Incidence Of Secondary Infections Research Articles

Medication use evaluation of tocilizumab implementation in COVID-19 treatment guidelines: A causal inference approach.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Introduction of new medications to health-system formularies is often not accompanied by assessments of their clinical impact on the local patient population. The growing availability of electronic health record (EHR) data and advancements in pharmacoepidemiology methods offer institutions the opportunity to monitor the medication implementation process and assess clinical effectiveness in the local clinical context. In this study, we applied novel causal inference methods to evaluate the effects of a formulary policy introducing tocilizumab therapy for critically ill patients with coronavirus disease 2019 (COVID-19). We conducted a medication use evaluation utilizing EHR data from patients admitted to a large medical center during the 6 months before and after implementation of a formulary policy endorsing the use of tocilizumab for treatment of COVID-19. The impact of tocilizumab on 28-day all-cause mortality was assessed using a difference-in-differences analysis, with ineligible patients serving as a nonequivalent control group, and a matched analysis guided by a target trial emulation framework. Safety endpoints assessed included the incidence of secondary infections and liver enzyme elevations. Our findings were benchmarked against clinical trials, an observational study, and a meta-analysis. Following guideline modification, tocilizumab was administered to 69% of eligible patients. This implementation was associated with a 3.1% absolute risk reduction in 28-day mortality (odds ratio, 0.86; number needed to treat to prevent one death, 32) attributable to the inclusion of tocilizumab in the guidelines and an additional 8.6% absolute risk reduction (odds ratio, 0.65; number needed to treat to prevent one death, 12) linked to its administration. These findings were consistent with estimates from published literature, although the effect estimates from the difference-in-differences analysis exhibited imprecision. Evaluating formulary management decisions through novel causal inference approaches offers valuable estimates of clinical effectiveness and the potential to optimize the impact of new medications on population outcomes.

Infection-related Hospitalizations During Immune Checkpoint Inhibitor Treatment Without Immunosuppressants.

Immunosuppressants are increasingly being used in the clinic to manage immune-related adverse effects. Consequently, the incidence of secondary infections associated with immunosuppression is increasing. However, little is known about primary infections during immune checkpoint inhibitor (ICI) treatment without immunosuppressants. We aimed to evaluate primary infectious diseases during antiprogrammed death ligand-1 immunotherapy without immunosuppressants. We retrospectively screened medical records of 233 patients who underwent ICI treatment for advanced non-small cell lung cancer between January 2014 and May 2018 at National Cancer Center, Republic of Korea. Subsequently, we evaluated the clinical characteristics and treatment outcomes of selected patients hospitalized for potential infectious disease without immunosuppressive treatment (n=80). Eight cases (3.4%) were identified as bacterial pneumonia (n=5) and cellulitis, inflamed epidermoid cyst, and wound infection (n=1 each). The bacterial pathogens Streptococcus pneumoniae and Haemophilus influenzae were identified in 4 patients with pneumonia. The period between the start of ICI treatment and infection varied between 3 and 189 days (median, 24.5 days). Five (62.5%) patients were infected within a month after ICI treatment initiation. All patients were treated with empirical antibiotics and discharged without complications. The median progression-free and overall survival for ICI treatment was 11.5 and 25.5 months, respectively. Six patients experienced ICI-associated adverse effects postinfection: Herpes zoster infection (n=4) and pneumonitis (n=2). Infectious disease independent of immunosuppression is a rare, but possible event in patients with lung cancer receiving ICI treatment. Clinical awareness would enable prompt diagnosis of primary infection during immunotherapy.

Characteristics and Clinical Prognosis of Septic Patients With Persistent Lymphopenia.

Background: Septic patients with persistent lymphopenia may be in an immunosuppressed state. Therefore, we evaluated and compared the clinical characteristics and outcomes of septic patients with persistent lymphopenia (≥2d) and those with nonpersistent lymphopenia. Methods: A retrospective cohort study was designed. A total of 1306 patients with sepsis who were attended to the First Affiliated Hospital of Dalian Medical University from March 2016 to August 2022 were included. The primary clinical outcome was 90d mortality. The secondary clinical outcomes were the length of stay, hospital mortality, 28d mortality, the incidence of secondary infection, and differences in clinical characteristics. Results: Among 1306 patients with sepsis, 913 (69.9%) patients developed persistent lymphopenia. Compared with patients with nonpersistent lymphopenia, patients with persistent lymphocytopenia were admitted to intensive care unit (75.7% vs 52.7%, P < .05), treated with mechanical ventilation (67.6% vs 39.2%, P < .05), positive rate of microbial culture pathogens (86.7% vs 71.2%, P < .05), SOFA [8.0 (6.0-10.0) vs 6.0 (4.0-8.0), P < .05], length of stay [17.0d (12.0-27.0) vs 13.0d (10.0-21.0), P < .05], hospital mortality (37.7% vs 24.2%, P < .05), 28d mortality (38.0% vs 22.9%, P < .05), and 90d mortality (51.2% vs 31.3%, P < .05) were higher. As the duration of lymphocytopenia increased, so did the mortality rate in hospital. In addition, the onset time of persistent lymphopenia was not associated with SOFA. But we found that the frequency of persistent lymphopenia during hospitalization was positively associated with SOFA. Conclusion: Septic patients with persistent lymphopenia have higher mortality, worse conditions, increased risk of secondary infection, and poor prognosis regardless of shock.

