Temporal Dynamics of Nasopharyngeal and Tracheal Severe Acute Respiratory Syndrome Coronavirus 2 Cycle Thresholds in Coronavirus Disease 2019 Patients With Tracheostomy.

In this study of 45 patients with COVID-19 undergoing tracheostomy, nasopharyngeal and tracheal cycle threshold (Ct) values were analyzed. Ct values rose to 37.9 by the time of tracheostomy and remained >35 postoperatively, demonstrating that persistent test positivity may not be associated with persistent transmissible virus in this population.

The Diagnostic Accuracy Of Procalcitonin for Urinary Tract Infection in Hospitalized Older Adults: a Prospective Study.

BACKGROUND: The diagnosis of urinary tract infection (UTI) is challenging among hospitalized older adults, particularly among those with altered mental status. OBJECTIVE: To determine the diagnostic accuracy of procalcitonin (PCT) for UTI in hospitalized older adults. DESIGN: We performed a prospective cohort study of older adults (≥65 years old) admitted to a single hospital with evidence of pyuria on urinalysis. PCT was tested on initial blood samples. The reference standard was a clinical definition that included the presence of a positive urine culture and any symptom or sign of infection referable to the genitourinary tract. We also surveyed the treating physicians for their clinical judgment and performed expert adjudication of cases for the determination of UTI. PARTICIPANTS: Two hundred twenty-nine study participants at a major academic medical center. MAIN MEASURES: We calculated the area under the receiver operating characteristic curve (AUC) of PCT for the diagnosis of UTI. KEY RESULTS: In this study cohort, 61 (27%) participants met clinical criteria for UTI. The median age of the overall cohort was 82.6 (IQR 74.9-89.7) years. The AUC of PCT for the diagnosis of UTI was 0.56 (95% CI, 0.46-0.65). A series of sensitivity analyses on UTI definition, which included using a decreased threshold for bacteriuria, the treating physicians' clinical judgment, and independent infectious disease specialist adjudication, confirmed the negative result. CONCLUSIONS: Our findings demonstrate that PCT has limited value in the diagnosis of UTI among hospitalized older adults. Clinicians should be cautious using PCT for the diagnosis of UTI in hospitalized older adults.

Impact of Severe Acute Respiratory Syndrome Coronavirus 2 Viral Load on Risk of Intubation and Mortality Among Hospitalized Patients With Coronavirus Disease 2019.

BACKGROUND: Patients hospitalized with coronavirus disease 2019 (COVID-19) frequently require mechanical ventilation and have high mortality rates. However, the impact of viral burden on these outcomes is unknown. METHODS: We conducted a retrospective cohort study of patients hospitalized with COVID-19 from 30 March 2020 to 30 April 2020 at 2 hospitals in New York City. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load was assessed using cycle threshold (Ct) values from a reverse transcription-polymerase chain reaction assay applied to nasopharyngeal swab samples. We compared characteristics and outcomes of patients with high, medium, and low admission viral loads and assessed whether viral load was independently associated with intubation and in-hospital mortality. RESULTS: We evaluated 678 patients with COVID-19. Higher viral load was associated with increased age, comorbidities, smoking status, and recent chemotherapy. In-hospital mortality was 35.0% (Ct <25; n = 220), 17.6% (Ct 25-30; n = 216), and 6.2% (Ct >30; n = 242) with high, medium, and low viral loads, respectively (P < .001). The risk of intubation was also higher in patients with a high viral load (29.1%) compared with those with a medium (20.8%) or low viral load (14.9%; P < .001). High viral load was independently associated with mortality (adjusted odds ratio [aOR], 6.05; 95% confidence interval [CI], 2.92-12.52) and intubation (aOR, 2.73; 95% CI, 1.68-4.44). CONCLUSIONS: Admission SARS-CoV-2 viral load among hospitalized patients with COVID-19 independently correlates with the risk of intubation and in-hospital mortality. Providing this information to clinicians could potentially be used to guide patient care.

Analysis of Multidrug Resistance in Staphylococcus aureus with a Machine Learning-Generated Antibiogram.

