcription and the polymerase chain reaction (RtPCR). This sequence was extended using anchored PCR to yield a partial, 517bp cDNA clone. This cDNA encodes a putative ITP prohormone which could be cleaved at two dibasic amino acid sites to yield a 72 residue active amidated peptide. The deduced amino acid sequence from the cDNA agrees completely with the amino acid sequence and molecular mass (8564Da) derived from analysis of purified ITP. Relative to a family of crustacean hyperglycaemic hormones (CHH), all six cysteine residues and many other amino acid residues are conserved in ITP, establishing that ITP is a homologue. However, CHH, crab eyestalk and CC extracts from distantly related insects have no action, whereas CC extracts from closely related insects are active on the locust ITP assay, showing that the bioassay is selective. Insect Sf9 cells transfected with a baculovirus containing our partial cDNA secreted a potent stimulant of locust ileal transport, confirming that the peptide encoded by our ITP clone has biological activity. The mRNA for ITP is restricted to the brain and CC. Interestingly, a related mRNA is observed in other tissues which are not active on the ITP bioassay.