Study on Italian Onion Cultivars/Ecotypes towards Onion Yellow Dwarf Virus (OYDV) Infection

The onion yellow dwarf virus (OYDV) represents a limiting biotic stress in onion (Allium cepa L.); little information is available regarding resistant varieties. In Italy, onion production is limited but represented by a wide diversity of ecotypes. A two-year trial was carried out to test the OYDV-susceptibility/tolerance of different Italian onion cultivars by rating symptom severity and plant growth parameters and assessing post-harvest secondary infections. The cultivar and ecotypes included in the study were characterized by simple sequence repeats (SSR) analysis, and the expression analysis of two genes (Eukaryotic translation initiation factors, EIFs) involved in potyvirus replication was also performed. Two susceptible and one tolerant cultivar were identified based on symptom expression and virus impact on plants. Although differences in growth parameters were limited to the first-year trial, the infection was correlated to a higher incidence of secondary infections in post-harvest, with altered water balance in infected bulbs. This correlation was also demonstrated during the long-term storage of bulbs. SSR analysis identified different clusters and only one gene isoform (EIF4eiso1) showed different expression levels in the OYDV/onion pathosystem. In conclusion, this study defines the genetic profile of Italian onion cultivars and provides evidence on susceptibility/tolerance features which will be useful in the future for the identification of viral resistance traits in onion.

2200. The Antibiotic Steward's Nightmare: Long-Term Antibiotics in An Infectious Disease Practice

Abstract Background The effects of long-term antibiotic use, including the frequency of recurrent infections and new-onset resistant infections, are not fully understood. The role of antibiotics in the disruption of the gut microbiota has been well-described, impacting insulin susceptibility and lipid deposition. Prolonged antibiotic use may have potential to be implicated in obesity, diabetes, and hyperlipidemia. There may also be an effect on the incidence of secondary infections with new organisms, the frequency of breakthrough infections from the index organism, and the selection for resistant infections. Methods This retrospective study evaluated 78 patients seen at an outpatient infectious disease practice. Inclusion criteria were patients with prescription of an oral antibiotic for 90 or more consecutive days between 9/1/18 and 12/31/2019, who utilize a health system pharmacy. Data was collected from patient charts at baseline prior to antibiotic initiation, and at time of most recent follow up after the initiation of antibiotic. Results Cephalexin (37.2%), azithromycin (34.6%) and amoxicillin (12.8%) were the most common antibiotics prescribed. Mean patient age was 69.4 years. Indications for antibiotic use included NTM infections (34.6% of cases), prosthetic joint infections (21.8%), recurrent UTIs (10.3%), and prosthetic valve infection (7.7%). 23.4% of patients experienced breakthrough infection with the index organism, while 21.8% experienced new, unrelated infection during follow-up, of which 52.9% had a resistant organism isolated. Mean BMI at baseline was 26.9, and BMI at follow-up was 27.3. The difference between baseline and follow-up BMI was not statistically significant (p=0.177). A1C, LDL, and cholesterol rose from baseline to follow-up, but did not reach statistical significance. Conclusion Patients on long-term antibiotics had a numerical increase in BMI, A1C, LDL, and cholesterol values following initiation, but those increases were not statistically significant. Recurrence of infection and emergence of resistance was common. The small sample size and limitation of studying patients from one practice within one health system pharmacy are limitations of the study. Further studies with larger sample sizes and comparative groups by diagnosis are needed. Disclosures All Authors: No reported disclosures

Calamity Of Secondary Dengue Virus Followed By Climatic Changes.

