Secondary Infections In Patients Research Articles

The usage of immunosuppressant agents and secondary infections in patients with COVID-19 in the intensive care unit: a retrospective study

Although COVID-19 infection is an immunosuppressant disease, many immunosuppressant agents, such as pulse methylprednisolone (PMP), dexamethasone (DXM), and tocilizumab (TCZ), were used during the pandemic. Secondary infections in patients with COVID-19 have been reported recently. This study investigated these agents’ effects on secondary infections and outcomes in patients with COVID-19 in intensive care units (ICUs). This study was designed retrospectively, and all data were collected from the tertiary intensive care units of six hospitals between March 2020 and October 2021. All patients were divided into three groups: Group I [GI, PMP (−), DXM (−) and TCZ (−)], Group II [GII, PMP (+), DXM (+)], and Group III [GIII, PMP (+), DXM (+), TCZ (+)]. Demographic data, PaO/FiO2 ratio, laboratory parameters, culture results, and outcomes were recorded. To compare GI-GII and GI-GIII, propensity score matching (PSM) was used by matching 14 parameters. Four hundred twelve patients with COVID-19 in the ICU were included in the study. The number of patients with microorganisms ≥ 2 was 279 (67.7%). After PSM, in GII and GIII, the number of (+) tracheal cultures and (+) bloodstream cultures detected different microorganisms ≥ 2 during the ICU period, neuropathy, tracheotomized patients, duration of IMV, and length of ICU stay were significantly higher than GI. The mortality rate was similar in GI and GII, whereas it was significantly higher in GIII than in GI. The use of immunosuppressant agents in COVID-19 patients may lead to an increase in secondary infections. In addition, increased secondary infections may lead to prolonged ICU stay, prolonged IMV duration, and increased mortality.

Risk factors for secondary infection after liver failure and effect of comprehensive nursing intervention.

In patients with liver failure (LF), the high rate of secondary infections, which are associated with poor prognosis, highlights the clinical significance of understanding the underlying risk factors and implementing targeted intervention programs. To investigate risk factors for secondary infections in patients with LF and evaluate the effectiveness of comprehensive nursing interventions. This retrospective study included 64 patients with LF, including 32 with and 32 without secondary infections. A questionnaire was used to collect data on age; laboratory parameters, including total and direct bilirubin, prothrombin time, blood ammonia, and other biochemical parameters; invasive procedures; and complications. Patients with secondary infections received comprehensive nursing intervention in addition to routine nursing care, whereas those without secondary infections received only routine nursing care to compare the effect of nursing intervention on outcomes. The infection rate, which was not associated with age or complications, was significantly associated with biochemical parameters and invasive procedures (P < 0.05). The infection rate was 61.6% in patients who had undergone invasive procedures and 32.1% in those who had not undergone invasive procedures during the hospital stay. The infection rate was also significantly associated with the type of LF (P < 0.05), with the lowest rate observed in patients with acute LF and the highest rate observed in those with subacute LF. The nursing satisfaction rate was 58.3% in the uninfected group and 91.7% in the infected group, indicating significantly higher satisfaction in the infected group (P < 0.05). In patients with LF, the rate of secondary infections was high and associated with biochemical parameters and type of LF. Comprehensive nursing intervention can improve patient satisfaction.

Effect of fasting plasma glucose level in severe fever and thrombocytopenia syndrome patients without diabetes.

Hyperglycemia is correlated with worse in-hospital outcomes in acute infectious diseases such as coronavirus disease 2019 (COVID-19) and severe fever with thrombocytopenia syndrome (SFTS). This study assessed the relationship between fasting plasma glucose (FPG) levels and in-hospital mortality, disease type, and secondary infections among individuals with SFTS without preexisting diabetes. The clinical data and laboratory results upon admission of 560 patients with SFTS without preexisting diabetes meeting the inclusion criteria at Wuhan Union Hospital were collected. FPG levels in surviving patients with SFTS subjects were significantly lower than those in patients with SFTS who had died (P<0.0001). In multivariate Cox regression, high FPG level (≥11.1 mmol/L) was a risk factor independently associated with the in-hospital death of patients with SFTS without preexisting diabetes. Similarly, the FPG levels in general patients with SFTS were significantly lower than those in patients with severe SFTS (P<0.0001). Multivariate logistic regression identified high FPG level (7.0-11.1 mmol/L) as a risk factor independently associated with SFTS severity. While FPG levels were comparable between patients with SFTS with and without secondary infection (P = 0.5521), logistic regression analysis revealed that high FPG levels were not a risk factor for secondary infection in patients with SFTS without preexisting diabetes. High FPG level on admission was an independent predictor of in-hospital death and severe disease in individuals with SFTS without preexisting diabetes. FPG screening upon admission and glycemic control are effective methods for improving the prognosis of patients with SFTS.

