Sequential Time to Positivity as a Prognostic Indicator in Staphylococcus aureus Bacteremia.

Background: We aimed to determine the factors associated with sequential blood culture time to positivity (STTP) and validate the previously defined time to positivity (TTP) ratio threshold of 1.5 in predicting adverse disease outcomes and mortality of Staphylococcus aureus bacteremia (SAB). Methods: We conducted an observational study of adult patients with SAB. The TTP ratio was calculated by dividing the TTP of the second blood culture by that of the first. Results: Of 186 patients, 69 (37%) were female, with a mean age of 63.6 years. Median TTP was 12 hours (interquartile range [IQR], 10-15 hours) from the initial and 21 hours (17-29) from sequential blood cultures. Methicillin-resistant S aureus (MRSA)-infected patients had significantly shorter STTPs (P < .001) and lower TTP ratios (P < .001) compared to patients with methicillin-susceptible S aureus (MSSA). A significant correlation between initial and STTP was observed in patients with MRSA (r = 0.42, P = .002) but not in those with MSSA. A higher rate of native valve endocarditis (NVE) significantly correlated with a TTP ratio of ≤1.5 (odds ratio, 2.65 [95% confidence interval, 1.3-5.6]; P = .01). The subgroup having an initial TTP <12 hours combined with a TTP ratio ≤1.5 showed the highest prevalence of NVE. Conclusions: The STTP varies based on methicillin susceptibility of S aureus isolate. This study suggests a potential clinical utility of the STTP to identify patients at a higher risk of NVE. However, prospective studies are required to validate these findings.

Coronary Stent Infections - A Systematic Review and Meta-Analysis.

BACKGROUND: Coronary stent infection (CSI) represents a rare but potentially fatal complication of percutaneous coronary interventions (PCI). A systematic review and meta-analysis of published reports was performed to profile CSI and its management strategies. METHODS: Online database searches were performed using MeSH and keywords. The primary outcome of the study was in-hospital mortality. A unique Artificial Intelligence-based predictive model was developed for need for delayed surgery and probability of survival on medical therapy alone. RESULTS: A total of 79 subjects were included in the study. Twenty eight (35.0 %) patients had type 2 diabetes mellitus. Subjects most commonly reported symptoms within the first week of the procedure (43 %). Fever was the most common initial symptom (72 %). Thirty eight percent of patients presented with acute coronary syndrome. The presence of mycotic aneurysms was described in 62 % of patients. Staphylococcus species were the most common (65 %) isolated organism. The primary outcome of in-hospital mortality was seen in a total of 24 patients out of 79 (30.3 %). A comparative univariate analysis comparing those encountering in-hospital mortality versus otherwise revealed the presence of structural heart disease (83 % mortality vs 17 % survival, p = 0.009), and the presence of non ST elevation acute coronary syndrome (11 % mortality vs 88 % survival, p = 0.03), to be a statistically significant factor predicting in-hospital mortality. In an analysis between patients with successful versus failed initial medical therapy, patients from private teaching hospitals (80.0 % vs 20.0 %; p = 0.01, n = 10) had a higher survival with medical therapy alone. CONCLUSION: CSI is a highly under-studied disease entity with largely unknown risk factors and clinical outcomes. Larger studies are needed to further define the characteristics of CSI. (PROSPERO ID CRD42021216031).

Pharmacist adjustment of preoperative antibiotic orders to the preferred preoperative antibiotic cefazolin for patients with penicillin allergy labeling.

PURPOSE: Emerging literature has detailed the safe use of cefazolin in patients with immunoglobulin E-mediated penicillin allergy labeling (PAL) such as hives and anaphylaxis. The purpose of this article is to detail efforts led by an antimicrobial stewardship pharmacist working with an interdisciplinary team to optimize preoperative antimicrobials in patients with PAL. METHODS: A pharmacist-led, interdisciplinary collaborative practice agreement (CPA) was activated in January 2020 to permit pharmacists to independently optimize preoperative antibiotics to the preferred cefazolin in patients with PAL if nonsevere or severe reactions had been reported. A patient registry was established covering the timeframe between January 8, 2020, and January 6, 2022. Reaction during surgery was assessed via 2-provider documentation, which included surgeon and anesthesiology staff documentation of any complications during the procedure related to a suspected allergic safety event. Utilization of cefazolin, clindamycin, and vancomycin for preoperative prophylaxis was monitored before and after implementation of the CPA. RESULTS: During the stated timeframe, 10,182 procedures and/or surgeries were completed on 1,572 (15.4%) patients with PAL and 659 (41.9%) patients previously reporting at least one reaction categorized as a severe reaction, which was hives for 71.2% of these patients. Of the 659 patients with PAL reporting a severe reaction, 356 received a preoperative cephalosporin (cefazolin, 98.8%; ceftriaxone, 1.2%) and tolerated it without a reported safety event, including 52 patients with PAL previously reporting anaphylaxis. An increase in preferred preoperative antimicrobial prophylaxis utilization was noted (cefazolin: 86% to 96.3%, P < 0.001; 2019 to 2021) with reductions noted in the use of nonpreferred preoperative antibiotics (clindamycin: 2.1% to 0.2%, P < 0.001; vancomycin: 3.2% to 0.4%, P < 0.001; 2019 to 2021). CONCLUSION: A pharmacist-led, interdisciplinary CPA increased preferred preoperative antimicrobial use in patients with PAL reporting severe allergic reactions, including hives and anaphylaxis, without reported safety events.