Madam, This is to bring your attention to a long-standing issue despite several activities devised to curb it. Being aware of the effect of drastic climatic changes, developing countries like Pakistan should remain alert about the emergence of infectious outbreaks. The stagnant water after heavy rainfall and flood is a ground for the breeding of dengue vector called Aedes aegypti mosquitoes. The virus is transmitted from one person to another through these mosquitoes. Lately, the surge in the cases of dengue virus was due to massive flooding in Pakistan in 2022. A total of 25932 cases were reported and 62 deaths were recorded during the dengue outbreak during the flood crisis of 2022[1]. Dengue virus comprises of four serotypes 1, 2, 3, and 4. A person infected by a distinct serotype of the virus gains immunity against it and future infection by the same DENV will not affect the person’s health but infection by a heterogenous serotype causes secondary infection in the form of dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Expansive capillary leakage in DHF due to an increase in the permeability of blood vessels can turn on a shock state called DSS. This deprivation of blood to highly functional organs like the brain, kidney, and heart puts them at risk of multi-organ failure [2]. The seasonal surge of secondary infection puts a burden on hospitals as the patient requires vigilant inpatient hospital care. The patient's health deteriorates further because of self-treatment at home with local herbs and over-the-counter (OTC) drugs [3]. As modern medicine is focused more on prevention than treatment, the need for the approval of the use of the dengue vaccine on high-risk individuals in an endemic country like Pakistan should be considered. The DENGVAXIA is a well-tolerated vaccine protecting against all the serotypes and is approved for use in individuals 9 to 45 years who are previously infected by the dengue virus in the past. [4] The vaccine will restrain the rise in DHF and DSS cases as it is for high-risk individuals who are already infected in the past thus curbing the incidence of secondary infection. Many endemic countries like the Philippines and Brazil have already taken a step against secondary dengue by granting the license of DENGVAXIA [5]. As Pakistan is developing country, approving the license for DENGVAXIA should be considered.

Adverse Events and Infectious Complications in the Critically Ill Treated by Plasma Exchange: A Five-Year Multicenter Cohort Study.

The aim of this study was to determine, in critically ill patients treated with therapeutic plasma exchange (TPE), the incidence of adverse events as well as the incidence of secondary infections and its predictive factors. A multicenter retrospective cohort study of an intensive care population treated with TPE to collect adverse events and infectious complications. The characteristics of patients who developed an infection after plasma exchange were compared with those of patients who did not. Four ICUs of French university hospitals. All adults admitted between January 1, 2015, and December 31, 2019, who received at least one plasma exchange session were included. None. A total of 711 TPE sessions were performed on 124 patients. The most frequent TPE indications were thrombotic microangiopathies (n = 32, 26%), myasthenia gravis (n = 25, 20%), and acute polyradiculoneuropathy (n = 12, 10%). Among the 124 patients, 22 (21%) developed arterial hypotension, 12 (12%) fever, and 9 (9%) electrolyte disturbance during TPE. Moreover, 60 (48%) presented at least one infectious complication: ventilator-associated pneumonia 42, pneumonia 13, bacteremia 18 (of which 6 catheter-related infections) viral reactivation 14. Independent risk factors for ICU-acquired infection were the ICU length of stay (24 vs. 7 d; hazard ratio [HR]: 1.09 [1.04-1.15], p < 0.001) and invasive mechanical ventilation (92% vs. 35%; HR: 16.2 [5.0-53.0], p < 0.001). In critically ill patients treated with TPE, adverse events occurring during the procedure remain moderately frequent and are mostly not life-threatening. Infectious complications, mainly ventilation-associated pneumonia, are frequent in this population. The need of mechanical ventilation and longer ICU stay is associated with an increased risk of infection.

Standardized Brazilian green propolis extract (EPP-AF®) in COVID-19 outcomes: a randomized double-blind placebo-controlled trial

SARS-CoV-2 and its different variants caused a “wave and wave” pandemic pattern. During the first wave we demonstrated that standardized Brazilian green propolis extract (EPP-AF®) reduces length of hospital stay in adult patients with COVID-19. Afterwards, we decided to evaluate the impact of EPP-AF in hospitalized patients during the third wave of the pandemic. BeeCovid2 was a randomized, double-blind, placebo-controlled clinical trial in hospitalized COVID-19 adult patients. Patients were allocated to receive an oral dose of 900 mg/day of EPP-AF® or placebo for 10 days. The primary outcome was length of hospital stay. Secondary outcomes included safety, secondary infection rate, duration of oxygen therapy dependency, acute kidney injury and need for intensive care. Patients were followed up for 28 days after admission. We enrolled 188 patients; 98 were assigned to the propolis group and 90 to the placebo group. The post-intervention length of hospital stay was of 6.5 ± 6.0 days in the propolis group versus 7.7 ± 7.1 days in the control group (95% CI − 0.74 [− 1.94 to 0.42]; p = 0.22). Propolis did not have significant impact on the need for oxygen supplementation or frequency of AKI. There was a significant difference in the incidence of secondary infection between groups, with 6.1% in the propolis group versus 18.9% in the control group (95% CI − 0.28 [0.1–0.76], p = 0.01). The use of EPP-AF was considered safe and associated with a decrease in secondary infections. The drug was not associated with a significant reduction in length of hospital stay. ClinicalTrials.gov (NCT04800224).

