The Impact of Colonization by Multi Drug Resistant Bacteria on Graft Survival, Risk of Infection, and Mortality in Recipients of Solid Organ Transplant: Systematic Review and Meta-analysis.

BACKGROUND: The Global increase in colonization by multidrug-resistant (MDR) bacteria poses a significant concern. The precise impact of MDR colonization in solid organ transplant recipients (SOTR) remains not well established. OBJECTIVES: Assess the impact of MDR colonization on SOTR's mortality, infection, or graft-loss. METHODS: . DATA SOURCE: Data from PROSPERO, OVID Medline, Ovid EMBASE, Wiley Cochrane Library, ProQuest Dissertations, Theses Global, and SCOPUS, were systematically reviewed spanning from inception until March 20, 2023. The study protocol was registered with PROSPERO (CRD42022290011) and followed the PRISMA guidelines. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, INTERVENTIONS, AND ASSESSMENT OF RISK OF BIAS: Cohorts and case-control studies that reported on adult SOTR colonized by Methicillin-resistant Staphylococcus-aureus (MRSA), Vancomycin-resistant Enterococci (VRE), Extended-spectrum beta-lactamase (ESBL) or carbapenem-resistant Enterobacteriaceae (CRE), or MDR-Pseudomonas, and compared to non-colonized, were included. Two reviewers assessed eligibility, conducted risk of bias evaluation using the Newcastle-Ottawa scale, and rated certainty of evidence using the GRADE approach. METHODS OF DATA SYNTHESIS: We employed RevMan for a meta-analysis using random-effects models to compute pooled odds-ratios (OR) and 95% confidence-intervals (CI). Statistical heterogeneity was determined using the I2 statistic. RESULTS: 15,202 SOTR (33 cohort, 6 case-control studies) were included, where Liver transplant and VRE colonization (25 and 14 studies) were predominant. MDR colonization significantly increased post-transplant one-year mortality (OR= 2.35, 95%CI 1.63-3.38) and mixed-infections (OR=10.74, 95%CI 7.56-12.26) across transplant types (p<0.001 and I2= 58%), but no detected impact on graft-loss (p=0.41, I2= 0%). Subgroup analysis indicated a higher association between CRE or ESBL colonization with outcomes (CRE: death OR=3.94, mixed-infections OR=24.8; ESBL: mixed-infections OR=10.3, no mortality data) compared to MRSA (Death: OR=2.25; Mixed-infection: OR=7.75) or VRE colonization (Death: p=0.20, Mixed-infections: OR=5.71). CONCLUSIONS: MDR colonization in SOTR, particularly CRE, is associated with increased mortality. Despite the low certainty of evidence, actions for preventing MDR colonization in transplant candidates are warranted.

A twist for tunable electronic and thermal transport properties of nanodevices.

Twisted graphene-layered materials with nonzero interlayer twist angles (θ) have recently become appealing, as they exhibit a range of attractive physical properties, which include a Mott insulating phase and superconductivity. In this study, we consider nanodevices constructed from zigzag graphene nanoribbons with a top rectangular benzenoid [6,3]-flake. Using density functional theory and a non-equilibrium Green's function approach, we explore how the electronic and thermal transport properties in such nanodevices can be tuned through a twist of the top flake by an angle 0° ≤ θ ≤ 8.8° for different stacking configurations. We found a strong dependency of the electronic structure on the stacking type, as well as on the twisting regime, specifically in AA-stacking devices. Electron and hole van Hove singularities (vHSs), which originate, respectively, from the flatness of the top of the valence band for the minor-spin component and the bottom of the conduction band for the major-spin component, are found very close to the Fermi level in the density of states and electronic transmission spectra of AA-stacking devices with a twist angle of 1.1°. We establish that these vHSs in AA-1.1° devices are stable at higher temperatures and, with the increased number of available states, lead to larger values of electron thermal conductivity and finally total thermal conductivity in AA-1.1°. Our work highlights the essential role of twisting and stacking for the fabrication of nanoscale charge and heat switches and spurs future studies of twisted layered structures.

