Impact of metagenomic next-generation sequencing on clinical decision-making at an academic medical center, a retrospective study, Iowa, 2020-2022.

We assessed the impact of metagenomic next-generation sequencing (mNGS) on patient care using previously established criteria. Among 37 patients receiving mNGS testing, 16% showed results that had a positive clinical impact. While mNGS results may offer valuable supplementary information, results should be interpreted within the broader clinical context and evaluation.

Helicobacter pylori Exposure in Nausea and Vomiting of Pregnancy Increases Risk of Preterm Delivery.

Background: Hyperemesis gravidarum (HG), a severe form of nausea and vomiting in pregnancy (NVP), is a leading indication for hospitalization in the first trimester. NVP and HG are associated with Helicobacter pylori (HP) infection in non-United States cohorts. How HP exposure and NVP interact to affect metabolic disturbance and pregnancy outcomes is not known. Materials and Methods: We designed a retrospective cohort study relating HP and NVP to serum electrolyte laboratory results, preterm delivery, and infant birth weight. Single academic institution discovery and independent multi-institutional validation cohorts included pregnant subjects with an HP test result. Associations of HP, NVP, and pregnancy outcomes were assessed with odds ratio calculations, Student's t-tests, and multivariate logistic regression. Results: Among subjects with positive HP test results, the prevalence of hyperemesis gravidarum (HG) was 0.025 (66 of 2671) and NVP was 0.27 (710 of 2671). Subjects with negative HP had prevalence of HG 0.015 (165 of 10,960) and NVP 0.22 (2392 of 10,960). History of HP exposure increased risk of NVP, including HG (odds ratio 1.3, 95% CI 1.1-1.4). Patients with HP exposure had lower serum potassium (mean difference 0.1 mEq/L) and bicarbonate (mean difference 0.3 mEq/L) during pregnancy than HP-negative patients (p < 0.01). Serum potassium was lowest in subjects with both NVP and HP exposure (mean 3.5 mEq/L [3.4-3.6], p < 0.0001). HP exposure alone carried increased risk for preterm delivery (OR 1.3 [1.1-1.4]). NVP alone increased risk of preterm delivery (OR 2.8 [2.5-3.1]) including second trimester delivery (OR 2.2 [1.7-2.8]). In multivariate analysis, HP exposure in the setting of NVP further increased risk of preterm delivery (adjusted OR 1.4 [1.0-1.9], p = 0.03). Conclusions: H. pylori exposure and diagnosis of NVP are individually associated with metabolic disturbances and adverse pregnancy outcomes such as preterm labor and delivery, and their combination further increases risk in US populations.

Antibiotic Recommendations for Treatment of Canine Stromal Corneal Ulcers.

The aim of the study was to identify the aerobic bacterial isolates and determine corresponding antibiotic susceptibility profiles in vitro in canine clinical specimens with stromal corneal ulcers, with the goal of providing recommendations for first-line treatment with antibiotics. A total of 198 canine corneal stromal ulcer samples were studied between 2018 and 2021. A corneal swab was collected and cultured under aerobic conditions. Bacterial organisms were identified at the species level by MALDI-TOF mass spectrometry. Antibiotic susceptibility testing for commonly used topical and systemic antibiotics was performed by disk diffusion. Bacterial growth was obtained from 80% of samples. A variety of bacterial species were identified wherein the most common specimens were represented by Staphylococcus pseudintermedius (22%), Staphylococcus epidermidis (12%), Staphylococcus capitis (11%), and Pseudomonas aeruginosa (10%). Based on the overall antibiotic susceptibility data, neopolybac alone (96%) or a combination of neopolybac with either ofloxacin or amikacin (each 99%) showed the best coverage for commonly isolated bacterial organisms from canine corneal stromal ulcers. Results of this study support the use of the combined antibiotics as the first-line response for the treatment of canine corneal stromal ulcers. A statically significant increase in acquired bacterial resistance was detected during the longitudinal data observation.

Hip periprosthetic joint infection due to Coxiella burnetii in an adult male.

