Trimethoprim-sulfamethoxazole dosing and outcomes of pulmonary nocardiosis.

BACKGROUND: Nocardia often causes pulmonary infection among those with chronic pulmonary disease or immunocompromising conditions. Trimethoprim-sulfamethoxazole (TMP-SMX) is recommended as first-line treatment, though little data exists regarding outcomes of different dosing regimens. METHODS: We performed a multicenter retrospective cohort study of adult patients with non-disseminated pulmonary nocardiosis initially treated with TMP-SMX monotherapy. Patients' initial TMP-SMX dosing was categorized as high- (> 10 mg/kg/day), intermediate- (5-10 mg/kg/day) or low-dose (< 5 mg/kg/day). Outcomes included one-year mortality, post-treatment recurrence, and dose adjustment or early discontinuation of TMP-SMX. SMX serum concentrations and their effect on management were also assessed. Inverse probability of treatment weighting was applied to Cox regression analyses. RESULTS: Ninety-one patients were included with 24 (26.4%), 37 (40.7%), and 30 (33.0%) treated with high-, intermediate-, and low-dose TMP-SMX, respectively. Patients who initially received low-dose (HR 0.07, 95% CI 0.01-0.68) and intermediate-dose TMP-SMX (HR 0.27, 95% CI 0.07-1.04) had lower risk of one-year mortality than the high-dose group. Risk of recurrence was similar between groups. Nineteen patients had peak SMX serum concentrations measured which resulted in 7 (36.8%) dose changes and was not associated with one-year mortality or recurrence. However, 66.7% of the high-dose group required TMP-SMX dose adjustment/discontinuation compared to 24.3% of the intermediate-dose and 26.7% of the low-dose groups (p = 0.001). CONCLUSIONS: Low- and intermediate-dose TMP-SMX for non-disseminated pulmonary nocardiosis were not associated with poor outcomes compared to high-dose therapy, which had a higher rate of dose adjustment/early discontinuation. Historically used high-dose TMP-SMX may not be necessary for management of isolated pulmonary nocardiosis.

Evaluation of germicidal ultraviolet-C disinfection in a real-world outpatient health care environment.

BACKGROUND: The coronavirus disease 2019 pandemic has highlighted the need for effective infection control in outpatient health care settings. Germicidal ultraviolet-C (GUV) light, known for inactivating microorganisms by damaging their deoxyribonucleic acid or ribonucleic acid, offers a potential solution. This study examines the efficacy of GUV air disinfection systems in real-world outpatient environments. METHODS: We deployed upper-room and far-UV GUV fixtures in 3 outpatient facilities, assessing their impact on bacterial loads through air and surface sampling and bioindicator tests. Occupancy was also monitored. RESULTS: While manual air and surface sampling did not show a significant difference in bacterial loads between control and Ultraviolet C-treated groups, bioindicator tests demonstrated a high level of spore inactivation (up to 99.7% for upper-room GUV and 96.26% for far-UV). Occupancy levels did not significantly influence these outcomes. DISCUSSION: The discrepancy between bioindicator efficacy and environmental sampling results suggests limitations in the latter's ability to accurately capture environmental bioburden. Bioindicators proved to be reliable for in-situ validation of Ultraviolet C surface disinfection. CONCLUSIONS: Bioindicators are effective for validating GUV surface disinfection efficacy in health care settings, though further research is needed to optimize environmental sampling methods for assessing GUV's impact on real-world bacterial loads.

Epidemiology, Timing, and Secondary Prophylaxis of Recurrent Nocardiosis.