The skip phenomenon in Staphylococcus aureus bacteremia: clinical implications.

Serial blood cultures (BCs) are integral in managing Staphylococcus aureus bacteremia (SAB) to determine complication risks and treatment response. Several studies recognized the skip phenomenon (SP)- the occurrence of intermittent negative BCs and recommend obtaining additional BCs to document clearance. We examined patients with SP to determine its clinical significance. Significant differences between those who did and did not manifest the SP included higher rates of injection drug use and community-onset SAB in the SP cohort. Longer SAB duration, high-grade SAB, and complicated bacteremia were more common in the SP group. In unadjusted outcome analyses, association of SP with hospital length of stay was not significant, although a higher risk of in-hospital mortality among SP patients approached significance. Analysis of hospital survivors revealed no significant differences in 90-day relapse or 1-year mortality. Clinical implications of patients with SAB and SP indicate that serial BCs are warranted to document bacterial clearance.

Incidence of Monomicrobial Staphylococcus aureus Bacteremia: A Population-Based Study in Olmsted County, Minnesota-2006 to 2020.

Background: Population-based studies of Staphylococcus aureus bacteremia (SAB) in the United States are limited. We provide a contemporary evaluation of SAB incidence in Olmsted County, Minnesota, from 2006 to 2020. Methods: This was a retrospective population-based study of all adult patients with SAB residing in Olmsted County from 1 January 2006 through 31 December 2020. Initial episodes of SAB were identified using the microbiology laboratory databases at both Olmsted Medical Center and Mayo Clinic Rochester. Results: Overall, 541 incident SAB cases were identified with a median age of 66.8 (interquartile range, 54.4-78.5) years, and 60.4% were male. Among these cases, 298 (56.2%) were due to methicillin-susceptible S aureus (MSSA) and 232 (43.8%) cases of methicillin-resistant S aureus (MRSA). The overall age- and sex-adjusted SAB incidence rate (IR) was 33.9 (95% confidence interval [CI], 31.0-36.8) cases/100 000 person-years (PY). Males had a higher age-adjusted IR of 46.0 (95% CI, 41.0-51.0) cases/100 000 PY compared to females (IR, 24.4 [95% CI, 21.1-27.7] cases/100 000 PY). Age- and sex-adjusted SAB IRs due to MSSA and MRSA were 18.7 and 14.6 cases/100 000 PY, respectively, and the percentage of incident SAB cases due to MRSA fluctuated across the study period. There was no apparent temporal trend in SAB incidence over the study period (P = .093). Conclusions: Our investigation represents the only contemporary population-based study in the United States. Despite the impression that SAB incidence may have increased based on Centers for Disease Control and Prevention surveillance data, our finding of no change in SAB incidence was somewhat unanticipated.

Clinical Significance of Staphylococcus aureus in a Single Positive Blood Culture Bottle.

Clinical significance of a single positive blood culture bottle (SPBCB) with Staphylococcus aureus is unclear. We aimed to assess the significance of an SPBCB by looking at the associated outcomes. We performed a retrospective, multicenter study of patients with an SPBCB with S aureus using data collected from both electronic health records and the clinical microbiology laboratory. Overall, 534 patients with S aureus bacteremia were identified and 118 (22.1%) had an SPBCB. Among cases with an SPBCB, 106 (89.8%) were classified as clinically significant whereas 12 (10.2%) were considered contaminated or of unclear significance. A majority (92.4%) of patients received antibiotic therapy, but patients with clinically significant bacteremia were treated with longer courses (25.9 vs 5.7 days, P < .001). Significant differences in both frequency of echocardiography (65.1% vs 84.6%, P < .001) and infective endocarditis diagnosis (3.8% vs 14.2%, P = .002) were seen in those with an SPBCB compared to those with multiple positive bottles. A longer hospital length of stay and higher 90-day, 6-month, and 1-year mortality rates were seen in patients with multiple positive blood culture bottles. An SPBCB with S aureus was common among our patients. While this syndrome has a more favorable prognosis as compared to those with multiple positive blood cultures, clinicians should remain concerned as it portends a risk of infective endocarditis and mortality.

