Real-World Incidence of Breakthrough Coronavirus Disease 2019 Hospitalization After Vaccination vs Natural Infection in a Large, Local, Empaneled Primary Care Population Using Time-to-Event Analysis.

We followed 106 349 primary care patients for 22 385 3099 person-days across 21 calendar months and documented 69 breakthrough coronavirus disease 2019 (COVID-19) hospitalizations: 65/102,613 (0.06%) among those fully vaccinated, 3/11 047 (0.03%) among those previously infected, and 1/7,313 (0.01%) among those with both statuses. These data give providers real-world context regarding breakthrough COVID-19 hospitalization risk.

Diffuse C4d staining of peritubular capillaries in renal allograft following bamlanivimab therapy.

Neutralizing monoclonal antibodies such as bamlanivimab emerged as promising agents in treating kidney transplant recipients with COVID-19. However, the impact of bamlanivimab on kidney allograft histology remains unknown. We report a case of a kidney transplant recipient who received bamlanivimab for COVID-19 with subsequent histologic findings of diffuse peritubular capillary C4d staining. A 33-year-old man with end-stage kidney disease secondary to hypertension who received an ABO compatible kidney from a living donor, presented for his 4-month protocol visit. He was diagnosed with COVID-19 44 days prior to his visit and had received bamlanivimab with an uneventful recovery. His 4-month surveillance biopsy showed diffuse C4d staining of the peritubular capillaries without other features of antibody-mediated rejection (ABMR). Donor-specific antibodies were negative on repeat evaluations. ABMR gene expression panel was negative. His creatinine was stable at 1.3 mg/dl, without albuminuria. Given the temporal relationship between bamlanivimab and our observations of diffuse C4d staining of the peritubular capillaries, we hypothesize that bamlanivimab might bind to angiotensin-converting enzyme 2, resulting in classical complement pathway and C4d deposition. We elected to closely monitor kidney function which has been stable at 6 months after the biopsy. In conclusion, diffuse C4d may present following bamlanivimab administration without any evidence of ABMR.

Clostridioides difficile Whole-genome Sequencing Differentiates Relapse With the Same Strain From Reinfection With a New Strain.

BACKGROUND: Current approaches in tracking Clostridioides difficile infection (CDI) and individualizing patient management are incompletely defined. METHODS: We recruited 468 subjects with CDI at Mayo Clinic Rochester between May and December 2016 and performed whole-genome sequencing (WGS) on C. difficile isolates from 397. WGS was also performed on isolates from a subset of the subjects at the time of a recurrence of infection. The sequence data were analyzed by determining core genome multilocus sequence type (cgMLST), with isolates grouped by allelic differences and the predicted ribotype. RESULTS: There were no correlations between C. difficile isolates based either on cgMLST or ribotype groupings and CDI outcome. An epidemiologic assessment of hospitalized subjects harboring C. difficile isolates with ≤2 allelic differences, based on standard infection prevention and control assessment, revealed no evidence of person-to-person transmission. Interestingly, community-acquired CDI subjects in 40% of groups with ≤2 allelic differences resided within the same zip code. Among 18 subjects clinically classified as having recurrent CDI, WGS revealed 14 with initial and subsequent isolates differing by ≤2 allelic differences, suggesting a relapse of infection with the same initial strain, and 4 with isolates differing by >50 allelic differences, suggesting reinfection. Among the 5 subjects classified as having a reinfection based on the timing of recurrence, 3 had isolates with ≤2 allelic differences between them, suggesting a relapse, and 2 had isolates differing by >50 allelic differences, suggesting reinfection. CONCLUSIONS: Our findings point to potential transmission of C. difficile in the community. WGS better differentiates relapse from reinfection than do definitions based on the timing of recurrence.

Reducing Broad-Spectrum Antimicrobial Use in Extracorporeal Membrane Oxygenation: Reduce AMMO Study.

