Suppressing Alpha-Hemolysin as Potential Target to Screen of Flavonoids to Combat Bacterial Coinfection

The rapid emergence of bacterial coinfection caused by cytosolic bacteria has become a huge threat to public health worldwide. Past efforts have been devoted to discover the broad-spectrum antibiotics, while the emergence of antibiotic resistance encourages the development of antibacterial agents. In essence, bacterial virulence is a factor in antibiotic tolerance. However, the discovery and development of new antibacterial drugs and special antitoxin drugs is much more difficult in the antibiotic resistance era. Herein, we hypothesize that antitoxin hemolytic activity can serve as a screening principle to select antibacterial drugs to combat coinfection from natural products. Being the most abundant natural drug of plant origins, flavonoids were selected to assess the ability of antibacterial coinfections in this paper. Firstly, we note that four flavonoids, namely, baicalin, catechin, kaempferol, and quercetin, have previously exhibited antibacterial abilities. Then, we found that baicalin, kaempferol, and quercetin have better inhibitions of hemolytic activity of Hla than catechin. In addition, kaempferol and quercetin, have therapeutic effectivity for the coinfections of Staphylococcus aureus and Pseudomonas aeruginosa in vitro and in vivo. Finally, our results indicated that kaempferol and quercetin therapied the bacterial coinfection by inhibiting S. aureus α-hemolysin (Hla) and reduced the host inflammatory response. These results suggest that antitoxins may play a promising role as a potential target for screening flavonoids to combat bacterial coinfection.

SARS-CoV-2 and Streptococcus pneumoniae Coinfection in a Previously Healthy Child

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in December 2019 in Wuhan, China. This novel coronavirus has been responsible for a pandemic that continues to devastate nations worldwide. COVID-19, like other viruses, causes pneumonia. However, unlike other viral respiratory tract infections such as influenza, bacterial coinfection in COVID-19 patients has uncommonly been described in adult and pediatric patients. We report a case of Streptococcus pneumoniae and COVID-19 coinfection in a previously healthy 4-year-old child.

Etiological significance of Corynebacterium spp. in the development of diseases of the respiratory tract

Corynebacterium spp. It is associated with inflammatory diseases of the respiratory tract (tracheitis, pharyngitis, rhinosinusitis, bronchitis, pneumonia, etc.). C. pseudodiphtheriticum can be the causative agent of bacterial coinfection in patients with a new coronavirus infection (COVID-19). The aim is to determine the pathogenic properties and resistance to antimicrobial drugs of Corynebacterium spp. strains to establish their etiological significance in the development of inflammatory diseases of the respiratory tract. Strains of Corynebacterium spp. isolated from patients with inflammatory diseases of the respiratory tract (43 pcs.) and practically healthy individuals (29 pcs.). Isolates were identified by mass spectrometric method (MALDI-TOF MS), their cytopathic effect in CHO-K1 cell culture, hemolytic, urease activity, antimicrobial drug resistance were determined. Strains of Corynebacterium spp. isolated from patients in the amount of 105 CFU/ml or more, practically healthy - 104 CFU/ml or less. Isolates of Corynebacterium spp. patients had a more pronounced cytopathic effect (83.7±11.1%) and were more often resistant to antimicrobial drugs than those isolated from practically healthy. To establish the etiological significance of Corynebacterium spp. isolates. in the development of inflammatory diseases of the respiratory tract, it is advisable to determine their amount in biological material (105 CFU/ml or more), the cytopathic effect on CHO-K1 cell culture, as well as the presence of multiple resistance to antimicrobial drugs. Differences in the characteristics of Corynebacterium spp. isolates. from patients with respiratory tract pathology and practically healthy individuals are associated with the strain, not the species, of corynebacteria.

325. Empiric Antibiotics for COVID-19 and the Utility of Procalcitonin

Background Bacterial coinfection in COVID-19 is infrequent, yet empiric antibiotic use is common. The objectives of this study were to investigate the effect of empiric antibiotics on time to resolution of COVID-19 pneumonia, elucidate the impact of COVID-19 on procalcitonin levels, and determine the incidence of respiratory bacterial coinfection. Methods This was a retrospective study of adult patients hospitalized with COVID-19 between June 1, 2020 and September 30, 2020. Patients were included if they had at least one procalcitonin level. They were excluded if admitted to an intensive care unit within 24 hours of presentation or received antibiotics for an indication besides pneumonia. Patients were stratified into 4 groups based on procalcitonin level and receipt of antibiotics. The primary outcome was time to clinical resolution of pneumonia. A key secondary outcome was incidence of confirmed respiratory bacterial coinfection. Results A total of 199 patients were included. Patients with a procalcitonin greater than 0.25 ng/mL who received antibiotics had a longer median time to clinical resolution of pneumonia, 8 days (95% CI, 4 to 11 days) vs. 3 or 4 days in other groups (P< 0.001). Additionally, this same group required greater baseline oxygen supplementation, had more comorbidities, and increased mortality compared to all other groups. Median time to clinical resolution of pneumonia was also longer in patients who received antibiotics compared to those who did not (5 vs. 4 days, P=0.017) and in those with a procalcitonin greater than 0.25 ng/mL compared to those with PCT less than or equal to 0.25 ng/mL (7 vs. 4 days, P< 0.001). Renal dysfunction was more prevalent in patients with an elevated procalcitonin (45% vs. 17.5%). The overall incidence of confirmed respiratory bacterial coinfection was 1.5%. Conclusion Irrespective of procalcitonin level, empiric antibiotics were not associated with a shorter time to resolution of COVID-19 pneumonia in non-critically ill patients. Elevated procalcitonin is likely a reflection of the severity of COVID-19 disease and baseline renal function rather than bacterial infection. Additionally, the overall incidence of confirmed bacterial coinfection in non-critically ill patients hospitalized with COVID-19 was low. Disclosures Kiya D. Mohadjer, PharmD, BCPS, BCIDP, Eli Lilly and Company (Shareholder)Gilead Sciences (Shareholder)