Native Vertebral Osteomyelitis in Patients with Staphylococcus Aureus Bacteremia.

BACKGROUND: The purpose of the study was to assess the epidemiology, risk factors and outcomes of native vertebral osteomyelitis (NVO) in patients with Staphylococcus aureus bacteremia (SAB). METHODS: A retrospective institutional review was conducted at Mayo Clinic, Minnesota. Patients aged ≥18 years with SAB who developed NVO from January 1, 2006 to December 31, 2020 were included and 3-month follow-up data were abstracted. Data pertaining to patient demographics, risk factors and outcomes were recorded using REDCap. A 1:2 nested case-control analysis was performed, and controls were matched according to age, sex and year of SAB diagnosis. RESULTS: A total of 103 patients had NVO. A majority (60.2%) of patients was male, with a median age of 62.0 years. Thirty-one (30.1%) cases were caused by methicillin-resistant S. aureus (MRSA). The lumbar spine was most commonly (57.6%) and the most commonly reported comorbid conditions included diabetes mellitus (36.9%) and coronary artery disease (27.2%). Mortality at three-month follow-up was 18.6%. Nested case-control analysis revealed that injection drug use (IDU) and tobacco consumption were significant risk factors associated with NVO, while chronic hemodialysis and chronic liver disease (CLD) were associated with a decreased risk of NVO. CONCLUSIONS: Atherosclerotic vascular disease was prominent in our contemporary cohort with NVO in the setting of SAB. Diabetes mellitus, tobacco consumption, older age and male sex likely contributed to this profile. Because IDU was associated with NVO, an increased number of cases should be anticipated among patients with IDU given the ongoing opioid epidemic in the United States.

Escalating incidence of infective endocarditis in Europe in the 21st century.

AIM: To provide a contemporary analysis of incidence trends of infective endocarditis (IE) with its changing epidemiology over the past two decades in Europe. METHODS: A systematic review was conducted at the Mayo Clinic, Rochester. Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus and Web of Science were searched for studies published between 1 January 2000 and 30 November 2020. All studies were independently reviewed by four referees and those that included a population-based incidence of IE in patients, irrespective of age, in Europe were included. Least squares regression was used to estimate pooled temporal trends in IE incidence. RESULTS: Of 9138 articles screened, 18 studies were included in the review. Elderly men predominated in all studies. IE incidence increased 4.1% per year (95% CI 1.8% to 6.4%) in the pooled regression analysis of eight studies that included comprehensive and consistent trends data. When trends data were weighted according to population size of individual countries, an increase in yearly incidence of 0.27 cases per 100 000 people was observed. Staphylococci and streptococci were the most common pathogens identified. The rate of surgical intervention ranged from 10.2% to 60.0%, and the rate of inpatient mortality ranged from 14.3% to 17.5%. In six studies that examined the rate of injection drug use, five of them reported a rate of less than 10%. CONCLUSION: Based on findings from our systematic review, IE incidence in Europe has doubled over the past two decades in Europe. Multiple factors are likely responsible for this striking increase. TRIAL REGISTERATION NUMBER: CRD42020191196.

E-cigarette or vaping product use-associated lung injury (EVALI) masquerading as COVID-19.

SARS-CoV-2, the novel coronavirus causing COVID-19, has caused a global pandemic resulting in over 4 million deaths globally (data current as of 14 July 2021). E-cigarette or vaping product use-associated lung injury (EVALI) is a type of acute lung injury of unclear pathogenesis. The two pathologies present with overlapping clinical symptoms, laboratory values and imaging, making them difficult to distinguish, especially in the setting of a global COVID-19 pandemic. We present the case of a 32-year-old woman treated for COVID-19 despite multiple negative SARS CoV-2 PCR tests and nucleocapsid antibody test. On further investigation, she endorsed use of E-cigarettes and was subsequently diagnosed with EVALI. The patient was treated with oral and intravenous steroids, resulting in significant improvement in her symptoms. This case highlights the challenge of diagnosing rarer aetiologies of respiratory distress during the COVID-19 pandemic.

A Framework for Outpatient Infusion of Antispike Monoclonal Antibodies to High-Risk Patients with Mild-to-Moderate Coronavirus Disease-19: The Mayo Clinic Model.