Incidence of valganciclovir-related leukopenia and neutropenia in solid organ transplant recipients at high risk of cytomegalovirus disease.

BACKGROUND: Valganciclovir (VGCV) prophylaxis is associated with an increased risk of hematologic side effects. We analyzed the impact of VGCV prophylaxis on leukopenia and neutropenia rates and explored risk factors for its occurrence. METHODS: Retrospective cohort study of adult cytomegalovirus (CMV)-seronegative solid organ transplantation (SOT) recipients of either CMV-seropositive (CMV D+/R-) or CMV-seronegative (CMV D-/R-) donors between July 2005 and March 2019. CMV D+/R- SOT recipients received 3-12 months of VGCV prophylaxis whereas CMV D-/R- SOT recipients received no VGCV prophylaxis. Competing risk regression was used to calculate risk factors for significant neutropenia (neutrophil count < 1000/µL). RESULTS: A total of 430 CMV-seronegative SOT recipients (median age of 52.1 years, 76.5% males) were included, of which 203 (47.2%) were CMV D+/R- and 227 (52.8%) CMV D-/R-. The unadjusted incidence rate ratio of significant neutropenia attributable to VGCV exposure in the first year post-transplant was 13.50 (95% confidence interval 7.36-27.11). Acute rejection occurred more frequently in neutropenic patients at 32.5% compared to 19.1% in those without neutropenia (p = .033). On multivariate analysis, VGCV prophylaxis for 1-90 days and 91-180 days versus no VGCV were the strongest risk factors for significant neutropenia with a sub-distribution hazard ratio of 39.6 (95% CI, 8.57-182.6) and 13.2 (95% CI, 5.46-32.0), respectively. CONCLUSIONS: VGCV prophylaxis is limited by high rates of neutropenia. Future prospective studies are needed to assess alternative CMV prophylactic strategies in SOT recipients.

Drug Resistance Assessed in a Phase 3 Clinical Trial of Maribavir Therapy for Refractory or Resistant Cytomegalovirus Infection in Transplant Recipients.

BACKGROUND: This drug resistance analysis of a randomized trial includes 234 patients receiving maribavir and 116 receiving investigator-assigned standard therapy (IAT), where 56% and 24%, respectively, cleared cytomegalovirus DNA at week 8 (treatment responders). METHODS: Baseline and posttreatment plasma samples were tested for mutations conferring drug resistance in viral genes UL97, UL54, and UL27. RESULTS: At baseline, genotypic testing revealed resistance to ganciclovir, foscarnet, or cidofovir in 56% of patients receiving maribavir and 68% receiving IAT, including 9 newly phenotyped mutations. Among them, 63% (maribavir) and 21% (IAT) were treatment responders. Detected baseline maribavir resistance mutations were UL27 L193F (n = 1) and UL97 F342Y (n = 3). Posttreatment, emergent maribavir resistance mutations were detected in 60 (26%) of those randomized to maribavir, including 49 (48%) of 103 nonresponders and 25 (86%) of the 29 nonresponders where viral DNA initially cleared then rebounded while on maribavir. The most common maribavir resistance mutations were UL97 T409M (n = 34), H411Y (n = 26), and C480F (n = 21), first detected 26 to 130 (median 56) days after starting maribavir. CONCLUSIONS: Baseline maribavir resistance was rare. Drug resistance to standard cytomegalovirus antivirals did not preclude treatment response to maribavir. Rebound in plasma cytomegalovirus DNA while on maribavir strongly suggests emerging drug resistance. CLINICAL TRIALS REGISTRATION: NCT02931539.

Systemic corticosteroids for outpatient respiratory viral infections in lung transplant recipients.

