Factors Associated with Poor Clinical and Microbiologic Outcomes in C. auris Bloodstream Infection: A Multicenter Retrospective Cohort Study.

BACKGROUND: C. auris has become a growing concern worldwide due to increases in incidence of colonization and reports of invasive infections. There are limited data on clinical factors associated with poor outcomes in patients with C. auris bloodstream infection (BSI). METHODS: We assembled a multicenter retrospective cohort of patients with C. auris BSI from two geographics areas in US healthcare settings. We collected data on demographic, clinical, and microbiologic characteristics to describe the cohort and constructed multivariate logistic regression models to understand risk factors for two clinical outcomes, all-cause mortality during facility admission, and blood culture clearance. RESULTS: Our cohort consisted of 187 patients with C. auris BSI (56.1% male, 55.6% age >65 years); 54.6% died by facility discharge and 66.9% (of 142 with available data) experienced blood culture clearance. Pitt bacteremia score at infection onset was associated with mortality (odds-ratio [95% confidence interval]: 1.19 [1.01,1.40] per 1-point increase). Hemodialysis was associated with a reduced odds of microbiologic clearance (0.15 [0.05,0.43]) and with mortality (3.08 [1.27,7.50]). CONCLUSIONS: The Pitt bacteremia score at the onset of C. auris BSI may be a useful tool in identifying patients at risk for mortality. Targeted infection prevention practices in patients receiving hemodialysis may be useful to limit poor outcomes.

Bloodstream Infection Risk, Incidence, and Deaths for Hospitalized Patients during Coronavirus Disease Pandemic.

Hospital-acquired infections are emerging major concurrent conditions during the coronavirus disease (COVID-19) pandemic. We conducted a retrospective review of hospitalizations during March‒October 2020 of adults tested by reverse transcription PCR for severe acute respiratory syndrome coronavirus 2. We evaluated associations of COVID-19 diagnosis with risk for laboratory-confirmed bloodstream infections (LCBIs, primary outcome), time to LCBI, and risk for death by using logistic and competing risks regression with adjustment for relevant covariates. A total of 10,848 patients were included in the analysis: 918 (8.5%) were given a diagnosis of COVID-19, and 232 (2.1%) had LCBIs during their hospitalization. Of these patients, 58 (25%) were classified as having central line‒associated bloodstream infections. After adjusting for covariates, COVID-19‒positive status was associated with higher risk for LCBI and death. Reinforcement of infection control practices should be implemented in COVID-19 wards, and review of superiority and inferiority ranking methods by National Healthcare Safety Network criteria might be needed.

Candida auris Invasive Infections during a COVID-19 Case Surge.

Clinical cases of C. auris noted during a COVID-19 surge led to an epidemiological, clinical, and genomic investigation. Evaluation identified a close genetic relationship but inconclusive epidemiologic link between all cases. Prolonged hospitalization due to critical illness from COVID-19 and use of antimicrobials may have contributed to clinical infections.

Linezolid- and Vancomycin-resistant Enterococcus faecium in Solid Organ Transplant Recipients: Infection Control and Antimicrobial Stewardship Using Whole Genome Sequencing.

BACKGROUND: Vancomycin-resistant enterococci are an important cause of healthcare-associated infections and are inherently resistant to many commonly used antibiotics. Linezolid is the only drug currently approved by the US Food and Drug Administration to treat vancomycin-resistant enterococci; however, resistance to this antibiotic appears to be increasing. Although outbreaks of linezolid- and vancomycin-resistant Enterococcus faecium (LR-VRE) in solid organ transplant recipients remain uncommon, they represent a major challenge for infection control and hospital epidemiology. METHODS: We describe a cluster of 4 LR-VRE infections among a group of liver and multivisceral transplant recipients in a single intensive care unit. Failure of treatment with linezolid in 2 cases led to a review of standard clinical laboratory methods for susceptibility determination. Testing by alternative methods including whole genome sequencing (WGS) and a comprehensive outbreak investigation including sampling of staff members and surfaces was performed. RESULTS: Review of laboratory testing methods revealed a limitation in the VITEK 2 system with regard to reporting resistance to linezolid. Linezolid resistance in all cases was confirmed by E-test method. The use of WGS identified a resistant subpopulation with the G2376C mutation in the 23S ribosomal RNA. Sampling of staff members' dominant hands as well as sampling of surfaces in the unit identified no contaminated sources for transmission. CONCLUSIONS: This cluster of LR-VRE in transplant recipients highlights the possible shortcomings of standard microbiology laboratory methods and underscores the importance of WGS to identify resistance mechanisms that can inform patient care, as well as infection control and antibiotic stewardship measures.

