Comparative safety of different antibiotic regimens for the treatment of outpatient community-acquired pneumonia among otherwise healthy adults.

BACKGROUND: Evidence is limited about the comparative safety of antibiotic regimens for treatment of community-acquired pneumonia (CAP). We compared the risk of adverse drug events (ADEs) associated with antibiotic regimens for CAP treatment among otherwise healthy, non-elderly adults. METHODS: We conducted an active comparator new-user cohort study (2007-2019) of commercially-insured adults 18-64 years diagnosed with outpatient CAP, evaluated via chest x-ray, and dispensed a same-day CAP-related oral antibiotic regimen. ADE follow-up duration ranged from 2-90 days (e.g., renal failure [14 days]). We estimated risk differences [RD] per 100 treatment episodes and risk ratios using propensity score weighted Kaplan-Meier functions. Ankle/knee sprain and influenza vaccination were considered as negative control outcomes. RESULTS: Of 145,137 otherwise healthy CAP patients without comorbidities, 52% received narrow-spectrum regimens (44% macrolide, 8% doxycycline) and 48% received broad-spectrum regimens (39% fluoroquinolone, 7% ß-lactam, 3% ß-lactam + macrolide). Compared to macrolide monotherapy, each broad-spectrum antibiotic regimen was associated with increased risk of several ADEs (e.g., ß-lactam: nausea/vomiting/abdominal pain [RD per 100, 0.32; 95% CI, 0.10-0.57]; non-Clostridioides difficile diarrhea [RD per 100, 0.46; 95% CI, 0.25-0.68]; vulvovaginal candidiasis/vaginitis [RD per 100, 0.36; 95% CI, 0.09-0.69]). Narrow-spectrum antibiotic regimens largely conferred similar risk of ADEs. We generally observed similar risks of each negative control outcome, indicating minimal confounding. CONCLUSIONS: Broad-spectrum antibiotics were associated with increased risk of ADEs among otherwise healthy adults treated for CAP in the outpatient setting. Antimicrobial stewardship is needed to promote judicious use of broad-spectrum antibiotics and ultimately decrease antibiotic-related ADEs.

SARS-CoV-2 anti-N antibodies among healthcare personnel without previous known COVID-19.

Objective: To measure SARS-CoV-2 anti-nucleocapsid (anti-N) antibody seropositivity among healthcare personnel (HCP) without a history of COVID-19 and to identify HCP characteristics associated with seropositivity. Design: Prospective cohort study from September 22, 2020, to March 3, 2022. Setting: A tertiary care academic medical center. Participants: 727 HCP without prior positive SARS-CoV-2 PCR testing were enrolled; 559 HCP successfully completed follow-up. Methods: At enrollment and follow-up 1-6 months later, HCP underwent SARS-CoV-2 anti-N testing and were surveyed on demographics, employment information, vaccination status, and COVID-19 symptoms and exposures. Results: Of 727 HCP enrolled, 27 (3.7%) had a positive SARS-CoV-2 anti-N test at enrollment. Seropositive HCPs were more likely to have a household exposure to COVID-19 in the past 30 days (OR 7.92, 95% CI 2.44-25.73), to have had an illness thought to be COVID-19 (4.31, 1.94-9.57), or to work with COVID-19 patients more than half the time (2.09, 0.94-4.77). Among 559 HCP who followed-up, 52 (9.3%) had a positive SARS-CoV-2 anti-N antibody test result. Seropositivity at follow-up was associated with community/household exposures to COVID-19 within the past 30 days (9.50, 5.02-17.96; 2.90, 1.31-6.44), having an illness thought to be COVID-19 (8.24, 4.44-15.29), and working with COVID-19 patients more than half the time (1.50, 0.80-2.78). Conclusions: Among HCP without prior positive SARS-CoV-2 testing, SARS-CoV-2 anti-N seropositivity was comparable to that of the general population and was associated with COVID-19 symptomatology and both occupational and non-occupational exposures to COVID-19.

Assessment of the characteristics of COVID-19 infection among healthcare personnel working in long-term care facilities.

