Secondary Infections in Patients with Extremely Severe COVID-19 During ECMO Therapy.

Up to 70% of patients hospitalized for COVID-19 need respiratory support, up to 10% need high-flow oxygen therapy, non-invasive and invasive ventilation. However, standard methods of respiratory support are ineffective in 0.4-0.5% of patients. In case of potentially reversible critical refractory respiratory failure that patients may require ECMO. Management of patients with extremely severe COVID-19 associates with numerous clinical challenges, including critical illness, multiple organ dysfunction, blood coagulation disorders, requiring prolonged ICU stay and care, use of multiple pharmacotherapies including immunosuppressive drugs. Pharmacological suppression of immunity is associated with a significant increase in the risk of secondary bacterial and fungal infections. Currently, data on epidemiology of secondary infections in patients with COVID-19 undergoing ECMO is limited. Aim. To study the prevalence and etiology of secondary infections associated with positive blood cultures in patients with extremely severe COVID-19 requiring ECMO. Materials and methods. A single-center retrospective non-interventional epidemiological study including 125 patients with extremely severe COVID-19 treated with ECMO in April 2020 to December 2021. Results. Out of 700 blood culture tests performed in 125 patients during the study, 250 tests were positive confirming bacteremia/fungemia. Isolated pathogens varied depending on the duration of ECMO: gram-positive bacteria (primarily coagulase-negative staphylococci) dominated from the initiation of ECMO support;increased duration of ECMO associated with an increasing the proportion of pathogens common in ICU (Klebsiella pneumoniae and/or Acinetobacter baumannii with extensively drug resistant and pan-drug resistant phenotypes, and vancomycin-resistant Enterococcus faecium). When ECMO lasted more than 7-14 days, opportunistic pathogens (Candida species, Stenotrophomonas maltophilia, Providencia stuartii, non-diphtheria corynebacteria, Burkholderia species and others) prevailed as etiological agents. Conclusion. Longer duration of ECMO resulted in increasing the rates of infectious complications. In patients undergoing ECMO for more than 14 days, the microbiological landscape becomes extremely diverse, which hampers choosing an empirical antimicrobial therapy. Since potential pathogens causing secondary infections in patients during ECMO are difficult to predict, rapid identification of rare opportunistic pathogens and their sensitivity profile, followed by targeted administration of antimicrobials, seems most beneficial.Copyright © 2023, V.A. Negovsky Research Institute of General Reanimatology. All rights reserved.

A Case Series of Kodamaea Ohmeri Infection: The Hidden Threat Unleashed

Intro: Kodamaea ohmeri, previously known as Pichia ohmeri, is an ascomycetous yeast that has emerged as an important cause of fungemia in immunocompromised patients. During the anamorphic stage this organism is also known as Candida guillermondii var. membranaefaciens. Method(s): We report five cases of Kodamaea ohmeri encountered from multicenter in Malaysia. Antifungal agent of choice will be discussed based on literature review. Finding(s): The cases were: (1) a contaminated peritoneal fluid in an adult patient on peritoneal dialysis;(2) a 60-year-old man with infected diabetic foot isolated K. ohmeri from a bone sample. Both cases discharged well without active antifungal fungal therapy. We observed fatality cases involving (3) an old man with underlying gastric adenocarcinoma who complicated with catheter- related bloodstream infection caused by K. ohmeri;(4) a patient with ventilator- associated pneumonia and septicaemic shock secondary to perforated terminal ileum;(5) and a severely ill COVID-19 stage 5b patient who passed away due to systemic fungaemia caused by K. ohmeri. Discussion(s): All three fatal cases received either amphotericin B or caspofungin as active antifungal agent. Literature evidence has shown that 40% of patient met demise despite on active antifungal agent, suggesting that currently no definitive antifungal agent proven to be a superior treatment option for K. ohmeri infection. Removal of indwelling medical device combined with antifungal therapy has favorable clinical outcome. Conclusion(s): Therefore, K. ohmeri infection in severely ill patients should be considered as a critical condition. Potential of alternative antifungal combinations need to be explored for an effective treatment option.Copyright © 2023

Candida lipolytica Bloodstream Infection in an Adult Patient with COVID-19 and Alcohol Use Disorder: A Unique Case and a Systematic Review of the Literature.

Candida lipolytica is an uncommon Candida species causing invasive fungemia. This yeast is mainly associated with the colonisation of intravascular catheters, complicated intra-abdominal infections, and infections in the paediatric population. Here, we report a case of C. lipolytica bloodstream infection in a 53-year-old man. He was admitted for an alcohol withdrawal syndrome and mild COVID-19. Among the primary risk factors for candidemia, only the use of broad-spectrum antimicrobials was reported. The empiric treatment was commenced with caspofungin and then targeted with intravenous fluconazole. Infective endocarditis was ruled out using echocardiography, and PET/TC was negative for other deep-seated foci of fungal infection. The patient was discharged after blood culture clearance and clinical healing. To the best of our knowledge, this is the first case of C. lipolytica candidemia in a patient with COVID-19 and alcohol use disorder. We performed a systematic review of bloodstream infections caused by C. lipolytica. Clinicians should be aware of the possibility of C. lipolytica bloodstream infections in patients with alcohol use disorder, especially in a COVID-19 setting.

