Epidemiology of healthcare-associated Pseudomonas aeruginosa in intensive care units: are sink drains to blame?

BACKGROUND: Pseudomonas aeruginosa (PA) is a common cause of healthcare-associated infection (PA-HAI) in the intensive care unit (ICU). AIM: To describe the epidemiology of PA-HAI in ICUs in Ontario, Canada, and to identify episodes of sink-to-patient PA transmission. METHODS: This was a prospective cohort study of patients in six ICUs from 2018 to 2019, with retrieval of PA clinical isolates, and PA-screening of antimicrobial-resistant organism surveillance rectal swabs, and of sink drain, air, and faucet samples. All PA isolates underwent whole-genome sequencing. PA-HAI was defined using US National Healthcare Safety Network criteria. ICU-acquired PA was defined as PA isolated from specimens obtained ≥48 h after ICU admission in those with prior negative rectal swabs. Sink-to-patient PA transmission was defined as ICU-acquired PA with close genomic relationship to isolate(s) previously recovered from sinks in a room/bedspace occupied 3-14 days prior to collection date of the relevant patient specimen. FINDINGS: Over ten months, 72 PA-HAIs occurred among 60/4263 admissions. The rate of PA-HAI was 2.40 per 1000 patient-ICU-days; higher in patients who were PA-colonized on admission. PA-HAI was associated with longer stay (median: 26 vs 3 days uninfected; P < 0.001) and contributed to death in 22/60 cases (36.7%). Fifty-eight admissions with ICU-acquired PA were identified, contributing 35/72 (48.6%) PA-HAIs. Four patients with five PA-HAIs (6.9%) had closely related isolates previously recovered from their room/bedspace sinks. CONCLUSION: Nearly half of PA causing HAI appeared to be acquired in ICUs, and 7% of PA-HAIs were associated with sink-to-patient transmission. Sinks may be an under-recognized reservoir for HAIs.

Lock-in amplification based on sigma-delta oversampling.

Synchronous detection is used to detect and measure very low-level signals in the presence of significant noise. A defining characteristic of this measurement approach is the use of a periodic probe signal to excite the system under test. This is followed by mixing of the reference signal and its phase-quadrature with the measured signal. Standard analog to digital converters are employed, usually with the mixing and filtering performed digitally. Most practical high-resolution analog to digital converters employ oversampled sigma-delta modulation and are incorporated as a separate functional block. This paper derives a processing algorithm that combines the oversampled analog to digital conversion with signal mixing into one functional block. There are several important advantages of this approach. The computational complexity of the lock-in amplifier is substantially reduced, with no loss of accuracy. Moreover, the requirement for high-resolution analog-to-digital conversion is relaxed; it is replaced with low-resolution high-rate sampling, which is typically much easier to realize in practice. Experimental results are presented to demonstrate the correctness of the technique as determined via theory and simulation.

Carbapenemase-producing Enterobacterales in hospital drains in Southern Ontario, Canada.

BACKGROUND: Hospital drains may be an important reservoir for carbapenemase-producing Enterobacterales (CPE). AIM: To determine prevalence of CPE in hospital drains exposed to inpatients with CPE, relatedness of drain and patient CPE, and risk factors for drain contamination. METHODS: Sink and shower drains in patient rooms and communal shower rooms exposed to 310 inpatients with CPE colonization/infection were cultured at 10 hospitals. Using short- and long-read whole-genome sequencing, inpatient and corresponding drain CPE were compared. Risk factors for drain contamination were assessed using multi-level modelling. FINDINGS: Of 1209 exposed patient room and communal shower room drains, 53 (4%) yielded 62 CPE isolates in seven (70%) hospitals. Of 49 CPE isolates in patient room drains, four (8%) were linked to prior room occupants. Linked drain/room occupant pairs included Citrobacter freundii ST18 isolates separated by eight single nucleotide variants (SNVs), related blaKPC-containing IncN3-type plasmids (different species), related blaKPC-3-containing IncN-type plasmids (different species), and related blaOXA-48-containing IncL/M-type plasmids (different species). In one hospital, drain isolates from eight rooms on two units were Enterobacter hormaechei separated by 0-6 SNVs. Shower drains were more likely to be CPE-contaminated than hand hygiene (odds ratio: 3.45; 95% confidence interval: 1.66-7.16) or patient-use (13.0; 4.29-39.1) sink drains. Hand hygiene sink drains were more likely to be CPE-contaminated than patient-use sink drains (3.75; 1.17-12.0). CONCLUSION: Drain contamination was uncommon but widely dispersed. Drain CPE unrelated to patient exposure suggests contamination by undetected colonized patients or retrograde (drain-to-drain) contamination. Drain types had different contamination risks.