Background: Nocardia tends to cause infection in immunocompromised patients or those with chronic pulmonary disease. Nocardia is known to recur, prompting the practice of secondary prophylaxis in patients perceived at high risk. However, few data exist regarding the epidemiology of recurrent nocardiosis or the effectiveness of secondary prophylaxis. Methods: We performed a multicenter, retrospective cohort study of adults diagnosed with nocardiosis from November 2011 to April 2022, including patients who completed primary treatment and had at least 30 days of posttreatment follow-up. Propensity score matching was used to analyze the effect of secondary prophylaxis on Nocardia recurrence. Results: Fifteen of 303 (5.0%) patients developed recurrent nocardiosis after primary treatment. Most recurrences were diagnosed either within 60 days (N = 6/15, 40.0%) or between 2 to 3 years (N = 4/15, 26.7%). Patients with primary disseminated infection tended to recur within 1 year, whereas later recurrences were often nondisseminated pulmonary infection. Seventy-eight (25.7%) patients were prescribed secondary prophylaxis, mostly trimethoprim-sulfamethoxazole (N = 67/78). After propensity-matching, secondary prophylaxis was not associated with reduced risk of recurrence (hazard ratio, 0.96; 95% confidence interval, .24-3.83), including in multiple subgroups. Eight (53.3%) patients with recurrent nocardiosis required hospitalization and no patients died from recurrent infection. Conclusions: Recurrent nocardiosis tends to occur either within months because of the same Nocardia species or after several years with a new species. Although we did not find evidence for the effectiveness of secondary prophylaxis, the confidence intervals were wide. However, outcomes of recurrent nocardiosis are generally favorable and may not justify long-term antibiotic prophylaxis for this indication alone.

Mortality After Nocardiosis: Risk Factors and Evaluation of Disseminated Infection.

Background: Nocardia primarily infects patients who are immunocompromised or those with chronic lung disease. Although disseminated infection is widely recognized as an important prognostic factor, studies have been mixed on its impact on outcomes of nocardiosis. Methods: We performed a retrospective cohort study of adults with culture-confirmed nocardiosis. Advanced infection was defined as disseminated infection, cavitary pulmonary infection, or pleural infection. The primary outcome was 1-year mortality, as analyzed by multivariable Cox regression. Results: Of 511 patients with culture growth of Nocardia, 374 (73.2%) who had clinical infection were included. The most common infection sites were pulmonary (82.6%), skin (17.9%), and central nervous system (14.2%). In total, 117 (31.3%) patients had advanced infection, including 74 (19.8%) with disseminated infection, 50 (13.4%) with cavitary infection, and 18 (4.8%) with pleural infection. Fifty-nine (15.8%) patients died within 1 year. In multivariable models, disseminated infection was not associated with mortality (hazard ratio, 1.16; 95% CI, .62-2.16; P = .650) while advanced infection was (hazard ratio, 2.48; 95% CI, 1.37-4.49; P = .003). N. farcinica, higher Charlson Comorbidity Index, and culture-confirmed pleural infection were also associated with mortality. Immunocompromised status and combination therapy were not associated with mortality. Conclusions: Advanced infection, rather than dissemination alone, predicted worse 1-year mortality after nocardiosis. N. farcinica was associated with mortality, even after adjusting for extent of infection. While patients who were immunocompromised had high rates of disseminated and advanced infection, immunocompromised status did not predict mortality after adjustment. Future studies should account for high-risk characteristics and specific infection sites rather than dissemination alone.

Candidemia in Patients With Cardiovascular Implantable Electronic Devices: Uncertainty in Management Based on Current International Guidelines.

Background: In contrast to bloodstream infection due to a variety of bacteria in patients with cardiovascular implantable electronic devices (CIED), there are limited data regarding candidemia and risk of CIED infection. Methods: All patients with candidemia and a CIED at Mayo Clinic Rochester between 2012 and 2019 were reviewed. Cardiovascular implantable electronic device infection was defined by (1) clinical signs of pocket site infection or (2) echocardiographic evidence of lead vegetations. Results: A total of 23 patients with candidemia had underlying CIED; 9 (39.1%) cases were community onset. None of the patients had pocket site infection. The duration between CIED placement and candidemia was prolonged (median 3.5 years; interquartile range, 2.0-6.5). Only 7 (30.4%) patients underwent transesophageal echocardiography and 2 of 7 (28.6%) had lead masses. Only the 2 patients with lead masses underwent CIED extraction, but device cultures were negative for Candida species. Two (33.3%) of 6 other patients who were managed as candidemia without device infection subsequently developed relapsing candidemia. Cardiovascular implantable electronic device removal was done in both patients and device cultures grew Candida species. Although 17.4% of patients were ultimately confirmed to have CIED infection, CIED infection status was undefined in 52.2%. Overall, 17 (73.9%) patients died within 90 days of diagnosis of candidemia. Conclusions: Although current international guidelines recommend CIED removal in patients with candidemia, the optimal management strategy remains undefined. This is problematic because candidemia alone is associated with increased morbidity and mortality as seen in this cohort. Moreover, inappropriate device removal or retention can both result in increased patient morbidity and mortality.