Analysis of factors influencing the risk of secondary infection in patients colonized or infected with multidrug-resistant Gram-negative bacteria following hospitalization

We seek to investigate the multifaceted factors influencing secondary infections in patients with multidrug-resistant Gram-negative bacteria (MDR-GNB) colonization or infection post-hospitalization. A total of 100 patients with MDR-GNB colonization or infection were retrospectively reviewed, encompassing those admitted to both the general ward and intensive care unit of our hospital from August 2021 to December 2022. Patients were categorized into the control group (non-nosocomial infection, n = 56) and the observation group (nosocomial infection, n = 44) based on the occurrence of nosocomial infection during hospitalization. Clinical data were compared between the two groups, including the distribution and antibiotic sensitivity of MDR-GNB before nosocomial infection. Significant differences were observed between the two groups in terms of age, underlying diseases, immune status, length of stay, and invasive medical procedures (P < 0.05). The observation group also had fewer patients practicing optimized hygiene, strict isolation, and antibiotic control than the control group (P < 0.05). Factors influencing the risk of secondary infection after hospitalization in patients colonized or infected with MDR-GNB included patient age, underlying diseases, immune status, length of hospitalization, medical invasive procedures, optimized hygiene, strict isolation, and antibiotic control (P < 0.05). The length of hospitalization and treatment cost in the observation group were higher than those in the control group (P < 0.05). This study comprehensively analyzes the intricate mechanisms of secondary infections in patients with MDR-GNB infections post-hospitalization. Key factors influencing infection risk include patient age, underlying diseases, immune status, length of hospitalization, medical invasive procedures, optimized hygiene, strict isolation, and antibiotic control.

The utility of procalcitonin for identifying secondary infections in patients with influenza or COVID-19 receiving extracorporeal membrane oxygenation.

Identifying secondary infections in patients receiving extracorporeal membrane oxygenation (ECMO) presents challenges due to the ECMO circuit's influence on traditional signs of infection. This study evaluates procalcitonin as a diagnostic marker for secondary infections in patients receiving ECMO with influenza or COVID-19 infection. Single-center retrospective cohort study. All adult patients receiving veno-venous ECMO with underlying influenza or COVID-19 from November 2017 to October 2021 were included. Patient demographics, time receiving ECMO, culture data, and procalcitonin levels were examined. The first procalcitonin within 3 days of infection was compared to negative workups that were collected at least 10 days from the last positive culture. Furthermore, we compared procalcitonin levels by the type of pathogen and site of infection. In this study, 84 patients with influenza or COVID-19 who received ECMO were included. A total of 276 procalcitonin labs were ordered in this cohort, with 33/92 (36%) of the secondary infections having an associated procalcitonin value. When comparing procalcitonin levels, there was no significant difference between the infection and negative workup groups [1 ng/mL (interquartile ranges, IQR: 0.4-1.2) versus 1.3 (0.5-4.3), p = 0.19]. Using 0.5 ng/mL as the cut-off, the sensitivity of procalcitonin was 67% and the specificity was 30%. In our cohort, the positive predictive value of procalcitonin was 14.5% and the negative predictive value was 84%. There was no difference in procalcitonin by type of organism or site of infection. Procalcitonin levels did not routinely decline even after an infection was identified. While procalcitonin is a proposed potential diagnostic marker for secondary infections in patients receiving ECMO, this single-center study demonstrated low sensitivity and specificity of procalcitonin in identifying secondary infections. Furthermore, there was no association of procalcitonin levels with etiology of infection when one was present. Procalcitonin should be used cautiously in identifying infections in veno-venous ECMO.

Agranulocytosis and secondary infection related to JAK inhibitors and IL-6 receptor blockers: a disproportionality analysis using the US Food and drug administration adverse event reporting system.