Multidrug resistance (MDR) surveillance consists of reporting MDR prevalence and MDR phenotypes. Detailed knowledge of the specific associations underlying MDR patterns can allow antimicrobial stewardship programs to accurately identify clinically relevant resistance patterns. We applied machine learning and graphical networks to quantify and visualize associations between resistance traits in a set of 1,091 Staphylococcus aureus isolates collected from one New York hospital between 2008 and 2018. Antimicrobial susceptibility testing was performed using reference broth microdilution. The isolates were analyzed by year, methicillin susceptibility, and infection site. Association mining was used to identify resistance patterns that consisted of two or more individual antimicrobial resistance (AMR) traits and quantify the association among the individual resistance traits in each pattern. The resistance patterns captured the majority of the most common MDR phenotypes and reflected previously identified pairwise relationships between AMR traits in S. aureus Associations between ß-lactams and other antimicrobial classes (macrolides, lincosamides, and fluoroquinolones) were common, although the strength of the association among these antimicrobial classes varied by infection site and by methicillin susceptibility. Association mining identified associations between clinically important AMR traits, which could be further investigated for evidence of resistance coselection. For example, in skin and skin structure infections, clindamycin and tetracycline resistance occurred together 1.5 times more often than would be expected if they were independent from one another. Association mining efficiently discovered and quantified associations among resistance traits, allowing these associations to be compared between relevant subsets of isolates to identify and track clinically relevant MDR.

Cost-effectiveness of ceftazidime-avibactam for treatment of carbapenem-resistant Enterobacteriaceae bacteremia and pneumonia.

Background: Ceftazidime/avibactam (CAZ-AVI) may improve outcomes among patients with carbapenem-resistant Enterobacteriaceae (CRE) infections compared to conventional therapies. However, CAZ-AVI's cost-effectiveness is unknown.Methods: We used a decision analytic model to estimate the health and economic consequences of CAZ-AVI-based therapy compared to colistin-based therapy (COL) for a hypothetical cohort of patients with CRE pneumonia or bacteremia over a 5-year horizon. Model inputs were from published sources and included CRE mortality with COL (41%), CAZ-AVI's absolute risk reduction in CRE mortality (23%), daily cost of CAZ-AVI ($926), risk of nephrotoxicity with COL (42%) and probability of discharge to long-term care (LTC) following CRE infection (56%). Outcomes included quality adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICER; $/QALY). 1-way and probabilistic sensitivity analyses were performed and ICERs were compared to willingness to pay standards of $100,000/QALY and $150,000/QALY.Results: In the base case, CAZ-AVI had an ICER of $95,000/QALY. At a $100,000/QALY threshold, results were sensitive to a number of variables including: the probability and cost of LTC, quality of life following CRE infection, CAZ-AVI's absolute risk reduction in mortality, all-cause mortality, daily cost of CAZ-AVI, and healthcare costs after CRE infection. The ICER did not exceed $150,000/QALY after varying all model inputs across a wide range of plausible values. In probabilistic sensitivity analysis, CAZ-AVI was the optimal strategy in 59% and 99% of simulations at $100,000/QALY and $150,000/QALY threshold, respectively.Conclusion: CAZ-AVI is a cost-effective treatment for CRE bacteremia and pneumonia based on accepted willingness to pay standards in the US.

Timely Use of Probiotics in Hospitalized Adults Prevents Clostridium difficile Infection: A Systematic Review With Meta-Regression Analysis.

BACKGROUND & AIMS: Systematic reviews have provided evidence for the efficacy of probiotics in preventing Clostridium difficile infection (CDI), but guidelines do not recommend probiotic use for prevention of CDI. We performed an updated systematic review to help guide clinical practice. METHODS: We searched MEDLINE, EMBASE, International Journal of Probiotics and Prebiotics, and The Cochrane Library databases for randomized controlled trials evaluating use of probiotics and CDI in hospitalized adults taking antibiotics. Two reviewers independently extracted data and assessed risk of bias and overall quality of the evidence. Primary and secondary outcomes were incidence of CDI and adverse events, respectively. Secondary analyses examined the effects of probiotic species, dose, timing, formulation, duration, and study quality. RESULTS: We analyzed data from 19 published studies, comprising 6261 subjects. The incidence of CDI in the probiotic cohort, 1.6% (54 of 3277), was lower than of controls, 3.9% (115 of 2984) (P < .001). The pooled relative risk of CDI in probiotic users was 0.42 (95% confidence interval, 0.30-0.57; I2 = 0.0%). Meta-regression analysis demonstrated that probiotics were significantly more effective if given closer to the first antibiotic dose, with a decrement in efficacy for every day of delay in starting probiotics (P = .04); probiotics given within 2 days of antibiotic initiation produced a greater reduction of risk for CDI (relative risk, 0.32; 95% confidence interval, 0.22-0.48; I2 = 0%) than later administration (relative risk, 0.70; 95% confidence interval, 0.40-1.23; I2 = 0%) (P = .02). There was no increased risk for adverse events among patients given probiotics. The overall quality of the evidence was high. CONCLUSIONS: In a systematic review with meta-regression analysis, we found evidence that administration of probiotics closer to the first dose of antibiotic reduces the risk of CDI by >50% in hospitalized adults. Future research should focus on optimal probiotic dose, species, and formulation. Systematic Review Registration: PROSPERO CRD42015016395.

