Negative Swab Research Articles

Predictive value of a positive pocket swab for the occurrence of device infection in implantable cardioverter defibrillator patients undergoing generator replacement or lead revision

Abstract Introduction Bacterial colonization of generator pockets in implantable cardioverter defibrillator (ICD) patients plays a key role in the development of device infection after revision surgery. Pocket swabs taken at revision may be useful for predicting device infection, but their prognostic value is not precisely known. Aim of the study was to evaluate the predictive value of positive pocket swabs for cardiac device infection in ICD patients undergoing revision surgery. Methods A total of 646 consecutive ICD patients from a prospective single-centre ICD-registry who underwent elective device replacement, system upgrade or lead revision between 2014 and 6/2023 were analyzed. Independent predictors for device infection were evaluated by a Cox regression analysis adjusting for age, gender, EF, insulin dependent diabetes, anticoagulation, multiple leads, revision surgery and the PADIT score. Results Positive pocket swabs were obtained in 12% of patients. The baseline characteristics of ICD patients with positive versus negative pocket swabs were similar (Table 1). With an average follow-up of 3 years, the infection rate in patients with positive pocket swabs was around 5 times higher than in patients with negative swabs (19% versus 4%, p < 0.001). In a Cox regression analysis, a positive pocket swab was the strongest independent predictor for device infection during follow-up (hazard ratio 4.26, 95% confidence interval 2.15 – 8.45, Table 2). Conclusion A positive swab from ICD-pockets in patients undergoing generator replacement or lead revision is an independent predictor of device infection during follow-up. These results support the routine collection of pocket swabs from patients undergoing revision surgery.Table 1Table 2

The effect of combination treatment with casirivimab and imdevimab versus standard antiviral therapy on clinical outcomes in hospitalized COVID-19 patients

BackgroundThe Coronavirus Disease of 2019 (COVID-19) pandemic motivated research efforts to address this catastrophe from the beginning of 2020 to the present. The year 2021 is coming to an end, and several developments in pharmacotherapy for COVID-19 have occurred. In terms of antiviral therapy, monoclonal antibody combinations have become one type of COVID-19 immunotherapy. Remdesivir and favipiravir are two antiviral medications typically used to treat COVID-19. Paxlovid (nirmatrelvir plus ritonavir) and molnupiravir are other antiviral agents used in COVID-19. The purpose of this study was to compare the effects of combinations of antibodies (casirivimab and imdevimab), remdesivir, and favipiravir on COVID-19 swab results in hospitalized patients with COVID-19 at discharge.MethodsThis research is a phase IV non-randomized controlled trial (< 300 patients as sample size) with no comparison to placebo. In this study, 265 COVID-19 patients confirmed by polymerase chain reaction (PCR) and indications for antiviral medication were non-randomized into three groups at a ratio of (1:2:2): REGN3048-3051 (group A), remdesivir (group B), and favipiravir (group C). A nonrandomized single-blind controlled study design was used. The study's medication was provided by the Hospital of Mansoura University. Following ethical approval, the study was conducted for approximately 6 months.ResultsCompared to remdesivir and favipiravir, casirivimab and imdevimab cause less hepatotoxicity, less renal impairment, and more negative swab results at discharge. The three tested antivirals also had no significant adverse effects. All three antivirals are considered safe based on these findings.ConclusionCompared with remdesivir and favipiravir, casirivimab and imdevimab result in better clinical outcomes. All three antivirals are safe and have no significant toxicity.Trial registration: Clinicaltrials.gov, NCT05502081, 16/08/2022.

Challenges in Diagnosis of COVID-19 Pneumonia under Ocrelizumab and De-Risking Strategies in Multiple Sclerosis—The Elephant Is (Still) in the Room

Severe SARS-CoV-2 infections may still be observed in people bearing risk factors, such as the use of anti-CD20 monoclonal antibodies (mAbs), which are adopted in several autoimmune disorders including multiple sclerosis (MS). COVID-19 diagnosis is routinely based on nasopharyngeal swab testing, but suboptimal sensitivity for SARS-CoV-2 detection compared to bronchoalveolar lavage (BAL) may lead to misdiagnosis in some cases. Such diagnostic issues were described in a few MS patients receiving anti-CD20 mAbs, including middle-aged people and lacking information on subsequent MS therapeutic management, a debated topic as no evidence-based guidance on de-risking strategies is currently available. Here, we report the case of a young MS patient who developed severe COVID-19 pneumonia under treatment with the anti-CD20 mAb ocrelizumab, and who was finally diagnosed with SARS-CoV-2 by BAL despite repeatedly negative nasopharyngeal swabs. Ocrelizumab was then discontinued, and treatment with a sphingosine-1 phosphate receptor modulator was started, followed by maintenance of clinical and radiological MS stability. Challenges in diagnosing COVID-19 pneumonia in people without risk factors other than immunomodulatory treatment are hence discussed, as well as potential strategies for de-risking MS therapies. The latter topic is increasingly debated based on raising concerns for potential long-term safety issues of high-efficacy treatments, including anti-CD20 mAbs.