Background: Given that the fight against coronavirus disease 2019 (COVID-19) is not over, we aimed to explore the occurrence of agranulocytosis and infectious complications in patients with and without COVID-19 following immunoregulatory therapy based on real-world data. Methods: This was a retrospective disproportionality analysis based on the US Food and Drug Administration Adverse Event Reporting System (FAERS). All cases reported between the first quarter of 2004 and the fourth quarter of 2022 about Janus kinase inhibitors (baricitinib, tofacitinib, ruxolitinib) and interleukin-6 receptor blockers (tocilizumab, sarilumab) were collected. Disproportionality analyses were conducted by reporting odds ratio (ROR) and information component (IC). Results: A total of 211,363 cases were recognized from the FDA Adverse Event Reporting System database. Data analysis showed that tocilizumab (reporting odds ratio: 3.18, 95% CI: 3.18-3.29; information component: 1.37, 95% CI: 1.31-1.42), sarilumab (ROR: 1.64, 95% CI: 1.55-1.73; IC: 0.61, 95% CI: 0.43-0.79), baricitinib (ROR: 3.42, 95% CI: 3.19-3.67; IC: 1.43, 95% CI: 1.21-1.65), tofacitinib (ROR: 2.53, 95% CI: 2.49-2.57; IC: 1.11, 95% CI: 1.05-1.16), and ruxolitinib (ROR: 1.87, 95% CI: 1.83-1.91; IC: 0.77, 95% CI: 0.70-0.84) were all associated with secondary infection. The association in the combination group was higher than that in the monotherapy group (ROR: 4.69, 95% CI: 4.53-4.86; IC: 1.73, 95% CI: 1.62-1.84). As for agranulocytosis, tocilizumab (ROR: 1.61, 95% CI: 1.53-1.69; IC: 0.67, 95% CI: 0.50-0.84) and ruxolitinib (ROR: 2.32, 95% CI: 2.21-2.43; IC: 1.18, 95% CI: 1.02-1.33) showed the significant signals. The association was higher in the combination group than in the monotherapy group (ROR: 2.36, 95% CI: 2.15-2.58; IC: 1.20, 95% CI: 0.90-1.51). Secondary infection after treatment with tofacitinib (ROR: 1.37, 95% CI: 1.02-1.84), tocilizumab (ROR: 1.46, 95% CI: 1.01-2.09), and sarilumab (ROR: 2.46, 95% CI: 1.10-5.50) was reported more frequently in COVID-19 than in non-COVID-19 patients. Conclusion: Both Janus kinase inhibitors and interleukin-6 receptor blockers are significantly associated with secondary infection and agranulocytosis, and the combined treatment further increases the association. The correlation with secondary infection in patients treated with tofacitinib, tocilizumab, and sarilumab is higher in COVID-19 than in non-COVID-19 patients.

Secondary infections in patients hospitalized for COVID-19 in the intensive care unit on a reference hospital in Barbacena - Minas Gerais

Secondary infections in patients hospitalized for COVID-19 in the intensive care unit on a reference hospital in Barbacena - Minas Gerais

Raoultella ornithinolytica: A Case Series of Clinical Presentations and its Role in Various Infections from a Tertiary Care Centre in Tumkur, Karnataka, India

Raoultella ornithinolytica (R. ornithinolytica), a Gram-negative bacillus, has characteristics resembling those of Klebsiella spp. This bacterium is present in soil and aquatic environments and seldom causes Healthcare-Associated Infections (HAIs). However, clinical features and outcomes of human infections caused by R. ornithinolytica have been reported for only a limited number of cases. Here, multiple cases of adult patients with clinical features of community-acquired infections at different body sites are presented. R. ornithinolytica was identified in the laboratory from respective samples sent for culture and sensitivity. These patients were treated with good outcomes. R. ornithinolytica is a saprophyte known to cause secondary infections in patients with risk factors and sometimes exhibits antibiotic resistance. However, all the patients presented to the institution recovered fully from the infections and were discharged.

Sepsis induces non-classic innate immune memory in granulocytes

Secondary infection in patients with sepsis triggers a new wave of inflammatory response, which aggravates organ injury and increases mortality. Trained immunity boosts a potent and nonspecific response to the secondary challenge and has been considered beneficial for the host. Here, using a murine model of polymicrobial infection, we find that the primary infection reprograms granulocytes to boost enhanced inflammatory responses to the secondary infection, including the excessive production of inflammatory cytokines, respiratory burst, and augmented phagocytosis capacity. However, these reprogramed granulocytes exhibit "non-classic" characteristics of innate immune memory. Two mechanisms are independently involved in the innate immune memory of granulocytes: a metabolic shift in favor of glycolysis and fatty acid synthesis and chromatin remodeling leading to the transcriptional inactivity of genes encoding inhibitors of TLR4-initiated signaling pathways. Counteracting the deleterious effects of stressed granulocytes on anti-infection immunity might provide a strategy to fight secondary infections during sepsis.