COVID-19 Is a Confounder of Increased Candida Airway Colonisation.

An increased incidence of invasive fungal infection was reported in SARS-CoV-2-infected patients hospitalised in the intensive care unit. However, the impact of COVID-19 on Candida airway colonisation has not yet been assessed. This study aimed to test the impact of several factors on Candida airway colonisation, including SARS-CoV-2 infection. We conducted a two-pronged monocentric retrospective study. First, we analysed the prevalence of positive yeast culture in respiratory samples obtained from 23 departments of the University Hospital of Marseille between 1 January 2018 and 31 March 2022. We then conducted a case-control study, comparing patients with documented Candida airway colonisation to two control groups. We observed an increase in the prevalence of yeast isolation over the study period. The case-control study included 300 patients. In the multivariate logistic regression, diabetes, mechanical ventilation, length of stay in the hospital, invasive fungal disease, and the use of antibacterials were independently associated with Candida airway colonisation. The association of SARS-CoV-2 infection with an increased risk of Candida airway colonisation is likely to be a consequence of confounding factors. Nevertheless, we found the length of stay in the hospital, mechanical ventilation, diabetes, and the use of antibacterials to be statistically significant independent risk factors of Candida airway colonisation.

A Case of Fatal Invasive Trichosporonosis in the Setting of Immunosuppression and Post-COVID-19 Pneumonia.

Trichosporon asahii is an opportunistic fungus that forms septate hyphae and pseudohyphae, resembling Candida albicans, and causes fungemia in susceptible individuals. Risk factors for T. asahii infection include immunosuppression, IV catheters, and malignancy. In the present case, a 67-year-old male with a history of renal transplant on immunosuppressive therapy was hospitalized for coronavirus disease 2019 (COVID-19) pneumonia. Despite treatment with steroids and broad initial antibiotic coverage with cefepime, doxycycline, and vancomycin, the patient underwent continual respiratory decline. His sputum culture on hospital day 10 was positive for non-candidal yeast, and despite subsequent appropriate empiric coverage with micafungin and amphotericin B, the patient continued to decline and ultimately died due to the resistance of T. asahii to these antifungals. This case highlights the importance of suspecting T. asahii as an infectious cause in patients whose cultures show non-candidal yeast and initiating appropriate antifungal treatment early in their treatment course.

Yeast Bloodstream Infections in the COVID-19 Patient: A Multicenter Italian Study (FiCoV Study).

Fungemia is a co-infection contributing to the worsening of the critically ill COVID-19 patient. The multicenter Italian observational study FiCoV aims to estimate the frequency of yeast bloodstream infections (BSIs), to describe the factors associated with yeast BSIs in COVID-19 patients hospitalized in 10 hospitals, and to analyze the antifungal susceptibility profiles of the yeasts isolated from blood cultures. The study included all hospitalized adult COVID-19 patients with a yeast BSI; anonymous data was collected from each patient and data about antifungal susceptibility was collected. Yeast BSI occurred in 1.06% of patients, from 0.14% to 3.39% among the 10 participating centers. Patients were mainly admitted to intensive or sub-intensive care units (68.6%), over 60 years of age (73%), with a mean and median time from the hospitalization to fungemia of 29 and 22 days, respectively. Regarding risk factors for fungemia, most patients received corticosteroid therapy during hospitalization (61.8%) and had a comorbidity (25.3% diabetes, 11.5% chronic respiratory disorder, 9.5% cancer, 6% haematological malignancies, 1.4% organ transplantation). Antifungal therapy was administered to 75.6% of patients, mostly echinocandins (64.5%). The fatality rate observed in COVID-19 patients with yeast BSI was significantly higher than that of COVID-19 patients without yeast BSI (45.5% versus 30.5%). Candida parapsilosis (49.8%) and C. albicans (35.2%) were the most fungal species isolated; 72% of C. parapsilosis strains were fluconazole-resistant (range 0-93.2% among the centers). The FiCoV study highlights a high prevalence of Candida BSIs in critically ill COVID-19 patients, especially hospitalized in an intensive care unit, a high fatality rate associated with the fungal co-infection, and the worrying spread of azole-resistant C. parapsilosis.

Endogenous Fungal Endophthalmitis following COVID-19 Hospitalization: Evidence from a Year-Long Observational Study.