INTRODUCTION: Respiratory viral infections (RVI) in lung transplant recipients (LTR) have variably been associated with rejection and chronic lung allograft dysfunction. Our center has used systemic corticosteroids to treat outpatient RVI in some cases, but evidence is limited. We reviewed all adult LTR diagnosed with outpatient RVI January 2017 to December 2019. The primary outcome was recovery of lung function (forced expiratory volume in 1 s [FEV1]) at next stable visit between 1 and 12 months postinfection, expressed as a ratio over stable preinfection FEV1 (FEV1 recovery ratio). METHODS: We identified 100 adult LTR with outpatient RVI diagnoses eligible for study, 36% of whom received corticosteroids. We modelled the adjusted association between corticosteroid use and FEV1 recovery ratio using linear regression. RESULTS: Steroid-treated patients had a lower FEV1 presentation ratio (0.92 vs. 1.04, p = .0070) and were more likely to have chronic lung allograft dysfunction at time of infection (25% vs. 5%, p = .0077). Mean FEV1 recovery ratio was 1.02 (SD 0.19) with no association with corticosteroid therapy via multivariable linear regression (p = .5888). CONCLUSIONS: Steroid treatment was not associated with FEV1 recovery. This suggests corticosteroids may not have a role in the management of RVI in this population.

Efficacy and safety of antimicrobial stewardship prospective audit and feedback in patients hospitalised with COVID-19 (COVASP): a pragmatic, cluster-randomised, non-inferiority trial.

BACKGROUND: The COVID-19 pandemic has been associated with increased antimicrobial use despite low rates of bacterial co-infection. Prospective audit and feedback is recommended to optimise antibiotic prescribing, but high-quality evidence supporting its use for COVID-19 is absent. We aimed to study the efficacy and safety of prospective audit and feedback in patients admitted to hospital for the treatment of COVID-19. METHODS: COVASP was a prospective, pragmatic, non-inferiority, small-unit, cluster-randomised trial comparing prospective audit and feedback plus standard of care with standard of care alone in adults admitted to three hospitals in Edmonton, AB, Canada, with COVID-19 pneumonia. All patients aged at least 18 years who were admitted from the community to a designated study bed with microbiologically confirmed SARS-CoV-2 infection in the preceding 14 days were included if they had an oxygen saturation of 94% or lower on room air, required supplemental oxygen, or had chest-imaging findings compatible with COVID-19 pneumonia. Patients were excluded if they were transferred in from another acute care centre, enrolled in another clinical trial that involved antibiotic therapy, expected to progress to palliative care or death within 48 h of hospital admission, or managed by any member of the research team within 30 days of enrolment. COVID-19 unit and critical care unit beds were stratified and randomly assigned (1:1) to the prospective audit and feedback plus standard of care group or the standard of care group. Patients were masked to their bed assignment but the attending physician and study team were not. The primary outcome was clinical status on postadmission day 15, measured using a seven-point ordinal scale. We used a non-inferiority margin of 0·5. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, NCT04896866, and is now closed. FINDINGS: Between March 1 and Oct 29, 2021, 1411 patients were screened and 886 were enrolled: 457 into the prospective audit and feedback plus standard of care group, of whom 429 completed the study, and 429 into the standard of care group, of whom 404 completed the study. Baseline characteristics were similar for both groups, with an overall mean age of 56·7 years (SD 17·3) and a median baseline ordinal scale of 4·0 (IQR 4·0-5·0). 301 audit and feedback events were recorded in the intervention group and 215 recommendations were made, of which 181 (84%) were accepted. Despite lower antibiotic use in the intervention group than in the control group (length of therapy 364·9 vs 384·2 days per 1000 patient days), clinical status at postadmission day 15 was non-inferior (median ordinal score 2·0 [IQR 2·0-3·0] vs 2·0 [IQR 2·0-4·0]; p=0·37, Mann-Whitney U test). Neutropenia was uncommon in both the intervention group (13 [3%] of 420 patients) and the control group (20 [5%] of 396 patients), and acute kidney injury occurred at a similar rate in both groups (74 [18%] of 421 patients in the intervention group and 76 [19%] of 399 patients in the control group). No intervention-related deaths were recorded. INTERPRETATION: This cluster-randomised clinical trial shows that prospective audit and feedback is safe and effective in optimising and reducing antibiotic use in adults admitted to hospital with COVID-19. Despite many competing priorities during the COVID-19 pandemic, antimicrobial stewardship should remain a priority to mitigate the overuse of antibiotics in this population. FUNDING: None.