Dermatological manifestations of fungal infection in patients with febrile neutropaenia: A review of the literature.

Febrile neutropaenia (FNP) is a common cause of morbidity and mortality in immunocompromised patients. Although most infections are caused by bacterial pathogens, fungal infections are becoming increasingly more common. Due to its rarity, the diagnosis of fungal infections in febrile neutropenic patients is often delayed. To provide current clinical features, epidemiology, aetiology, diagnosis and treatment of cutaneous involvement of fungal infection in patients with FNP. A retrospective literature review of PubMed was performed, with no language or publishing data restrictions, yielding 116 results. We queried each case for cutaneous lesions associated with fungal pathogens in FNP. We found 54 publications with 215 reported cases of cutaneous manifestations of fungal injury in patients with FNP. This study is limited in that it is a literature review of a disease that is likely underreported. Cutaneous lesions caused by yeasts such as Candida and Trichosporon manifest as diffuse erythematous papules and usually do not develop central necrosis or eschar, while moulds will present as tender nodules that subsequently develop eschar and necrosis. Recognising the cutaneous manifestations of fungal disease can assist in the diagnosis and management of these infections.

Influence of Minimum Inhibitory Concentration in Clinical Outcomes of Enterococcus faecium Bacteremia Treated With Daptomycin: Is it Time to Change the Breakpoint?

BACKGROUND: Daptomycin has become a front-line antibiotic for multidrug-resistant Enterococcus faecium bloodstream infections (BSIs). We previously showed that E. faecium strains with daptomycin minimum inhibitory concentrations (MICs) in the higher end of susceptibility frequently harbor mutations associated with daptomycin resistance. We postulate that patients with E. faecium BSIs exhibiting daptomycin MICs of 3-4 µg/mL treated with daptomycin are more likely to have worse clinical outcomes than those exhibiting daptomycin MICs ≤2 µg/mL. METHODS: We conducted a multicenter retrospective cohort study that included adult patients with E. faecium BSI for whom initial isolates, follow-up blood culture data, and daptomycin administration data were available. A central laboratory performed standardized daptomycin MIC testing for all isolates. The primary outcome was microbiologic failure, defined as clearance of bacteremia ≥4 days after the index blood culture. The secondary outcome was all-cause in-hospital mortality. RESULTS: A total of 62 patients were included. Thirty-one patients were infected with isolates that exhibited daptomycin MICs of 3-4 µg/mL. Overall, 34 patients had microbiologic failure and 25 died during hospitalization. In a multivariate logistic regression model, daptomycin MICs of 3-4 µg/mL (odds ratio [OR], 4.7 [1.37-16.12]; P = .014) and immunosuppression (OR, 5.32 [1.20-23.54]; P = .028) were significantly associated with microbiologic failure. Initial daptomycin dose of ≥8 mg/kg was not significantly associated with evaluated outcomes. CONCLUSIONS: Daptomycin MICs of 3-4 µg/mL in the initial E. faecium blood isolate predicted microbiological failure of daptomycin therapy, suggesting that modification in the daptomycin breakpoint for enterococci should be considered.

Wastewater based surveillance can be used to reduce clinical testing intensity on a university campus.