Enteral citrulline supplementation versus placebo on SOFA score on day 7 in mechanically ventilated critically ill patients: the IMMUNOCITRE randomized clinical trial

BackgroundRestoring plasma arginine levels through enteral administration of L-citrulline in critically ill patients may improve outcomes. We aimed to evaluate whether enteral L-citrulline administration reduced organ dysfunction based on the Sequential Organ Failure Assessment (SOFA) score and affected selected immune parameters in mechanically ventilated medical intensive care unit (ICU) patients.MethodsA randomized, double-blind, multicenter clinical trial of enteral administration of L-citrulline versus placebo for critically ill adult patients under invasive mechanical ventilation without sepsis or septic shock was conducted in four ICUs in France between September 2016 and February 2019. Patients were randomly assigned to receive enteral L-citrulline (5 g) every 12 h for 5 days or isonitrogenous, isocaloric placebo. The primary outcome was the SOFA score on day 7. Secondary outcomes included SOFA score improvement (defined as a decrease in total SOFA score by 2 points or more between day 1 and day 7), secondary infection acquisition, ICU length of stay, plasma amino acid levels, and immune biomarkers on day 3 and day 7 (HLA-DR expression on monocytes and interleukin-6).ResultsOf 120 randomized patients (mean age, 60 ± 17 years; 44 [36.7%] women; ICU stay 10 days [IQR, 7–16]; incidence of secondary infections 25 patients (20.8%)), 60 were allocated to L-citrulline and 60 were allocated to placebo. Overall, there was no significant difference in organ dysfunction as assessed by the SOFA score on day 7 after enrollment (4 [IQR, 2–6] in the L-citrulline group vs. 4 [IQR, 2–7] in the placebo group; Mann‒Whitney U test, p = 0.9). Plasma arginine was significantly increased on day 3 in the treatment group, while immune parameters remained unaffected.ConclusionAmong mechanically ventilated ICU patients without sepsis or septic shock, enteral L-citrulline administration did not result in a significant difference in SOFA score on day 7 compared to placebo.Trial registration: ClinicalTrials.gov Identifier NCT02864017 (date of registration: 11 August 2016).

Secondary infections in critically ill patients with COVID-19 receiving steroid therapy.

Secondary infections can occur during or after the treatment of an initial infection. Glucocorticoids may decrease mortality in patients with severe COVID-19; however, risk of secondary infection is not well described. Our primary objective was to investigate the risk of secondary infection among critically ill patients with COVID-19 treated with glucocorticoids. We examined patients with COVID-19 being treated in the intensive care unit at two academic medical centers from 1 to 7/2020. One hundred-seven patients were included. Of these, 31 received steroids and 76 patients did not. Analysis of the larger cohort was performed followed by a matched pairs analysis of 22 steroid and 22 non-steroid patients. Secondary infection was seen in 14 patients (45.2%) receiving steroids compared to 35(46.1%) not receiving steroids (p = 0.968). Secondary infections were most frequently encountered in the respiratory tract. Escherichia coli and Staphylococcus aureus were the most frequently identified organisms. Mortality was 16.1% in the steroid-treated group compared to 23.7% in the control group (p = 0.388). After performing matched pairs analysis and multivariable logistic regression there was no significant difference between secondary infection or mortality and steroid receipt. Secondary infections were common among critically ill patients with COVID-19, but the incidence of secondary infection was not significantly impacted by steroid treatment.