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) in critically ill adults is increasing. There are currently no guidelines for antimicrobial prophylaxis. We analyzed 7 years of prophylactic antimicrobial use across 3 time series for patients on ECMO at our institution in the development, improvement, and streamlining of our ECMO antimicrobial prophylaxis protocol. METHODS: In this quasi-experimental interrupted time series analysis, we evaluated the impact of an initial ECMO antimicrobial prophylaxis protocol, implemented in 2014, on antimicrobial use and National Healthcare Safety Network-reportable infection rates. Then, following a revision and streamlining of the protocol in November 2018, we reevaluated the same metrics. RESULTS: Our study population included 338 intensive care unit patients who received ECMO between July 2011 and November 2019. After implementation of the first version of the protocol, we did not observe significant changes in antimicrobial use or infection rates in these patients; however, following revision and streamlining of the protocol, we demonstrated a significant reduction in broad-spectrum antimicrobial use for prophylaxis in patients on ECMO without any evidence of a compensatory increase in infection rates. CONCLUSIONS: Our final protocol significantly reduces broad-spectrum antimicrobial use for prophylaxis in patients on ECMO. We propose a standard antimicrobial prophylaxis regimen for patients on ECMO based on current evidence and our experience.Summary: There are no guidelines for antimicrobial prophylaxis in patients on extracorporeal membrane oxygenation (ECMO). A rational approach employing concepts of antimicrobial stewardship can drive logical antimicrobial selection for prophylaxis in patients on ECMO without adversely impacting outcomes.

Postoperative Surgical Site Infections: Understanding the Discordance Between Surveillance Systems.

OBJECTIVE: To characterize agreement in the ascertainment of surgical site infections (SSIs) between the National Surgical Quality Improvement Program (NSQIP), National Healthcare Safety Network (NHSN), and administrative data. BACKGROUND: The NSQIP, NHSN, and administrative data are the primary systems used to monitor and report SSIs for the purpose of quality control and benchmarking of hospitals and surgeons. These systems have different methods for identifying SSIs. METHODS: We queried the NHSN, NSQIP, and administrative data systems for patients who had an operation at 1 of 4 hospitals within a single health system between January 2013 and September 2015. The detection of an SSI during a postoperative hospitalization was the outcome of analysis. Any SSI detected by one (or more) of these systems was analyzed by 2 reviewers to determine the presence of discrete elements of documentation constituting evidence of SSI. Concordance between the 3 systems (NHSN, NSQIP, and administrative data) was analyzed using Cohen's kappa. RESULTS: After application of appropriate exclusion criteria, a cohort of 9447 inpatient operations was analyzed. In total, 130 SSIs were detected by 1 or more of the 3 systems, with reported SSI rates of 0.5% (NHSN), 0.7% (administrative data), and 1.0% (NSQIP). Of these 130 SSIs, only 17 SSIs were reported by all 3 systems. The concordance between these 3 systems was moderate (kappa values NSQIP-NHSN = 0.50 [0.40-0.60], administrative-NHSN = 0.36 [0.24-0.47], and administrative-NSQIP = 0.47 [0.38-0.57]). Chart review found that reasons for discordance were related to issues of different criteria as well as inaccuracies. CONCLUSION: There is significant discordance in the determination of SSIs reported by the NHSN, NSQIP, and administrative data. The differences and limitations of each of these systems have to be recognized, especially when using these data for quality reports and pay for performance.

Reducing catheter-associated urinary tract infections in the ICU.

PURPOSE OF REVIEW: Patients in the ICU are at higher risk for catheter-associated urinary tract infection (CAUTI) due to more frequent use of catheters and lower threshold for obtaining urine cultures. This review provides a summary of CAUTI reduction strategies that are specific to the intensive care setting. RECENT FINDINGS: The surveillance definition for CAUTI is imprecise and measures catheter-associated bacteriuria rather than true infection. Alternatives have been proposed, but CAUTI rates measured by this definition are currently required to be reported to the Centers for Medicare and Medicaid Services and high CAUTI rates can result in financial penalties. Although CAUTI may not directly result in significant patient harm, it has several indirect patient safety implications and CAUTI reduction has several benefits. Various bundles have been successful at reducing CAUTI both in individual institutions and on larger scales such as healthcare networks and entire states. SUMMARY: CAUTI reduction is possible in the ICU through a combination of reduced catheter usage, improved catheter care and stewardship of urine cultures.

Infections in Neurocritical Care.

Neurointensive care (NICU) patients experience complex infectious disease challenges. Central nervous system (CNS) infections are difficult to diagnose and treat, and post-neurosurgical patients are vulnerable to a unique set of healthcare-acquired infections (HAI) in addition to those typical of critically ill patients. The purpose of this review is to summarize the approach to suspected infection in the NICU and discuss management of several infectious syndromes in the NICU setting.

Preoperative risk prediction of surgical site infection requiring hospitalization or reoperation in patients undergoing vascular surgery.

