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.