Between May and June 2021, healthcare personnel at two long-term care facilities underwent SARS-CoV-2 anti-nucleocapsid immunoglobulin G testing and completed a survey on COVID-19 exposures and symptoms. Antibody positivity rate was 8.9%. Similar rates of COVID-19 exposure occurred in non-occupational and occupational settings, with high self-reported adherence to workplace infection prevention practices.

Impact of Gram-Negative Bacilli Resistance Rates on Risk of Death in Septic Shock and Pneumonia.

Background: Sepsis is a major cause of morbidity and mortality worldwide. When selecting empiric antibiotics for sepsis, clinicians are encouraged to use local resistance rates, but their impact on individual outcomes is unknown. Improved methods to predict outcomes are needed to optimize treatment selection and improve antibiotic stewardship. Methods: We expanded on a previously developed theoretical model to estimate the excess risk of death in gram-negative bacilli (GNB) sepsis due to discordant antibiotics using 3 factors: the prevalence of GNB in sepsis, the rate of antibiotic resistance in GNB, and the mortality difference between discordant and concordant antibiotic treatments. We focused on ceftriaxone, cefepime, and meropenem as the anti-GNB treatment backbone in sepsis, pneumonia, and urinary tract infections. We analyzed both publicly available data and data from a large urban hospital. Results: Publicly available data were weighted toward culture-positive cases. Excess risk of death with discordant antibiotics was highest in septic shock and pneumonia. In septic shock, excess risk of death was 4.53% (95% confidence interval [CI], 4.04%-5.01%), 0.6% (95% CI, .55%-.66%), and 0.19% (95% CI, .16%-.21%) when considering resistance to ceftriaxone, cefepime, and meropenem, respectively. Results were similar in pneumonia. Local data, which included culture-negative cases, showed an excess risk of death in septic shock of 0.75% (95% CI, .57%-.93%) for treatment with discordant antibiotics in ceftriaxone-resistant infections and 0.18% (95% CI, .16%-.21%) for cefepime-resistant infections. Conclusions: Estimating the excess risk of death for specific sepsis phenotypes in the context of local resistance rates, rather than relying on population resistance data, may be more informative in deciding empiric antibiotics in GNB infections.

Gut microbiome correlates of recurrent urinary tract infection: a longitudinal, multi-center study.

Background: Urinary tract infections (UTI) affect approximately 250 million people annually worldwide. Patients often experience a cycle of antimicrobial treatment and recurrent UTI (rUTI) that is thought to be facilitated by a gut reservoir of uropathogenic Escherichia coli (UPEC). Methods: 125 patients with UTI caused by an antibiotic-resistant organism (ARO) were enrolled from July 2016 to May 2019 in a longitudinal, multi-center cohort study. Multivariate statistical models were used to assess the relationship between uropathogen colonization and recurrent UTI (rUTI), controlling for clinical characteristics. 644 stool samples and 895 UPEC isolates were interrogated for taxonomic composition, antimicrobial resistance genes, and phenotypic resistance. Cohort UTI gut microbiome profiles were compared against published healthy and UTI reference microbiomes, as well as assessed within-cohort for timepoint- and recurrence-specific differences. Findings: Risk of rUTI was not independently associated with clinical characteristics. The UTI gut microbiome was distinct from healthy reference microbiomes in both taxonomic composition and antimicrobial resistance gene (ARG) burden, with 11 differentially abundant taxa at the genus level. rUTI and non-rUTI gut microbiomes in the cohort did not generally differ, but gut microbiomes from urinary tract colonized patients were elevated in E. coli abundance 7-14 days post-antimicrobial treatment. Corresponding UPEC gut isolates from urinary tract colonizing lineages showed elevated phenotypic resistance against 11 of 23 tested drugs compared to non-colonizing lineages. Interpretation: The gut microbiome is implicated in UPEC urinary tract colonization during rUTI, serving as an ARG-enriched reservoir for UPEC. UPEC can asymptomatically colonize the gut and urinary tract, and post-antimicrobial blooms of gut E. coli among urinary tract colonized patients suggest that cross-habitat migration of UPEC is an important mechanism of rUTI. Thus, treatment duration and UPEC populations in both the urinary and gastrointestinal tract should be considered in treating rUTI and developing novel therapeutics. Funding: This work was supported in part by awards from the U.S. Centers for Disease Control and Prevention Epicenter Prevention Program (grant U54CK000482; principal investigator, V.J.F.); to J.H.K. from the Longer Life Foundation (an RGA/Washington University partnership), the National Center for Advancing Translational Sciences (grants KL2TR002346 and UL1TR002345), and the National Institute of Allergy and Infectious Diseases (NIAID) (grant K23A1137321) of the National Institutes of Health (NIH); and to G.D. from NIAID (grant R01AI123394) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant R01HD092414) of NIH. R.T.'s research was funded by the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation; grant 402733540). REDCap is Supported by Clinical and Translational Science Award (CTSA) Grant UL1 TR002345 and Siteman Comprehensive Cancer Center and NCI Cancer Center Support Grant P30 CA091842. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

