Evaluating Methicillin-Resistant Staphylococcus aureus Polymerase Chain Reaction Nasal Screening as a Tool for Antimicrobial Stewardship.

INTRODUCTION: Initiation of broad-spectrum empiric antibiotics is common when infection is suspected in hospitalized adults. The benefits of early utilization of effective antibiotics are well documented. However, the negative effects of inappropriate antibiotic use have led to antimicrobial stewardship mandates. Recent data demonstrate the utility of methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reaction (PCR) nasal screening to steward anti-MRSA empiric antibiotics in pneumonia. We hypothesize that MRSA PCR nasal swabs would also be effective to rule out other MRSA infection to effectively limit unnecessary antibiotics for any infectious source. METHODS: We performed a single-center retrospective chart review of all adult patient encounters from October 2019-July 2021 with MRSA PCR nasal testing. We then reviewed all charts to evaluate for the presence of infections based on source cultures results, as the gold standard. Sensitivity, specificity, negative predictive value, and positive predictive value were calculated from 2 × 2 contingency tables. RESULTS: Among all patients with MRSA nasal screening, 1189 patients had any infection. Prevalence of MRSA nasal carriage among patients screened was 12%. Prevalence of MRSA infection among all infections was 7.5%. MRSA nasal swabs demonstrated a negative predictive value of 100% for MRSA urinary tract infection, 97.9% for MRSA bacteremia, 97.8% for MRSA pneumonia, 92.1% for MRSA wound infection, and 96.6% for other MRSA infections. Overall, MRSA PCR nasal swabs had a sensitivity of 68.5%, specificity of 90.1%, positive predictive value of 23.7%, and negative predictive value of 98.5% for any infections. CONCLUSIONS: MRSA PCR nasal swabs have a high negative predictive value for all infections. Our data support the use of MRSA PCR nasal swabs to rule out MRSA infection and thereby allow early de-escalation of MRSA coverage in hospitalized patients requiring empiric antibiotics. Implementation of MRSA screening could decrease antibiotic-associated morbidity, resistance, and costs. More studies should be conducted to validate these results and support these findings.

Gut microbial disruption in critically ill patients with COVID-19 associated pulmonary aspergillosis (preprint)

Objectives: COVID-19 disease can be exacerbated by Aspergillus superinfection (CAPA). The causes of CAPA are not yet fully understood. Recently, alterations in the gut microbiome have been associated with a complicating course and increasing severity of COVID-19 disease, most likely via immunological mechanisms. Aim of this study was to investigate a potential association between severe CAPA and alterations in the gut and bronchial microbiota. Methods: We performed 16S rRNA gene amplicon sequencing of stool and bronchial samples from a total of 16 COVID-19 patients with CAPA and 26 patients without CAPA. All patients were admitted to the intensive care unit. Results were carefully tested for potential influences on the microbiome during hospitalization. Results: We found that late in COVID-19 disease, CAPA patients exhibited a trend towards reduced gut microbial diversity. Furthermore, late stage CAPA disease showed an increased presence of Staphylococcus epidermidis in the gut. This is not found in late non-CAPA cases or early disease. The analysis of bronchial samples did not show significant results. Conclusions: This is the first study showing alterations in the gut microbiome accompany severe CAPA and possibly influence the hosts immunological response. In particular, an increase of Staphylococcus epidermidis in the intestine could be of importance.

Potential for bacteriophage therapy for Staphylococcus aureus pneumonia with influenza A coinfection.

The ability of influenza A virus to evolve, coupled with increasing antimicrobial resistance, could trigger an influenza pandemic with great morbidity and mortality. Much of the 1918 influenza pandemic mortality was likely due to bacterial coinfection, including Staphylococcus aureus pneumonia. S. aureus resists many antibiotics. The lack of new antibiotics suggests alternative antimicrobials, such as bacteriophages, are needed. Potential delivery routes for bacteriophage therapy (BT) include inhalation and intravenous injection. BT has recently been used successfully in compassionate access pulmonary infection cases. Phage lysins, enzymes that hydrolyze bacterial cell walls and which are bactericidal, are efficacious in animal pneumonia models. Clinical trials will be needed to determine whether BT can ameliorate disease in influenza and S. aureus coinfection.