Predictive values of methicillin-resistant Staphylococcus aureus nasal swabs for pneumonia in burn ICU patients

Introduction/ObjectiveThis retrospective cohort study aimed to determine the sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) of MRSA nasal swabs for pneumonia in burn-injured intensive care unit (ICU) patients. MethodsPatients 18 years or older admitted to the Burn ICU at a tertiary medical center from 2016 to 2021 were included if they had any burns, a pneumonia ICD-10 code, an MRSA nasal swab obtained during admission, and any respiratory cultures associated with at least five consecutive days of antibiotics. ResultsThere were 267 occurrences of pneumonia across 136 patients. MRSA nasal swabs had an overall sensitivity of 39 %, specificity of 98.7 %, PPV of 84.2 %, and NPV of 89.9 %. MRSA nasal swabs obtained less than seven days from antibiotic initiation had a specificity of 98.6 % and NPV of 98.6 %; meanwhile, swabs obtained at least seven days from antibiotic initiation had a specificity of 98.7 % and NPV of 86.4 %. ConclusionsThe high specificity and NPV indicate that negative MRSA nasal swabs obtained less than seven days from antibiotic initiation may be used to de-escalate anti-MRSA antibiotics in clinically stable burn-injured patients with suspicion of pneumonia. The decrease in NPV suggests that it may be beneficial to obtain a repeat swab periodically.

Establishment of ELISA method for canine adenovirus type 1.

Canine adenovirus (CAdV) had a high prevalence in fox populations and induced fox encephalitis. No ELISA kits specifically for CAdV-1 antigen had been commercialized for foxes in China. It is crucial to develop a rapid and accurate ELISA method for detecting of CAdV-1. The monoclonal antibodies (mAbs, IgG1A) and HRP-labeled polyclonal antibodies (pAbs) were used to establish the ELISA method in this experiment. The results showed that the optimal concentration and coating time for the mAbs (IgG1A) were 2.15 μg/mL and overnight at 4°C, respectively. The dilution ratio of the HRP-labeled pAbs was 1:2000. Five percent skimmed milk was selected as the blocking agent. The optimal incubation times for blocking, CAdV-1, and HRP-labeled pAbs were all 1 h. The cut-off value for negative rectal swab was determined to be 0.366 ± 0.032. The maximum dilution ratio was 100 TCID50/mL. The ELISA method was positive to CAdV-1, and that was negative to CAdV-2, Canine Parvovirus (CPV) and Canine Distempervirus (CDV). The ELISA method showed good repeatability, sensitivity, and specificity. Compared with RT-PCR, the sensitivity, specificity, and coincidence rates of the ELISA method were 93.75, 90.9, and 92.86%, respectively. These results indicate that the established ELISA method can be used for the large-scale screening and epidemiology surveillance of CAdV-1 in foxes.

Anti-RBD Antibody Levels and IFN-γ-Specific T Cell Response Are Associated with a More Rapid Swab Reversion in Patients with Multiple Sclerosis after the Booster Dose of COVID-19 Vaccination.

This study investigated the incidence and severity of SARS-CoV-2 breakthrough infections (BIs) and the time to swab reversion in patients with multiple sclerosis (PwMS) after the booster dose of COVID-19 mRNA vaccines. We enrolled 64 PwMS who had completed the three-dose mRNA vaccine schedule and had never experienced COVID-19 before. Among the 64 PwMS, 43.8% had BIs with a median time since the third vaccine dose of 155 days. BIs occurred more frequently in ocrelizumab-treated patients (64.7%). Patients with a relapsing-remitting MS course showed a reduced incidence of BIs compared with those with a primary-progressive disease (p = 0.002). Having anti-receptor-binding domain (RBD) antibodies represented a protective factor reducing the incidence of BIs by 60% (p = 0.042). The majority of BIs were mild, and the only severe COVID-19 cases were reported in patients with a high Expanded Disability Status Scale score (EDSS > 6). The median time for a negative swab was 11 days. Notably, fingolimod-treated patients take longer for a swab-negativization (p = 0.002). Conversely, having anti-RBD antibodies ≥ 809 BAU/mL and an IFN-γ-specific T cell response ≥ 16 pg/mL were associated with a shorter time to swab-negativization (p = 0.051 and p = 0.018, respectively). In conclusion, the immunological protection from SARS-CoV-2 infection may differ among PwMS according to DMTs.