Outcomes of transplant recipients with pretransplant Nocardia colonization or infection.

BACKGROUND: Specific pretransplant infections have been associated with poor posttransplant outcomes. However, the impact of pretransplant Nocardia isolation has not been studied. METHODS: We performed a retrospective study from three centers in Arizona, Florida, and Minnesota of patients with Nocardia infection or colonization who subsequently underwent solid organ or hematopoietic stem cell transplantation from November 2011 through April 2022. Outcomes included posttransplant Nocardia infection and mortality. RESULTS: Nine patients with pretransplant Nocardia were included. Two patients were deemed colonized with Nocardia, and the remaining seven had nocardiosis. These patients underwent bilateral lung (N = 5), heart (N = 1), heart-kidney (N = 1), liver-kidney (N = 1), and allogeneic stem cell transplantation (N = 1) at a median of 283 (interquartile range [IQR] 152-283) days after Nocardia isolation. Two (22.2%) patients had disseminated infection, and two were receiving active Nocardia treatment at the time of transplantation. One Nocardia isolate was resistant to trimethoprim-sulfamethoxazole (TMP-SMX) and all patients received TMP-SMX prophylaxis posttransplant, often for extended durations. No patients developed posttransplant nocardiosis during a median follow-up of 1.96 (IQR 0.90-6.33) years. Two patients died during follow-up, both without evidence of nocardiosis. CONCLUSIONS: This study did not identify any episodes of posttransplant nocardiosis among nine patients with pretransplant Nocardia isolation. As patients with the most severe infections may have been denied transplantation, further studies with larger sample sizes are needed to better analyze any impact of pretransplant Nocardia on posttransplant outcomes. However, among patients who receive posttransplant TMP-SMX prophylaxis, these data suggest pretransplant Nocardia isolation may not impart a heightened risk of posttransplant nocardiosis.

Body temperature and infection in critically ill patients on continuous kidney replacement therapy.

PURPOSE: Continuous kidney replacement therapy (CKRT) is an increasingly common intervention for critically ill patients with kidney failure. Because CKRT affects body temperature, detecting infections in patients on CKRT is challenging. Understanding the relation between CKRT and body temperature may facilitate earlier detection of infection. METHODS: We retrospectively reviewed adult patients (≥ 18 years) admitted to the intensive care unit at Mayo Clinic in Rochester, Minnesota, from December 1, 2006, through November 31, 2015, who required CKRT. We summarized central body temperatures for these patients according to the presence or absence of infection. RESULTS: We identified 587 patients who underwent CKRT during the study period, of whom 365 had infections, and 222 did not have infections. We observed no statistically significant differences in minimum (P = .70), maximum (P = .22), or mean (P = .55) central body temperature for patients on CKRT with infection vs. those without infection. While not on CKRT (before CKRT initiation and after cessation), all three body temperature measurements were significantly higher in patients with infection than in those without infection (all P < .02). CONCLUSION: Body temperature is insufficient to indicate an infection in critically ill patients on CKRT. Clinicians should remain watchful for other signs, symptoms, and indications of infection in patients on CKRT because of expected high infection rates.

Comparison of Oral and Intravenous Definitive Antibiotic Therapy for Beta-Hemolytic Streptococcus Species Bloodstream Infections from Soft Tissue Sources: a Propensity Score-Matched Analysis.