A 53-Year-Old Man Presents to the ED With Shortness of Breath, Cough, and Fever.

CASE PRESENTATION: A 53-year-old man presented to the ED at a time of low severe acute respiratory syndrome coronavirus 2, also known as coronavirus disease 2019 (COVID-19), prevalence and reported 2 weeks of progressive shortness of breath, dry cough, headache, myalgias, diarrhea, and recurrent low-grade fevers to 39°C for 1 week with several days of recorded peripheral capillary oxygen saturation of 80% to 90% (room air) on home pulse oximeter. Five days earlier, he had visited an urgent care center where a routine respiratory viral panel was reportedly negative. A COVID-19 reverse transcriptase polymerase chain reaction test result was pending at the time of ED visit. He reported a past medical history of gastroesophageal reflux disease that was treated with famotidine. Travel history included an out-of-state trip 3 weeks earlier, but no recent international travel.

Broad-spectrum, patient-adaptable inhaled niclosamide-lysozyme particles are efficacious against coronaviruses in lethal murine infection models (preprint)

Niclosamide (NIC) has demonstrated promising in vitro antiviral efficacy against SARS-CoV-2, the causative agent of the COVID-19 pandemic. Though NIC is already FDA-approved, the oral formulation produces systemic drug levels that are too low to inhibit SARS-CoV-2. As an alternative, direct delivery of NIC to the respiratory tract as an aerosol could target the primary site of for SARS-CoV-2 acquisition and spread. We have developed a niclosamide powder suitable for delivery via dry powder inhaler, nebulizer, and nasal spray through the incorporation of human lysozyme (hLYS) as a carrier molecule. This novel formulation exhibits potent in vitro and in vivo activity against MERS-CoV and SARS-CoV-2 and protects against methicillin-resistance staphylococcus aureus pneumonia and inflammatory lung damage. The suitability of the formulation for all stages of the disease and low-cost development approach will ensure wide-spread utilization.

Surgical masks decontamination for reuse by members of the public: feasibility study and development of home-based methods (preprint)

This study aims to propose decontamination methods that are suitable for use by members of the public to cope with the shortage of surgical masks during the current COVID-19 pandemic. 3-ply surgical masks were subjected to different decontamination protocols (heat, chemical, ultraviolet irradiation) to assess their abilities to achieve at least 4-log reduction of two common respiratory pathogens, H1N1 Influenza A virus, a single-stranded RNA enveloped virus similar to SARS-CoV-2 and Staphylococcus aureus, a Gram-positive bacterium that is more resistant to decontamination than single stranded RNA enveloped virus. Decontaminated surgical masks were assessed for differences in breathability, particle filtration efficiency and bacteria filtration efficiency as compared with non-decontaminated masks. The number of decontamination cycles that the 3-ply surgical masks could undergo without significant changes in breathability and filtration efficiencies were also determined. It was found that surgical masks decontaminated by either soaking for 60 min in 0.5% (v/v) aqueous hydrogen peroxide solution, or 30 min of soaking in 0.05% - 0.5% (v/v) aqueous sodium hypochlorite diluted from household bleach or ultraviolet irradiation by a surface dose of 13.5 kJ/m2 were able to achieve at least a 4-log reduction of both Staphylococcus aureus and H1N1 Influenza A virus spiked on surgical mask test swatches. No significant changes in breathability and filtration efficiencies of the surgical masks were observed after ten decontamination cycles of hydrogen peroxide or diluted bleach treatment or 30 cycles of ultraviolet irradiation. 