The Expanding Role of Antimicrobial Stewardship Programs in Hospitals in the United States: Lessons Learned from a Multisite Qualitative Study.

BACKGROUND: Misuse of antibiotics can lead to the development of antibiotic resistance, which adversely affects morbidity, mortality, length of stay, and cost. To combat the threat of antimicrobial resistance, The Joint Commission and the Centers for Medicare & Medicaid Services have initiated or proposed requirements for hospitals to have antimicrobial stewardship programs (ASPs), but implementation remains challenging. A key-informant interview study was conducted to describe the characteristics and innovative strategies of leading ASPs. METHODS: Semistructured interviews were conducted with 12 program leaders at four ASPs in the United States, chosen by purposive sampling on the basis of national reputation, scholarship, and geography. Questions focused on ASP implementation, program structure, strengths, weaknesses, lessons learned, and future directions. Content analysis was used to identify dominant themes. RESULTS: Three major themes were identified. The first was evolution of ASPs from a top-down structure to a more diffuse approach involving unit-based pharmacists, multidisciplinary staff, and shared responsibility for antimicrobial prescribing under the ASPs' leadership. The second theme was integration of information technology (IT) systems, which enabled real-time interventions to optimize antimicrobial therapy and patient management. The third was barriers to technology integration, including limited resources for data analysis and poor interoperability between software systems. CONCLUSION: The study provides valuable insights on program implementation at a sample of leading ASPs across the United States. These ASPs used expansion of personnel to amplify the ASP's impact and integrated IT resources into daily work flow to improve efficiency. These findings can be used to guide implementation at other hospitals and aid in future policy development.

Complications and Mortality Following Total Hip Arthroplasty in the Octogenarians: An Analysis of a National Database.

BACKGROUND: As advances in medicine have increased life expectancy, more octogenarians are undergoing total hip arthroplasty (THA) than ever before. Concerns exist, however, about the safety of performing this elective procedure in this age group. The purpose of this study is to determine the 30-day complications associated with THA patients over 80 years of age and to identify high-risk patients. METHODS: We queried the American College of Surgeons-National Surgical Quality Improvement Program database for all patients who underwent primary THA from 2011 to 2014. Demographic variables, medical comorbidities, and 30-day complication, readmission, and reoperation rates were compared between patients under vs over 80 years of age. A multivariate logistic regression analysis was then performed to identify independent risk factors of poor short-term outcomes. RESULTS: Of the total 66,839 patients who underwent THA, 7198 (11%) patients were 80 years of age or older. Octogenarians had a higher overall complication rate (29% vs 15%, P < .001) and a higher mortality rate (0.9% vs 0.1%, P < .001). When controlling for other comorbidities, age over 80 years is an independent risk factor for mortality (odds ratio 2.02, 95% confidence interval 1.25-3.26, P = .004) and complications (odds ratio 1.41, 95% confidence interval 1.30-1.525, P < .001) following THA. Malnutrition and chronic kidney disease are also independent risk factors for readmission, complications, and mortality (all P < .05). CONCLUSION: THA in patients older than 80 years old are at an increased risk of complications and mortality. Octogenarian patients should be counseled on their risk profile, particularly those with malnutrition and chronic kidney disease.

Clinical and Molecular Evidence of Atovaquone and Azithromycin Resistance in Relapsed Babesia microti Infection Associated With Rituximab and Chronic Lymphocytic Leukemia.

Babesiosis treatment failures with standard therapy have been reported, but the molecular mechanisms are not well understood. We describe the emergence of atovaquone and azithromycin resistance associated with mutations in the binding regions of the target proteins of both drugs during treatment of an immunosuppressed patient with relapsing babesiosis.

Babesia microti: from Mice to Ticks to an Increasing Number of Highly Susceptible Humans.

Babesia microti, a zoonotic intraerythrocytic parasite, is the primary etiological agent of human babesiosis in the United States. Human infections range from subclinical illness to severe disease resulting in death, with symptoms being related to host immune status. Despite advances in our understanding and management of B. microti, the incidence of infection in the United States has increased. Therefore, research focused on eradicating disease and optimizing clinical management is essential. Here we review this remarkable organism, with emphasis on the clinical, diagnostic, and therapeutic aspects of human disease.