Clinical testing has been a vital part of the response to and suppression of the COVID-19 pandemic; however, testing imposes significant burdens on a population. College students had to contend with clinical testing while simultaneously dealing with health risks and the academic pressures brought on by quarantines, changes to virtual platforms, and other disruptions to daily life. The objective of this study was to analyze whether wastewater surveillance can be used to decrease the intensity of clinical testing while maintaining reliable measurements of diseases incidence on campus. Twelve months of human health and wastewater surveillance data for eight residential buildings on a university campus were analyzed to establish how SARS-CoV-2 levels in the wastewater can be used to minimize clinical testing burden on students. Wastewater SARS-CoV-2 levels were used to create multiple scenarios, each with differing levels of testing intensity, which were compared to the actual testing volumes implemented by the university. We found that scenarios in which testing intensity fluctuations matched rise and falls in SARS-CoV-2 wastewater levels had stronger correlations between SARS-CoV-2 levels and recorded clinical positives. In addition to stronger correlations, most scenarios resulted in overall fewer weekly clinical tests performed. We suggest the use of wastewater surveillance to guide COVID-19 testing as it can significantly increase the efficacy of COVID-19 surveillance while reducing the burden placed on college students during a pandemic. Future efforts should be made to integrate wastewater surveillance into clinical testing strategies implemented on college campuses.

Persistent colonization of Candida auris among inpatients rescreened as part of a weekly surveillance program.

We established a surveillance program to evaluate persistence of C. auris colonization among hospitalized patients. Overall, 17 patients (34%) had ≥1 negative result followed by a positive test, and 7 (41%) of these patients had ≥2 consecutive negative tests.

Operational impact of decreased turnaround times for Candida auris screening tests in a tertiary academic medical center.

Objective: Assess turnaround time (TAT) and cost-benefit of on-site C. auris screening and its impact on length of stay (LOS) and costs compared to reference laboratories. Design: Before-and-after retrospective cohort study. Setting: Large-tertiary medical center. Methods: We validated an on-site polymerase chain reaction-based testing platform for C. auris and retrospectively reviewed hospitalized adults who screened negative before and after platform implementation. We constructed multivariable models to assess the association of screening negative with hospital LOS/cost in the pre and postimplementation periods. We adjusted for confounders such as demographics and indwelling device use, and compared TATs for all samples tested. Results: The sensitivity and specificity of the testing platform were 100% and 98.11%, respectively, compared to send-out testing. The clinical cohort included 287 adults in the pre and 1,266 postimplementation period. The TAT was reduced by more than 2 days (3 (interquartile range (IQR): 2.0, 7.0) vs 0.42 (IQR: 0.24, 0.81), p < 0.001). Median LOS was significantly lower in the postimplementation period; however, this was no longer evident after adjustment. In relation to total cost, the time period had an effect of $6,965 (95% CI: -$481, $14,412); p = 0.067) on reducing the cost. The median adjusted total cost per patient was $7,045 (IQR: $3,805, $13,924) less in the post vs the preimplementation period. Conclusions: Our assessment did not find a statistically significant change in LOS, nevertheless, on-site testing was not cost-prohibitive for the institution. The value of on-site testing may be supported if an institutional C. auris reduction strategy emphasizes faster TATs.

Monkeypox viral nucleic acids detected using both DNA and RNA extraction workflows.

Molecular methods have been used to detect human pathogens in wastewater with sampling typically performed at wastewater treatment plants (WWTP) and upstream locations within the sewer system. A wastewater-based surveillance (WBS) program was established at the University of Miami (UM) in 2020, which included measurements of SARS-CoV-2 levels in wastewater from its hospital and within the regional WWTP. In addition to the development of a SARS-CoV-2 quantitative PCR (qPCR) assay, qPCR assays to detect other human pathogens of interest were also developed at UM. Here we report on the use of a modified set of reagents published by the CDC to detect nucleic acids of Monkeypox virus (MPXV) which emerged during May of 2022 to become a concern worldwide. Samples collected from the University hospital and from the regional WWTP were processed through DNA and RNA workflows and analyzed by qPCR to detect a segment of the MPXV CrmB gene. Results show positive detections of MPXV nucleic acids in the hospital and wastewater treatment plant wastewater which coincided with clinical cases in the community and mirrored the overall trend of nationwide MPXV cases reported to the CDC. We recommend the expansion of current WBS programs' methods to detect a broader range of pathogens of concern in wastewater and present evidence that viral RNA in human cells infected by a DNA virus can be detected in wastewater.