Leveraging Bluetooth low-energy technology to improve contact tracing among healthcare personnel in hospital setting during the coronavirus disease 2019 (COVID-19) pandemic.

To improve contact tracing for healthcare workers, we built and configured a Bluetooth low-energy system. We predicted close contacts with great accuracy and provided an additional contact yield of 14.8%. This system would decrease the effective reproduction number by 56% and would unnecessarily quarantine 0.74% of employees weekly.

Seroprevalence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies among healthcare personnel in the Midwestern United States, September 2020-April 2021.

Objective: To determine the prevalence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) IgG nucleocapsid (N) antibodies among healthcare personnel (HCP) with no prior history of COVID-19 and to identify factors associated with seropositivity. Design: Prospective cohort study. Setting: An academic, tertiary-care hospital in St. Louis, Missouri. Participants: The study included 400 HCP aged ≥18 years who potentially worked with coronavirus disease 2019 (COVID-19) patients and had no known history of COVID-19; 309 of these HCP also completed a follow-up visit 70-160 days after enrollment. Enrollment visits took place between September and December 2020. Follow-up visits took place between December 2020 and April 2021. Methods: At each study visit, participants underwent SARS-CoV-2 IgG N-antibody testing using the Abbott SARS-CoV-2 IgG assay and completed a survey providing information about demographics, job characteristics, comorbidities, symptoms, and potential SARS-CoV-2 exposures. Results: Participants were predominately women (64%) and white (79%), with median age of 34.5 years (interquartile range [IQR], 30-45). Among the 400 HCP, 18 (4.5%) were seropositive for IgG N-antibodies at enrollment. Also, 34 (11.0%) of 309 were seropositive at follow-up. HCP who reported having a household contact with COVID-19 had greater likelihood of seropositivity at both enrollment and at follow-up. Conclusions: In this cohort of HCP during the first wave of the COVID-19 pandemic, ∼1 in 20 had serological evidence of prior, undocumented SARS-CoV-2 infection at enrollment. Having a household contact with COVID-19 was associated with seropositivity.

Addition of aminoglycosides reduces recurrence of infections with multidrug-resistant Gram-negative bacilli in patients with sepsis and septic shock.

OBJECTIVES: Aminoglycosides and ß-lactams have been recommended for treatment of sepsis/septic shock despite a lack of mortality benefit. Previous studies have examined resistance emergence for the same bacterial isolate using old dosing regimens and during a narrow follow-up window. We hypothesised that combination regimens employing aminoglycosides will decrease the cumulative incidence of infections due to multidrug-resistant (MDR) Gram-negative bacilli (GNB) compared with ß-lactams alone. METHODS: All adult patients admitted to Barnes Jewish Hospital between 2010 and 2017 with a diagnosis of sepsis/septic shock were included in this retrospective cohort study. Patients were divided into two treatment groups, with and without aminoglycosides. Patient demographics, severity of presentation, administered antibiotics, follow-up cultures with susceptibility results for a period of 4-60 days, and mortality were extracted. After propensity score matching, a Fine-Gray subdistribution proportional hazards model summarised the estimated incidence of subsequent infections with MDR-GNB in the presence of all-cause death as a competing risk. RESULTS: A total of 10 212 septic patients were included, with 1996 (19.5%) treated with at least two antimicrobials including one aminoglycoside. After propensity score matching, the cumulative incidence of MDR-GNB infections between 4-60 days was lower in the combination group (incidence at 60 days 0.073, 95% CI 0.062-0.085) versus patients not receiving aminoglycosides (0.116, 95% CI 0.102-0.130). Patients aged ≤65 years and with haematological malignancies had a larger treatment effect in subgroup analyses. CONCLUSION: Addition of aminoglycosides to ß-lactams may protect against subsequent infections due to MDR-GNB in patients with sepsis/septic shock.