PURPOSE: To describe cases of endogenous fungal endophthalmitis (EFE) post-recovery from or hospitalization for coronavirus disease 2019 (COVID-19). METHODS: This prospective audit involved patients with suspected endophthalmitis referred to a tertiary eye care center over a one-year period. Comprehensive ocular examinations, laboratory studies, and imaging were performed. Confirmed cases of EFE with a recent history of COVID-19 hospitalization±intensive care unit admission were identified, documented, managed, followed up, and described. RESULTS: Seven eyes of six patients were reported; 5/6 were male, and the mean age was 55. The mean duration of hospitalization for COVID-19 was approximately 28 days (14-45); the mean time from discharge to onset of visual symptoms was 22 days (0-35). All patients had underlying conditions (5/6 hypertension; 3/6 diabetes mellitus; 2/6 asthma) and had received dexamethasone and remdesivir during their COVID-related hospitalization. All presented with decreased vision, and 4/6 complained of floaters. Baseline visual acuity ranged from light perception (LP) to counting fingers (CF). The fundus was not visible in 3 out of 7 eyes; the other 4 had "creamy-white fluffy lesions" at the posterior pole as well as significant vitritis. Vitreous taps were positive for Candida species in six and Aspergillus species in one eye. Anti-fungal treatment included intravenous amphotericin B followed by oral voriconazole and intravitreal amphotericin B. Three eyes underwent vitrectomy; the systemic health of two patients precluded surgery. One patient (with aspergillosis) died; the others were followed for 7-10 months - the final visual outcome improved from CF to 20/200-20/50 in 4 eyes and worsened (hand motion to LP) or did not change (LP), in two others. CONCLUSION: Ophthalmologists should maintain a high index of clinical suspicion for EFE in cases with visual symptoms and a history of recent COVID-19 hospitalization and/or systemic corticosteroid use - even without other well-known risk factors.

Diagnostic significance of secondary bacteremia in patients with COVID-19.

OBJECTIVES: We investigated the occurrence of non-respiratory bacterial and fungal secondary infections, causative organisms, impact on clinical outcomes, and association between the secondary pathogens and mortality in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: This was a retrospective cohort study that included data from inpatients with COVID-19 from multiple centers participating in the Japan COVID-19 Taskforce (April 2020 to May 2021). We obtained demographic, epidemiological, and microbiological data throughout the course of hospitalization and analyzed the cases of COVID-19 complicated by non-respiratory bacterial infections. RESULTS: Of the 1914 patients included, non-respiratory bacterial infections with COVID-19 were diagnosed in 81 patients (4.2%). Of these, 59 (3.1%) were secondary infections. Bacteremia was the most frequent bacterial infection, occurring in 33 cases (55.9%), followed by urinary tract infections in 16 cases (27.1%). Staphylococcus epidermidis was the most common causative organism of bacteremia. Patients with COVID-19 with non-respiratory secondary bacterial infections had significantly higher mortality, and a multivariate logistic regression analysis demonstrated that those with bacteremia (aOdds Ratio = 15.3 [5.97-39.1]) were at higher risk of death. Multivariate logistic regression analysis showed that age, male sex, use of steroids to treat COVID-19, and intensive care unit admission increased the risk for nosocomial bacteremia. CONCLUSIONS: Secondary bacteremia is an important complication that may lead to poor prognosis in cases with COVID-19. An appropriate medical management strategy must be established, especially for patients with concomitant predisposing factors.

The Sickest COVID-19 Patients During the First Wave of the Epidemic: Strong Clinical Evidence for Acute Tubular Injury

Background: From March through June 2020, SARS-CoV-2 virus surged through the New York Metropolitan area, killing 43,000 in NY and NJ. The sickest patients had both respiratory failure and severe acute kidney injury (AKI), were intubated and on dialysis. Method(s): Seventy intubated patients with severe covid and severe AKI requiring dialysis were treated in 2 north Jersey hospital ICU during this period. Their records were reviewed, focusing particularly during the period of AKI onset to identify potential renal insults - hypotension and shock, secondary infections, and inflammation markers. Result(s): Following admission, respiratory failure quickly progressed, and intubation occurred 3.3 +/- 3.7 days after admission. AKI became evident 1.5 days later (4.7 +/- 4.8 days after admission), and dialysis was initiated 5.4 +/- 6.6 days after AKI onset. Serum creatinine at the start of dialysis was 6.44 +/- 3.40 mg/dl. Around the onset of AKI (start of dialysis +/- 5 days), hemodynamic and clinical instability were rampant. Hypotension requiring vasopressors occurred in 83%;oliguria developed in 79% and worsened to anuria in 33%. Bacteremia and fungemia complicated this period in 28% and 10%. The inflammatory markers - CRP, d-dimer, ferritin, interleukin-6 and ESR, were extremely elevated. Fifty-two patients (74%) died during the hospitalization, 17.7 +/- 11.8 days from admission. Renal function improved in only 1 of these patients. Eighteen patients (26%) survived, and were discharged 63 +/- 15 days after admission. Fifteen (83%) of them regained renal function after requiring dialysis for 20 +/- 15 days. Their serum creatinine decreased to 1.15 +/- 0.63 mg/dl at discharge. Some went through a polyuric phase. Most of these survivors had severe medical problems. Over the next 3.5 months, 5 of them died. Conclusion(s): The following clinical aspects were highly suggestive of acute tubular injury: - onset of AKI during severe hemodynamic instability, intubation, pressor use, secondary infections and intense inflammation;- the rapid progression to uremia;- oliguria early in AKI;some with polyuric phase that preceded improvement of renal function;- short period of dialysis and marked improvement of renal function 8 weeks after onset in 83% of the survivors.