Characterization of Microbial Co-infections in the Respiratory Tract of hospitalized COVID-19 patients (preprint)

Summary Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of Coronavirus disease 2019 (COVID-19). However, microbial composition of the respiratory tract and other infected tissues, as well as their possible pathogenic contributions to varying degrees of disease severity in COVID-19 patients remain unclear. Method Between January 27 and February 26, 2020, serial clinical specimens (sputum, nasal and throat swab, anal swab and feces) were collected from a cohort of hospitalized COVID-19 patients, including 8 mildly and 15 severely ill patients (requiring ICU admission and mechanical ventilation), in the Guangdong province, China. Total RNA was extracted and ultra-deep metatranscriptomic sequencing was performed in combination with laboratory diagnostic assays. Co-infection rates, the prevalence and abundance of microbial communities in these COVID-19 patients were determined. Findings Notably, respiratory microbial co-infections were exclusively found in 84.6% of severely ill patients (11/13), among which viral and bacterial co-infections were detected by sequencing in 30.8% (4/13) and 69.2% (9/13) of the patients, respectively. In addition, for 23.1% (3/13) of the patients, bacterial co-infections with Burkholderia cepacia complex (BCC) and Staphylococcus epidermidis were also confirmed by bacterial culture. Further, a time-dependent, secondary infection of B. cenocepacia with expressions of multiple virulence genes in one severely ill patient was demonstrated, which might be the primary cause of his disease deterioration and death one month after ICU admission. Interpretation Our findings identified distinct patterns of co-infections with SARS-CoV-2 and various respiratory pathogenic microbes in hospitalized COVID-19 patients in relation to disease severity. Detection and tracking of BCC-associated nosocomial infections are recommended to improve the pre-emptive treatment regimen and reduce fatal outcomes of hospitalized patients infected with SARS-CoV-2. Funding National Science and Technology Major Project of China, National Major Project for Control and Prevention of Infectious Disease in China, the emergency grants for prevention and control of SARS-CoV-2 of Ministry of Science and Technology and Guangdong province, Guangdong Provincial Key Laboratory of Genome Read and Write, Guangdong Provincial Academician Workstation of BGI Synthetic Genomics, and Shenzhen Engineering Laboratory for Innovative Molecular Diagnostics.

Vaporized H2O2 decontamination against surrogate viruses for the reuse of N95 respirators in the COVID-19 emergency (preprint)

Decontamination of N95 respirators has become critical to alleviate PPE shortages for healthcare workers in the current COVID-19 emergency. The factors that are considered for the effective reuse of these masks are the fit, filter efficiency and decontamination/disinfection level both for SARS-CoV-2, which is the causative virus for COVID-19, and for other organisms of concern in the hospital environment such as Staphylococcus aureus or Clostridium difficile. In its guidance entitled 'Recommendations for Sponsors Requesting EUAs for Decontamination and Bioburden Reduction Systems for Surgical Masks and Respirators During the Coronavirus Disease 2019 (COVID19) Public Health Emergency' (May 2020)[1], the FDA recommends a 6-log10 reduction in either the most resistant bacterial spores for the system or in a mycobacterium species to authorize the use of a decontamination method of N95 respirators for single or multiple users. While the goal is primarily inactivation against SARS-CoV-2, testing of decontamination methods against the virus may not always be available. For decontamination methods considered for only single users, the recommendation is a 6-log10 reduction in the infective virus concentration of 3 non-enveloped viruses or in the concentration of two Gram (+) and two Gram (-) bacteria. Based on these recommendations, we explored the efficacy of vaporized H2O2 (VHP) treatment of N95 respirators against surrogate viruses covering a wide range of disinfection resistance for emergency decontamination and reuse to alleviate PPE shortages for healthcare workers in the COVID-19 emergency.

Severe immune thrombocytopenic purpura in critical COVID-19.