OBJECTIVE: The objective of this study was to develop a surgical site infection (SSI) prediction score for risk assessment before elective vascular surgery. METHODS: We conducted a nested case-control study among patients who underwent elective vascular (abdominal aortic and peripheral arterial) surgery from January 1, 2003, to December 31, 2007, at Mayo Clinic (Rochester, Minn) an academic tertiary surgical center. Cases were patients with SSI requiring hospitalization; controls (one or two per case) were matched on type of procedure and date of surgery. Clinical data were collected by chart review. A risk score based on preoperative variables was developed using multivariable logistic regression and bootstrap resampling. The C statistic, equivalent to the area under the receiver operating characteristic curve, was used to assess discrimination. Calibration was assessed by plotting percentile risk groups of model-predicted values against observed proportions of subjects with SSI. RESULTS: Eighty-four cases were compared with 160 controls. Preoperative variables independently associated with SSI risk were critical limb ischemia, previous SSI, prior revascularization procedure, and chronic obstructive pulmonary disease. A prediction model containing these variables was developed (model and risk score C statistic of 0.737 and 0.727, respectively). The calibration curve did not appear to deviate appreciably from the 45-degree line of identity. CONCLUSIONS: We developed an SSI risk score based on noninvasive preoperative variables with acceptable discrimination and calibration. This tool needs prospective and external validation.

Mayo Clinic Reduces Catheter-Associated Urinary Tract Infections Through a Bundled 6-C Approach.

The primary CAUTI reduction strategies of ensuring aseptic technique during catheter placement and reducing urinary catheter utilization were already in place at our institution. A multidisciplinary team approach, which entailed the use of QI methodology and engagement of frontline staff, resulted in the identification of additional strategies to reduce CAUTI. By implementing these strategies, we successfully reduced CAUTIs and have sustained this reduction through March 2016. The tools created during this project can be easily adapted for use at other institutions.

From pandemic to endemic: Divergence of COVID-19 positive-tests and hospitalization numbers from SARS-CoV-2 RNA levels in wastewater of Rochester, Minnesota.

Traditionally, public health surveillance relied on individual-level data but recently wastewater-based epidemiology (WBE) for the detection of infectious diseases including COVID-19 became a valuable tool in the public health arsenal. Here, we use WBE to follow the course of the COVID-19 pandemic in Rochester, Minnesota (population 121,395 at the 2020 census), from February 2021 to December 2022. We monitored the impact of SARS-CoV-2 infections on public health by comparing three sets of data: quantitative measurements of viral RNA in wastewater as an unbiased reporter of virus level in the community, positive results of viral RNA or antigen tests from nasal swabs reflecting community reporting, and hospitalization data. From February 2021 to August 2022 viral RNA levels in wastewater were closely correlated with the oscillating course of COVID-19 case and hospitalization numbers. However, from September 2022 cases remained low and hospitalization numbers dropped, whereas viral RNA levels in wastewater continued to oscillate. The low reported cases may reflect virulence reduction combined with abated inclination to report, and the divergence of virus levels in wastewater from reported cases may reflect COVID-19 shifting from pandemic to endemic. WBE, which also detects asymptomatic infections, can provide an early warning of impending cases, and offers crucial insights during pandemic waves and in the transition to the endemic phase.

Impact of a change in universal gloving protocol on rates of central line-related bloodstream infection, Clostridioides difficile, and vancomycin-resistant Enterococcus.

In this retrospective cohort of adult hematology-oncology and transplant patients, discontinuation of universal gloving did not result in significant changes in rates of central line-associated bloodstream infection, Clostridioides difficile infection, or vancomycin-resistant Enterococcus colonization. Active surveillance and subsequent isolation may be a viable alternative strategy to universal precautions.

Hybrid Immunity Provides Protective Advantage Over Vaccination or Prior Remote Coronavirus Disease 2019 Alone.

Background: The protective efficacy of prior coronavirus disease 2019 (COVID-19) with or without vaccination remains unknown. This study sought to understand if 2 or more messenger RNA (mRNA) vaccine doses provide additional protection in patients with prior infection, or if infection alone provides comparable protection. Methods: We conducted a retrospective cohort study of the risk of COVID-19 from 16 December 2020 through 15 March 2022, among vaccinated and unvaccinated patients of all ages with and without prior infection. A Simon-Makuch hazard plot illustrated the incidence of COVID-19 between groups. Multivariable Cox proportional hazards regression was used to examine the association of demographics, prior infection, and vaccination status with new infection. Results: Among 101 941 individuals with at least 1 COVID-19 polymerase chain reaction test prior to 15 March 2022, 72 361 (71.0%) received mRNA vaccination and 5957 (5.8%) were previously infected. The cumulative incidence of COVID-19 was substantially higher throughout the study period for those previously uninfected and unvaccinated, and lowest for those previously infected and vaccinated. After accounting for age, sex, and the interaction between vaccination and prior infection, a reduction in reinfection risk was noted during the Omicron and pre-Omicron phases of 26% (95% confidence interval [CI], 8%-41%; P = .0065) to 36% (95% CI, 10%-54%; P = .0108), respectively, among previously infected and vaccinated individuals, compared to previously infected subjects without vaccination. Conclusions: Vaccination was associated with lower risk of COVID-19, including in those with prior infection. Vaccination should be encouraged for all including those with prior infection, especially as new variants emerge and variant-specific booster vaccines become available.