Coxiella burnetii is an obligate intracellular Gram-negative bacterium. "Query fever" (Q fever) first described in 1939 is a disease caused by Coxiella burnetii. This bacterium infects animals including goats, sheep, and cattle, and has been recognized as a pathogen causing acute illness in humans. A patient living on a farm with a history of a right total hip arthroplasty presented with right hip pain. Arthrocentesis revealed a total nucleated count of 4288 (93% neutrophils), however his synovial fluid culture remained negative. His Q fever phase I IgG and phase II IgG were elevated at 1:4096 and 1:2048, respectively. He underwent incision and drainage with exchange of the femoral head and acetabular component, with retention of the femoral stem. PCR of tissue samples returned positive for Coxiella burnettii. He was diagnosed with a persistent localized prosthetic joint infection (PJI) of the right hip. Coxiella burnetii PJI is a rare but increasingly recognized form of persistent localized Q fever infection. Q fever should be considered in the differential diagnosis of culture-negative PJI, especially among patients with exposure to sheep, goats, or cattle. Initial screening for Coxiella burnetii includes serology, but tissue PCR and immunohistochemical staining may be obtained to confirm joint infection.

Coronavirus disease 2019 (COVID-19) among nonphysician healthcare personnel by work location at a tertiary-care center, Iowa, 2020-2021.

We describe COVID-19 cases among nonphysician healthcare personnel (HCP) by work location. The proportion of HCP with coronavirus disease 2019 (COVID-19) was highest in the emergency department and lowest among those working remotely. COVID-19 and non-COVID-19 units had similar proportions of HCP with COVID-19 (13%). Cases decreased across all work locations following COVID-19 vaccination.

Blood culture practices in patients with a central line at an academic medical center-Iowa, 2020.

We analyzed blood-culture practices to characterize the utilization of the Infectious Diseases Society of America (IDSA) recommendations related to catheter-related bloodstream infection (CRBSI) blood cultures. Most patients with a central line had only peripheral blood cultures. Increasing the utilization of CRBSI guidelines may improve clinical care, but may also affect other quality metrics.

Impact on time to active antimicrobial therapy with 24-hour pharmacist review of Accelerate Pheno BC Kit results.

The Accelerate Pheno platform provides rapid identification and susceptibility data. We demonstrate successful incorporation of 24-hour pharmacist review of Accelerate Pheno results that reduced the number of patients going >3 hours from result without an order for active antimicrobial therapy from 29 (2.8%) of 1,043 to 9 (0.85%) of 1,053 (P < .001).

Association between job role and coronavirus disease 2019 (COVID-19) among healthcare personnel, Iowa, 2021.

We describe the association between job roles and coronavirus disease 2019 (COVID-19) among healthcare personnel. A wide range of hazard ratios were observed across job roles. Medical assistants had higher hazard ratios than nurses, while attending physicians, food service workers, laboratory technicians, pharmacists, residents and fellows, and temporary workers had lower hazard ratios.

Pelvic and central nervous system tuberculosis complicated by a paradoxical response manifesting as a spinal tuberculoma: a case report.

BACKGROUND: The post-partum period is a risk factor for tuberculosis (TB), possibly including the period after miscarriage as illustrated here. This case demonstrates how non-specific symptoms can hide widely disseminated TB. CASE PRESENTATION: A healthy 26-year-old female with a history of recent miscarriage presented to the emergency department with non-specific symptoms of headache, abdominal pain, and sub-acute fevers. She had immigrated to the United States from the Marshall Islands 9 years prior. Two months prior to presentation she had a miscarriage at 18 weeks of pregnancy. On admission, transvaginal ultrasound revealed retained products of conception and abdominal computed tomography revealed findings consistent with tubo-ovarian abscesses and peritonitis. The obstetrics and gynecology service performed dilation and curettage (D&C) to remove retained products of conception. Acid-fast bacilli cultures from cerebrospinal fluid as well as specimens from D&C and intra-abdominal abscesses subsequently all grew TB. She was diagnosed with TB meningitis, peritonitis, endometritis, and tubo-ovarian abscesses. Her treatment course was complicated by a paradoxical response resulting in a spinal tuberculoma causing lower extremity weakness. The tuberculoma was treated with surgical decompression as well as continuation of treatment with anti-tubercular chemotherapy and steroids. CONCLUSION: Disseminated and extrapulmonary TB can present with non-specific symptoms. Recognition of risk factors for TB is critical for prompt diagnostic evaluation and treatment of this deadly disease. A paradoxical reaction needs to be taken into consideration when any new neurological symptoms occur during TB treatment.