CAUSES OF DEATH AMONG MEDICAL ICU (MICU) PATIENTS WITH PNEUMONIA DUE TO COVID-19 IN A SAFETY NET HOSPITAL

SESSION TITLE: Studies on COVID-19 Infections Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: COVID-19 infection has a wide spectrum of clinical presentation ranging from asymptomatic carriers to severe critical illness associated with high morbidity and mortality. Although severe COVID-19 disease is associated primarily with pulmonary dysfunction and hypoxemia, many patients with lung disease can be supported by invasive mechanical ventilation allowing for other causes or complications to be the primary factor leading to death. The contribution of pulmonary dysfunction to the primary cause of death is not well-described. METHODS: We performed a retrospective cohort study of adult patients (age ≥ 18 years) admitted to the MICU at Los Angeles County + University of Southern California (LAC + USC) hospital from April 2020 to December 2020 with a primary diagnosis of COVID-19 pneumonia associated with documented in-hospital death. Data including baseline patient characteristics, primary cause of death and/or circumstance prior to withdrawal of care, and disease course were collected. The primary organ system responsible for death was defined as the organ dysfunction that most directly resulted in the patient’s death or impacted the decision for withdrawal of life support with details adapted from Ketcham, et al (Crit Care, 2020). RESULTS: We identified 86 patients who were admitted to the ICU that met inclusion criteria for review, of which 75% were male and 93% were Latino/Hispanic. Mean age on admission was 64 years. Of the 86 patients, 47 (54%) died from a primary pulmonary cause, 28 (32%) died from sepsis, 5 (6%) died from neurologic causes, and 4 (5%) died from either renal or hemorrhagic causes. Of the 47 patients who died primarily from pulmonary causes, 34 (72%) died from hypoxemic respiratory failure, 8 (17%) died from hypercapnic respiratory failure, and 5 (11%) died from combined respiratory failure. Of the 28 patients who died primarily from sepsis, 13 (46%) died from pneumonia, 7 (25%) died from fungemia, and 3 (11%) died from bacteremia with an identified source. Overall, 58 (67%) patients had multi-organ failure at time of death. Mean time from symptom onset to death was 27 days. Of the 69 patients who were intubated, mean times from admission to intubation and intubation to death was 4 and 19 days respectively. Only 1 patient who died underwent tracheostomy. CONCLUSIONS: We found that pulmonary dysfunction was the primary cause of death in the first year of the pandemic in our patient population at our single center MICU. Future studies are needed to further evaluate the primary cause of death in COVID-19 infection throughout the pandemic as medical management evolved and virus variant changed with time. CLINICAL IMPLICATIONS: Our study confirmed that a majority of patients with severe COVID-19 pneumonia died from hypoxemic respiratory failure. Further studies regarding COVID-19 interventions should focus on therapies to improve oxygenation. DISCLOSURES: No relevant relationships by Christopher Do No relevant relationships by Luis Huerta No relevant relationships by Janice Liebler

A FOUR-BODING FUTURE: POLYVIRAL INFECTION WITH SARS-COV-2, PARAINFLUENZA VIRUS TYPE 3, INFLUENZA A, AND ADENOVIRUS

SESSION TITLE: COVID-19 Co-Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Over the past 2 years, SARS-CoV-2 has been undergoing research regarding its immunopathology, with its understanding continuously evolving. We present a case of severe respiratory failure from viral co-infection with SARS-CoV-2, parainfluenza virus III, influenza A, and adenovirus. CASE PRESENTATION: A 42-year-old female with no respiratory or immunological comorbidities, was admitted with respiratory failure that progressed within days to severe septic shock and refractory hypoxemia requiring venovenous extracorporeal membrane oxygenation (VV-ECMO). On initial laboratory evaluation, her nasopharyngeal swab sample tested positive for SARS-CoV-2, Parainfluenza virus III, Influenza A, and Adenovirus on our institute's ROCHE PCR detection test. This was then confirmed with an endotracheal sample and a BAL sample, each of which tested positive for the above 4 viruses. The patient had no prior history of lung disease, autoimmune disorder, immunodeficiency, or malignancy. Serum immunoglobulin levels were within normal range, and the patient tested negative for HIV. She was not on any immunomodulators, and had no known contacts with individuals with polyviral infection. Her presentation had been usual, with 6 days of fever, shortness of breath, extreme fatigue, coughing, and diarrhea. She had initially received treatment with remdesivir, tocilizumab, and dexamethasone. But these tests were noted to be positive prior to her receiving any therapies. Her hospital course was complicated by septic shock, refractory hypoxemia, secondary ventilator associated pneumonia, and fungemia, requiring invasive mechanical ventilation, inhaled nitric oxide, vasopressors, broad spectrum antimicrobials, and eventually rescue by VV-ECMO. She slowly recovered over 6 weeks, received a tracheostomy and was discharged to a long-term acute care hospital for continued rehabilitation and weaning from mechanical ventilation. At 1 year follow up, she has made a full recovery with no residual respiratory limitation. DISCUSSION: Co-infection is defined as infection at diagnosis within 7 days of initial primary infection, whereas, secondary infection develops after 7 days. Co-infection of respiratory viruses, though uncommon, has been reported. Their detection has improved with the use of PCR testing. Simultaneous infection of COVID-19 and usual respiratory viruses has also been documented. Effect of co-infection on disease severity is a result of interaction of viruses among themselves and with the host. CONCLUSIONS: COVID-19 research has mainly focused on SARS-CoV-2 effects on the human host, but with it evolving into an endemic, its interaction and co- and superinfection with other pathogens is imperative. Further research into such interactions of SARS-CoV2 are required to help develop preventative and therapeutic measures. Reference #1: Lansbury L, Lim B, Baskaran V, Lim WS. Co-infections in people with covid-19: A systematic review and meta-analysis. SSRN Electronic Journal. 2020. Reference #2: Kim D, Quinn J, Pinsky B, Shah NH, Brown I. Rates of co-infection between SARS-COV-2 and other respiratory pathogens. JAMA. 2020;323(20):2085. Reference #3: DaPalma T, Doonan BP, Trager NM, Kasman LM. A systematic approach to virus–virus interactions. Virus Research. 2010;149(1):1-9. DISCLOSURES: No relevant relationships by Vinita Kusupati No relevant relationships by Jyoti Lenka No relevant relationships by Rachel Tan