Do Post-debridement Cultures have a Role in Reduction of Infection in Open Fractures? Report of 166 Cases and Literature Review.

To evaluate the role of post-debridement cultures in the prevention of future infection following open fractures. Retrospective Cohort Study and Literature Review. Division of Orthopaedic Surgery, Sultan Qaboos University Hospital, Academic and tertiary health care, Muscat, Oman. A total of 166 patients from a cohort study and 539 patients from the literature review with open fractures. There were 640 cumulative patients fit the inclusion and exclusion criteria. Using predetermined inclusion and exclusion criteria, data on all open fractures were gathered from the electronic health system of a single institution between 2010 and 2019. PubMed and Embase electronic databases were also searched for relevant articles relating to post-surgical debridement culture and its correlation with future infection. Assessing the benefit, role of post-debridement cultures in the prevention of future infection following open fractures. Combining the results of this retrospective cohort study and previously published data, there were 640 Gustilo-Anderson grades II and III open fractures which had post-debridement screening. Eighty-eight patients (13.8%) developed an infection, out of which 16 had positive post- debridement cultures (18.2%). Only four grew similar organisms at screening and infection stages, two of which had different antibiotic resistance patterns at the infection stage. Seventy-two fractures had negative post-debridement screening swabs (81.8%). Of the 59 (9.2%) fractures with positive screening only four (6.8% of the infected fractures) developed later deep infection. All these 59 cases had culture-guided antibiotic treatment, with or without surgical debridement. Although the bacterial growth of post-debridement cultures is low, post-debridement screening as part of a comprehensive management protocol may have a role in reducing deep infection in open fractures. This is particularly the case in Gustilo and Anderson type 3 open fractures, the risk of infection is high. The poor association between organisms isolated from screening and those from subsequent deep infection may mean that the later infective organisms have been acquired from a secondary colonisation source after the debridement. III. Kindi NA, Abri FA, Yaseen A, et al. Do Post-debridement Cultures have a Role in Reduction of Infection in Open Fractures? Report of 166 Cases and Literature Review. Strategies Trauma Limb Reconstr 2024;19(2):94-98.

Exploring early COVID-19 therapies, variants, and viral clearance dynamics: Insights from a high-risk outpatients study

This retrospective observational study investigates the impact of early COVID-19 therapies, including antivirals and monoclonal antibodies (mAbs), on time to achieve negative swab results in high-risk outpatients infected with specific Omicron sublineages. The study enrolled 104 patients from Luigi Sacco Hospital in Milan between December 2021 and March 2023, categorizing them based on the Omicron sublineage they were infected with (BA.1, BA.2, BA.4/BA.5) and the early treatment they received (antivirals or mAbs). Key data collected included demographic and clinical characteristics, initial and follow-up cycle threshold (Ct) values from qPCR tests, and the interval between swabs. The median age of the participants was 63 years (Interquartile Range [IQR] 54.0-76.5), and 55.8% were male. Among the patients, 15 received mAbs (14.4%), and 99 received antiviral treatments (95.2%) - specifically, Paxlovid (51.9%), Molnupiravir (21.1%), and Remdesivir (12.5%). No patients required hospitalization or experienced mortality during the one-month follow-up period. Regarding Omicron sublineages, 23 patients (22.1%) were infected with BA.1, 53 (51%) with BA.2, and 28 (26.9%) with BA.4/BA.5. The median interval between the initial and follow-up swabs was 6 days (IQR 6.0-7.0). Initial Ct values had a median of 18.5 (IQR 16.5-22.1), which increased to a median of 30.5 (IQR 27.1-33.0) at follow-up, indicating a reduction in viral load. A non-significant trend suggested that patients infected with BA.2 and BA.4/BA.5 sublineages might experience a faster increase in Ct values—indicating quicker viral load reduction - compared to those infected with BA.1, regardless of treatment type. However, this trend did not achieve statistical significance (p=0.609), likely due to the limited sample size and the absence of a clear trend curve. In summary, the study did not find a significant association between specific early therapies and the time to achieve swab negativization. These findings underscore the complex dynamics of viral clearance and highlight the need for further research with larger patient cohorts to refine treatment protocols for high-risk COVID-19 patients