Beta-hemolytic streptococci are common causes of bloodstream infection (BSI). There is emerging data regarding oral antibiotics for BSI but limited for beta-hemolytic streptococcal BSI. We conducted a retrospective study of adults with beta-hemolytic streptococcal BSI from a primary skin/soft tissue source from 2015 to 2020. Patients transitioned to oral antibiotics within 7 days of treatment initiation were compared to those who continued intravenous therapy, after propensity score matching. The primary outcome was 30-day treatment failure (composite of mortality, infection relapse, and hospital readmission). A prespecified 10% noninferiority margin was used for the primary outcome. We identified 66 matched pairs of patients treated with oral and intravenous antibiotics as definitive therapy. Based on an absolute difference in 30-day treatment failure of 13.6% (95% confidence interval 2.4 to 24.8%), the noninferiority of oral therapy was not confirmed (P = 0.741); on the contrary, the superiority of intravenous antibiotics is suggested by this difference. Acute kidney injury occurred in two patients who received intravenous treatment and zero who received oral therapy. No patients experienced deep vein thrombosis or other vascular complications related to treatment. In patients treated for beta-hemolytic streptococcal BSI, those who transitioned to oral antibiotics by day 7 showed higher rates of 30-day treatment failure than propensity-matched patients. This difference may have been driven by underdosing of oral therapy. Further investigation into optimal antibiotic choice, route, and dosing for definitive therapy of BSI is needed.

Risk factors and prophylaxis for nocardiosis in solid organ transplant recipients: A nested case-control study.

BACKGROUND: Nocardia is an opportunistic pathogen that primarily affects immunocompromised individuals, including solid organ transplant (SOT) recipients. Up to 2.65% of SOT recipients develop nocardiosis; however, few studies have examined risk factors and prophylaxis for nocardiosis. METHODS: We performed a multicenter, matched nested case-control study of adult SOT recipients with culture-confirmed nocardiosis from 2000 through 2020. Controls were matched up to 2:1 by sex, first transplanted organ, year of transplant, transplant center, and adequate post-transplant follow-up. Multivariable conditional logistic regression was performed to analyze associations with nocardiosis. Cox proportional hazards regression compared 12-month mortality between infection and uninfected patients. RESULTS: One hundred and twenty-three SOT recipients were matched to 245 uninfected controls. Elevated calcineurin inhibitor level, acute rejection, cytomegalovirus infection, lymphopenia, higher prednisone dose, and older age were significantly associated with nocardiosis while trimethoprim-sulfamethoxazole prophylaxis was protective (odds ratio [OR] .34; 95% confidence interval [CI] .13-.84). The effect of prophylaxis was similar, though not always statistically significant, in sensitivity analyses that only included prophylaxis dosed more than twice-per-week (OR .30; 95% CI .11-.80) or restricted to years 2015-2020 (OR .33, 95% CI .09-1.21). Nocardiosis was associated with increased 12-month mortality (hazard ratio 5.47; 95% confidence interval 2.42-12.35). CONCLUSIONS: Multiple measures of immunosuppression and lack of trimethoprim-sulfamethoxazole prophylaxis were associated with nocardiosis in SOT recipients. Effectiveness of prophylaxis may be related to trimethoprim-sulfamethoxazole dose or frequency. Trimethoprim-sulfamethoxazole should be preferentially utilized over alternative agents in SOT recipients with augmented immunosuppression or signs of heightened immunocompromise.

Leptotrichia Bacteremia: 10-Year Retrospective Clinical Analysis and Antimicrobial Susceptibility Profiles.