Improving healthcare worker adherence to the use of transmission-based precautions through application of human factors design: a prospective multi-centre study.

A key component of transmission-based precautions (TBPs) is the use of personal protective equipment (PPE) but healthcare worker (HCW) adherence remains suboptimal. A human factors-based intervention was implemented to improve adherence to TBPs including (i) improved signage, (ii) standardized placement of signage, (iii) introduction of a mask with integrated face shield, and (iv) improvement in PPE availability. Donning of the correct PPE by HCWs improved significantly (79.7 vs 56.4%; P < 0.001). This approach may be more effective than education alone, but further study is required to determine sustainability and subsequent impact on transmission of healthcare-associated infections.

Association of hematopoietic cell transplantation-specific comorbidity index with resource utilization after allogeneic transplantation.

Comorbidities affect clinical outcomes and costs in medicine. The hematopoietic cell transplantation (HCT)-specific comorbidity index (HCT-CI) predicts mortality risk after HCT. Its association with resource utilization (RU) is unknown. In this single-center, retrospective study, we examined the association of HCT-CI with RU (readmissions, length of hospital stay (LOS) and days out of hospital alive (DOHA)) in first 100 days (n=328) and 1 year (n=226) in allogeneic HCT patients from January 2010 to June 2014. Age, disease risk, conditioning and use of antithymocyte globulin were significantly different in the four groups with HCT-CI 0 to1 (n=138), 2 (n=56), 3 (n=55) or ⩾4 (n=79). Although the readmissions were higher in the first 100 days for patients with HCT-CI >0-1 (P=0.03), they were not significantly different in patients over 1 year (P=0.13). In the multivariable analysis, patients with HCT-CI score of >0 to 1 had increased LOS and fewer DOHA in both 100 days and 1 year after HCT. In this exploratory analysis, we found that HCT-CI >0 to 1 is associated with increased RU after allogeneic HCT. Recognizing predictors of RU can identify patients at risk of high utilization and help understand what drives health-care costs.

"Choosing Wisely Canada" and antimicrobial stewardship: A shared focus on reducing unnecessary care.

There is a growing movement in medicine which recognizes that some tests, treatments or procedures do not add value for patients, and may even cause harm. The "Choosing Wisely Canada" campaign is a grassroots, physician-led campaign to engage physicians and patients in conversations about overuse of unnecessary tests, treatments and procedures to improve the quality of health care. This article reviews the underlying principles of this campaign and its spread across Canada. It also highlights the alignment between the principles of Choosing Wisely Canada with those of antimicrobial stewardship, which share similar motivations, challenges and opportunities.

Pelagic to demersal transition in a coral-reef fish, the orbicular batfish Platax orbicularis.

Behavioural and ecological observations were made on young, reared Platax orbicularis in Opunohu Bay, Moorea, French Polynesia, during their transition from the pelagic, dispersive stage to the reef-orientated demersal stage. Seventy-two young P. orbicularis (17-75 mm standard length, LS ) were released in the pelagic zone and 20 (40-70 mm LS ) adjacent to the reefs. Swimming speed was slow (mean 5·2 cm s(-1) ) and independent of size. An ontogenetic descent was observed: the smallest P. orbicularis swam at the surface, medium-sized P. orbicularis swam in midwater (mean 5-13 m) and the largest P. orbicularis swam to the bottom, where many lay on their sides. Platax orbicularis swam southerly on average, away from the ocean and into the bay. Smaller P. orbicularis were more likely to swim directionally than larger individuals. Young P. orbicularis released near reef edges swam at similar, but more variable speeds (mean 6·6 cm s(-1) ). About half of those released near reefs swam away, but fewer swam away from an inshore fringing reef than from a patch reef near the bay mouth. Many P. orbicularis swam up the slope onto the reef top, but the little settlement observed was near the reef base. Average, near-reef swimming direction was also southerly. Some reef residents, in particular the triggerfish Balistapus undulatus, harassed young P. orbicularis.