Association between SARS-CoV-2 Symptoms, Ct Values, and Serological Response in Vaccinated and Unvaccinated Healthcare Personnel.

BACKGROUND: SARS-CoV-2 vaccines are effective at reducing symptomatic and asymptomatic COVID-19. Limited studies have compared symptoms, threshold cycle (Ct) values from reverse transcription (RT)-PCR testing, and serological testing results between previously vaccinated vs unvaccinated populations with SARS-CoV-2 infection. METHODS: Healthcare personnel (HCP) with a positive SARS-CoV-2 RT-PCR test within the previous 14 to 28 days completed surveys including questions about demographics, medical conditions, social factors, and symptoms of COVID-19. Ct values were observed, and serological testing was performed for anti-nucleocapsid (anti-N) and anti-Spike (anti-S) antibodies at enrollment and 40 to 90 days later. Serological results were compared to HCP with no known SARS-CoV-2 infection and negative anti-N testing. RESULTS: There were 104 unvaccinated/not fully vaccinated and 77 vaccinated HCP with 2 doses of an mRNA vaccine at time of infection. No differences in type or duration of symptoms were reported (P = 0.45). The median (interquartile range [IQR]) Ct was 21.4 (17.6-24.6) and 21.5 (18.1-24.6) for the unvaccinated and vaccinated HCP, respectively. Higher anti-N IgG was observed in unvaccinated HCP (5.08 S/CO, 3.08-6.92) than vaccinated (3.61 signal to cutoff ratio [S/CO], 2.16-5.05). Anti-S IgG was highest among vaccinated HCP with infection (34 285 aribitrary units [AU]/mL, 17 672-61 775), followed by vaccinated HCP with no prior infection (1452 AU/mL, 791-2943), then unvaccinated HCP with infection (829 AU/mL, 290-1555). Anti-S IgG decreased 1.56% (0.9%-1.79%) per day in unvaccinated and 0.38% (0.03%-0.94%) in vaccinated HCP. CONCLUSIONS: Vaccinated HCP infected with SARS-CoV-2 reported comparable symptoms and had similar Ct values relative to unvaccinated. However, vaccinated HCP had increased and prolonged anti-S and decreased anti-N response relative to unvaccinated.

Knowledge, beliefs, and practices related to coronavirus disease 2019 (COVID-19) infection and vaccination in healthcare personnel working at nonacute care facilities.

OBJECTIVE: To characterize experiences, beliefs, and perceptions of risk related to coronavirus disease 2019 (COVID-19), infection prevention practices, and COVID-19 vaccination among healthcare personnel (HCP) at nonacute care facilities. DESIGN: Anonymous survey. SETTING: Three non-acute-care facilities in St. Louis, Missouri. PARTICIPANTS: In total, 156 HCP responded to the survey, for a 25.6% participation rate). Among them, 32% had direct patient-care roles. METHODS: Anonymous surveys were distributed between April-May 2021. Data were collected on demographics, work experience, COVID-19 exposure, knowledge, and beliefs about infection prevention, personal protective equipment (PPE) use, COVID-19 vaccination, and the impact of COVID-19. RESULTS: Nearly all respondents reported adequate knowledge of how to protect oneself from COVID-19 at work (97%) and had access to adequate PPE supplies (95%). Many HCP reported that wearing a mask or face shield made communication difficult (59%), that they had taken on additional responsibilities due to staff shortages (56%), and that their job became more stressful because of COVID-19 (53%). Moreover, 28% had considered quitting their job. Most respondents (78%) had received at least 1 dose of COVID-19 vaccine. Common reasons for vaccination were a desire to protect family and friends (84%) and a desire to stop the spread of COVID-19 (82%). Potential side effects and/or inadequate vaccine testing were cited as the most common concerns by unvaccinated HCP. CONCLUSIONS: A significant proportion of HCP reported increased stress and responsibilities at work due to COVID-19. The majority were vaccinated. Improving workplace policies related to mental health resources and sick leave, maintaining access to PPE, and ensuring clear communication of PPE requirements may improve workplace stress and burnout.