#4229 SECONDARY BACTERIAL AND FUNGAL INFECTIONS IN COVID-19 PATIENTS WITH ACUTE KIDNEY INJURY AND RELATION WITH CYTOKINE STORM SYNDROME

Abstract Background and Aims Both COVID-19 and acute kidney injury (AKI) are associated with impaired host immunity. Virus-induced immunosuppression, overuse of antibiotics and corticosteroids are COVID-19 related factors, while dysregulation of the inflammatory response, increased volemia, hemodialysis catheters are AKI-related factors which favor secondary infections. We aimed to search the relation between markers of cytokine storm syndrome (interleukin-6 – IL-6; ferritin; C-reactive protein – CRP) and incidence of secondary infections and to identify the microorganisms involved in secondary infections in patients admitted with acute kidney injury and COVID-19 patients. Method Patients with both COVID-19 and AKI admitted in the 2nd and 3rd waves of the COVID-19 pandemic (May-December 2021) in an COVID-only hospital were included in this retrospective analysis. Diagnosis of AKI was established according to KDIGO creatinine-based criteria. Obstructive AKI cases were excluded. AKI was classified as A-AKI when it was diagnosed at the moment of admission and HA-AKI when it developed during hospitalization. Bacterial and/or fungal infections and the sites of positive cultures were registered in all patients. Colonizations with nonpathogenic microorganisms were excluded. Median values of IL-6, ferritin and CRP (maxim levels recorded during hospitalization) were compared between infected and non-infected patients. Results A total of 247 patients with AKI+COVID-19 were included in the study: 146 had A-AKI and 101 had HA-AKI. Secondary bacterial and fungal infections were registered in 111 patients (44.93%) cumulating 161 positive urine, blood, hemodialysis catheter tip, sputum, wounds, feces and tracheal intubation tubes cultures. Secondary infections were noted significantly more frequent in HA-AKI cases than in A-AKI cases: 61.38% (62 patients) vs 33.56% (49 patients) – Fischer exact test, p&amp;lt;0.001. The responsible microorganisms and the sites of positive culture are presented in Table 1. Median values of IL-6, ferritin and CRP (maximum levels recorded during hospitalization) were significantly higher in infected patients than in non-infected patients (Table 2) in the entire study group. IL-6 was significantly higher in infected HA-AKI patients when compared with infected A-AKI (231.40 pg/mL vs 124 pg/mL; p = 0.015), but no significant difference was found between the two subgroups of infected AKI patients regarding median ferritin levels (2481.5 ng/mL vs 1785 ng/mL; p = 0.324) or regarding median CRP values (206.27 mg/L vs 179.59 mg/L; p = 0.546). Conclusion Incidence of secondary bacterial and/or fungal infections in patients admitted with AKI and COVID-19 was very high in our study and it was associated with more severe altered markers of cytokine storm syndrome. Secondary infections in COVID-19 patients are important drivers of hospital-acquired AKI or they can aggravate its evolution.

Outcomes of patients hospitalized for COVID-19, secondary infections, antimicrobial use during SARS-CoV-2 delta and omicron variants

Background: The SARS-CoV-2 omicron variant has been associated with increased transmissibility and less severe disease than the SARS-CoV-2 delta variant. Low rates of secondary infections and excess empiric antimicrobial use were reported early in the pandemic. Comparisons between later variants are not as well documented. We evaluated outcomes for SARS-CoV-2 delta- and omicron-variant surges with emphases on COVID-19–related treatment, secondary infections, and antimicrobial utilization. Methods: A single-center, observational, retrospective study was conducted for SARS-CoV-2–positive patients admitted to our 548-bed community teaching hospital between November and December 2021 (SARS-CoV-2 delta-variant–predominant phase) and January–February 2022 (SARS-CoV-2 omicron-variant–predominant phase). Demographic and outcome data were obtained from the institutional data warehouse and were compared between groups. Secondary infections were defined as positive blood and respiratory culture results during admission, with likely contaminants excluded. Mann-Whitney U tests were used to evaluate continuous variables, and t tests were used to analyze categorical variables. P ≤ .05 was considered statistically significant. Results: In total, 1,297 patients were included: 787 (60.7%) in SARS-CoV-2 delta-variant–predominant phase and 510 (39.3%) in SARS-CoV-2 omicron-variant–predominant phase. Patients in SARS-CoV-2 omicron-variant–predominant phase were more often vaccinated (37.7% vs 55%; P &lt; .001), required lower rates of ICU care (16.0% vs 11.6%; P = .025), and required less intubation (13% vs 6.3%; P &lt; .001). Utilization of remdesivir (51.0% vs 32.2%; P &lt; .001), dexamethasone (70.8% vs 43.3%; P &lt; .001), and tocilizumab or baricitinib (14.5% vs 5.3%; P &lt; .001) decreased during the SARS-CoV-2 omicron-variant–predominant phase. Length of stay (5 days vs 4 days; P &lt; .001) and 30-day mortality also decreased during this period (16.40% vs 9.8%; P = .001). Infectious diseases consultation increased during the SARS-CoV-2 omicron-variant–predominant phase (39.8% vs 45.5%; P = .042). There was no significant difference in patients with positive blood cultures (3.4% vs 1.8%; P = .074), but there was a significant decrease in positive respiratory cultures (5.8% vs 2.7%; P = .009), combining for an overall reduction (8.4% vs 4.1%; P = .003). The incidence of overall antimicrobial use increased during the omicron-predominant phase (36.1% vs 41.8%; P = .04), and duration was lower (5 days vs 4 days; P &lt; .001). Antimicrobial class-specific duration was unchanged, with the exception of decreased gram-positive agents (3 days vs 2 days; P = .012). Conclusions: Our results confirm previous reports of reduced disease severity during the SARS-CoV-2 omicron-variant–predominant period. The incidence of secondary infections decreased, driven by a reduction in respiratory infections. Antimicrobials were used at increased rates and for shorter durations during the SARS-CoV-2 omicron-variant–predominant period.Disclosures: None