Comparing Complication Rates of Midline Catheter vs Peripherally Inserted Central Catheter. A Systematic Review and Meta-analysis.

Background: Peripherally inserted central catheters (PICCs) and midlines are commonly used devices for reliable vascular access. Infection and thrombosis are the main adverse effects of these catheters. We aimed to evaluate the relative risk of complications from midlines and PICCs. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies. The primary outcomes were catheter-related bloodstream infection (CRBSI) and thrombosis. Secondary outcomes evaluated included mortality, failure to complete therapy, catheter occlusion, phlebitis, and catheter fracture. The certainty of evidence was assessed using the GRADE approach. Results: Of 8368 citations identified, 20 studies met the eligibility criteria, including 1 RCT and 19 observational studies. Midline use was associated with fewer patients with CRBSI compared with PICCs (odds ratio [OR], 0.24; 95% CI, 0.15-0.38). This association was not observed when we evaluated risk per catheter. No significant association was found between catheters when evaluating risk of localized thrombosis and pulmonary embolism. A subgroup analysis based on location of thrombosis showed higher rates of superficial venous thrombosis in patients using midlines (OR, 2.30; 95% CI, 1.48-3.57). We did not identify any significant difference between midlines and PICCs for the secondary outcomes. Conclusions: Our findings suggest that patients who use midlines might experience fewer CRBSIs than those who use PICCs. However, the use of midline catheters was associated with greater risk of superficial vein thrombosis. These findings can help guide future cost-benefit analyses and direct comparative RCTs to further characterize the efficacy and risks of PICCs vs midline catheters.

Incidence of Respiratory Syncytial Virus Infection in Older Adults Before and During the COVID-19 Pandemic.

Importance: Little is known about the burden and outcomes of respiratory syncytial virus (RSV)-positive acute respiratory infection (ARI) in community-dwelling older adults. Objective: To assess the incidence of RSV-positive ARI before and during the COVID-19 pandemic, and to assess outcomes for RSV-positive ARI in older adults. Design, Setting, and Participants: This was a community-based cohort study of adults residing in southeast Minnesota that followed up with 2325 adults aged 50 years or older for 2 RSV seasons (2019-2021) to assess the incidence of RSV-positive ARI. The study assessed outcomes at 2 to 4 weeks, 6 to 7 months, and 12 to 13 months after RSV-positive ARI. Exposure: RSV-positive and -negative ARI. Main Outcomes and Measures: RSV status was the main study outcome. Incidence and attack rates of RSV-positive ARI were calculated during each RSV season, including before (October 2019 to April 2020) and during (October 2020 to April 2021) COVID-19 pandemic, and further calculated during non-RSV season (May to September 2021) for assessing impact of COVID-19. The self-reported quality of life (QOL) by Short-Form Health Survey-36 (SF-36) and physical functional measures (eg, 6-minute walk and spirometry) at each time point was assessed. Results: In this study of 2325 participants, the median (range) age of study participants was 67 (50-98) years, 1380 (59%) were female, and 2240 (96%) were non-Hispanic White individuals. The prepandemic incidence rate of RSV-positive ARI was 48.6 (95% CI, 36.9-62.9) per 1000 person-years with a 2.50% (95% CI, 1.90%-3.21%) attack rate. No RSV-positive ARI case was identified during the COVID-19 pandemic RSV season. Incidence of 10.2 (95% CI, 4.1-21.1) per 1000 person-years and attack rate of 0.42%; (95% CI, 0.17%-0.86%) were observed during the summer of 2021. Based on prepandemic RSV season results, participants with RSV-positive ARI (vs matched RSV-negative ARI) reported significantly lower QOL adjusted mean difference (limitations due to physical health, -16.7 [95% CI, -31.8 to -1.8]; fatigue, -8.4 [95% CI, -14.3 to -2.4]; and difficulty in social functioning, -11.9 [95% CI, -19.8 to -4.0] within 2 to 4 weeks after RSV-positive ARI [ie, short-term outcome]). Compared with participants with RSV-negative ARI, those with RSV-positive ARI also had lower QOL (fatigue: -4.0 [95% CI, -8.5 to -1.3]; difficulty in social functioning, -5.8 [95% CI, -10.3 to -1.3]; and limitation due to emotional problem, -7.0 [95% CI, -12.7 to -1.3] at 6 to 7 months after RSV-positive ARI [intermediate-term outcome]; fatigue, -4.4 [95% CI, -7.3 to -1.5]; difficulty in social functioning, -5.2 [95% CI, -8.7 to -1.7] and limitation due to emotional problem, -5.7 [95% CI, -10.7 to -0.6] at 12-13 months after RSV-positive ARI [ie, long-term outcomes]) independent of age, sex, race and/or ethnicity, socioeconomic status, and high-risk comorbidities. Conclusions and Relevance: In this cohort study, the burden of RSV-positive ARI in older adults during the pre-COVID-19 period was substantial. After a reduction of RSV-positive ARI incidence from October 2020 to April 2021, RSV-positive ARI re-emerged during the summer of 2021. RSV-positive ARI was associated with significant long-term lower QOL beyond the short-term lower QOL in older adults.