Endocarditis caused by Rhodotorula infection.

Rhodotorula is an emerging opportunistic fungal pathogen that is rarely reported to cause endocarditis. We describe a case involving a patient who developed endocarditis due to Rhodotorula mucilaginosa and Staphylococcus epidermidis, proven by culture and histopathology. The case illustrates the unique diagnostic and therapeutic challenges relevant to Rhodotorula spp.

Cost-effectiveness of blood donor screening for Babesia microti in endemic regions of the United States.

BACKGROUND: Babesia microti is the leading reported cause of red blood cell (RBC) transfusion-transmitted infection in the United States. Donor screening assays are in development. STUDY DESIGN AND METHODS: A decision analytic model estimated the cost-effectiveness of screening strategies for preventing transfusion-transmitted babesiosis (TTB) in a hypothetical cohort of transfusion recipients in Babesia-endemic areas of the United States. Strategies included: 1) no screening; 2) Uniform Donor Health History Questionnaire (UDHQ), "status quo"; 3) recipient risk targeting using donor antibody and polymerase chain reaction (PCR) screening; 4) universal endemic donor antibody screening; and 5) universal endemic donor antibody and PCR screening. Outcome measures were TTB cases averted, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs; $/QALY). We assumed a societal willingness to pay of $1 million/QALY based on screening for other transfusion-transmitted infections. RESULTS: Compared to no screening, the UDHQ avoids 0.02 TTB cases per 100,000 RBC transfusions at an ICER of $160,000/QALY whereas recipient risk-targeted strategy using antibody/PCR avoids 1.62 TTB cases per 100,000 RBC transfusions at an ICER of $713,000/QALY compared to the UDHQ. Universal endemic antibody screening avoids 3.39 cases at an ICER of $760,000/QALY compared to the recipient risk-targeted strategy. Universal endemic antibody/PCR screening avoids 3.60 cases and has an ICER of $8.8 million/QALY compared to universal endemic antibody screening. Results are sensitive to blood donor Babesia prevalence, TTB transmission probability, screening test costs, risk and severity of TTB complications, and impact of babesiosis diagnosis on donor quality of life. CONCLUSION: Antibody screening for Babesia in endemic regions is appropriate from an economic perspective based on the societal willingness to pay for preventing infectious threats to blood safety.

High touch surface bioburden associated with the use of disinfectants with and without continuously active disinfection in ambulatory care settings.

A quaternary ammonium and alcohol-based disinfectant with reported continuous activity demonstrated reduced microbial buildup on surfaces over time compared to routine disinfectants without continuous activity in in vitro and hospital studies. We compared these disinfectants in ambulatory settings and found no difference in bioburden on high-touch surfaces over time.

Low Utilization of Lead Extraction Among Patients With Infective Endocarditis and Implanted Cardiac Electronic Devices.

BACKGROUND: Cardiac implantable electronic device (CIED)-associated infections are associated with substantial morbidity, mortality, and costs. Guidelines have cited endocarditis as a Class I indication for transvenous lead removal/extraction (TLE) among patients with CIEDs. OBJECTIVES: The authors sought to study utilization of TLE among hospital admissions with infective endocarditis using a nationally representative database. METHODS: Using the Nationwide Readmissions Database (NRD), 25,303 admissions for patients with CIEDs and endocarditis between 2016 and 2019 were evaluated on the basis of International Classification of Diseases-10th Revision, Clinical-Modification (ICD-10-CM) codes. RESULTS: Among admissions for patients with CIEDs and endocarditis, 11.5% were managed with TLE. The proportion undergoing TLE increased significantly from 2016 to 2019 (7.6% vs 14.9%; P trend < 0.001). Procedural complications were identified in 2.7%. Index mortality was significantly lower among patients managed with TLE (6.0% vs 9.5%; P < 0.001). Presence of Staphylococcus aureus infection, implantable cardioverter-defibrillator, and large hospital size were independently associated with TLE management. TLE management was less likely with older age, female sex, dementia, and kidney disease. After adjustment for comorbidities, TLE was independently associated with significantly lower odds of mortality (adjusted OR: 0.47; 95% CI: 0.37-0.60 by multivariable logistic regression, and adjusted OR: 0.51; 95% CI: 0.40-0.66 by propensity score matching). CONCLUSIONS: Utilization of lead extraction among patients with CIEDs and endocarditis is low, even in the presence of low rates of procedural complications. Lead extraction management is associated with significantly lower mortality, and its use has trended upward between 2016 and 2019. Barriers to TLE for patients with CIEDs and endocarditis require investigation.