Leptotrichia species are anaerobic, Gram-negative bacilli increasingly recognized as pathogens capable of causing invasive infections such as bloodstream infection (BSI), particularly among immunocompromised patients. However, there is a paucity of data regarding epidemiology, antimicrobial susceptibility, optimal treatment, and clinical outcomes among patients with Leptotrichia bacteremia. Patient risk factors, treatment approaches, and outcomes of a retrospective cohort of adult patients with Leptotrichia BSI at a tertiary medical center (Mayo Clinic Rochester [MCR]) were evaluated. Concurrently, species, temporal trends, and antimicrobial susceptibility testing (AST) results of Leptotrichia isolates submitted to a reference laboratory (Mayo Clinic Laboratories) over the past 10 years were examined. We identified 224 blood culture isolates of Leptotrichia species, with 26 isolates from patients treated at MCR. The most frequent species included L. trevisanii (49%), L. buccalis (24%), and L. wadei (16%). Leptotrichia species demonstrated >90% susceptibility to penicillin, metronidazole, ertapenem, and piperacillin-tazobactam. However, 96% (74/77) of isolates were resistant to moxifloxacin. For patients treated at MCR, the mean patient age was 55 years (standard deviation [SD], 17), with 9 females (35%), and all were neutropenic at the time of BSI. The primary sources of infection were gastrointestinal (58%), intravascular catheter (35%), and odontogenic (15%). Patients were treated with metronidazole (42%), piperacillin-tazobactam (27%), or carbapenems (19%). The mean duration of treatment was 11 days (SD, 4.5), with a 60-day all-cause mortality of 19% and no microbiologic relapse. Leptotrichia species are rare but important causes of BSI in neutropenic patients. Due to evolving antimicrobial susceptibility profiles, a review of AST results is necessary when selecting optimal antimicrobial therapy.

Rebound Phenomenon After Nirmatrelvir/Ritonavir Treatment of Coronavirus Disease 2019 (COVID-19) in High-Risk Persons.

In a cohort of 483 high-risk patients treated with nirmatrelvir/ritonavir for COVID-19, 2 patients (0.4%) required hospitalization by day 30. Four patients (0.8%) experienced rebound of symptoms, which were generally mild, at a median of 9 days after treatment, and all resolved without additional COVID-19-directed therapy.

Outcomes of Nocardiosis and Treatment of Disseminated Infection in Solid Organ Transplant Recipients.

BACKGROUND: Nocardia is an environmental pathogen with a predilection for causing opportunistic infections in immunocompromised patients, including solid organ transplant (SOT) recipients. Although risk factors have been identified for developing nocardiosis in this population, little is known regarding clinical factors resulting in poor outcomes. We evaluated a cohort of SOT recipients with nocardiosis for associations with 12-month mortality. METHODS: We performed a multicenter retrospective cohort study of adult SOT recipients diagnosed with culture-confirmed nocardiosis from 2000 to 2020. Patients were followed for 12 months after diagnosis, unless abbreviated by mortality. Multivariable Cox regression was performed to analyze associations with 12-month mortality. A subgroup analysis of patients with disseminated nocardiosis was performed to analyze treatment variables. RESULTS: A total of 125 SOT recipients met inclusion criteria; 12-month mortality was 16.8%. Liver transplantation (hazard ratio [HR] 3.52; 95% confidence interval [CI] 1.27-9.76) and time from symptom onset to presentation (HR 0.92/d; 95% CI 0.86-0.99) were independently associated with 12-month mortality, whereas disseminated infection was not (HR 1.23; 95% CI 0.49-3.13). No treatment-specific factors were significantly associated with mortality in 33 patients with disseminated nocardiosis, although survivors had a higher rate of linezolid use. CONCLUSIONS: This study identified 2 independent associations with 12-month mortality, representing demographics and infection severity. Disseminated infection was not independently associated with poor outcomes, and specific sites of infection may be more important than dissemination itself. No treatment-specific factors were associated with mortality, though this analysis was likely underpowered. Further study of treatment strategies based on specific Nocardia syndromes is warranted.

Curbing the Delta Surge: Clinical Outcomes After Treatment With Bamlanivimab-Etesevimab, Casirivimab-Imdevimab, or Sotrovimab for Mild to Moderate Coronavirus Disease 2019.