Predicting COVID-19 cases using SARS-CoV-2 RNA in air, surface swab and wastewater samples.

Genomic footprints of pathogens shed by infected individuals can be traced in environmental samples, which can serve as a noninvasive method of infectious disease surveillance. The research evaluates the efficacy of environmental monitoring of SARS-CoV-2 RNA in air, surface swabs and wastewater to predict COVID-19 cases. Using a prospective experimental design, air, surface swabs, and wastewater samples were collected from a college dormitory housing roughly 500 students from March to May 2021 at the University of Miami, Coral Gables, FL. Students were randomly screened for COVID-19 during the study period. SARS-CoV-2 concentration in environmental samples was quantified using Volcano 2nd Generation-qPCR. Descriptive analyses were conducted to examine the associations between time-lagged SARS-CoV-2 in environmental samples and COVID-19 cases. SARS-CoV-2 was detected in air, surface swab and wastewater samples on 52 (63.4 %), 40 (50.0 %) and 57 (68.6 %) days, respectively. On 19 (24 %) of 78 days SARS-CoV-2 was detected in all three sample types. COVID-19 cases were reported on 11 days during the study period and SARS-CoV-2 was also detected two days before the case diagnosis on all 11 (100 %), 9 (81.8 %) and 8 (72.7 %) days in air, surface swab and wastewater samples, respectively. SARS-CoV-2 detection in environmental samples was an indicator of the presence of local COVID-19 cases and a 3-day lead indicator for a potential outbreak at the dormitory building scale. Proactive environmental surveillance of SARS-CoV-2 or other pathogens in multiple environmental media has potential to guide targeted measures to contain and/or mitigate infectious disease outbreaks within communities.

Correlative analysis of wastewater trends with clinical cases and hospitalizations through five dominant variant waves of COVID-19.

Wastewater-based epidemiology (WBE) has been utilized to track community infections of Coronavirus Disease 2019 (COVID-19) by detecting RNA of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), within samples collected from wastewater. The correlations between community infections and wastewater measurements of the RNA can potentially change as SARS-CoV-2 evolves into new variations by mutating. This study analyzed SARS-CoV-2 RNA, and indicators of human waste in wastewater from two sewersheds of different scales (University of Miami (UM) campus and Miami-Dade County Central District wastewater treatment plant (CDWWTP)) during five internally defined COVID-19 variant dominant periods (Initial, Pre-Delta, Delta, Omicron and Post-Omicron wave). SARS-CoV-2 RNA quantities were compared against COVID-19 clinical cases and hospitalizations to evaluate correlations with wastewater SARS-CoV-2 RNA. Although correlations between documented clinical cases and hospitalizations were high, prevalence for a given wastewater SARS-CoV-2 level varied depending upon the variant analyzed. The correlative relationship was significantly steeper (more cases per level found in wastewater) for the Omicron-dominated period. For hospitalization, the relationships were steepest for the Initial wave, followed by the Delta wave with flatter slopes during all other waves. Overall results were interpreted in the context of SARS-CoV-2 virulence and vaccination rates among the community.

COVID-19 Prediction using Genomic Footprint of SARS-CoV-2 in Air, Surface Swab and Wastewater Samples.