Real-World Impact of the Accelerate PhenoTest BC Kit on Patients With Bloodstream Infections in the Improving Outcomes and Antimicrobial Stewardship Study: A Quasiexperimental Multicenter Study.

BACKGROUND: Bloodstream infections (BSIs) are a leading cause of morbidity and mortality. The Improving Outcomes and Antimicrobial Stewardship study seeks to evaluate the impact of the Accelerate PhenoTest BC Kit (AXDX) on antimicrobial use and clinical outcomes in BSIs. METHODS: This multicenter, quasiexperimental study compared clinical and antimicrobial stewardship metrics, prior to and after implementation of AXDX, to evaluate the impact this technology has on patients with BSIs. Laboratory and clinical data from hospitalized patients with BSIs (excluding contaminants) were compared between 2 arms, 1 that underwent testing on AXDX (post-AXDX) and 1 that underwent alternative organism identification and susceptibility testing (pre-AXDX). The primary outcomes were time to optimal therapy (TTOT) and 30-day mortality. RESULTS: A total of 854 patients with BSIs (435 pre-AXDX, 419 post-AXDX) were included. Median TTOT was 17.2 hours shorter in the post-AXDX arm (23.7 hours) compared with the pre-AXDX arm (40.9 hours; P<.0001). Compared with pre-AXDX, median time to first antimicrobial modification (24.2 vs 13.9 hours; P<.0001) and first antimicrobial deescalation (36.0 vs 27.2 hours; P=.0004) were shorter in the post-AXDX arm. Mortality (8.7% pre-AXDX vs 6.0% post-AXDX), length of stay (7.0 pre-AXDX vs 6.5 days post-AXDX), and adverse drug events were not significantly different between arms. Length of stay was shorter in the post-AXDX arm (5.4 vs 6.4 days; P=.03) among patients with gram-negative bacteremia. CONCLUSIONS: For BSIs, use of AXDX was associated with significant decreases in TTOT, first antimicrobial modification, and time to antimicrobial deescalation.

Coronavirus disease 2019 (COVID-19) incidence after exposures in shared patient rooms in a tertiary-care center in Iowa, July 2020-May 2021.

The incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure in shared patient rooms was low at our institution: 1.8 per 1,000 shared-room patient days. However, the secondary attack rate (21.6%) was comparable to that reported in household exposures. Lengthier exposures were associated with SARS-CoV-2 conversion. Hospitals should implement measures to decrease shared-room exposures.

Coronavirus disease 2019 (COVID-19) admission screening and assessment of infectiousness at an academic medical center in Iowa, 2020.

OBJECTIVE: Patients admitted to the hospital may unknowingly carry severe acute respiratory coronavirus virus 2 (SARS-CoV-2), and hospitals have implemented SARS-CoV-2 admission screening. However, because SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) assays may remain positive for months after infection, positive results may represent active or past infection. We determined the prevalence and infectiousness of patients who were admitted for reasons unrelated to COVID-19 but tested positive for SARS-CoV-2 on admission screening. METHODS: We conducted an observational study at the University of Iowa Hospitals & Clinics from July 7 to October 25, 2020. All patients admitted without suspicion of COVID-19 were included, and medical records of those with a positive admission screening test were reviewed. Infectiousness was determined using patient history, PCR cycle threshold (Ct) value, and serology. RESULTS: In total, 5,913 patients were screened and admitted for reasons unrelated to COVID-19. Of these, 101 had positive admission RT-PCR results; 36 of these patients were excluded because they had respiratory signs/symptoms on admission on chart review. Also, 65 patients (1.1%) did not have respiratory symptoms. Finally, 55 patients had Ct values available and were included in this analysis. The median age of the final cohort was 56 years and 51% were male. Our assessment revealed that 23 patients (42%) were likely infectious. The median duration of in-hospital isolation was 5 days for those likely infectious and 2 days for those deemed noninfectious. CONCLUSIONS: SARS-CoV-2 was infrequent among patients admitted for reasons unrelated to COVID-19. An assessment of the likelihood of infectiousness using clinical history, RT-PCR Ct values, and serology may help in making the determination to discontinue isolation and conserve resources.