Impact of Stewardship Pharmacist Driven MRSA Nasal Surveillance and De-escalation of Anti-MRSA Therapy

Background: Intravenous vancomycin is commonly used as initial empiric coverage for pneumonia but is often unnecessary. MRSA nasal surveillance cultures (MRSA nasal swab) have been highlighted in recent literature and the 2019 IDSA Pneumonia Treatment Guidelines as a tool to avoid unnecessary MRSA coverage in pneumonia. A negative MRSA nasal swab can be utilized by clinicians to de-escalate anti-MRSA therapies for pneumonia. The purpose of this study is to determine if implementing stewardship pharmacist driven MRSA nasal surveillance increases use of the test and reduces the inappropriate use of vancomycin for MRSA coverage in patients with pneumonia. Method: This study was a retrospective chart review and was approved by the Trinity Health of New England Institutional Review Board. For this initiative, a stewardship pharmacist evaluated all patients receiving vancomycin for anti-MRSA therapy at Saint Francis Hospital and Medical Center in Hartford, CT. If the patient’s indication was pneumonia and a MRSA nasal swab had not been ordered, the pharmacist contacted the patient’s provider and requested an order for it. Upon receipt of a negative MRSA nasal swab result, the pharmacist recommended discontinuation of vancomycin to the provider if appropriate. Outcomes from the first four weeks of the pharmacist-driven initiative (April 10, 2023 to May 5, 2023) were compared to the four weeks prior to the initiative (March 13, 2023 to April 7, 2023) as a control group. The primary outcome of this study was percentage of patients who received a MRSA nasal swab. Secondary outcomes included percentage of patients who had vancomycin appropriately de-escalated based on MRSA nasal swab results and mean length of vancomycin therapy. Result: 116 patients met inclusion criteria: 61 in the control group and 55 in the intervention group. Percentage of swabs ordered increased from 36.1% (22/61) without pharmacist intervention to 80.0% (44/55) with pharmacist intervention (p &lt; 0 .0001). There were also increased rates of vancomycin de-escalation in patients with pharmacist intervention, with 58.2% (32/55) of patients in the intervention group having vancomycin discontinued following a negative MRSA swab compared to 19.7% (12/61) in the control group (p &lt; 0 .0001). Conclusion: The results suggest implementing a pharmacist driven MRSA nasal surveillance program into practice could increase the number of MRSA nasal swabs ordered and in turn promote more timely de-escalation of vancomycin in patients with pneumonia. The results from this study can be used to support the wide-spread use of pharmacist driven MRSA nasal surveillance protocols at other institutions.

Swab Testing to Optimize Pneumonia treatment with empiric Vancomycin (STOP-Vanc): study protocol for a randomized controlled trial.

Background: Vancomycin, an antibiotic with activity against Methicillin-resistant Staphylococcus aureus (MRSA), is frequently included in empiric treatment for community-acquired pneumonia (CAP) despite the fact that MRSA is rarely implicated in CAP. Conducting polymerase chain reaction (PCR) testing on nasal swabs to identify the presence of MRSA colonization has been proposed as an antimicrobial stewardship intervention to reduce the use of vancomycin. Observational studies have shown reductions in vancomycin use after implementation of MRSA colonization testing, and this approach has been adopted by CAP guidelines. However, the ability of this intervention to safely reduce vancomycin use has yet to be tested in a randomized controlled trial. Methods: STOP-Vanc is a pragmatic, prospective, single center, non-blinded randomized trial. Adult patients with suspicion for CAP who are receiving vancomycin and admitted to the Medical Intensive Care Unit at Vanderbilt University Medical Center will be screened for eligibility. Eligible patients will be enrolled and randomized in a 1:1 ratio to either receive MRSA nasal swab PCR testing in addition to usual care (intervention group), or usual care alone (control group). PCR testing results will be transmitted through the electronic health record to the treating clinicians. Primary providers of intervention group patients with negative swab results will also receive a page providing clinical guidance recommending discontinuation of vancomycin. The primary outcome will be vancomycin-free hours alive, defined as the number of hours alive and free of the use of vancomycin within the first seven days following trial enrollment estimated using a proportional odds ratio model. Secondary outcomes include 30-day all-cause mortality and time alive off vancomycin. Discussion: STOP-Vanc will provide the first randomized controlled trial data regarding the use of MRSA nasal swab PCR testing to guide antibiotic de-escalation. This study will provide important information regarding the effect of MRSA PCR testing and antimicrobial stewardship guidance on clinical outcomes in an intensive care unit setting. Trial registration: This trial was registered on ClinicalTrials.gov on February 22, 2024. (ClinicalTrials.gov identifier: NCT06272994).