Immune-Based Therapy for Hospitalized Patients With COVID-19 and Risk of Secondary Infections: A Systematic Review and Meta-analysis.

Background: Immune-based therapies are standard-of-care treatment for coronavirus disease 2019 (COVID-19) patients requiring hospitalization. However, safety concerns related to the potential risk of secondary infections may limit their use. Methods: We searched OVID Medline, Ovid EMBASE, SCOPUS, Cochrane Library, clinicaltrials.gov, and PROSPERO in October 2020 and updated the search in November 2021. We included randomized controlled trials (RCTs). Pairs of reviewers screened abstracts and full studies and extracted data in an independent manner. We used RevMan to conduct a meta-analysis using random-effects models to calculate the pooled risk ratio (RR) and 95% CI for the incidence of infection. Statistical heterogeneity was determined using the I 2 statistic. We assessed risk of bias for all studies and rated the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation methodology. We conducted a meta-regression using the R package to meta-explore whether age, sex, and invasive mechanical ventilation modified risk of infection with immune-based therapies. The protocol is registered with PROSPERO (CRD42021229406). Results: This was a meta-analysis of 37 RCTs including 32 621 participants (mean age, 60 years; 64% male). The use of immune-based therapy for COVID-19 conferred mild protection for the occurrence of secondary infections (711/15 721, 4.5%, vs 616/16 900, 3.6%; RR, 0.82; 95% CI, 0.71-0.95; P = .008; I 2 = 28%). A subgroup analysis did not identify any subgroup effect by type of immune-based therapies (P = .85). A meta-regression revealed no impact of age, sex, or mechanical ventilation on the effect of immune-based therapies on risk of infection. Conclusions: We identified moderate-certainty evidence that the use of immune-based therapies in COVID-19 requiring hospitalization does not increase the risk of secondary infections.

Cutaneous lesions in a solid organ transplant recipient: A diagnostic dilemma.

We present the case of a 66-year-old female with a history of renal transplant in 1999 with new onset fevers and diffuse skin ulcerations. In this article, we present the diagnostic studies, differential diagnosis, and treatment decisions for the case.

Polygenic Innate Immunity Score to Predict the Risk of Cytomegalovirus Infection in CMV D+/R- Transplant Recipients. A Prospective Multicenter Cohort Study.

Several genetic polymorphisms of the innate immune system have been described to increase the risk of cytomegalovirus (CMV) infection in transplant patients. The aim of this study was to assess the impact of a polygenic score to predict CMV infection and disease in high risk CMV transplant recipients (heart, liver, kidney or pancreas). On hundred and sixteen CMV-seronegative recipients of grafts from CMV-seropositive donors undergoing heart, liver, and kidney or pancreas transplantation from 7 centres were prospectively included for this purpose during a 2-year period. All recipients received 100-day prophylaxis with valganciclovir. CMV infection occurred in 61 patients (53%) at 163 median days from transplant, 33 asymptomatic replication (28%) and 28 CMV disease (24%). Eleven patients (9%) had recurrent CMV infection. Clinically and/or functionally relevant single nucleotide polymorphisms (SNPs) from TLR2, TLR3, TLR4, TLR7, TLR9, AIM2, MBL2, IL28, IFI16, MYD88, IRAK2 and IRAK4 were assessed by real time polymerase chain reaction (RT-PCR) or sequence-based typing (PCR-SBT). A polygenic score including the TLR4 (rs4986790/rs4986791), TLR9 (rs3775291), TLR3 (rs3775296), AIM2 (rs855873), TLR7 (rs179008), MBL (OO/OA/XAO), IFNL3/IL28B (rs12979860) and IFI16 (rs6940) SNPs was built based on the risk of CMV infection and disease. The CMV score predicted the risk of CMV disease with an AUC of the model of 0.68, with sensitivity and specificity of 64.3 and 71.6%, respectively. Even though further studies are needed to validate this score, its use would represent an effective model to develop more robust scores predicting the risk of CMV disease in donor/recipient mismatch (D+/R-) transplant recipients.

Efficacy and safety of antimicrobial stewardship prospective audit and feedback in patients hospitalized with COVID-19: A protocol for a pragmatic clinical trial.