The administration of spike monoclonal antibody treatment to patients with mild to moderate COVID-19 is very challenging. This article summarizes essential components and processes in establishing an effective spike monoclonal antibody infusion program. Rapid identification of a dedicated physical infrastructure was essential to circumvent the logistical challenges of caring for infectious patients while maintaining compliance with regulations and ensuring the safety of our personnel and other patients. Our partnerships and collaborations among multiple different specialties and disciplines enabled contributions from personnel with specific expertise in medicine, nursing, pharmacy, infection prevention and control, electronic health record (EHR) informatics, compliance, legal, medical ethics, engineering, administration, and other critical areas. Clear communication and a culture in which all roles are welcomed at the planning and operational tables are critical to the rapid development and refinement needed to adapt and thrive in providing this time-sensitive beneficial therapy. Our partnerships with leaders and providers outside our institutions, including those who care for underserved populations, have promoted equity in the access of monoclonal antibodies in our regions. Strong support from institutional leadership facilitated expedited action when needed, from a physical, personnel, and system infrastructure standpoint. Our ongoing real-time assessment and monitoring of our clinical program allowed us to improve and optimize our processes to ensure that the needs of our patients with COVID-19 in the outpatient setting are met.

Association between high vancomycin minimum inhibitory concentration and clinical outcomes in patients with methicillin-resistant Staphylococcus aureus bacteraemia - A retrospective cohort study.

The purpose of this study is to determine the role of high (≥ 1.5 mg/L) vancomycin minimum inhibitory concentration (VMIC) in predicting clinical outcomes in patients with methicillin-resistant Staphylococcus aureus bacteraemia (MRSAB). A retrospective study was conducted at Mayo Clinic, Minnesota. Patients ≥ 18 years with a 3-month follow-up were included. Outcomes were defined as 30-day all-cause in-hospital mortality, median duration of bacteraemia, metastatic infectious complications, and relapse of MRSAB. A total of 475 patients with MRSAB were identified, and 93 (19.6%) of them had high VMIC isolates. Sixty-four percent of patients were male with a mean age of 69.0 years. Active solid organ malignancy and skin and soft tissue infection as source of MRSAB were associated with high VMIC, while septic arthritis as a complication was significantly associated with low VMIC on multivariate analysis. Eighty-one (17.1%) patients died within 30 days of hospitalization, with no significant difference in mortality rates between the two groups. In-hospital mortality, median duration of bacteraemia, and metastatic infectious complications were not significantly associated with high VMIC MRSAB.

Remdesivir in Coronavirus Disease 2019 (COVID-19) treatment: a review of evidence.

COVID-19 is an infectious disease caused by a novel ß-coronavirus, belonging to the same subgenus as the Severe Acute Respiratory Syndrome (SARS) virus. Remdesivir, an investigational broad-spectrum antiviral agent has previously demonstrated in vitro activity against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and in vivo efficacy against other related coronaviruses in animal models. Its safety profile has been tested in a compassionate use setting for patients with COVID-19. The current therapeutic studies demonstrate clinical effectiveness of remdesivir in COVID-19 patients by shortening time to clinical recovery, and hospital stay. In this review, we critically analyze the current evidence of remdesivir against COVID-19 and dissect the aspects over its safety and efficacy. Based on existing data, remdesivir can be regarded as a potential therapeutic agent against COVID-19. Further large-scale, randomized placebo-controlled clinical trials are, however, awaited to validate these findings.

Temporal Trends of Infective Endocarditis in North America From 2000 to 2017-A Systematic Review.

BACKGROUND: The objective of this paper was to examine temporal changes of infective endocarditis (IE) incidence and epidemiology in North America. METHODS: A systematic review was conducted at Mayo Clinic, Rochester. Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science were searched for studies published between January 1, 2000, and May 31, 2020. Four referees independently reviewed all studies, and those that reported a population-based incidence of IE in patients aged 18 years and older in North America were included. RESULTS: Of 8588 articles screened, 14 were included. Overall, IE incidence remained largely unchanged throughout the study period, except for 2 studies that demonstrated a rise in incidence after 2014. Five studies reported temporal trends of injection drug use (IDU) prevalence among IE patients with a notable increase in prevalence observed. Staphylococcus aureus was the most common pathogen in 7 of 9 studies that included microbiologic findings. In-patient mortality ranged from 3.7% to 14.4%, while the percentage of patients who underwent surgery ranged from 6.4% to 16.0%. CONCLUSIONS: The overall incidence of IE has remained stable among the 14 population-based investigations in North America identified in our systematic review. Standardization of study design for future population-based investigations has been highlighted for use in subsequent systematic reviews of IE.