Importance: Genomic footprints of pathogens shed by infected individuals can be traced in environmental samples. Analysis of these samples can be employed for noninvasive surveillance of infectious diseases. Objective: To evaluate the efficacy of environmental surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for predicting COVID-19 cases in a college dormitory. Design: Using a prospective experimental design, air, surface swabs, and wastewater samples were collected from a college dormitory from March to May 2021. Students were randomly screened for COVID-19 during the study period. SARS-CoV-2 in environmental samples was concentrated with electronegative filtration and quantified using Volcano 2 nd Generation-qPCR. Descriptive analyses were conducted to examine the associations between time-lagged SARS-CoV-2 in environmental samples and clinically diagnosed COVID-19 cases. Setting: This study was conducted in a residential dormitory at the University of Miami, Coral Gables campus, FL, USA. The dormitory housed about 500 students. Participants: Students from the dormitory were randomly screened, for COVID-19 for 2-3 days / week while entering or exiting the dormitory. Main Outcome: Clinically diagnosed COVID-19 cases were of our main interest. We hypothesized that SARS-CoV-2 detection in environmental samples was an indicator of the presence of local COVID-19 cases in the dormitory, and SARS-CoV-2 can be detected in the environmental samples several days prior to the clinical diagnosis of COVID-19 cases. Results: SARS-CoV-2 genomic footprints were detected in air, surface swab and wastewater samples on 52 (63.4%), 40 (50.0%) and 57 (68.6%) days, respectively, during the study period. On 19 (24%) of 78 days SARS-CoV-2 was detected in all three sample types. Clinically diagnosed COVID-19 cases were reported on 11 days during the study period and SARS-CoV-2 was also detected two days before the case diagnosis on all 11 (100%), 9 (81.8%) and 8 (72.7%) days in air, surface swab and wastewater samples, respectively. Conclusion: Proactive environmental surveillance of SARS-CoV-2 or other pathogens in a community/public setting has potential to guide targeted measures to contain and/or mitigate infectious disease outbreaks. Key Points: Question: How effective is environmental surveillance of SARS-CoV-2 in public places for early detection of COVID-19 cases in a community?Findings: All clinically confirmed COVID-19 cases were predicted with the aid of 2 day lagged SARS-CoV-2 in environmental samples in a college dormitory. However, the prediction efficiency varied by sample type: best prediction by air samples, followed by wastewater and surface swab samples. SARS-CoV-2 was also detected in these samples even on days without any reported cases of COVID-19, suggesting underreporting of COVID-19 cases.Meaning: SARS-CoV-2 can be detected in environmental samples several days prior to clinical reporting of COVID-19 cases. Thus, proactive environmental surveillance of microbiome in public places can serve as a mean for early detection of location-time specific outbreaks of infectious diseases. It can also be used for underreporting of infectious diseases.

Relationships between SARS-CoV-2 in Wastewater and COVID-19 Clinical Cases and Hospitalizations, with and without Normalization against Indicators of Human Waste.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in wastewater has been used to track community infections of coronavirus disease-2019 (COVID-19), providing critical information for public health interventions. Since levels in wastewater are dependent upon human inputs, we hypothesize that tracking infections can be improved by normalizing wastewater concentrations against indicators of human waste [Pepper Mild Mottle Virus (PMMoV), ß-2 Microglobulin (B2M), and fecal coliform]. In this study, we analyzed SARS-CoV-2 and indicators of human waste in wastewater from two sewersheds of different scales: a University campus and a wastewater treatment plant. Wastewater data were combined with complementary COVID-19 case tracking to evaluate the efficiency of wastewater surveillance for forecasting new COVID-19 cases and, for the larger scale, hospitalizations. Results show that the normalization of SARS-CoV-2 levels by PMMoV and B2M resulted in improved correlations with COVID-19 cases for campus data using volcano second generation (V2G)-qPCR chemistry (r s = 0.69 without normalization, r s = 0.73 with normalization). Mixed results were obtained for normalization by PMMoV for samples collected at the community scale. Overall benefits from normalizing with measures of human waste depend upon qPCR chemistry and improves with smaller sewershed scale. We recommend further studies that evaluate the efficacy of additional normalization targets.

Organizational readiness assessment in acute and long-term care has important implications for antibiotic stewardship for asymptomatic bacteriuria.

BACKGROUND: Prior to implementing an antibiotic stewardship intervention for asymptomatic bacteriuria (ASB), we assessed institutional barriers to change using the Organizational Readiness to Change Assessment. METHODS: Surveys were self-administered on paper in inpatient medicine and long-term care units at 4 Veterans Affairs facilities. Participants included providers, nurses, and pharmacists. The survey included 7 subscales: evidence (perceived strength of evidence) and six context subscales (favorability of organizational context). Responses were scored on a 5-point Likert-type scale. RESULTS: One hundred four surveys were completed (response rate = 69.3%). Overall, the evidence subscale had the highest score; the resources subscale (mean 2.8) was significantly lower than other subscales (P < .001). Scores for budget and staffing resources were lower than scores for training and facility resources (P < .001 for both). Pharmacists had lower scores than providers for the staff culture subscale (P = .04). The site with the lowest scores for resources (mean 2.4) also had lower scores for leadership and lower pharmacist effort devoted to stewardship. CONCLUSIONS: Although healthcare professionals endorsed the evidence about nontreatment of ASB, perceived barriers to antibiotic stewardship included inadequate resources and leadership support. These findings provide targets for tailoring the stewardship intervention to maximize success.