Clinical and occupational risk factors for coronavirus disease 2019 (COVID-19) in healthcare personnel.

Objective: To identify characteristics associated with positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) polymerase chain reaction (PCR) tests in healthcare personnel. Design: Retrospective cohort study. Setting: A multihospital healthcare system. Participants: Employees who reported SARS-CoV-2 exposures and/or symptoms of coronavirus disease 2019 (COVID-19) between March 30, 2020, and September 20, 2020, and were subsequently referred for SARS-CoV-2 PCR testing. Methods: Data from exposure and/or symptom reports were linked to the corresponding SARS-CoV-2 PCR test result. Employee demographic characteristics, occupational characteristics, SARS-CoV-2 exposure history, and symptoms were evaluated as potential risk factors for having a positive SARS-CoV-2 PCR test. Results: Among 6,289 employees who received SARS-CoV-2 PCR testing, 873 (14%) had a positive test. Independent risk factors for a positive PCR included: working in a patient care area (relative risk [RR], 1.82; 95% confidence interval [CI], 1.37-2.40), having a known SARS-CoV-2 exposure (RR, 1.20; 95% CI, 1.04-1.37), reporting a community versus an occupational exposure (RR, 1.87; 95% CI, 1.49-2.34), and having an infected household contact (RR, 2.47; 95% CI, 2.11-2.89). Nearly all HCP (99%) reported symptoms. Symptoms associated with a positive PCR in a multivariable analysis included loss of sense of smell (RR, 2.60; 95% CI, 2.09-3.24) or taste (RR, 1.75; 95% CI, 1.40-2.20), cough (RR, 1.95; 95% CI, 1.40-2.20), fever, and muscle aches. Conclusions: In this cohort of >6,000 healthcare system and academic medical center employees early in the pandemic, community exposures, and particularly household exposures, were associated with greater risk of SARS-CoV-2 infection than occupational exposures. This work highlights the importance of COVID-19 prevention in the community and in healthcare settings to prevent COVID-19.

Longitudinal analysis of risk factors associated with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among hemodialysis patients and healthcare personnel in outpatient hemodialysis centers.

In this prospective, longitudinal study, we examined the risk factors for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among a cohort of chronic hemodialysis (HD) patients and healthcare personnel (HCPs) over a 6-month period. The risk of SARS-CoV-2 infection among HD patients and HCPs was consistently associated with a household member having SARS-CoV-2 infection.

Antibodies in healthcare personnel following severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) infection.

In a prospective cohort of healthcare personnel (HCP), we measured severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) nucleocapsid IgG antibodies after SARS-CoV-2 infection. Among 79 HCP, 68 (86%) were seropositive 14-28 days after their positive PCR test, and 54 (77%) of 70 were seropositive at the 70-180-day follow-up. Many seropositive HCP (95%) experienced an antibody decline by the second visit.

Coronavirus disease 2019 (COVID-19) vaccine breakthrough infections among healthcare personnel, December 2020-April 2021.

Coronavirus disease 2019 (COVID-19) vaccine effectiveness in the early months of vaccine availability was high among healthcare personnel (HCP) at 88.3% for 2-doses. Among those testing positive for severe acute respiratory coronavirus virus 2 (SARS-CoV-2), those with breakthrough infection after vaccination were more likely to have had a non-work-related SARS-CoV-2 exposure compared to unvaccinated HCP.