Does Antimicrobial Prophylaxis in Patients with Specific Comorbidities Reduce the Risk of Infection after Simple Cystourethroscopy?

INTRODUCTION: We evaluated whether antimicrobial prophylaxis decreases rates of post-procedural infection (urinary tract infection or sepsis) after simple cystourethroscopy for patients with specific comorbidities. METHODS: We utilized Epic® reporting software to conduct a retrospective review of all simple cystourethroscopy procedures performed by providers in our urology department from August 4, 2014 to December 31, 2019. Data collected included patient comorbidities, antimicrobial prophylaxis administration and incidence of post-procedural infection. Mixed effects logistic regression models were utilized to estimate the effects of antimicrobial prophylaxis and patient comorbidities on the odds of post-procedural infection. RESULTS: Antimicrobial prophylaxis was given for 7,001 (78%) of 8,997 simple cystourethroscopy procedures. Overall, 83 (0.9%) post-procedural infections occurred. The estimated odds of post-procedural infection were lower when antimicrobial prophylaxis was given compared to those without prophylaxis (OR 0.51, 95% CI 0.35-0.76; p <0.01). The number needed to treat with antimicrobial prophylaxis to prevent 1 post-procedural infection was 100. None of the comorbidities evaluated showed significant benefit from antimicrobial prophylaxis for prevention of post-procedural infection. CONCLUSIONS: Overall, the rate of post-procedural infection after simple office cystourethroscopy was low (0.9%). Though antimicrobial prophylaxis decreased the odds of post-procedural infection overall, the number needed to treat was high (100). Antibiotic prophylaxis was not shown to significantly reduce the risk of post-procedural infection in any of the comorbidity groups we evaluated. These findings suggest that the comorbidities evaluated in this study should not be used to recommend antibiotic prophylaxis for simple cystourethroscopy.

Meningitis Caused by the Live Varicella Vaccine Virus: Metagenomic Next Generation Sequencing, Immunology Exome Sequencing and Cytokine Multiplex Profiling.

Varicella vaccine meningitis is an uncommon delayed adverse event of vaccination. Varicella vaccine meningitis has been diagnosed in 12 children, of whom 3 were immunocompromised. We now report two additional cases of vaccine meningitis in twice-immunized immunocompetent children and we perform further testing on a prior third case. We used three methods to diagnose or investigate cases of varicella vaccine meningitis, none of which have been used previously on this disease. These include metagenomic next-generation sequencing and cytokine multiplex profiling of cerebrospinal fluid and immunology exome analysis of white blood cells. In one new case, the diagnosis was confirmed by metagenomic next-generation sequencing of cerebrospinal fluid. Both varicella vaccine virus and human herpesvirus 7 DNA were detected. We performed cytokine multiplex profiling on the cerebrospinal fluid of two cases and found ten elevated biomarkers: interferon gamma, interleukins IL-1RA, IL-6, IL-8, IL-10, IL-17F, chemokines CXCL-9, CXCL-10, CCL-2, and G-CSF. In a second new case, we performed immunology exome sequencing on a panel of 356 genes, but no errors were found. After a review of all 14 cases, we concluded that (i) there is no common explanation for this adverse event, but (ii) ingestion of an oral corticosteroid burst 3-4 weeks before onset of vaccine meningitis may be a risk factor in some cases.