Metaproteomic Analysis of Nasopharyngeal Swab Samples to Identify Microbial Peptides in COVID-19 Patients.

During the COVID-19 pandemic, impaired immunity and medical interventions resulted in cases of secondary infections. The clinical difficulties and dangers associated with secondary infections in patients necessitate the exploration of their microbiome. Metaproteomics is a powerful approach to study the taxonomic composition and functional status of the microbiome under study. In this study, the mass spectrometry (MS)-based data of nasopharyngeal swab samples from COVID-19 patients was used to investigate the metaproteome. We have established a robust bioinformatics workflow within the Galaxy platform, which includes (a) generation of a tailored database of the common respiratory tract pathogens, (b) database search using multiple search algorithms, and (c) verification of the detected microbial peptides. The microbial peptides detected in this study, belong to several opportunistic pathogens such as Streptococcus pneumoniae, Klebsiella pneumoniae, Rhizopus microsporus, and Syncephalastrum racemosum. Microbial proteins with a role in stress response, gene expression, and DNA repair were found to be upregulated in severe patients compared to negative patients. Using parallel reaction monitoring (PRM), we confirmed some of the microbial peptides in fresh clinical samples. MS-based clinical metaproteomics can serve as a powerful tool for detection and characterization of potential pathogens, which can significantly impact the diagnosis and treatment of patients.

#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.

Invasive fungal disease in COVID-19 patients: a single-center prospective observational study.

Invasive fungal diseases (IFDs) are caused by fungal infections that manifest as serious secondary infections in patients with COVID-19. The increased morbidity and mortality rates are most frequently observed in patients with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated candidiasis (CAC). CAPA is the most frequently encountered infection with an incidence rate of 0.7-7.7%, while CAC is a less common and less studied fungal infection in COVID-19 patients. The present article is a prospective observational single-center study that was conducted between 1 September 2021 and 24 December 2021, involving 6,335 patients who were admitted to COVID Hospital "Batajnica," University Clinical Center of Serbia, Belgrade. Of the 6,335 patients hospitalized during the four-month period of the study, 120 patients (1.86%) who had a proven diagnosis of IFD were included in the study. These patients were divided into two groups: CAPA patients (n = 63) and CAC patients (n = 56); however, one of the 120 patients was diagnosed with Cryptoccocus neoformans infection. The mean age of the study population was 65.7 ± 13.9 years, and 78 (65.5%) of them were men. The patients were identified to have the following non-malignant comorbidities: arterial hypertension in 62 (52.1%) patients, diabetes mellitus in 34 (28.65), pre-existing lung damage similar to that observed in COPD and asthma in 20 (16.8%), and chronic renal insufficiency in 13 (10.9%) patients. The hematological malignancies were found to be the most prevalent malignancies and were identified in 20 (16.8%) patients, particularly in CAPA patients [11 (17.5%); p < 0.041]. Fiberoptic bronchoscopy with bronchoalveolar lavage fluid (BALF) and microscopic examination confirmed the presence of fungal infections in 17 (14.3%) patients. Serology testing was also performed in the majority of cases. Antibodies against Aspergillus spp. and Candida spp. were predominantly found in CAPA patients (p < 0.001). The patients were also tested for the presence of (1-3)-β-D glucan (p < 0.019), galactomannan, and mannan in the specimens. Blood cultures were found to be positive in 45 (37.8%) patients, mostly in CAC patients. Mechanical ventilation was applied in 41 (34.5%) patients, while a non-invasive technique, such as continuous positive airway pressure (CPAP) or high-flow nasal cannula (HFNC), was used in 20 (16.8%) patients. The following antifungals were administered: echinocandins in 42 (35.3%), voriconazole in 30 (25.2%), and fluconazole in 27 (22.7%) patients. Most of the patients received systemic corticosteroids (mainly methylprednisolone), while 11 (9.16%) received favipiravir, 32 (26.67%) remdesivir, 8 (6.67%) casirivimab/imdevimab, and 5 (4.16%) sotrovimab. The outcome was lethal in 76 (63.9%) patients, predominantly CAC patients (p < 0.001). Invasive fungal disease is a severe complication associated with COVID-19 and accounts for increased mortality in these patients. Early identification and appropriate treatment may provide a favorable outcome.