COVID-19-INDUCED IMMUNOSUPPRESSION LEADING TO SECONDARY INFECTION AS DISSEMINATED COCCIDIOIDOMYCOSIS

SESSION TITLE: Post-COVID-19 Infection Complications SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Coccidioidomycosis caused by the fungi C. immitis and C. Posadasii is well known to be endemic to the Southwest United States. Less than 1% of these infections will manifest as extrapulmonary symptoms and multiple sites causing dissemination fungemia [1]. Risk factors for disseminated infection include exogenous immunosuppression, immunodeficiency, pregnancy, and ethnic backgrounds of African and Filipino descent [2]. CASE PRESENTATION: A 39-year-old previously immunocompetent Congolese male with recent onset of recurrent skin abscess, and positive testing for COVID-19 three week prior (not treated with steroids). He presents with shortness of breath, back pain, fevers after recently migrating from the Southwest region to the Midwest. Upon admission imaging with Computed Tomography (CT) revealed extensive pulmonary infiltrates (Fig 1), intra-abdominal abscesses, and magnetic resonance imaging revealing (MRI) osteomyelitis of the thoracic (Fig 2) and lumbar spine (Fig 3). His work of breathing continued to worsen, requiring prompt intubation, and he was initiated on a broad-spectrum antimicrobial regimen, including fluconazole, voriconazole, cefepime and vancomycin. Immunoglobulins, HIV and oxidative burst testing was unremarkable. Cultures from image-guided aspiration of the psoas abscess, incision, and drainages of skin abscess and bronchoalveolar lavage fluid were all positive for coccidioidomycosis, transitioned to amphotericin B. Course complicated with the development of multidrug-resistance pseudomonas aerogenes VAP treated with inhaled tobramycin and meropenem. He developed progressive acute respiratory distress syndrome with refractory hypoxemia. After 3 weeks of antimicrobial and anti-fungal treatment, a decision was made to transfer the patient to a lung transplant center, however, due to ongoing fungemia, he was deemed to be not a candidate for extracorporeal membrane exchange and lung transplantation. About a month into his hospitalization, the family decided to withdraw care. DISCUSSION: Reactivation of latent coccidiomycosis has been largely studied in the immunosuppressed population that includes HIV, hematological malignancies, and diabetes mellitus, however little is known about this fungal infection in the immunosuppressed state in the setting of COVID-19. Thus far only two case reports have been reported of co-infection if COVID-19 and pulmonary coccidioidomycosis [3]. The days of the COVID-19 pandemic might contribute to further delays in diagnosing this fungal infection due to similarities of pulmonary manifestation. CONCLUSIONS: This case demonstrates a COVID-19 infection leading to an immunosuppressed status resulting in disseminated infection from reactivation of latent coccidiomycosis. As a result, physicians must maintain a high level of suspicion for superimposed fungal infections in those with even relative immunosuppression from a recent COVID infection. Reference #1: Odio CD, Marciano BE, Galgiani JN, Holland SM. Risk Factors for Disseminated Coccidioidomycosis, United States. Emerg Infect Dis. 2017;23(2):308-311. doi:10.3201/eid2302.160505 Reference #2: Hector RF, Laniado-Laborin R. Coccidioidomycosis–a fungal disease of the Americas. PLoS Med. 2005;2(1):e2. doi:10.1371/journal.pmed.0020002 Reference #3: Shah AS, Heidari A, Civelli VF, et al. The Coincidence of 2 Epidemics, Coccidioidomycosis and SARS-CoV-2: A Case Report. Journal of Investigative Medicine High Impact Case Reports. January 2020. doi:10.1177/2324709620930540 DISCLOSURES: No relevant relationships by Stephen Doyle No relevant relationships by Connor McCalmon No relevant relationships by John Parent No relevant relationships by Jay Patel No relevant relationships by Angela Peraino No relevant relationships by Keval Ray

Bloodstream Infections in a COVID-19 Non-ICU Department: Microbial Epidemiology, Resistance Profiles and Comparative Analysis of Risk Factors and Patients' Outcome.