Early initiation of combined therapy in severely immunocompromised patients with COVID-19: a retrospective cohort study

This single-centre retrospective cohort study reports on the results of a descriptive (non-comparative) retrospective cohort study of early initiation of antivirals and combined monoclonal antibody therapy (mAbs) in 48 severely immunocompromised patients with COVID-19. The study assessed the outcomes and the duration of viral shedding. The patients started early combined therapy (ECT) a median of 2 days (interquartile range [IQR]: 1–3 days) after the diagnosis of SARS-CoV-2 infection. Except for 1 patient who died due COVID-19-related respiratory failure, patients had their first negative nasopharyngeal swab result after a median of 11 days (IQR: 6–17 days) after starting combined therapy. There were no reports of severe side effects. During a follow-up period of 512 days (interquartile range [IQR]: 413–575 days), 6 patients (12.5%) died and 16 (33.3%) were admitted to hospital. Moreover, 12 patients (25%) were diagnosed with SARS-CoV-2 reinfection a median of 245 days (IQR: 138–401 days) after starting combined treatment. No relapses were reported. Although there was no comparison group, these results compare favourably with the outcomes of severely immunocompromised patients with COVID-19 reported in the literature.

Clinical Outcome and 7-Day Virological Clearance in High-Risk Patients with Mild-Moderate COVID-19 Treated with Molnupiravir, Nirmatrelvir/Ritonavir, or Remdesivir.

We compared the effectiveness and virological clearance (VC) at day 7 (T7) post-treatment with molnupiravir, nirmatrelvir/ritonavir, and remdesivir in SARS-CoV-2-infected patients at high risk(HR) for clinical progression. We conducted a retrospective study enrolling HR patients with mild-to-moderate COVID-19 (Jan-Oct 2022) treated with nirmatrelvir/ritonavir or molnupiravir or 3days of remdesivir. We investigated clinical recovery at T7 (resolution of symptoms for ≥ 72h or all-cause death), VC at T7 (PCR/antigenic negative nasopharyngeal swab), and median time to VC (days from symptom onset to the first negative swab). Factors associated with VC were investigated by logistic regression. In the study, 92/376 (43.8%) patients received molnupiravir, 150/376 (24.7%) nirmatrelvir/ritonavir, and 134/376 (31.5%) remdesivir. Forty-nine (13%) patients were unvaccinated or incompletely vaccinated. Patients treated with nirmatrelvir/ritonavir were younger and presented immunodeficiencies more frequently; remdesivir was used more commonly in patients hospitalized for other diseases. A high proportion of patients obtained clinical recovery without differences among the therapies (97.5% for molnupiravir, 98.3% for nirmatrelvir/ritonavir, and 93.6% for remdesivir); 12 (3.7%) patients died. Nirmatrelvir/ritonavir was associated with a higher proportion of T7 VC and a shorter time to VC compared to molnupiravir/remdesivir, also after adjustment for age and immunodeficiency (AOR 0.445 RDV vs. NMV-r, 95% CI 0.240-0.826, p = 0.010; AOR 0.222 MNP vs. NMV-r, 95% CI 0.105-0.472, p < 0.001). SARS-COV-2 antiviral treatments are an excellent therapeutic strategy in HR patients. Nirmatrelvir/ritonavir showed a higher proportion of VC as early as 7days after treatment, confirming its likely superiority in indirect comparisons.

Is Streptococcus pyogenes a pathogen or passenger in uncomplicated acute sore throat? A systematic review and meta-analysis