Effects of the Selective Decontamination of the Digestive Tract (SDD) on Pulmonary Secondary Infections in Patients with COVID-19 Acute Respiratory Distress Syndrome: A Retrospective Single Centre Experience

Definitive data on the incidence rate of ventilator-associated pneumonia (VAP) in COVID-19 are still lacking, ranging from 29 to 58%. To date, most of the existing literature refers to patients who are not subjected to VAP prevention with selective decontamination of the digestive tract (SDD). We retrospectively collected data on all COVID-19 patients admitted to our ICU during the second phase of the pandemic with the aim of assessing the occurrence of VAP and the related mortality at 30 days and comparing our findings with the available literature. Of 213 patients, only 74 were eligible for the analysis. An incidence of 6.90 VAP per 1000 days of mechanical ventilation was detected. Apart from a smoking habit (0% vs. 10%, p &lt; 0.005) and diabetes (14% vs. 54%, p = 0.026), patients who developed VAP did not differ significantly from those who did not regarding comorbidities, steroid use, and the severity of COVID-19. VAP were predominantly caused by mono-microbial Gram-negative or fungal infections. Mortality was significantly higher in those who developed VAP (86 vs. 33%, p = 0.002). Our evidence aligned with the available literature in assuming a possible role of SDD in reducing the incidence of VAP in COVID-19 patients, with a possible impact on related mortality and costs.

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.

Secondary Infections in Critical Patients with COVID-19 Associated ARDS in the ICU: Frequency, Microbiologic Characteristics and Risk Factors.

To determine frequency, microbiologic characteristics and risks of secondary infections in patients with Coronavirus disease 2019 (COVID-19) associated acute respiratory distress syndrome (ARDS). An Observational study. COVID-19 intensive care unit (ICU), University of Health Sciences, Diskapı Yildirim Beyazit Research and Training Hospital, Turkey, from July 2020 to January 2021. Demographic data of the COVID-19 patients with ARDS, was collected with reference to (age, gender), comorbidities, illness scores, ICU management modalities, hospital, and ICU stay durations and ICU outcomes. Secondary infections [bloodstream infection (BSI), possible lower respiratory tract infection (pLRTI) or urinary tract infections (UTI)], microbiologic pathogens, and resistant patterns were recorded. A total of 205 COVID-19-related ARDS patients were included in this study. Out of them, 61 (29.8%) were diagnosed with secondary infection, 27 (13.1%) had at least one BSI, 20 (9.8%) had at least one pLRTI, and 34 (16.6%) had at least one UTI. Gram-negative pathogens were the most common cause of secondary infections (66/91, 72.5%). Klebsiella spp for BSI (10/19, 52.6%), Acinetobacter baumannii for pLRTI (10/18, 55.6%), and Escherichia coli for UTI (29/40, 72.5%) were the main causative agents. Among all Gram-negative bacteria, Carbapenem resistant was 62.1% (41/66) and extended-spectrum beta-lactamases positivity was 22.7% (15/66). At multivariable analysis, application of mechanical ventilation (MV) longer than 48 h, central catheterisation longer than 72 h, ICU stay longer than 10 days, and the time from hospitalisation to admission to the ICU longer than 48 h were associated with secondary infections. Patients with COVID-19 associated ARDS had a high rate of secondary infections. In order to reduce secondary infection in these patients, MV duration and ICU stay should be shortened and invasive catheters should be removed as soon as possible. SARS-CoV-2, COVID-19, Acute respiratory distress syndrome,Secondary infections.

Serine/Threonine Phosphatase Calcineurin Orchestrates the Intrinsic Resistance to Micafungin in the Human-Pathogenic Fungus Mucor circinelloides.