COVID-19 is a new disease with many undescribed clinical manifestations. We report herein a case of severe immune thrombocytopenic purpura (ITP) in a critical COVID-19 patient. A patient presented a severe episode of immune thrombocytopenia (< 10 × 109/L) 20 days after admission for a critical COVID-19. This thrombocytopenia was associated with a life-threatening bleeding. Response to first-line therapies was delayed as it took up to 13 days after initiation of intravenous immunoglobulin and high-dose dexamethasone to observe an increase in platelet count. COVID-19 may be associated with late presenting severe ITP. Such ITP may also be relatively resistant to first-line agents. Hematological manifestations of COVID-19, such as the ones associated with life-threatening bleeding, must be recognized.

Hospital-acquired infective endocarditis during Covid-19 pandemic (preprint)

Background. The COVID pandemic has had a major impact on healthcare in hospitals, including the diagnosis and treatment of infections. Hospital-acquired infective endocarditis (HAIE) is a severe complication of medical procedures that has shown a progressive increase in recent years. Objectives. to determine whether the incidence of HAIE during the first two months of the epidemic (March-April 2020) was higher than previously observed and to describe the clinical characteristics of these cases. The probability of studied event (HAIE) during the studied period was calculate by Poisson distribution. Results. Four cases of HAIE were diagnosed in our institution during the study period. The incidence of HAIE during the study period was 2/patient-month and 0.25/patient-month during the previous 5 years (p=0.024). Two cases appeared during admission for COVID-19 with pulmonary involvement treated with metilprednisolone and tocilizumab. The other two cases were admitted to the hospital during the epidemic. All cases underwent central venous and urinary catheterization during admission. The etiology of HAIE was Enterococcus faecalis (2 cases), Staphylococcus aureus and Candida albicans (one case each). A source of infection was identified in three cases (central venous catheter, peripheral venous catheter, sternal wound infection, respectively). One patient was operated on. There were no fatalities during the first 30 days of follow-up. Conclusion. The incidence of HAIE during COVID-19 pandemic in our institution was higher than usual. In order to reduce the risk of this serious infection, optimal catheter care, appropriate use of corticosteroids and interleukin antagonists and early treatment of every local infection should be prioritized during coronavirus outbreaks.

Efficacy of moist heat decontamination against various pathogens for the reuse of N95 respirators in the COVID-19 emergency (preprint)

Decontamination of N95 respirators has become critical to alleviate PPE shortages for healthcare workers in the current COVID-19 emergency. The factors that are considered for the effective reuse of these masks are the fit, filter efficiency and decontamination/disinfection level both for SARS-CoV2, which is the causative virus for COVID-19, and for other organisms of concern in the hospital environment such as Staphylococcus aureus or Clostridium difficile. The efficacy of inactivation or eradication against various pathogens should be evaluated thoroughly to understand the level of afforded disinfection. Methods commonly used in the sterilization of medical devices such as ionizing radiation, vaporized hydrogen peroxide, and ethylene oxide can provide a high level of disinfection, defined as a 6 log10 reduction, against bacterial spores, considered the most resistant microorganisms. CDC guidance on the decontamination and reuse of N95s also includes the use of moist heat (60{degrees}C, 80% relative humidity, 15-30 min) as a possible recommendation based on literature showing preservation of fit efficiency and inactivation of H1N1 on spiked masks. Here, we explored the efficacy of using moist heat under these conditions as a decontamination method for an N95 respirator (3M 1860S, St. Paul, MN) against various pathogens with different resistance; enveloped RNA viruses, Gram (+/-) bacteria, and non-enveloped viruses.

Panton-Valentine Leukocidin-Secreting Staphylococcus aureus Pneumonia Complicating COVID-19.

Necrotizing pneumonia induced by Panton-Valentine leukocidin-secreting Staphylococcus aureus is a rare but life-threatening infection that has been described in patients after they had influenza. We report a fatal case of this superinfection in a young adult who had coronavirus disease.