Asymptomatic Pre-Operative COVID-19 Screening for Essential and Elective Surgeries: Early Results of Universal Screening at a Midwestern Academic Medical Center.

BACKGROUND: During the novel Coronavirus 2019 (COVID-19) worldwide pandemic, viral testing has largely focused on patients presenting with fever and respiratory symptoms. Although Centers for Disease Control has reported 1,551,095 cases in the United States as of May 21, 2020, asymptomatic infection rates remain unknown within the U.S., especially in geographically disparate regions. METHODS: On April 7, 2020 our hospital established universal SARS-CoV-2 screening using RT-PCR RNA detection from nasopharyngeal swabs from asymptomatic patients prior to essential and elective surgeries. This study included 1,997 asymptomatic patients undergoing surgical procedures and 1,797 admitted for medical management at a Midwestern academic hospital between April 7, 2020 and May 21, 2020. RESULTS: As of May 21, asymptomatic testing for SARS-CoV-2 infection had been completed for 1,997 surgical patients and 1,797 non-surgical patients. Initial testing was positive in 26 patients, with an additional four positive tests occurring during repeat testing when greater than 48 hours had elapsed since initial testing. Overall asymptomatic infection rate was 0.79%. Asymptomatic infection rate was significantly lower in surgical patients (0.35% vs. 1.28%, p=0.001). Surgical patients tended to be older than non-surgical patients, although this was not statistically significant (51, IQR 27-65 vsx 46, IQR 28-64, p=0.057). Orthopedic surgery patients were significantly younger than those from other surgical services (42 vs. 53 yrs, p<0.001), however orthopedic and non-orthopedic surgical patients had similar asymptomatic infection rates (0.70% vs. 0.25%, p=0.173). CONCLUSION: Among asymptomatic patients tested at a Midwestern academic medical center, 0.79% were infected with SARS-CoV-2 virus. These findings will help guide screening protocols at medical centers while providing essential and elective procedures during the COVID-19 pandemic. While the asymptomatic infection rate was low, this data substantiates the threat of asymptomatic infections and potential for community viral spread. These results may not be generalizable to large urban population centers or areas with high concentrations of COVID-19, each region must use available data to evaluate the risk-benefit ratio of universal testing vs universal contact precautions.Level of Evidence: IV.

MRSA strains with distinct accessory genes predominate at different ages in cystic fibrosis.

RATIONALE: Methicillin resistant Staphylococcus aureus (MRSA) is prevalent and consequential in cystic fibrosis (CF). Whole genome sequencing (WGS) could reveal genomic differences in MRSA associated with poorer outcomes or detect MRSA transmission. OBJECTIVES: To identify MRSA genes associated with low lung function and potential MRSA transmission in CF. METHODS: We collected 97 MRSA isolates from 74 individuals with CF from 2017 and performed short-read WGS. We determined sequence type (ST) and the phylogenetic relationship between isolates. We aligned accessory genes from 25 reference genomes to genome assemblies, classified isolates by accessory gene content, and correlated the accessory genome to clinical outcomes. RESULTS: The most prevalent ST were ST5 (N = 55), ST8 (N = 15), and ST105 (N = 14). Closely related MRSA strains were shared by family members with CF, but rarely between unrelated individuals. Three clusters of MRSA were identified by accessory genome content. Cluster A, including ST5 and ST105, was highly prevalent at all ages. Cluster B, including ST8, was more limited to younger patients. Cluster C included 6 distantly related strains. Patients 20 years old and younger infected with Cluster A had lower forced expiratory volume in the first second (FEV1 ) and higher sputum biomass compared to similar-aged patients with Cluster B. CONCLUSIONS: In this CF cohort, we identified MRSA subtypes that predominate at different ages and differ by accessory gene content. The most prevalent cluster of MRSA, including ST5 and ST105, was associated with lower FEV1 . ST8 MRSA was more common in younger patients and thus has the potential to rise in prevalence as these patients age.