OBJECTIVE: To describe and compare the clinical outcomes of bamlanivimab-etesevimab, casirivimab-imdevimab, and sotrovimab treatment of mild to moderate coronavirus disease 2019 (COVID-19) during the severe acute respiratory coronavirus 2 (SARS-CoV-2) B.1.617.2 Delta surge. METHODS: This is a retrospective study of high-risk patients who received bamlanivimab-etesevimab, casirivimab-imdevimab, and sotrovimab for mild to moderate COVID-19 between August 1, 2021, and December 1, 2021. Rates of severe disease, hospitalization, intensive care unit admission, and death were assessed. RESULTS: Among 10,775 high-risk patients who received bamlanivimab-etesevimab, casirivimab-imdevimab, or sotrovimab for mild to moderate COVID-19 during the Delta surge, 287 patients (2.7%) developed severe disease that led to hospitalization, oxygen supplementation, or death within 30 days after treatment. The rates of severe disease were low among patients treated with bamlanivimab-etesevimab (1.2%), casirivimab-imdevimab (2.9%), and sotrovimab (1.6%; P<.01). The higher rate of severe outcomes among patients treated with casirivimab-imdevimab may be related to a significantly lower COVID-19 vaccination rate in that cohort. Intensive care unit admission was comparable among patients treated bamlanivimab-etesevimab, casirivimab-imdevimab, or sotrovimab (1.0%, 1.0%, and 0.4%, respectively). CONCLUSION: This real-world study of a large cohort of high-risk patients shows low rates of severe disease, hospitalization, intensive care unit admission, and mortality after treatment with bamlanivimab-etesevimab, casirivimab-imdevimab, and sotrovimab for mild to moderate COVID-19 during the SARS-CoV-2 Delta surge.

Rates of Severe Outcomes After Bamlanivimab-Etesevimab and Casirivimab-Imdevimab Treatment of High-Risk Patients With Mild to Moderate Coronavirus Disease 2019.

Bamlanivimab-etesevimab and casirivimab-imdevimab are authorized by the US Food and Drug Administration for emergency treatment of mild to moderate coronavirus disease 2019 (COVID-19) in high-risk persons. There has been no study comparing their clinical efficacy. In this retrospective study of 681 patients with mild to moderate COVID-19 during a period dominated by severe acute respiratory syndrome coronavirus 2 wild-type and alpha variants, 25 patients (3.7%) had progression to a severe outcome requiring hospitalization and oxygen supplementation within 30 days after monoclonal antibody infusion. Severe outcome was significantly higher among the 181 patients who were treated with casirivimab-imdevimab when compared with the 500 patients who received bamlanivimab-etesevimab (21 [6.6%] vs 13 [2.6%]; P=.01). Patients treated with casirivimab-imdevimab had higher odds of severe outcomes compared with those who received bamlanivimab-etesevimab (odds ratio, 2.67; 95% CI, 1.17 to 6.06). The demographic and clinical characteristics, and the time to monoclonal antibody infusion, of the 2 treatment cohorts were not significantly different. The reason behind this significant difference in the clinical outcomes is unclear, but our observations emphasize potential efficacy differences among antispike monoclonal antibodies against COVID-19. Further clinical studies using larger cohorts of patients are needed to confirm or refute these observations.

Utility of Follow-up Coronavirus Disease 2019 (COVID-19) Antigen Tests After Acute Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Among Healthcare Personnel.

We report the utility of rapid antigen tests (RAgT) in a cohort of US healthcare personnel with coronavirus disease 2019 (COVID-19) infection who met symptom criteria to return to work at day 5 or later of isolation. In total, 11.9% of initial RAgT were negative. RAgT can be helpful to guide return to work decisions.

Contemporary experience of Abiotrophia, Granulicatella and Gemella bacteremia.