ObjectivesThe objective was to estimate the probability that finding a Streptococcus pyogenes (Group A Streptococcus) in a throat swab in a patient with a sore throat reflects the aetiology. We also investigated to what extent this is influenced by age, carrier rates of S. pyogenes and climate zone. MethodsWe conducted a comprehensive search of Medline and Scopus up until October 2023 for case-control studies reporting the prevalence of S. pyogenes in patients with a sore throat and healthy controls. We only included studies with separate data for children and adults. We used the positive and negative etiologic predictive values (P-EPV and N-EPV) to estimate the probability of a link between a sore throat and a finding of S. pyogenes. ResultsWe included 15 studies in our meta-analysis. The overall P-EPV for children and adults were 63% (49-74%) and 92% (87-95%), respectively. The P-EPV rose to 83% (64-93%) for children and 94% (90-97%) for adults when only patients with 3-4 Centor criteria were included. The overall N-EPV was 97% (96-98%) for children and 96% (95-97%) for adults. ConclusionDetecting S. pyogenes in adult patients with an uncomplicated acute sore throat is useful to rule in S. pyogenes as the likely aetiologic agent. The P-EPV significantly increased for children when those with 3-4 Centor criteria were selected. A negative throat swab is always useful for both children and adults to rule out S. pyogenes as the cause of sore throat.

Dual structure-switching aptamer-mediated signal amplification cascade for SARS-CoV-2 detection

Since the outbreak of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) at the end of 2019, the spread of the virus has posed a significant threat to public health and the global economy. This work proposed a one-step, dual-structure-switching aptamer-mediated signal amplification cascade for rapid and sensitive detection of the SARS-CoV-2 nucleocapsid protein. This system consisted of two DNA aptamers with structure-switching functionality and fuel DNA, where a cascade of strand hybridization and displacement triggered fluorescence generation and signal amplification. This aptamer-based amplification cascade required neither an amplification stage using enzymes nor pre-processing steps such as washing, viral isolation, and gene extraction. The assay could distinguish SARS-CoV-2 from other respiratory viruses and detect up to 1.0 PFU/assay of SARS-CoV-2 within 30 min at room temperature. In 35 nasopharyngeal clinical samples, the assay accurately assessed 25 positive and 10 negative clinical swab samples, which were confirmed using quantitative polymerase chain reaction. The strategy reported herein can help detect newly emerging pathogens and biomarkers of various diseases in liquid samples. In addition, the developed detection system consisting of only DNA and fluorophores can be widely integrated into liquid biopsy platforms for disease diagnosis.

Significance of colonization by antibiotic-resistant organisms prior to congenital heart disease surgery in children from low- to middle-income countries sent by non-governmental organizations to Switzerland.

Children with congenital heart disease (CHD) from low- to middle-income countries (LMIC) are suspected to have a high prevalence of antibiotic-resistant microorganisms (ARMOs) carriage, but data are currently lacking. Carriage of ARMOs could impact the post-operative course in pediatric intensive care unit (PICU). The aim of the study was to assess the prevalence of ARMOs carriage in children with CHD from LMIC and its impact on post-operative outcomes. This was a retrospective monocentric study from 01/2019 to 12/2022. Included patients were children (0-18 years) from a LMIC admitted after CHD surgery and with AMRO screening performed the week before. Infections and post-operative evolution were compared based on ARMOs carriage status. Among 224 surgeries (median age 38.5 months (IQR 22-85.5)), ARMOs carriage was evidenced in 95 cases (42.4%). Main organisms isolated were Extended Spectrum Beta-Lactamase (ESBL) producing E. coli (75/224) 33.5%)) and ESBL-K. pneumoniae (30/224) 13.4%)). Median mechanical ventilation duration was 1 day (IQR 0-1), PICU stay 3 days (IQR 2-4) and hospital stay 6.5 days (IQR 5-10). A total of 17 infectious episodes occurred in 15 patients, mostly consisting in hospital-acquired pneumonia (HAP) (12/17). Only two infections were caused by a colonizing ARMO. Occurrence of infections and patients' outcome were similar between ARMO carriers and non-carriers. Higher use of carbapenems (6 (6.3%) vs 1 (0.8%), p = 0.04) and a trend to a higher use of vancomycin (14 (13.7%) vs 9 (6.9%), p = 0.04) in case of ARMOs carriage. Applying current guidelines, negative swab screening could have led to sparing most of empirical vancomycin therapy (11/12) for HAP based on current guidelines. Prevalence of AMROs carriage is high in children from LMIC and has a limited impact on patients' outcome. However, ARMOs carriage leads to higher consumption of antibiotics. Screening may help saving use of broad-spectrum antibiotic in non-carrier patients.