Predictors of humoral response to SARS-CoV-2 mRNA vaccine BNT162b2 in patients receiving maintenance dialysis.

Objective: Patients on dialysis are at high risk for severe COVID-19 and associated morbidity and mortality. We examined the humoral response to SARS-CoV-2 mRNA vaccine BNT162b2 in a maintenance dialysis population. Design: Single-center cohort study. Setting and participants: Adult maintenance dialysis patients at 3 outpatient dialysis units of a large academic center. Methods: Participants were vaccinated with 2 doses of BNT162b2, 3 weeks apart. We assessed anti-SARS-CoV-2 spike antibodies (anti-S) ∼4-7 weeks after the second dose and evaluated risk factors associated with insufficient response. Definitions of antibody response are as follows: nonresponse (anti-S level, <50 AU/mL), low response (anti-S level, 50-839 AU/mL), and sufficient response (anti-S level, ≥840 AU/mL). Results: Among the 173 participants who received 2 vaccine doses, the median age was 60 years (range, 28-88), 53.2% were men, 85% were of Black race, 86% were on in-center hemodialysis and 14% were on peritoneal dialysis. Also, 7 participants (4%) had no response, 27 (15.6%) had a low response, and 139 (80.3%) had a sufficient antibody response. In multivariable analysis, factors significantly associated with insufficient antibody response included end-stage renal disease comorbidity index score ≥5 and absence of prior hepatitis B vaccination response. Conclusions: Although most of our study participants seroconverted after 2 doses of BNT162b2, 20% of our cohort did not achieve sufficient humoral response. Our findings demonstrate the urgent need for a more effective vaccine strategy in this high-risk patient population and highlight the importance of ongoing preventative measures until protective immunity is achieved.

Individualized Risk Prediction Tool for Serious Wound Complications After Mastectomy With and Without Immediate Reconstruction.

BACKGROUND: A greater proportion of patients with surgical risk factors are undergoing immediate breast reconstruction after mastectomy, resulting in the need for better risk prediction to inform decisions about the procedure. The objective of this study was to leverage clinical data to restructure a previously developed risk model to predict serious infectious and noninfectious wound complications after mastectomy alone and mastectomy plus immediate reconstruction for use during a surgical consultation. METHODS: The study established a cohort of women age 21 years or older treated with mastectomy from 1 July 2010 to 31 December 2015 using electronic health records from two hospitals. Serious infectious and non-infectious wound complications, defined as surgical-site infection, dehiscence, tissue necrosis, fat necrosis requiring hospitalization, or surgical treatment, were identified within 180 days after surgery. Risk factors for serious wound complications were determined using modified Poisson regression, with discrimination and calibration measures. Bootstrap validation was performed to correct for overfitting. RESULTS: Among 2159 mastectomy procedures, 1410 (65.3%) included immediate implant or flap reconstruction. Serious wound complications were identified after 237 (16.8%) mastectomy-plus-reconstruction and 30 (4.0%) mastectomy-only procedures. Independent risk factors for serious wound complications included immediate reconstruction, bilateral mastectomy, higher body mass index, depression, and smoking. The optimism-corrected C statistic of the risk prediction model was 0.735. CONCLUSIONS: Immediate reconstruction, bilateral mastectomy, obesity, depression, and smoking were significant risk factors for serious wound complications in this population of women undergoing mastectomy. Our risk prediction model can be used to counsel women before surgery concerning their individual risk of serious wound complications after mastectomy.

Persisting uropathogenic Escherichia coli lineages show signatures of niche-specific within-host adaptation mediated by mobile genetic elements.