BACKGROUND: Bloodstream infections (BSI) caused by highly resistant pathogens in non-ICU COVID-19 departments pose important challenges. METHODS: We performed a comparative analysis of incidence and microbial epidemiology of BSI in COVID-19 vs. non-COVID-19, non-ICU departments between 1 September 2020-31 October 2021. Risk factors for BSI and its impact on outcome were evaluated by a case-control study which included COVID-19 patients with/without BSI. RESULTS: Forty out of 1985 COVID-19 patients developed BSI. The mean monthly incidence/100 admissions was 2.015 in COVID-19 and 1.742 in non-COVID-19 departments. Enterococcus and Candida isolates predominated in the COVID-19 group (p < 0.001 and p = 0.018, respectively). All Acinetobacter baumannii isolates were carbapenem-resistant (CR). In the COVID-19 group, 33.3% of Klebsiella pneumoniae was CR, 50% of Escherichia coli produced ESBL and 19% of Enterococcus spp. were VRE vs. 74.5%, 26.1% and 8.8% in the non-COVID-19 group, respectively. BSI was associated with prior hospitalization (p = 0.003), >2 comorbidities (p < 0.001), central venous catheter (p = 0.015), severe SARS-CoV-2 pneumonia and lack of COVID-19 vaccination (p < 0.001). In the multivariate regression model also including age and multiple comorbidities, only BSI was significantly associated with adverse in-hospital outcome [OR (CI95%): 21.47 (3.86-119.21), p < 0.001]. CONCLUSIONS: BSI complicates unvaccinated patients with severe SARS-CoV-2 pneumonia and increases mortality. BSI pathogens and resistance profiles differ among COVID-19/non-COVID-19 departments, suggesting various routes of pathogen acquisition.

Occurrence of Candidemia in Patients with COVID-19 Admitted to Five ICUs in France.

Whether severe COVID-19 is by itself a significant risk factor for the development of candidemia currently remains an open question as conflicting results have been published. We aim to assess the occurrence of candidemia in patients with severe COVID-19 admitted to the intensive care unit (ICU). We conducted a retrospective study on patients with severe SARS-CoV-2-related pneumonia admitted to 5 ICUs in France who were specifically screened for fungal complications between March 2020 and January 2021. The study population included a total of 264 patients; the median age was 56 years old and most of them were male (n = 186; 70.5%) and immunocompetent (n = 225; 87.5%), and 62.7% (n = 153/244) were on extracorporeal membrane oxygenation support. Microbiological analysis included 4864 blood culture samples and beta-glucan test performed on 975 sera. Candidemia was diagnosed in 13 (4.9%) patients. The species involved were mainly C. albicans (n = 6) and C. parapsilosis (n = 5). Almost all patients (12/13; 92.3%) had a colonization by yeasts. ICU mortality was not significantly impacted by the occurrence of candidemia. Unrelated positive beta-glucan tests were observed in 49 patients (23.4%), including 6 with mold infections and 43 with false positive results. In our series, patients with severe SARS-CoV-2-related pneumonia seemed at low risk of developing invasive candidiasis.

Fungal Bloodstream Co-infection by Trichosporon asahii in a COVID-19 Critical Patient: Case Report and Literature Review.

Opportunistic infections are serious complications in critically ill COVID-19 patients, especially co-infections with bacterial and fungal agents. Here we report a rare case of bloodstream co-infection by Trichosporon asahii, an emerging yeast, and Acinetobacterbaumannii, an opportunistic nosocomial pathogen, both multidrug resistant, in a tertiary hospital from southern Brazil. A review of the literature regarding similar cases is also included. Treatment with multiple antimicrobials failed, and the patient progressed to death four days after the diagnosis of bacteremia and fungemia.