513 Predictive Values of MRSA Nasal Swabs for Pneumonia in Burn ICU Patients

Abstract Introduction Sepsis in burn-injured patients remains a leading cause of mortality in those who survive initial resuscitation. Methicillin-resistant Staphylococcus aureus (MRSA) is a common causative pathogen for pneumonia in burn-injured patients. Studies evaluating the predictive value of MRSA nasal swabs for pneumonia have largely excluded the burn-injured population. Methods Patients 18 years or older admitted to the Burn ICU at a tertiary medical center from 2016 to 2021 were included if they had any burns, a pneumonia ICD-10 code, an MRSA nasal swab obtained during admission, and any respiratory cultures associated with at least five consecutive days of antibiotics. Results There were 267 instances of pneumonia across 136 patients included. MRSA nasal swabs had an overall sensitivity of 39%, specificity of 98.7%, positive predictive value (PPV) of 84.2%, and negative predictive value (NPV) of 89.9%. MRSA nasal swabs obtained less than seven days from antibiotic initiation had a specificity of 98.6% and NPV of 98.6%; meanwhile, swabs obtained at least seven days from antibiotic initiation had a specificity of 98.7% and NPV of 86.4%. Conclusions The high specificity and NPV indicate that negative MRSA nasal swabs obtained less than seven days from antibiotic initiation may be used to de-escalate anti-MRSA antibiotics in clinically stable burn-injured patients with suspicion of pneumonia. The decrease in NPV suggests that it may be beneficial to obtain a repeat swab periodically or upon suspicion of pneumonia. Applicability of Research to Practice This study is the first to measure the sensitivity, specificity, PPV, and NPV of the MRSA PCR nasal swab in a cohort comprised only of patients admitted to a burn intensive care unit. The findings support the use of the MRSA nasal swab as a tool to aid in the decision to initiate or de-escalate anti-MRSA antimicrobials for pneumonia.

Accelerated Development of a COVID-19 Lateral Flow Test in an Academic Setting: Lessons Learned.

The COVID-19 pandemic further demonstrated the need for usable, reliable, and cost-effective point-of-care diagnostics that can be broadly deployed, ideally for self-testing at home. Antigen tests using more-detectable reporter labels (usually at the cost of reader complexity) achieve better diagnostic sensitivity, supporting the value of higher-analytical-sensitivity reporter technologies in lateral flow.We developed a new approach to simple, inexpensive lateral flow assays (LFAs) of great sensitivity, based on the glow stick peroxyoxalate chemistry widely used in emergency settings and in children's toys. At the peak of the COVID-19 pandemic, we had the opportunity to participate in the pandemic-driven NIH Rapid Acceleration of Diagnostics (RADx) initiative aiming to develop a deployable lateral flow diagnostic for SARS-CoV-2 nucleoprotein based on our novel glow stick-inspired light-emitting reporter technology. During this project, we screened more than 250 antibody pairs for analytical sensitivity and specificity directly in LFA format, using recombinant nucleoprotein and then gamma-irradiated virions spiked into negative nasal swab extracts. Membranes and other LFA materials and swabs and extraction reagent components also were screened and selected. Optimization of conjugate preparation and spraying as well as pretreatment/conditioning of the sample pad led to the final optimized LFA strip. Technology development also included optimization of excitation liquid enclosed in disposable droppers, design of a custom cartridge and smartphone-based reader, and app development, even a prototype reader usable with any mobile phone. Excellent preclinical performance was first demonstrated with contrived samples and then with leftover clinical samples. Moving beyond traditional academic focus areas, we were able to establish a quality management system (QMS), produce large numbers of customized LFA cassettes by contract injection molding, build in-house facilities to assemble and store thousands of complete tests for verification and validation and usability studies, and source kitting/packaging services and quality standard reagents and build partnerships for clinical translation, regulatory guidance, scale up, and market deployment. We were not able to bring this early stage technology to the point of commercialization within the limited time and resources available, but we did achieve strong proof-of-concept and advance translational aspects of the platform including initial high-performance LFAs, reading by the iPhone app using only a $2 plastic dark box with no lens, and convenient, usable excitation liquid packaging in droppers manufacturable in very large numbers.In this Account, we aim to provide a concise overview of our 18-month sprint toward the practical development of a deployable antigen lateral flow assay under pandemic conditions and the challenges and successes experienced by our team. We highlight what it takes to coach a technically savvy but commercially inexperienced academic team through the accelerated translation of an early stage technology into a useful product. Finally, we provide a guided tutorial and workflow to empower others interested in the rapid development of translatable LFAs.