Large-scale genomic studies have identified within-host adaptation as a hallmark of bacterial infections. However, the impact of physiological, metabolic, and immunological differences between distinct niches on the pathoadaptation of opportunistic pathogens remains elusive. Here, we profile the within-host adaptation and evolutionary trajectories of 976 isolates representing 119 lineages of uropathogenic Escherichia coli (UPEC) sampled longitudinally from both the gastrointestinal and urinary tracts of 123 patients with urinary tract infections. We show that lineages persisting in both niches within a patient exhibit increased allelic diversity. Habitat-specific selection results in niche-specific adaptive mutations and genes, putatively mediating fitness in either environment. Within-lineage inter-habitat genomic plasticity mediated by mobile genetic elements (MGEs) provides the opportunistic pathogen with a mechanism to adapt to the physiological conditions of either habitat, and reduced MGE richness is associated with recurrence in gut-adapted UPEC lineages. Collectively, our results establish niche-specific adaptation as a driver of UPEC within-host evolution.

Isolation of SARS-CoV-2 in Viral Cell Culture in Immunocompromised Patients With Persistently Positive RT-PCR Results.

Immunocompromised adults can have prolonged acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive RT-PCR results, long after the initial diagnosis of coronavirus disease 2019 (COVID-19). This study aimed to determine if SARS-CoV-2 virus can be recovered in viral cell culture from immunocompromised adults with persistently positive SARS-CoV-2 RT-PCR tests. We obtained 20 remnant SARS-CoV-2 PCR positive nasopharyngeal swabs from 20 immunocompromised adults with a positive RT-PCR test ≥14 days after the initial positive test. The patients' 2nd test samples underwent SARS-CoV-2 antigen testing, and culture with Vero-hACE2-TMPRSS2 cells. Viral RNA and cultivable virus were recovered from the cultured cells after qRT-PCR and plaque assays. Of 20 patients, 10 (50%) had a solid organ transplant and 5 (25%) had a hematologic malignancy. For most patients, RT-PCR Ct values increased over time. There were 2 patients with positive viral cell cultures; one patient had chronic lymphocytic leukemia treated with venetoclax and obinutuzumab who had a low viral titer of 27 PFU/mL. The second patient had marginal zone lymphoma treated with bendamustine and rituximab who had a high viral titer of 2 x 106 PFU/mL. Most samples collected ≥7 days after an initial positive SARS-CoV-2 RT-PCR had negative viral cell cultures. The 2 patients with positive viral cell cultures had hematologic malignancies treated with chemotherapy and B cell depleting therapy. One patient had a high concentration titer of cultivable virus. Further data are needed to determine risk factors for persistent viral shedding and methods to prevent SARS-CoV-2 transmission from immunocompromised hosts.

Lack of association of post-discharge prophylactic antibiotics with decreased risk of surgical site infection following spinal fusion.

OBJECTIVES: To determine the prevalence and factors associated with post-discharge prophylactic antibiotic use after spinal fusion and whether use was associated with decreased risk of surgical site infection (SSI). METHODS: Persons aged 10-64 years undergoing spinal fusion between 1 January 2010 and 30 June 2015 were identified in the MarketScan Commercial Database. Complicated patients and those coded for infection from 30 days before to 2 days after the surgical admission were excluded. Outpatient oral antibiotics were identified within 2 days of surgical discharge. SSI was defined using ICD-9-CM diagnosis codes within 90 days of surgery. Generalized linear models were used to determine factors associated with post-discharge prophylactic antibiotic use and with SSI. RESULTS: The cohort included 156 446 fusion procedures, with post-discharge prophylactic antibiotics used in 9223 (5.9%) surgeries. SSIs occurred after 2557 (1.6%) procedures. Factors significantly associated with post-discharge prophylactic antibiotics included history of lymphoma, diabetes, 3-7 versus 1-2 vertebral levels fused, and non-infectious postoperative complications. In multivariable analysis, post-discharge prophylactic antibiotic use was not associated with SSI risk after spinal fusion (relative risk 0.98; 95% CI 0.84-1.14). CONCLUSIONS: Post-discharge prophylactic oral antibiotics after spinal fusion were used more commonly in patients with major medical comorbidities, more complex surgeries and those with postoperative complications during the surgical admission. After adjusting for surgical complexity and infection risk factors, post-discharge prophylactic antibiotic use was not associated with decreased SSI risk. These results suggest that prolonged prophylactic antibiotic use should be avoided after spine surgery, given the lack of benefit and potential for harm.