Teamwork and safety climate affect antimicrobial stewardship for asymptomatic bacteriuria.

OBJECTIVE: In preparation for a multisite antibiotic stewardship intervention, we assessed knowledge and attitudes toward management of asymptomatic bacteriuria (ASB) plus teamwork and safety climate among providers, nurses, and clinical nurse assistants (CNAs). DESIGN: Prospective surveys during January-June 2018. SETTING: All acute and long-term care units of 4 Veterans' Affairs facilities. METHODS: The survey instrument included 2 previously tested subcomponents: the Kicking CAUTI survey (ASB knowledge and attitudes) and the Safety Attitudes Questionnaire (SAQ). RESULTS: A total of 534 surveys were completed, with an overall response rate of 65%. Cognitive biases impacting management of ASB were identified. For example, providers presented with a case scenario of an asymptomatic patient with a positive urine culture were more likely to give antibiotics if the organism was resistant to antibiotics. Additionally, more than 80% of both nurses and CNAs indicated that foul smell is an appropriate indication for a urine culture. We found significant interprofessional differences in teamwork and safety climate (defined as attitudes about issues relevant to patient safety), with CNAs having highest scores and resident physicians having the lowest scores on self-reported perceptions of teamwork and safety climates (P < .001). Among providers, higher safety-climate scores were significantly associated with appropriate risk perceptions related to ASB, whereas social norms concerning ASB management were correlated with higher teamwork climate ratings. CONCLUSIONS: Our survey revealed substantial misunderstanding regarding management of ASB among providers, nurses, and CNAs. Educating and empowering these professionals to discourage unnecessary urine culturing and inappropriate antibiotic use will be key components of antibiotic stewardship efforts.

Resident Physician Knowledge of Urine Testing and Treatment Over Four Years.

We surveyed resident physicians at 2 academic medical centers regarding urinary testing and treatment as they progressed through training. Demographics and self-reported confidence were compared to overall knowledge using clinical vignette-based questions. Overall knowledge was 40% in 2011 and increased to 48%, 55%, and 63% in subsequent years (P<.001).Infect Control Hosp Epidemiol 2018;39:616-618.

Treatment considerations in vancomycin-resistant enterococcal bacteremia: daptomycin or linezolid? A review.

BACKGROUND: Vancomycin resistant enterococcal bloodstream infections are an important cause of morbidity and mortality in hospitalized patients. AIM OF THE REVIEW: A search of the literature was undertaken to determine the optimal antimicrobial therapy for the management of vancomycin resistant enterococcal bloodstream infections. METHOD: MEDLINE, EMBASE, and the Cochrane Library (unrestricted to time or language) were searched for studies of vancomycin resistant enterococcal bloodstream infections in adults reporting outcomes of direct comparisons of linezolid versus daptomycin on November 26, 2012. Studies of basic science, reviews, commentaries, pharmacologic, epidemiologic, or pediatric studies, and those studies examining conditions other than enterococcal bacteremia, a single antimicrobial agent or other antimicrobials were excluded. RESULTS: 226 studies were screened for eligibility and yielded eight studies evaluating a total of 807 patients. Inter-rater agreement was 100 %. Qualitative evaluation of the studies was performed using the Newcastle-Ottawa scale. No randomized controlled trials were identified. All studies were retrospective cohorts and non-randomized. 458 (57 %) patients treated with linezolid and 349 (43 %) with daptomycin were analyzed. Variable comorbidities and severity of illness were described in the included studies and reported here for comparison. CONCLUSION: The optimal treatment of vancomycin resistant enterococcal bloodstream infections is yet to be determined. Well-designed prospective studies are needed to lend more convincing evidence regarding choice of antimicrobial therapy for this important multidrug resistant organism.