Advancing SERS Diagnostics in COVID‐19 with Rapid, Accurate, and Label‐Free Viral Load Monitoring in Clinical Specimens via SFNet Enhancement

AbstractThis study presents an integrated approach combining surface‐enhanced Raman spectroscopy (SERS) with a specialized deep learning algorithm, SFNet, to offer a rapid, accurate, and label‐free alternative for COVID‐19 diagnosis and viral load quantification. The SiO2‐coated silver nanorod arrays are employed as the SERS substrates, fabricated using a reliable and effective glancing angle deposition technique. A dataset of 4800 SERS spectra from 120 positive and 120 negative inactivated clinical human nasopharyngeal swabs are collected directly on the SERS substrates without any labels. A SFNet algorithm is tailored to adapt to the unique spectral features inherent to SERS data, achieving a test accuracy of 98.5% and a blind test accuracy of 99.04%. Moreover, an optimized SFNet algorithm unveils the capability of estimating SARS‐CoV‐2 viral loads, accurately predicting the cycle threshold values (Ct values) of the three vital gene fragments with a root mean square error (RMSE) of 1.627 (1.3 for blind test). The methodology is substantiated using actual clinical specimens and completed in &lt;15 min, thereby strengthening its real‐world point‐of‐care applicability. This rapid and precise yet label‐free modality competes favorably with classical reverse‐transcription real‐time polymerase chain reaction (RT‐PCR) and marks an advancement in SERS‐based sensor algorithms.

May high blood viscosity predict cardiac involvement in COVID-19 patients?

Aims: Assessing the effects of whole blood viscosity (WBV) on prognosis and deterioration in cardiac parameters in COVID-19 patients after recovery using cardiac magnetic resonance imaging (CMRI) and echocardiography is the purpose of this study. Methods: The study involved 70 patients. Patients who had COVID-19 pneumonia were admitted to the hospital. All patients met the eligibility criteria if they remained symptom-free of respiratory and cardiac symptoms and had negative swab test results at the end of the isolation period, for at least two weeks following the positive swab test result. Transthoracic echocardiography was performed within 24 hours prior to CMRI. WBV was measured in centipoises (cP) at 208 seconds-1 shear rate. The median value of WBV was calculated for the entire study population, which was subsequently utilized to divide the population into two subgroups. These were designated as high WBV and low WBV subgroups. Results: Elevated levels of hemoglobin, hematocrit, total protein, C-reactive protein, D-dimer, and fibrinogen were observed in individuals with high WBV. Conversely, TAPSE, S, and FAC were notably reduced in those with high WBV. Notably, CMRI revealed significant increases in native T1, native T2 mapping signal, and extracellular volume among patients with high WBV. Furthermore, in individuals with high WBV, there was a significant decrease in right ventricle stroke volume and right ventricle ejection fraction, accompanied by a notable increase in right ventricle end-systolic volume. Conclusion: WBV values measured during hospital admission may have early and late prognostic importance for COVID-19 infection.

Epidemiology of healthcare-associated Pseudomonas aeruginosa in intensive care units: are sink drains to blame?

Pseudomonas aeruginosa (PA) is a common cause of healthcare-associated infection (PA-HAI) in the intensive care unit (ICU). To describe the epidemiology of PA-HAI in ICUs in Ontario, Canada, and to identify episodes of sink-to-patient PA transmission. This was a prospective cohort study of patients in six ICUs from 2018 to 2019, with retrieval of PA clinical isolates, and PA-screening of antimicrobial-resistant organism surveillance rectal swabs, and of sink drain, air, and faucet samples. All PA isolates underwent whole-genome sequencing. PA-HAI was defined using US National Healthcare Safety Network criteria. ICU-acquired PA was defined as PA isolated from specimens obtained ≥48h after ICU admission in those with prior negative rectal swabs. Sink-to-patient PA transmission was defined as ICU-acquired PA with close genomic relationship to isolate(s) previously recovered from sinks in a room/bedspace occupied 3-14 days prior to collection date of the relevant patient specimen. Over ten months, 72PA-HAIs occurred among 60/4263 admissions. The rate of PA-HAI was 2.40 per 1000 patient-ICU-days; higher in patients who were PA-colonized on admission. PA-HAI was associated with longer stay (median: 26 vs 3 days uninfected; P < 0.001) and contributed to death in 22/60 cases (36.7%). Fifty-eight admissions with ICU-acquired PA were identified, contributing 35/72 (48.6%) PA-HAIs. Four patients with five PA-HAIs (6.9%) had closely related isolates previously recovered from their room/bedspace sinks. Nearly half of PA causing HAI appeared to be acquired in ICUs, and 7% of PA-HAIs were associated with sink-to-patient transmission. Sinks may be an under-recognized reservoir for HAIs.