Infectious complications among individuals with clinical monoclonal B-cell lymphocytosis (MBL): a cohort study of newly diagnosed cases compared to controls.

Although the risk of progression from monoclonal B-cell lymphocytosis (MBL) to chronic lymphocytic leukemia (CLL) has been well characterized, it is unknown whether other common complications associated with CLL, such as increased risk of infection, occurs in individuals with MBL. We used the Mayo CLL database to identify cohorts of individuals with newly diagnosed MBL (n=154) or newly diagnosed CLL (n=174) who resided within 50 miles of Mayo Clinic. A cohort of 689 adult patients seen for a general medical examination who resided within 50 miles of Mayo clinic and who enrolled in a case-control study of non-Hodgkin lymphoma (NHL) was used as a comparison cohort. Hospitalization with infection was more common among individuals with MBL (25/154; 16.2%), and CLL (32/174; 18.4%) than controls (18/689; 2.6%). On pooled multivariable Cox proportional hazards analysis of all 1017 patients (controls, MBL and CLL), male sex (hazards ratio (HR)=2.3; P=0.002), major co-morbid health problems (HR=1.7, P=0.04), the presence of CLL (HR=3.2, P<0.001), treatment for progressive CLL (HR=2.4, P=0.001) and the presence of MBL (HR=3.0, P=0.001) were independently associated with risk of hospitalization for infection. These results suggest the risk of serious infection in clinical MBL is substantially greater than the risk of progression requiring treatment.

Allogeneic stem cell transplant for myelofibrosis patients over age 60: likely impact of the JAK2 inhibitors.

The myeloproliferative neoplasm, myelofibrosis (MF), has only one therapeutic intervention that is potentially curative in these individuals, specifically that of allogeneic stem cell transplantation (ASCT). ASCT has been utilized up to this juncture, primarily in younger individuals with higher risk disease. There is more limited data on outcomes in individuals over the age of 60 years. The choice of an individualized therapeutic intervention for a patient with MF is a very complex issue and is dependent on several factors. The first factor being their overall prognosis with their illness (which can vary from a median of 2 years in high-risk patients to over 10 years in low-risk patients) and the potential impact of a therapeutic intervention not only on survival but also on quality of life. Current available therapies have been strictly palliative for disease-associated anemia and/or splenomegaly. At present, we have a new generation of inhibitors of JAK2 (Ruxolitinib, CYT387, SB1518, TG101348, with others in development), which have been shown to improve splenomegaly, improve symptomatic burden of illness and improve quality of life. In addition, these inhibitors of JAK2 may have an impact on the natural history of MF, but confirmation of the presence and degree of this impact is still pending. Clinical availability of JAK2 inhibitors may alter the timing of transplant in marginal transplant candidates (that is, those over the age of 60), may have a role preceding ASCT to improve spleen size and performance status before transplant and might be frontline therapy in intermediate and high-risk patients who are not candidates for ASCT.

Immunophenotypic and gene expression analysis of monoclonal B-cell lymphocytosis shows biologic characteristics associated with good prognosis CLL.

Monoclonal B-cell lymphocytosis (MBL) is a hematologic condition wherein small B-cell clones can be detected in the blood of asymptomatic individuals. Most MBL have an immunophenotype similar to chronic lymphocytic leukemia (CLL), and 'CLL-like' MBL is a precursor to CLL. We used flow cytometry to identify MBL from unaffected members of CLL kindreds. We identified 101 MBL cases from 622 study subjects; of these, 82 individuals with MBL were further characterized. In all, 91 unique MBL clones were detected: 73 CLL-like MBL (CD5(+)CD20(dim)sIg(dim)), 11 atypical MBL (CD5(+)CD20(+)sIg(+)) and 7 CD5(neg) MBL (CD5(neg)CD20(+)sIg(neg)). Extended immunophenotypic characterization of these MBL subtypes was performed, and significant differences in cell surface expression of CD23, CD49d, CD79b and FMC-7 were observed among the groups. Markers of risk in CLL such as CD38, ZAP70 and CD49d were infrequently expressed in CLL-like MBL, but were expressed in the majority of atypical MBL. Interphase cytogenetics was performed in 35 MBL cases, and del 13q14 was most common (22/30 CLL-like MBL cases). Gene expression analysis using oligonucleotide arrays was performed on seven CLL-like MBL, and showed activation of B-cell receptor associated pathways. Our findings underscore the diversity of MBL subtypes and further clarify the relationship between MBL and other lymphoproliferative disorders.

Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial.

We have studied a three-drug combination with cyclophosphamide, bortezomib and dexamethasone (CyBorD) on a 28-day cycle in the treatment of newly diagnosed multiple myeloma (MM) patients to assess response and toxicity. The primary endpoint of response was evaluated after four cycles. Thirty-three newly diagnosed, symptomatic patients with MM received bortezomib 1.3 mg/m(2) intravenously on days 1, 4, 8 and 11, cyclophosphamide 300 mg/m(2) orally on days 1, 8, 15 and 22 and dexamethasone 40 mg orally on days 1-4, 9-12 and 17-20 on a 28-day cycle for four cycles. Responses were rapid with a mean 80% decline in the sentinel monoclonal protein at the end of two cycles. The overall intent to treat response rate (>or= partial response) was 88%, with 61% of very good partial response or better (>or=VGPR) and 39% of complete/near complete response (CR/nCR). For the 28 patients who completed all four cycles of therapy, the CR/nCR rate was 46% and VGPR rate was 71%. All patients undergoing stem cell harvest had a successful collection. Twenty-three patients underwent stem cell transplantation (SCT) and are evaluable through day 100 with CR/nCR documented in 70% and >or=VGPR in 74%. In conclusion, CyBorD produces a rapid and profound response in patients with newly diagnosed MM with manageable toxicity.

Rescue from failed growth factor and/or chemotherapy HSC mobilization with G-CSF and plerixafor (AMD3100): an institutional experience.

Auto-SCT has been shown to be a potentially curative treatment for a variety of hematological malignancies. Auto-SCT is dependent on the successful mobilization and collection of hematopoietic stem cells to ensure engraftment. The inability to mobilize sufficient number of hematopoietic stem cells using standard cytokine-assisted mobilization strategies excludes eligible patients from potentially curative auto-SCT. Plerixafor (AMD3100; Mozobil), a novel bicyclam antagonist of the SDF-1alpha/CXCR4 complex, has been reported previously to augment PBSC mobilization in patients undergoing their first planned stem cell mobilization and collection attempt. In our experience, 17 of 20 patients otherwise eligible for auto-SCT who failed previous mobilization attempts had successful mobilization of CD34(+) hematopoietic stem cells with one apheresis procedure, and an additional patient required two aphereses procedures, when treated with the combination of plerixafor and G-CSF on a compassionate use protocol available at our institution.

AOT-based microemulsions accelerate the 1,3-cycloaddition of benzonitrile oxide to N-ethylmaleimide.

We studied the 1,3-dipolar cycloaddition of benzonitrile oxide to N-ethylmaleimide in AOT/isooctane/water microemulsions at 25.0 degrees C and found the reaction rate to be roughly 150 and 35 times greater than that in isooctane and pure water, respectively. The accelerating effect of the microemulsion is the combined result of an increase in the local concentrations of the reactants through incorporation into the interface and of the intrinsic rate of the process through electrostatic interactions with the headgroups in the surfactant.

Water in oil microemulsions as reaction media for a Diels-Alder reaction between N-ethylmaleimide and cyclopentadiene.

The Diels-Alder reaction between N-ethylmaleimide and cyclopentadiene in water/AOT/isooctane microemulsions, where AOT denotes sodium bis(2-ethylhexyl)sulfosuccinate, was studied. The rate of the reaction was found to be higher than that obtained in pure isooctane, irrespective of the particular microemulsion composition used. The efficiency of this catalytic action ranged from a factor of 3 at low water contents (viz., W = [H2O]/[AOT] = 2) to 15 at W = 35. On the basis of these results, the reaction takes place simultaneously in the continuous medium and at the microemulsion interface. The favorable arrangement of the reactants at the interface results in more than 95% of the reaction occurring in this microenvironment. The kinetic analysis revealed the rate constant at the microemulsion interface to change with the water content. For small W values a bimolecular rate constant at the interface close to that observed in hexane was obtained. This value increases with W and for W > 20, a value close to that obtained in ethanol was found. This can be ascribed to the absence of hydrogen bonding at the microemulsion interface as well as the accelerating effects due to enforced hydrophobic interactions.