Epidemiology of secondary infection after snakebites in center-west Brazil.

Snakebites represent a significant health problem in tropical countries, with an annual incidence of 2.7 million cases worldwide. The incidence of secondary infections after snake bites is also high and is usually caused by bacteria from the oral cavity of snakes. Morganella morganii has been identified as an important cause of infections and has been guiding antibiotic therapy in several regions of Brazil and the world. We performed a retrospective cross-sectional evaluation of snakebites in hospitalized patients between January 2018 and November 2019 and selected those with secondary infection in their medical records. During the period, 326 cases of snakebites were treated, and 155 (47.5%) of them eventually had secondary infections. However, only seven patients underwent culture of soft tissue fragments, in which three cases were negative culture results, while Aeromonas hydrophila was identified in four cases. Of these, 75% were resistant to ampicillin/sulbactam, 50% had intermediate sensitivity to imipenem, and 25% had intermediate sensitivity to piperacillin/tazobactam. Trimethoprim/sulfamethoxazole (TMP-SMX) was not tested on any strain. Of the 155 cases that progressed to secondary infections, 48.4% (75) were empirically treated with amoxicillin/clavulanate, 41.9% (65) with TMP-SMX, and 32 (22%) of these 144 cases required a change to a second regimen, and 10 of these 32 patients required a third therapeutic regimen. Wild animals act as reservoirs of resistant bacteria because their oral cavity favors biofilm formation, which explains the finding of A. hydrophila with a reduced sensitivity profile in this study. This fact is essential for the appropriate choice of empirical antibiotic therapy.

Immunomodulators for severe coronavirus disease-2019 in transplant patients: Do they increase the risk of secondary infection?

Current guidelines recommend immunomodulators, tocilizumab or baricitinib, for the management of severe coronavirus disease-2019 (COVID-19) in patients with increasing oxygen requirements. Given their immunosuppressive effects, there is a concern for higher rates of infection among transplant recipients. A retrospective cohort study of transplant patients with severe COVID-19 between April 2020 and January 2022 was performed at the Mayo Clinic. The primary outcome was incidence of secondary infections after COVID-19 diagnosis. Secondary outcomes were 90-day mortality, ventilatory days, and thromboembolic events. A total of 191 hospitalized transplant patients were studied, including 77 (40.3%) patients who received an immunomodulator. Overall, 89% were solid organ transplant recipients, with kidney as the most common transplanted organ (50.3%). The majority (89.0%) required oxygen supplementation on admission, and 39.8% of these patients required mechanical ventilation during the hospital course. There was no significant difference in the incidence of secondary infections between those who received or did not receive an immunomodulator (p=.984). Likewise, there was no difference in 90-day mortality between patients who received or did not receive an immunomodulator (p=.134). However, higher mortality was observed among patients that developed a secondary infection (p<.001). The use of immunomodulators in transplant patients with severe COVID-19 was not significantly associated with an increased risk of secondary infections. Secondary infections were associated with higher risk of all-cause mortality. Future studies of larger cohorts are needed to explore the effect of immunomodulators on survival among transplant patients with COVID-19.

Late diagnosis of rhinocerebral mucormycosis in patients with COVID-19 (case studies)

From the beginning of the COVID-19 pandemic, the incidence of secondary infections (both bacterial and fungal) has increased due to immune suppression associated with the use of corticosteroids or broad-spectrum antibiotics as a part of COVID-19 treatment protocol, which may exacerbate a pre-existing fungal disease or cause a new infection. Ophthalmologists are often involved in taking medical and surgical decisions in these complex cases. In this regard, a strong clinical suspicion should be applied to possible secondary fungal infections in COVID-19. Their early diagnosis and treatment may reduce mortality due to COVID-19 associated rhinocerebral mucormycosis (ROCM). This article describes two clinical cases of late detection of ROCM with two different scenarios, and compare the features of these cases with the literature data.