BACKGROUND: The use of broad-spectrum antibiotics is widespread in patients with COVID-19 despite a low prevalence of bacterial co-infection, raising concerns for the accelerated development of antimicrobial resistance. Antimicrobial stewardship (AMS) is vital but there are limited randomized clinical trial data supporting AMS interventions such as prospective audit and feedback (PAF). High quality data to demonstrate safety and efficacy of AMS PAF in hospitalized COVID-19 patients are needed. METHODS AND DESIGN: This is a prospective, multi-center, non-inferiority, pragmatic randomized clinical trial evaluating AMS PAF intervention plus standard of care (SOC) versus SOC alone. We include patients with microbiologically confirmed SARS-CoV-2 infection requiring hospital admission for severe COVID-19 pneumonia. Eligible ward beds and critical care unit beds will be randomized prior to study commencement at each participating site by computer-generated allocation sequence stratified by intensive care unit versus conventional ward in a 1:1 fashion. PAF intervention consists of real time review of antibacterial prescriptions and immediate written and verbal feedback to attending teams, performed by site-based AMS teams comprised of an AMS pharmacist and physician. The primary outcome is clinical status at post-admission day 15 measured using a 7-point ordinal scale. Patients will be followed for secondary outcomes out to 30 days. A total of 530 patients are needed to show a statistically significant non-inferiority, with 80% power and 2.5% one-sided alpha assuming standard deviation of 2 and the non-inferiority margin of 0.5. DISCUSSION: This study protocol presents a pragmatic clinical trial design with small unit cluster randomization for AMS intervention in hospitalized COVID-19 that will provide high-level evidence and may be adopted in other clinical situations. TRIAL REGISTRATION: This study is being performed at the University of Alberta and is registered at ClinicalTrials.gov (NCT04896866) on May 17, 2021.

Association between gut colonization of vancomycin-resistant enterococci and liver transplant outcomes.

BACKGROUND: Vancomycin-resistant enterococci (VRE) colonization is common in liver transplant recipients and has been associated with worse posttransplant outcomes. METHODS: We conducted a retrospective cohort study at the University of Alberta Hospital including patients who underwent a liver transplant between September 2014 and December 2017. RESULTS: Of 343 patients, 68 (19.8%) had pretransplant VRE colonization and 27 (27/275, 9.8%) acquired VRE posttransplant, 67% were males and the median age was 56.5 years. VRE colonized patients at baseline had higher MELD scores and required longer posttransplant hospitalization. VRE colonization was associated with increased risk of early acute kidney injury (AKI) (64% vs. 52%, p = .044), clinically significant bacterial/fungal infection (29% vs. 17%, p = .012) and invasive VRE infection (5% vs. 1%, p = .017). Mortality at 2 years was 13% in VRE-colonized versus 7% in noncolonized (p = .085). On multivariate analysis, VRE colonization increased the risk of posttransplant AKI (HR 1.504, 95% CI: 1.077-2.100, p = .017) and clinically significant bacterial or fungal infection at 6 months (HR 2.038, 95% CI: 1.222-3.399, p = .006), and was associated with nonsignificant trend toward increased risk of mortality at 2 years posttransplant (HR 1.974 95% CI 0.890-4.378; p = .094). CONCLUSIONS: VRE colonization in liver transplant patients is associated with increased risk of early AKI, clinically significant infections, and a trend toward increased mortality at 2 years.

International survey of human herpes virus 8 screening and management in solid organ transplantation.