BACKGROUND: Abiotrophia, Granulicatella, and Gemella are gastrointestinal microbiota, gram-positive cocci that behave like viridans group streptococci. Despite the low incidence of bacteremia from these organisms, they can lead to infective endocarditis (IE) and other clinical syndromes. Due to scant data, we aim to describe detailed clinical features, management, and outcomes of patients with bacteremia from these organisms. METHODS: We reviewed all adult patients who developed Abiotrophia, Granulicatella, or Gemella bacteremia from 2011 to 2020, at Mayo Clinic. RESULTS: We identified 238 patients with positive blood culture for these organisms. Of those, 161 (67.6%) patients were deemed to have bacteremia of clinical significance; 62 (38.5%) were neutropenic, - none of whom were diagnosed with IE. The primary source of bacteremia for the neutropenic group was the gastrointestinal tract. Among 161 patients, echocardiography was obtained in 88 (54.7%) patients, especially those with unknown sources of bacteremia. A total of 19 cases had IE: 5 (26.3%) Abiotrophia, 11 (57.9%) Granulicatella, and 3 (15.8%) Gemella. Based on known IE scoring systems, the negative predictive value at established cutoffs for these scores, performed with our cohort were 95.9%, 100% and 97.9% for NOVA, HANDOC and DENOVA scores, respectively. We also found that the penicillin-non-susceptible rate was high in Abiotrophia (66.7%) and Granulicatella (53.7%). CONCLUSIONS: We described unique characteristics of Abiotrophia, Granulicatella, and Gemella bacteremia at our institution. Clinical significance, clinical syndrome, their proclivity of endocarditis, and susceptibility pattern should be thoroughly reviewed when encountering these organisms.

Effectiveness of Monoclonal Antibodies in Preventing Severe COVID-19 With Emergence of the Delta Variant.

Anti-spike monoclonal antibodies have proven invaluable in preventing severe outcomes from COVID-19, including hospitalization and death. The rise of the SARS-CoV-2 delta variant begs the question of whether monoclonal antibodies maintain similar efficacy now as they had when the alpha and beta variants predominated, when they were first assessed and approved. We used a retrospective cohort to compare rates of severe outcomes in an epoch in which alpha and beta were predominant compared with delta. A total of 5356 patients were infused during the alpha/beta variant-predominant (n=4874) and delta variant-predominant (n=482) era. Overall, odds of severe infection were 3.0% of patients in the alpha/beta-predominant era compared with 4.9% in the delta-predominant cohort. The unadjusted odds ratio (OR) was higher for severe disease in the delta era (OR, 1.67; 95% CI, 0.96 to 2.89), particularly when adjusted for Charlson Comorbidity Index (adjusted OR, 2.04; 95% CI, 1.30 to 3.08). The higher odds of severe infection could be due to a more virulent delta variant, although the possibility of decreased anti-spike monoclonal antibody effectiveness in the clinical setting cannot be excluded. Research into the most effective strategies for using and improving anti-spike monoclonals for the treatment of emerging variants is warranted.

Diagnostic Value of 16S Ribosomal RNA Gene Polymerase Chain Reaction/Sanger Sequencing in Clinical Practice.

BACKGROUND: Accurate microbiologic diagnosis is important for appropriate management of infectious diseases. Sequencing-based molecular diagnostics are increasingly used for precision diagnosis of infections. However, their clinical utility is unclear. METHODS: We conducted a retrospective analysis of specimens that underwent 16S ribosomal RNA (rRNA) gene polymerase chain reaction (PCR) followed by Sanger sequencing at our institution from April 2017 through March 2019. RESULTS: A total of 566 specimens obtained from 460 patients were studied. Patients were considered clinically infected or noninfected based on final diagnosis and management. In 17% of patients, 16S rRNA PCR/sequencing was positive and in 5% of patients, this test led to an impact on clinical care. In comparison, bacterial cultures were positive in 21% of patients. Specimens with a positive Gram stain had 12 times greater odds of having a positive molecular result than those with a negative Gram stain (95% confidence interval for odds ratio, 5.2-31.4). Overall, PCR positivity was higher in cardiovascular specimens (37%) obtained from clinically infected patients, with bacterial cultures being more likely to be positive for musculoskeletal specimens (P < .001). 16S rRNA PCR/sequencing identified a probable pathogen in 10% culture-negative specimens. CONCLUSION: 16S rRNA PCR/sequencing can play a role in the diagnostic evaluation of patients with culture-negative infections, especially those with cardiovascular infections.