458: EVALUATION OF TOCILIZUMAB ON CLINICAL OUTCOMES IN CRITICALLY ILL PATIENTS WITH COVID-19

Introduction: Markedly elevated pro-inflammatory cytokines, including interleukin-6 (IL-6), are associated with severe COVID-19. Blocking inflammation may prevent disease progression. Tocilizumab is a monoclonal antibody that reduces inflammation by blocking the IL-6 receptor, potentially having an impact on improving outcomes in patients with COVID-19. The objective of this study was to evaluate the use of tocilizumab in critically ill patients with COVID-19. Methods: This multicenter, retrospective study included adults admitted to an intensive care unit (ICU) with severe COVID-19 from June 2020 to November 2021. Patients were placed into two groups: those who received one dose of tocilizumab in addition to dexamethasone, and those who received dexamethasone alone. Patients were matched on age, sex, C-reactive protein (CRP) level, and time from symptom onset to hospitalization. The primary endpoint was hospital length of stay (LOS). Secondary endpoints were ICU LOS, in-hospital all-cause mortality, number of mechanically ventilated days, and incidence of secondary infections. Results: 120 patients were included (60 patients per group). The mean age was 57 years old, 60% were male, and the median time from symptom onset to hospitalization was 7 days. The median CRP level in the tocilizumab + dexamethasone group vs the dexamethasone group was 140.6 and 143 mg/L, respectively. The median hospital LOS was 11 days (IQR 8-17) in the tocilizumab + dexamethasone group vs 13 days (IQR 8 – 22.8) in the dexamethasone group. In-hospital all-cause mortality occurred in 17 patients (28%) in the tocilizumab + dexamethasone group vs 16 patients (26%) in the dexamethasone group. Of the 26 patients in the tocilizumab + dexamethasone group and 24 patients in the dexamethasone group that were mechanically ventilated, the median number of mechanically ventilated days was 10 (IQR 5 – 18.3) vs 10.5 (5 – 18.8), respectively. Secondary infections were similar in both groups. Conclusions: In this retrospective study evaluating tocilizumab in addition to dexamethasone for severe COVID-19 treated in the ICU, tocilizumab did not show a benefit in clinical outcomes. Given the size of the study and its limitations, these findings should be interpreted with caution and require confirmation by larger studies.

289. Prolonged Corticosteroid Usage, Associated Infectious Complications, and High Mortality in Adult Patients with COVID-19

Abstract Background Based on the RECOVERY trial, the NIH strongly recommends systemic corticosteroids for COVID-19 pneumonia with hypoxia. The study demonstrated reduced 28-day mortality after dexamethasone 6mg daily for up to 10 days compared to SOC alone. In practice, physicians may continue therapy for longer periods if potential benefit outweighs potential risk. Little is known about adverse events associated with prolonged corticosteroid use in patients with COVID-19; however, in general, this can increase risk for bacterial or fungal infections. This study aimed to explore the incidence of secondary infections during extended corticosteroid use for COVID-19. Methods A retrospective study was performed in adults at two community hospitals between September 2020 and May 2021 with a diagnosis of respiratory failure secondary to COVID-19 infection. Those with at least one new, laboratory-confirmed secondary infection during hospitalization after at least 10 cumulative days of corticosteroids were included. Demographic characteristics, clinical data and outcomes were extracted from the medical records. Quantitative analyses was performed using SPSS v27.0 and R. Results Of over 1,500 COVID-19 admissions within the timeframe, 73 patients met inclusion criteria (Table 1). No patient received immunomodulators for COVID-19 treatment. Patients had a median of 18 days on corticosteroids (range 10-65 days) prior to first positive culture. There were 130 positive cultures identified in blood, urine, and sputum samples (Figure 1), including polymicrobical cultures, yielding 34 clinically relevant organisms (Table 2). Hospital course was complicated by septic shock (68.5%), worsening of lung function (76.7%), and acute organ damage (57.5%); 55 (75%) patients expired during index admission. Conclusion Patients with COVID-19 on extended courses of corticosteroids have relatively higher rates of clinically significant invasive secondary infections and associated poor outcomes. Given there is limited information suggesting improved outcomes with these prolonged courses, risk to benefit analysis must be considered when deciding whether to extend corticosteroid treatment for more than 10 days for COVID-19. Disclosures All Authors: No reported disclosures.

Incidence and Microbiology of Hospital-Acquired Infections in COVID-19 Patients between the First and the Second Outbreak of the SARS-CoV-2 Pandemic: A Retrospective, Observational Study.