Prospective Validation of PREDICT and Its Impact on the Transesophageal Echocardiography Use in Management of Staphylococcus aureus Bacteremia.

BACKGROUND: Infective endocarditis (IE) is the most feared complication of Staphylococcus aureus bacteremia (SAB). Transesophageal echocardiogram (TEE) is generally recommended for all patients with SAB; however, supporting data for this are limited. We previously developed a scoring system, "PREDICT," that quantifies the risk of IE and identifies patients who would most benefit most from undergoing TEE. The current prospective investigation aims to validate this score. METHODS: We prospectively screened all consecutive adults (≥18 years) hospitalized with SAB at 3 Mayo Clinic sites between January 2015 and March 2017. RESULTS: Of 220 patients screened, 199 with SAB met study criteria and were included in the investigation. Of them, 23 (11.6%) patients were diagnosed with definite IE within 12 weeks of initial presentation based on modified Duke's criteria. Using the previously derived PREDICT model, the day 1 score of ≥4 had a sensitivity of 30.4% and a specificity of 93.8%, whereas a day 5 score of ≤2 had a sensitivity and negative-predictive value of 100%. Additional factors including surgery or invasive procedure in the past 30 days, prosthetic heart valve, and higher number of positive blood culture bottles in the first set of cultures were associated with increased risk of IE independent of the day 5 risk score. CONCLUSIONS: We validated the previously developed PREDICT scoring tools for stratifying risk of IE, and the need for undergoing a TEE, among cases of SAB. We also identified other factors with predictive potential, although larger prospective studies are needed to further evaluate possible enhancements to the current scoring system.

GM-CSF Neutralization With Lenzilumab in Severe COVID-19 Pneumonia: A Case-Cohort Study.

OBJECTIVE: To assess the efficacy and safety of lenzilumab in patients with severe coronavirus disease 2019 (COVID-19) pneumonia. METHODS: Hospitalized patients with COVID-19 pneumonia and risk factors for poor outcomes were treated with lenzilumab 600 mg intravenously for three doses through an emergency single-use investigational new drug application. Patient characteristics, clinical and laboratory outcomes, and adverse events were recorded. We also identified a cohort of patients matched to the lenzilumab patients for age, sex, and disease severity. Study dates were March 13, 2020, to June 18, 2020. All patients were followed through hospital discharge or death. RESULTS: Twelve patients were treated with lenzilumab; 27 patients comprised the matched control cohort (untreated). Clinical improvement, defined as improvement of at least 2 points on the 8-point ordinal clinical endpoints scale, was observed in 11 of 12 (91.7%) patients treated with lenzilumab and 22 of 27 (81.5%) untreated patients. The time to clinical improvement was significantly shorter for the lenzilumab-treated group compared with the untreated cohort with a median of 5 days versus 11 days (P=.006). Similarly, the proportion of patients with acute respiratory distress syndrome (oxygen saturation/fraction of inspired oxygen<315 mm Hg) was significantly reduced over time when treated with lenzilumab compared with untreated (P<.001). Significant improvement in inflammatory markers (C-reactive protein and interleukin 6) and markers of disease severity (absolute lymphocyte count) were observed in patients who received lenzilumab, but not in untreated patients. Cytokine analysis showed a reduction in inflammatory myeloid cells 2 days after lenzilumab treatment. There were no treatment-emergent adverse events attributable to lenzilumab. CONCLUSION: In high-risk COVID-19 patients with severe pneumonia, granulocyte-macrophage colony-stimulating factor neutralization with lenzilumab was safe and associated with faster improvement in clinical outcomes, including oxygenation, and greater reductions in inflammatory markers compared with a matched control cohort of patients hospitalized with severe COVID-19 pneumonia. A randomized, placebo-controlled clinical trial to validate these findings is ongoing (NCT04351152).

Acute infection of Viabahn stent graft in the popliteal artery.

Peripheral stents are increasingly used for treatment of peripheral arterial disease, yet all implanted devices are potentially at risk for infection. We describe a 51-year-old man who underwent stenting in the femoropopliteal artery and presented 3 days later with leg pain, fever, and evidence of peripheral stigmata of embolization. Blood cultures grew methicillin-resistant Staphylococcus aureus and remained persistently positive despite antibiotic therapy. At surgical exploration, the popliteal artery had essentially been disintegrated by the infection, with only visible stent graft maintaining arterial continuity. Acute stent graft infections are rare and must be managed promptly to reduce morbidity.