HISTOPLASMOSE MEDULAR REFRATÁRIA AO TRATAMENTO: RELATO DE CASO

Objetivo: Relatar um caso de histoplasmose com acometimento medular em um Hospital Universitário no Sul do Brasil. Descrição do caso: Masculino, 39 anos, trabalhador rural. Histórico de internação em dezembro de 2020 para investigação de pancitopenia, hepatoesplenomegalia, febre e perda ponderal, sendo diagnosticado com histoplasmose pulmonar e medular e iniciado o uso de Itraconazol 200 mg 2x/dia. Evoluiu com melhora clínica, exames de março de 2021 traziam hemoglobina 11,6;leucócitos 2.150;plaquetas 86 mil;bilirrubinas totais 0,91. Em abril, é admitido no pronto socorro por quadro de icterícia, astenia, hemoptise e epistaxe iniciado há 4 dias. Constatou-se hemoglobina 6,5;leucócitos 1.620;plaquetas 5 mil, proteína C reativa > 12 mg/dl, DHL 707 U/L, bilirrubina total 16 mg/dL. Sorologias negativas. Tomografia de tórax exibiu extensas opacidades com atenuação em vidro fosco, bilaterais e com distribuição predominantemente central associadas a leve espessamento liso dos septos interlobulares, sendo sugestivo de processo infeccioso/inflamatório. Teste PCR para Covid-19 negativo. Tomografia de abdome com esplenomegalia de 28 cm e áreas hipodensas sem realce ao contraste, bem como líquido subcapsular, as quais poderiam representar áreas de infarto esplênico por degeneração líquida/necrose. Linfonodomegalias junto à veia porta com 1,8 cm e na cadeia paracaval direita com 1,6 cm. Prosseguiu-se investigação com mielograma, cujo laudo mostrou série vermelha com precursores eritroides sem displasia, normocelular;série branca hipercelular, sem excesso de formas jovens, com pelo menos 5 macrófagos com grânulos citoplasmáticos sugestivos de causa infecciosa ativados com sinais de hematofagocitose;e megacariócitos presentes sem displasias. Foi considerada a hipótese de histoplasmose aguda persistente. Iniciado Anfotericina B lipídica e realizado suporte transfusional. Posteriormente, pesquisa de anticorpos anti-Histoplasma capsulatum resultou positivo para banda M, e anatomopatológico evidenciou medula óssea acentuadamente hipercelular, com população celular de aparência histiocitária e citoplasma amplo e claro, por vezes contendo elementos hematopoiéticos fagocitados, sem formação de granulomas. Apesar da otimização das medidas terapêuticas, houve evolução para óbito. Discussão e conclusão: A histoplasmose é uma doença granulomatosa sistêmica causada pelo Histoplasma capsulatum, que, em imunocompetentes, costuma ser autolimitada e assintomática, com evolução satisfatória. Todavia, alguns pacientes desenvolvem a forma disseminada progressiva, que ocorre em 1:2.000 pacientes com infecção aguda. Para indivíduos sem acometimento do sistema nervoso central, o tratamento é feito com anfotericina B ou um derivado azólico, como o itraconazol. Neste caso, como o paciente apresentava doença grave, optou-se pela anfotericina B, que erradica a fungemia e atinge níveis séricos terapêuticos com rapidez. O descalonamento para itraconazol pode ser realizado se condições clínicas favoráveis. A literatura sugere que o tratamento por um ano é capaz de reduzir recaídas, mas é possível estendê-lo por mais tempo na presença de imunossupressão irreversível. Se não houver boa tolerância farmacológica, tem-se como opções fluconazol, posaconazol ou voriconazol.

Do the surgical outcomes differ between Non- COVID pulmonary mucormycosis and COVID associated pulmonary mucormycosis after surgical resection A comparative analysis

Objectives: This study aims at reporting the surgical outcomes of COVID Associated Pulmonary Mucormycosis (CAPM) with special emphasis on surgical mortality. This study also compares the surgical outcomes between Non-COVID Pulmonary Mucormycosis (NCPM) and CAPM. Methods: This prospective observational study was conducted in a dedicated thoracic surgical unit in Gurugram over 18 months which includes 25 patients. An analysis of demography, perioperative variables including complications were carried out. Various parameters were analysed to assess the factors affecting mortality. Results: Out of 25 patients, male-female ratio was 16:9 (64%:36%), with a mean age of 54.8 years (range, 33-72 years). Diabetes was the most common predisposing factor in 17 patients (68%). A total of 8 patients (32%) were on supplemental oxygen (1-4 lit/min) at the time of surgery. Extent of surgery was non-anatomical wedge resection in 5 patients (20%), lobectomy/bi-lobectomy in 18 patients (72%) and pneumonectomy in 2 patients (8%). Commonest complication was prolonged air leak (> 7 days) in 5 patients (20%). There were 5 peri-operative deaths (20%), all due to persistent fungal sepsis. ECOG scale > 2 (P = <0.001) and pneumonectomy (P = 0.02) were the predictors of mortality. On comparison with NCPM, no difference in the postoperative complications (P = 1.00) and mortality (P = 1.00) was observed. Conclusion: Aggressive surgical resection with clear margins should be offered in CAPM whenever feasible. In appropriately selected patients, surgical resection is safe and efficacious. Surgery for CAPM was not associated with higher post-operative complications including mortality compared to NCPM.

Infection prevention for extremely low birth weight infants in the NICU.

Extremely preterm infants are particularly vulnerable to systemic infections secondary to their immature immune defenses, prolonged hospitalizations, delays in enteral feeding, early antibiotic exposure, and need for life-sustaining invasive interventions. There have been several evidence-based practices for infection prevention in this population, such as human milk feedings, utilization of "bundle checklists" and decolonization of pathogenic organisms. Other practices, such as the use of probiotics, human milk-derived fortifiers, and antifungal prophylaxis are more controversial and require further investigation regarding the risks and benefits of such interventions. This chapter examines the susceptibility of the preterm newborn infant to invasive infections and describes several strategies for infection prevention, along with the associated limitations of such practices. It also addresses the various gaps in our understanding of preventing infections in this population, and the need for additional large multi-center randomized controlled trials. Additionally, the role of the SARs-CoV-2 global pandemic and associated strategies for infection prevention in the NICU are discussed.