Procedures such as solid-organ transplants and cancer treatments can leave many patients in an immunocompromised state. This leads to their increased susceptibility to opportunistic diseases such as fungal infections. Mucormycosis infections are continually emerging and pose a serious threat to immunocompromised patients. Recently there has been a sharp increase in mucormycosis cases as a secondary infection in patients battling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Mucorales fungi are notorious for presenting resistance to most antifungal drugs. The absence of effective means to treat these infections results in mortality rates approaching 100% in cases of disseminated infection. One of the most effective antifungal drug classes currently available is the echinocandins. Echinocandins seem to be efficacious in the treatment of many other fungal infections. Unfortunately, susceptibility testing has found that echinocandins have little to no effect on Mucorales fungi. In this study, we found that the model Mucorales Mucor circinelloides genome carries three copies of the genes encoding the echinocandin target protein β-(1,3)-d-glucan synthase (fksA, fksB, and fksC). Interestingly, we found that exposing M. circinelloides to micafungin significantly increased the expression of the fksA and fksB genes, resulting in an increased accumulation of β-(1,3)-d-glucan on the cell walls. However, this overexpression of the fks genes is not directly connected to the intrinsic resistance. Subsequent investigation discovered that the serine/threonine phosphatase calcineurin regulates the expression of fksA and fksB, and the deletion of calcineurin results in a decrease in expression of all three fks genes. Deletion of calcineurin also results in a lower minimum effective concentration (MEC) of micafungin. In addition, we found that duplication of the fks gene is also responsible for the intrinsic resistance, in which lack of either fksA or fksB led a lower MEC of micafungin. Together, these findings demonstrate that calcineurin and fks gene duplication contribute to the intrinsic resistance to micafungin we observe in M. circinelloides.

Association between Vitamin D Status and Secondary Infections in Patients with Severe COVID-19 Admitted in the Intensive Care Unit of a Tertiary-Level Hospital in Turkey.

There are several studies showing that the vitamin D status can determine risk of COVID-19 infections, severity and mortality from coronavirus disease 2019 (COVID-19). However, the association between vitamin D (25(OH)D) and secondary infections in the prognosis of COVID-19 patients has not been reported yet. The aim was to investigate whether the vitamin D status affects the rates of secondary infections in patients with severe COVID-19 hospitalized in the intensive care unit (ICU) of a tertiary-level hospital in Turkey. The data of 194 patients with diagnosis of severe COVID-19 who were admitted to the ICU from March 2020 to June 2021 and older than 18 years were evaluated in this retrospective study. The patients were divided into two groups according to total serum 25(OH)D level as normal group (≥20 ng/mL) and low group (<20 ng/mL). The 25(OH)D level was low in 118 (60.8%) and normal in 76 (39.2%) patients. The mean age of the low group was significantly higher than that of the normal group (67.02 ± 14.47 vs. 61.70 ± 14.38; p = 0.013). The systolic and diastolic blood pressure as well as the Glasgow coma scale score of the low group were significantly lower than that of the normal group (p = 0.004, 0.002 and 0.001, respectively). The intubation rate and APACHE (Acute Physiology and Chronic Health Evaluation) score of the low group was significantly higher than that of the normal group (p = 0.001). The platelets number and blood pH decreased, and the neutrophil/lymphocyte ratio, procalcitonin, lactate, urea, creatinine and lactate dehydrogenase concentrations increased significantly in the low group (p < 0.05). The mortality rate was 79.7% in the low group and 22.4% in the normal group (p < 0.001). Microbiological growth was observed in 68.6% of the normal group and 52.6% of the normal group (p = 0.025). The number of cultures with resistant bacteria was significantly higher in the low group (25.9%) than that in the normal group (17.5%) (p = 0.035). The severe COVID-19 patients hospitalized with vitamin D deficiency may have increased risks of poor prognosis and mortality due to secondary infections in the ICU.

Metatranscriptomic Analysis Reveals Disordered Alterations in Oropharyngeal Microbiome during the Infection and Clearance Processes of SARS-CoV-2: A Warning for Secondary Infections

This study was conducted to investigate oropharyngeal microbiota alterations during the progression of coronavirus disease 2019 (COVID-19) by analyzing these alterations during the infection and clearance processes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The diagnosis of COVID-19 was confirmed by using positive SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR). The alterations in abundance, diversity, and potential function of the oropharyngeal microbiome were identified using metatranscriptomic sequencing analyses of oropharyngeal swab specimens from 47 patients with COVID-19 (within a week after diagnosis and within two months after recovery from COVID-19) and 40 healthy individuals. As a result, in the infection process of SARS-CoV-2, compared to the healthy individuals, the relative abundances of Prevotella, Aspergillus, and Epstein-Barr virus were elevated; the alpha diversity was decreased; the beta diversity was disordered; the relative abundance of Gram-negative bacteria was increased; and the relative abundance of Gram-positive bacteria was decreased. After the clearance of SARS-CoV-2, compared to the healthy individuals and patients with COVID-19, the above disordered alterations persisted in the patients who had recovered from COVID-19 and did not return to the normal level observed in the healthy individuals. Additionally, the expressions of several antibiotic resistance genes (especially multi-drug resistance, glycopeptide, and tetracycline) in the patients with COVID-19 were higher than those in the healthy individuals. After SARS-CoV-2 was cleared, the expressions of these genes in the patients who had recovered from COVID-19 were lower than those in the patients with COVID-19, and they were different from those in the healthy individuals. In conclusion, our findings provide evidence that potential secondary infections with oropharyngeal bacteria, fungi, and viruses in patients who have recovered from COVID-19 should not be ignored; this evidence also highlights the clinical significance of the oropharyngeal microbiome in the early prevention of potential secondary infections of COVID-19 and suggests that it is imperative to choose appropriate antibiotics for subsequent bacterial secondary infection in patients with COVID-19.