Monkeypox 2022: Gearing Up for Another Potential Public Health Crisis.

Monkeypox virus, a member of the Orthopoxvirus genus, was first identified as the etiology of monkeypox in 1970 in the Democratic Republic of Congo and remains endemic in regions of Central and West Africa. Following the most recent outbreak of monkeypox in multiple countries throughout Europe and North America, the infection has been declared a public health emergency by the Centers for Disease Control and Prevention. Within this report, we aim to provide clinicians with a focused overview of the epidemiology, clinical manifestation, diagnosis, and approaches to treat and prevent monkeypox infection amidst the global outbreak.

Clinical Characteristics and Outcomes of Patients With SARS-CoV-2 Reinfection.

Objective: To examine the clinical characteristics, risk of hospitalization, and mortality of patients diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection. Patients and Methods: We retrospectively reviewed all patients with SARS-CoV-2 reinfection at all Mayo Clinic sites between May 23, 2020, and June 30, 2021 (the period before the emergence of the Delta variant in the United States). The reinfection was defined as a positive SARS-CoV-2 test more than or equal to 90 days after initial infection or 45-89 days after with symptomatic second episode. Vaccination status was classified as fully vaccinated, first dose, and unvaccinated. Comparative analysis of baseline characteristics and comorbidities was performed by hospitalization and vaccination status. The survival analysis of the hospitalized patients was performed using Cox proportional hazard regression. Results: Among the 554 patients reinfected with SARS-CoV-2, 59 (10.6%) were pediatric, and 495 (89.4%) were adults. The median age was 13.9 years (interquartile range, 8.5-16.5 years) for the pediatric and 50.2 years (interquartile range, 28.4-65.6 years) for the adult population. Among the adult patients, the majority were unvaccinated (83.4%, n=413), and the duration to reinfection from initial infection was the longest in the fully vaccinated group (P<.001). Forty-two (75%) out of 56 patients were seropositive within 7 days of reinfection. In hospitalized adult patients, Charlson Comorbidity Index was an independent risk factor for mortality (adjusted hazard ratio, 0.35; 95% CI, 0.19-0.51). Conclusion: In this study, most adult patients with SARS-CoV-2 reinfection were unvaccinated. Furthermore, the duration to reinfection was longest in fully vaccinated individuals. Seropositivity was common among adult patients.

Metagenomic shotgun sequencing of blood to identify bacteria and viruses in leukemic febrile neutropenia.

Despite diagnostic advances in microbiology, the etiology of neutropenic fever remains elusive in most cases. In this study, we evaluated the utility of a metagenomic shotgun sequencing based assay for detection of bacteria and viruses in blood samples of patients with febrile neutropenia. We prospectively enrolled 20 acute leukemia patients and obtained blood from these patients at three time points: 1) anytime from onset of neutropenia until before development of neutropenic fever, 2) within 24 hours of onset of neutropenic fever, 3) 5-7 days after onset of neutropenic fever. Blood samples underwent sample preparation, sequencing and analysis using the iDTECT® Dx Blood v1® platform (PathoQuest, Paris, France). Clinically relevant viruses or bacteria were detected in three cases each by metagenomic shotgun sequencing and blood cultures, albeit with no concordance between the two. Further optimization of sample preparation methods and sequencing platforms is needed before widespread adoption of this technology into clinical practice.