BACKGROUND: HHV-8/Kaposi Sarcoma herpesvirus has been associated with a broad spectrum of diseases in solid organ transplant (SOT) recipients. Primary donor-derived infection can be associated with severe and rapidly fatal non-neoplastic disease, and diagnosis is made with high HHV-8 DNAemia. METHODS: We carried out an international survey to investigate the current approach to HHV-8 screening, and management in SOT since a protocol has not been established by international guidelines. RESULTS: A total of 51 transplant centers from 15 countries filled out the survey. HHV-8-associated diseases in SOT have been diagnosed during the previous 5 years in 67% of centers. Pretransplant serological screening is performed in 17 centers (33%), and posttransplant HHV-8 nucleic acid testing (NAT) monitoring is performed in 21 centers (41%). Performing HHV-8 NAT monitoring and serological screening were found associated with having diagnosed in the previous 5 years a non-malignant HHV-8-associated disease. CONCLUSIONS: Serological pretransplant screening of donors and recipients and post-transplant HHV-8 NAT monitoring recommendations should be standardized. Even though serological assays are not optimal, they could contribute to increasing knowledge on epidemiology and management of HHV-8-associated diseases after SOT.

Real-life experience with ceftolozane/tazobactam in Canada: results from the CLEAR (Canadian LEadership on Antimicrobial Real-life usage) registry.

OBJECTIVES: Ceftolozane/tazobactam is a cephalosporin/ß-lactamase inhibitor combination with activity against Gram-negative bacilli. Here we report the use of ceftolozane/tazobactam in Canada using a national registry. METHODS: The CLEAR registry uses a REDCapTM online survey to capture details associated with clinical use of ceftolozane/tazobactam. RESULTS: Data from 51 patients treated in 2020 with ceftolozane/tazobactam are available. Infections treated included hospital-acquired bacterial pneumonia (37.3% of patients), ventilator-associated bacterial pneumonia (15.7%), bone and joint infection (11.8%), complicated intra-abdominal infection (7.8%) and complicated skin and skin-structure infection (7.8%). Moreover, 17.6% of patients had bacteraemia and 47.1% were in intensive care. Ceftolozane/tazobactam was primarily used as directed therapy for Pseudomonas aeruginosa infections (92.2% of patients). Ceftolozane/tazobactam was used because of resistance to (86.3%), failure of (11.8%) or adverse effects from (2.0%) previously prescribed antimicrobials. Ceftolozane/tazobactam susceptibility testing was performed on isolates from 88.2% of patients. Ceftolozane/tazobactam was used in combination with another antimicrobial active against Gram-negative bacilli in 39.2% of patients [aminoglycosides (15.7%), fluoroquinolones (9.8%) and colistin/polymyxin B (7.8%)]. The dosage regimen was customised in all patients based on creatinine clearance. The treatment duration was primarily >10 days (60.8% of patients), with microbiological success in 60.5% and clinical success in 64.4% of patients. Moreover, 7.8% of patients had adverse effects not requiring drug discontinuation. CONCLUSION: In Canada, ceftolozane/tazobactam is used as directed therapy to treat a variety of severe infections caused by multidrug-resistant P. aeruginosa. It is commonly used in combination with other antimicrobials with relatively high microbiological/clinical cure rates and an excellent safety profile.

Pneumocystis jirovecii: a review with a focus on prevention and treatment.

Introduction: Pneumocystis jirovecii (PJ) is an opportunistic fungal pathogen that can cause severe pneumonia in immunocompromised hosts. Risk factors for Pneumocystis jirovecii pneumonia (PJP) include HIV, organ transplant, malignancy, certain inflammatory or rheumatologic conditions, and associated therapies and conditions that result in cell-mediated immune deficiency. Clinical signs of PJP are nonspecific and definitive diagnosis requires direct detection of the organism in lower respiratory secretions or tissue. First-line therapy for prophylaxis and treatment remains trimethoprim-sulfamethoxazole (TMP-SMX), though intolerance or allergy, and rarely treatment failure, may necessitate alternate therapeutics, such as dapsone, pentamidine, atovaquone, clindamycin, primaquine and most recently, echinocandins as adjunctive therapy. In people living with HIV (PLWH), adjunctive corticosteroid use in treatment has shown a mortality benefit.Areas covered: This review article covers the epidemiology, pathophysiology, diagnosis, microbiology, prophylaxis indications, prophylactic therapies, and treatments.Expert opinion: TMP-SMX has been first-line therapy for treating and preventing pneumocystis for decades. However, its adverse effects are not uncommon, particularly during treatment. Second-line therapies may be better tolerated, but often sacrifice efficacy. Echinocandins show some promise for new combination therapies; however, further studies are needed to define optimal antimicrobial therapy for PJP as well as the role of corticosteroids in those without HIV.