202. Vintage or Vogue? The Utility of Procalcitonin for Identifying Secondary Infections in Patients With Influenza or Covid-19 Receiving Extracorporeal Membrane Oxygenation

Abstract Background Secondary infections in patients receiving extracorporeal membrane oxygenation (ECMO) are difficult to identify as many signs traditionally associated with infection, such as temperature, are partially controlled by the ECMO circuit. This study analyzes the utility of procalcitonin (PCT) as a diagnostic marker in identifying secondary infections in patients receiving ECMO with influenza or COVID-19. Methods A single center retrospective study was performed on patients receiving ECMO with underlying influenza or COVID-19 from November 2017 to October 2021. Patient demographics, time receiving ECMO, culture data, and PCT levels were extracted. The first PCT within three days of an infection designated positive was compared to negative values, PCT extracted from patients without an identified infection or any PCT 10 days after the most recent infection. Furthermore, PCT levels were compared by type of pathogen as well as site of infection via Mann-Whitney U tests. Results 84 patients (77% males) met inclusion criteria with median age of 43 (interquartile range (IQR): 35-51). Median ECMO time was 416 hours (IQR: 232-824), with 64 (76%) of the patients admitted for COVID-19. A total of 276 (3.3 per patient) PCT were ordered during the study period. Of the 92 infections identified, 33 (36%) had an associated PCT value with 19 (58%) PCT collected on the day of positive culture, 10 (32%) within one day, and 4 (12%) collected two to three days after positive culture. There was no significant difference between median PCT value among the infection group (1.0 IQR: 0.40-1.19) compared to the non-infectious group (1.27 IQR: 0.47-4.26, p= 0.19), between Gram-positive and Gram-negative infections (1.09 IQR: 0.43-2.70 vs. 0.95 IQR: 0.4-1.29 p= 0.35) or between bloodstream infections and respiratory infections (1.3 IQR 0.45-2.70 vs. 0.55 IQR: 0.4-1.38, p=0.35). PCT does not decline after infection is identified (Figure 1). Procalcitonin Trends Figure 1.Procalcitonin levels do not statistically decline over the course of an infection. Conclusion While PCT has been proposed as a potential diagnostic marker for secondary infections in patients receiving ECMO, this single center study did not demonstrate utility of PCT in identifying secondary infections. Furthermore, there was no association of PCT levels with either the site of infection or type of infectious organism. Disclosures All Authors: No reported disclosures.

A Review Article on the Therapeutic Potential of Medicinal Plants for Prevention and Treatment of Secondary Infection in Patients with COVID-19

:COVID-19 is an infectious disease, caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) that is rapidly spreading all over the world and responsible for the international health crisis. In an earlier period, various synthetic antiviral drugs and clinical therapies have been used to control the viral infection but at present, there is no specific treatment available for COVID-19 infection. Several approaches like ritonavir, lopinavir, hydroxychloroquine, and chloroquine have been proposed. India is a hub of medicinal plants, so there is a chance to find out the way to combat the COVID-19 pandemic. The medicinal herbal formulations may enhance the immunity and come up with a powerful antiviral drug, which is an urgent need to control the outbreak of coronavirus. In this review article, we have discussed epidemiology, clinical outcomes, treatment, and prevention of this novel epidemic coronavirus from medicinal herbal formulations perspective. We have also emphasized the reported antiviral activity and immunity-boosting property of the Indian medicinal plants. This article also suggests that the drug or formulation obtained from medicinal plant sources may have low fatal outcomes, quick response, and safe in the management and prevention of this pandemic outbreak.