With almost 638 million cases and over 6 million deaths worldwide, the SARS-CoV-2 pandemic represents an unprecedented healthcare challenge. Although the management and natural history of COVID-19 patients have changed after the introduction of active therapies and vaccination, the development of secondary infections complicates hospital stay. This is a single-center, retrospective, observational study that explores the incidence and microbiology of hospital-acquired infections (HAIs) in two subsequent populations of hospitalized patients with COVID-19. Demographic, pre-hospitalization baseline characteristics, therapeutic options and microbiology data about secondary infections were collected for a total of 1153 cases. The second population appeared to have a higher median age (73 vs. 63 years, respectively), comorbidities (median Charlson Comorbidity Index Score was 4 vs. 1, respectively) and incidence of secondary infections (23.5% vs. 8.2%) with respect to the first. A higher incidence of multi-drug resistant organisms (MDROs), including difficult-to-treat resistant (DTR) Pseudomonas, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), was also observed. Both patients' characteristics and poor adherence to standard hygiene and infection control protocols may have contributed to the higher incidence of these events and may have impacted on the natural history of the disease. In-hospital mortality rates were similar, despite the introduction of active therapies against COVID-19 (24.7% vs. 23.5%, respectively). The incidence of HAIs may have contributed to the unchanged mortality and prompts for more effective antimicrobial stewardship and infection control procedures in COVID-19.

Bacterial and fungal coinfections among patients with COVID-19 in Zanjan, Northwest of Iran; a single-center observational with meta-analysis of the literature.

There is a poor understanding about the prevalence and characteristics of secondary bacterial and fungal infections among Coronavirus diseases 2019 (COVID-19) superinfection in hospitalized patients. Four hundred COVID-19-proven patients were enrolled in this study. Nasal swabs for molecular assay (Real-time PCR) and sputum samples for further microbiological assays were collected. Following a broad-spectrum search, a meta-analysis was performed using StatsDirect software (version 2.7.9) according to the DerSimonian and Laird method applying the random-effects models. Streptococcus spp. (21.5%) and Staphylococcus spp. (16.7%) had the highest prevalence of bacterial coinfection among the COVID-19 patients, while Acinetobacter spp. had the lowest prevalence (4.2%). Among fungal coinfections, Candida albicans was the most prevalent (6.7%), and Aspergillus spp. was the lowest (2%). Males, elderly patients, patients with a history of underlying diseases and drug use, patients who showed acute clinical symptoms, and patients with a prolonged hospital stay had a higher incidence of secondary infections (P-value <0.05). The pooled prevalence for bacterial and fungal coinfections was 33.52% (95% CI: 18.12 to 50.98; I2: 99.4%; P-value: <0.0001). We suggest designing additional research with a larger target population and diagnostic molecular analyses to depict a more realistic view of the coinfection status.

Evolutionary conservation of leptin effects on wound healing in vertebrates: Implications for veterinary medicine.

In mammals, the cytokine hormone leptin promotes wound healing by increasing inflammation, cellular recruitment, angiogenic regrowth, and re-epithelialization; however, it is not known whether leptin has conserved actions on wound healing in other vertebrates. Here, we tested the hypothesis that leptin promotes both the quality and speed of wound healing in the South African clawed frog, Xenopus laevis. First, fluorescent immunohistochemistry using a polyclonal antibody specific to Xenopus leptin showed that in juvenile dorsal skin, leptin protein is expressed in the dorsal epidermal layer, as well in blood vessel endothelial cells and sensory nerves that run along the base of the dermis. Injection of recombinant Xenopus leptin (rXleptin) stimulates phosphorylated STAT3 (pSTAT3), indicative of leptin-activated JAK/STAT signaling in the epidermis. Similar to mammals, leptin protein expression increases at the wound site after injury of the epidermis. We then cultured “punch-in-a-punch” full-thickness dorsal skin explants in three doses of rXleptin (0, 10, and 100 ng/ml) and showed that leptin treatment doubled the rate of wound closure after 48 h relative to skin punches cultured without leptin. Food restriction prior to wound explant culture reduced the amount of wound closure, but leptin injection prior to euthanasia rescued closure to similar control levels. Leptin treatment also significantly reduced bacterial infection of these epidermal punches by 48 h in culture. This study shows that leptin is likely an endogenous promoter of wound healing in amphibians. Leptin-based therapies have the potential to expedite healing and reduce the incidence of secondary infections without toxicity issues, the threat of antibiotic resistance, or environmental antibiotic contamination. The conservation of leptin’s actions on wound healing also suggests that it may have similar veterinary applications for other exotic species.