Donor Graft Cytomegalovirus Serostatus and the Risk of Arterial and Venous Thrombotic Events in Seronegative Recipients After Non-Thoracic Solid Organ Transplantation.

BACKGROUND: Cytomegalovirus (CMV) is the most common opportunistic pathogen, following solid organ transplantation (SOT), that leads to direct and indirect effects. The aim of this study was to assess the impact of CMV exposure at transplantation on the rate of posttransplant thrombotic events (TEs). METHODS: We conducted a retrospective cohort study of patients transplanted at the University of Alberta Hospital between July 2005 and January 2018. We included adult SOT CMV-seronegative recipients at transplantation who received an allograft from either a seropositive donor (D+/R-) or a seronegative donor (D-/R-). RESULTS: A total of 392 SOT recipients were included: 151 (39%) liver, 188 (48%) kidney, 45 (11%) pancreas, and 8 (2%) other transplants. The mean age was 47 years, 297 (76%) were males, and 181 (46%) had a CMV D+/R- donor. Patients in the CMV D+/R- cohort were slightly older (51 years versus 48 years in the D-/R- cohort; P = .036), while other variables, including cardiovascular risk factors and pretransplant TEs, were not different between groups. Overall, TEs occurred in 35 (19%) patients in the CMV D+/R- group, versus 21 (10%) in the CMV D-/R- group, at 5 years of follow-up (P = .008); the incidence rates per 100 transplant months were 5.12 and 1.02 in the CMV D+/R- and CMV D-/R- groups, respectively (P = .003). After adjusting for potential confounders with a Cox regression model, a CMV D+/R- transplantation was independently associated with an increased risk of a TE over 5 years (adjusted hazard ratio, 3.027; 95% confidence interval, 1.669-5.488). CONCLUSIONS: A CMV D+/R- transplantation is associated with an increased risk of a TE posttransplantation.

How do I manage a patient with enterococcal bacteraemia?

BACKGROUND: Enterococcal bacteraemia (EB) is common, particularly in the nosocomial setting, and its management poses a challenge for clinicians and microbiologists. OBJECTIVES: The aim was to summarize the more relevant features of EB and to provide a practical state-of-the-art on the topics that more directly affect its management. SOURCES: Pubmed articles from inception to 31 May 2020. CONTENT: The following topics are covered: epidemiological, clinical and microbiological characteristics and factors associated with prognosis of EB; diagnosis and work-up, including the use of echocardiography to rule out endocarditis; antibiotic management with special focus on antimicrobial resistance and complicated EB; and the role of infectious disease consultation and the use of bundles in EB. In addition, three clinical vignettes are presented to illustrate the practical application of the guidance provided, and major gaps in the current evidence supporting EB management are discussed. IMPLICATIONS: EB is associated with large burdens of morbidity and mortality, particularly among fragile and immunosuppressed patients presenting complicated bacteraemia due to multidrug-resistant enterococci. Most cases of EB are caused by Enterococcus faecalis, followed by E. faecium. EB often presents as polymicrobial bacteraemia. Rapidly identifying patients at risk of EB is crucial for timely application of diagnostic techniques and empiric therapy. Early alert systems and rapid diagnostic techniques, such as matrix-assisted desorption ionization-time of flight mass spectrometry, especially if used together with infectious disease consultation within bundles, appear to improve management and prognosis of EB. Echocardiography is also key in the work-up of EB and should probably be more extensively used, although its exact indications in EB are still debated. Multidisciplinary approaches are warranted due to the complexity and severity of EB.

Effect of prospective audit and feedback on inpatient fluoroquinolone use and appropriateness of prescribing.

We report the effect of prospective audit and feedback (PAF) on inpatient fluoroquinolone (FQN) prescriptions. During the PAF period, FQN use decreased from 39.19 to 29.58 days of therapy per 1,000 patient days (P < .001) and appropriateness improved from 68% to 88% (P < .001). High-yield indications to target included noninfectious urinary tract and respiratory presentations.