Characteristics of procalcitonin in hospitalized COVID-19 patients and clinical outcomes of antibiotic use stratified by procalcitonin levels.

We examined the characteristics of pro-calcitonin (PCT) in hospitalized COVID-19 patients (cohort 1) and clinical outcomes of antibiotic use stratified by PCT in non-critically ill patients without bacterial co-infection (cohort 2). Retrospective reviews were performed in adult, hospitalized COVID-19 patients during March-May 2020. For cohort 1, we excluded hospital transfers, renal disease and extra-pulmonary infection without isolated pathogen(s). For cohort 2, we further excluded microbiologically confirmed infection, 'do not resuscitate ± do not intubate' status, and intensive care unit (ICU). For cohort 1, PCT was compared between absent/low-suspicion and proven bacterial co-infections. Factors associated with elevated PCT and sensitivity/specificity/PPV/NPV of PCT cutoffs for identifying bacterial co-infections were explored. For cohort 2, clinical outcomes including mechanical ventilation within 5 days (MV5) were compared between the antibiotic and non-antibiotic groups stratified by PCT ≥ 0.25 µg/L. Nine hundred and twenty four non-ICU and 103 ICU patients were included (cohort 1). The median PCT was higher in proven vs. absent/low-suspicion of bacterial co-infection. Elevated PCT was significantly associated with proven bacterial co-infection, ICU status and oxygen requirement. For PCT ≥ 0.25 µg/L, sensitivity/specificity/PPV/NPV were 69/65/6.5/98% (non-ICU) and 75/33/8.6/94% (ICU). For cohort 2, 756/1305 (58%) patients were included. Baseline characteristics were balanced between the antibiotic and non-antibiotic groups except PCT ≥ 0.25 µg/L (antibiotic:non-antibiotic = 59%:24%) and tocilizumab use (antibiotic:non-antibiotic = 5%:2%). 23% (PCT < 0.25 µg/L) and 58% (PCT ≥ 0.25 µg/L) received antibiotics. Antibiotic group had significantly higher rates of MV5. COVID-19 severity inferred from ICU status and oxygen requirement as well as the presence of bacterial co-infections were associated with elevated PCT. PCT showed poor PPV and high NPV for proven bacterial co-infections. The use of antibiotics did not show improved clinical outcomes in COVID-19 patients with PCT ≥ 0.25 µg/L outside of ICU when bacterial co-infections are of low suspicion.

Improving Antibiotic Stewardship for Inpatients with Reported Beta-Lactam Allergies and Limited Access to Penicillin Skin Testing.

BACKGROUND: Penicillin allergy is commonly reported, but true allergy is rare. Inpatients with reported beta-lactam allergy are often treated with alternative antibiotics. Penicillin skin testing (PST) is not universally available for inpatients. METHODS: We designed a four-phase quality improvement project aimed to increase the percentage of inpatients on medical services with reported beta-lactam allergy who safely receive beta-lactam antibiotics at two hospitals with limited access to PST. First, we updated our hospital guideline to allow for cephalosporin graded challenge without antecedent PST. Second, we educated physicians, physician assistants, and nurses about the new guideline and beta-lactam allergy classification and management. Third, we designed a pocket card to reinforce the education. Last, we used antimicrobial stewardship software to screen our daily census to identify opportunities to improve management of patients with reported beta-lactam allergies. RESULTS: We observed a 29.2% increase in the percentage of patients who received beta-lactam antibiotics (excluding carbapenems) among those with reported beta-lactam allergy, from 42.2% (470/1,115) at baseline to 54.5% (379/696), p < 0.001, during the project period. There was a decrease in the use of alternative antibiotics, no change in hospital-onset Clostridioides difficile cases, and no increase in the number of infectious disease or allergy consults. The number of graded challenges increased during the project period, without any anaphylaxis events. CONCLUSION: A multiphase quality improvement project aimed to improve management of beta-lactam allergies and access to graded challenges led to an increase in beta-lactam utilization without an increase in anaphylaxis, even with limited access to PST.

Real-world implementation and impact of a rapid carbapenemase detection test in an area endemic for carbapenem-resistant Enterobacterales.

A retrospective study was conducted to describe the impact of a molecular assay to detect the most common carbapenemase genes in carbapenem-resistant Enterobacterales isolates recovered in culture. Carbapenemases were detected in 69% of isolates, and assay results guided treatment modifications or epidemiologic investigation in 20% and 4% of cases, respectively.