Epidemiology of Candidemia Rates during COVID-19 and Comparison of Outcomes in Candidemia between COVID-19 and Non-COVID-19 Patients

Background. Fungemia is associated with high rates of morbidity, mortality and increase in length of hospital stay. Several studies have recognized increased rates of candidemia since the COVID-19 pandemic. Methods. A retrospective cohort study was conducted at a tertiary healthcare system in Detroit, Michigan to evaluate the impact of the COVID-19 pandemic on incidence of candidemia. The "pre COVID-19" timeframe was defined as January - May 2019 while the "during COVID-19" timeframe was January - May 2020. To compare incidence and patient characteristics between cohorts, t-tests and chi-square analysis was used. Additional sub-analysis was performed in candidemia patients during COVID-19 timeframe comparing outcomes of patients based on COVID-19 status. A Fisher Exact and Satterthwaite Test were used for analysis of categorical and continuous variables, respectively. Results. Overall, 46 cases of candidemia were identified in both the pre COVID-19 and during COVID-19 periods. Pre COVID-19, the average number of cases was 3.0 ± 1.2 per month. The incidence more than doubled during COVID-19 to 6.2 ± 4.2 cases per month (p = 0.14) (Figure 1). No significant differences in patient demographics were detected between cohorts, however, patients in the COVID-19 cohort had higher rates of corticosteroid use, mechanical ventilation and vasopressors (Table 1). In the 2020 period, 31 patients developed candidemia and 12 (38.7%) patients tested SARS-CoV-2 positive. On average, COVID-19 patients developed candidemia 12.1 days from admission, compared to 17.8 days in the COVID-19 negative cohort (p = 0.340). Additionally, COVID-19 patients with candidemia coinfection were significantly more likely to expire;83.3% (n=10) COVID-19 patients expired compared to 36.8 (n=7) in the COVID-19 negative cohort (p = 0.025) (Table 2). Conclusion. The prevalence of fungemia markedly increased during the COVID-19 surge. Increased use of corticosteroids and broad spectrum antimicrobials, prolonged use of central venous catheters and prolonged ICU length of stay likely contributed to this increase. Patients who developed candidemia co-infection with COVID-19 were found to have poorer outcomes as compared to those who were SARS-CoV-2 negative or untested.

Characteristics and Outcomes in Hospitalized Patients with Covid-19 Complicated by Fungemia: A Single Center Retrospective Study

Background. Covid19 caused by SARS-CoV2 can lead to significant morbidity and mortality. Fungemia is a rare hospital-associated infection and there are limited data regarding its association with Covid19. We reviewed all cases of fungemia in our Covid19 cohort at Stony Brook University Hospital (SBUH). Methods. We conducted a retrospective medical record review of patients admitted with Covid19 in a 3-month interval. We reviewed positive blood cultures for fungi and recorded co-morbidities, co-infections, length of stay, treatments, and outcomes (survival vs death). There were 60 positive blood cultures for fungi in 25 unique patients (Table 1);in prior years < 30 per year reported at SBUH. Collation of each unique identified fungal species from fungal blood cultures in patients hospitalized with Covid-19 Results. During a 3 month interval at the local peak of the pandemic 1398 patients hospitalized with Covid19 at SBUH, 25 cases of fungemia were detected;C. albicans (CA) n=8,32%, non C albicans species (nCA) n=16,64%, and C. neoformans n=1,4%, 17/25 (68%) also with bacteremia during same hospitalization. In same 3 months there were 264 cases of bacteremia and Covid19 co-infection. Demographics and medical co-morbidities of fungemic patients are in Table 2. Majority were men (76%). No difference between fungaemic (FC) and total cohort (TC) in median age (62 vs 62), DM p=0.31, HTN p=1.0, COPD p=0.12. Within FC, DM was higher in nCA group (58.8%) vs CA group (37%). Mortality was 40% in FC vs 15% in TC, p< 0.001. Within FC mortality was 56% in nCA and 25% in CA group. C. parapsilosis was the most common nCA species isolated with 43% mortality. FC more likely to require ICU and mechanical ventilation (88% vs 15%, p< 0.0001) and had longer median length of stay 42 days vs 22 days. The median time from admission to fungaemia was 21d, from central line placement 19d, Table 3. Of FC 21 (84%) were treated with steroids/Tocilizumab concurrently. Of note, no mortality was recorded in the 4 patients that did not receive steroids/Tocilizumab. PCT and WBC were significantly higher at time of fungemia as compared to admission, Table 3. Relevant patient characteristics and laboratory parameters in patients hospitalized with Covid19 and fungemia Conclusion. Fungemia in hospitalized patients with COVID-19 is associated with higher mortality. We observed higher fatality in non C. albicans infections. Prolonged use of central line catheters and concurrent treatment with steroids/tociluzimab are likely high-risk factors for development of fungemia.