1189. COVID 19 Infection in Children in Colombia, Experience from a Nationwide Network (CORONARED)

Background Worldwide SARS-CoV-2 infections increase every day. Despite the infection is less severe in children, it can be severe and associated with complications. However, local data remain scarce. We sought to describe epidemiological and clinical characteristics of COVID-19 infection in this population across different age groups. Methods Observational, multicenter study across 23 Colombian hospitals from 22 different territories. We included all patients from 0 months to 17 years with confirmed SARS-CoV-2 infection by either antigen or RT-PCR testing. Results From March 1, 2020, to October 31, 2021, we identified 1,186 patients: neonates (88), 1 to 3 months (130), 4 to 23 months (306), 2 to 4 years (169), 5 to 11 years (229) and 12 to 18 years (226) with confirmed COVID-19 infection. Of those,77(6.2%) were asymptomatic, 631(53.2%) hospitalized, 132(11.2%) required PICU. 58 cases met WHO definition of MIS-C. Patients less than 24 months of age were characterized by fever (74%) and more respiratory distress (30.1%) compared to other groups. Patients >5yo seemed to have a more severe presentation. They had more gastrointestinal (GI) symptoms (31% vs 37.8%), had more need for ICU care given presentation with shock increased with age ( >5yo 9.5%; 5-12yo 10.6%; 12-18yo 11.5%). Lab markers including thrombocytopenia and Lymphopenia were more common on this age group. Antibiotic treatment was common (%%) especially in neonates (40.9%), despite bacterial coinfection was rare (8.7%), length of hospitalization was longer in older than 2-year-old groups. 23(1.9%) patients died, similar across different age groups. Heat map by age group Conclusion COVID-19 infection in Colombian children presented differently across different age groups. Children older than 5 years had a more severe clinical course and prolonged hospital stays. Clinical findings according to age groups could help clinicians in characterizing and identifying COVID 19 infections in Children. Disclosures Ivan Felipe Gutiérrez Tobar, n/a, Pfizer and MSD (Advisor or Review Panel member, Research Grant or Support, Speaker’s Bureau, Has received support from Pfizer and MSD for participation in congresses and has received conference payments from Pfizer)Pfizer and MSD (Speaker’s Bureau, Other Financial or Material Support, Has received support from Pfizer for participation in congresses) Juan P. Rojas -Hernandez, Candidate for doctorate in Public Health, Pfizer (Other Financial or Material Support, Has received support from Pfizer for participation in congresses) Eduardo López Medina, n/a, Pfizer (Other Financial or Material Support, Has received support from Pfizer for participation in congresses)

1536Antimicrobial resistance in the emerging COVID-19 pandemic

Background Inappropriate usage of antibiotics among COVID-19 patients can raise disastrous effects on antimicrobial resistance management and antibiotic stewardship programs. A study from USA reported 71% of COVID-19 patients received antibiotics while only 4% had bacterial co-infection. Similar findings were reported from a review of data from COVID-19 cases in Asia, which reported more than 70% of the patient receiving antibiotics however less than 10% on average had bacterial coinfection. The World Health Organisation discourages the use of antibiotics for mild cases of COVID-19, however they recommend it for severe cases at increased risk of secondary bacterial infection and death. This review aims to discuss the usage of antibiotics in COVID-19 patients pointing the role of bacterial coinfections, types of antibiotics used, and antibiotic resistance. Methods We systematically searched Medline, Cochrane library, Google Scholar for eligible studies published from 1st January 2020 till 29th May 2021. We included English language articles. We included patients of all age groups, in all settings. Primary outcome variable was bacterial coinfection and antimicrobial usage among COVID-19 patients. Results Less than 10% of the hospitalised COVID-19 patients had bacterial Co-infection. Antibiotics used among COVID-19 positives were moxifloxacin, ceftriaxone, azithromycin, piperacillin-tazobactam, levofloxacin, meropenem, etc. Conclusions Low proportion of COVID-19 patients had bacterial co-infection. Routine usage of antibiotics among COVID-19 positives should be discouraged. Key messages Bacterial co-infection among COVID-19 patients is low and therefore misuse of antibiotics among them should be discouraged.

Fungal, Parasitological, and bacterial coinfection in a severely ill COVID-19 patient in Peru

COVID-19 patients are prone to co-infections during their hospitalization. These co-infections are challenging as they involve longer hospital stays, high costs, and higher mortality risk. Here we present a case of a patient with multi-infection by resistant parasites, fungi, and bacteria during his hospitalization in a Peruvian hospital

Macrophage Polarization Modulated by Porcine Circovirus Type 2 Facilitates Bacterial Coinfection

Polarization of macrophages to different functional states is important for mounting responses against pathogen infections. Macrophages are the major target cells of porcine circovirus type 2 (PCV2), which is the primary causative agent of porcine circovirus–associated disease (PCVAD) leading to immense economic losses in the global swine industry. Clinically, PCV2 is often found to increase risk of other pathogenic infections yet the underlying mechanisms remain to be elusive. Here we found that PCV2 infection skewed macrophages toward a M1 status through reprogramming expression of a subset of M1-associated genes and M2-associated genes. Mechanistically, induction of M1-associated genes by PCV2 infection is dependent on activation of nuclear factor kappa B (NF-κB) and c-jun N-terminal kinase (JNK) signaling pathways whereas suppression of M2-associated genes by PCV2 is via inhibiting expression of jumonji domain containing-3 (JMJD3), a histone 3 Lys27 (H3K27) demethylase that regulates M2 activation of macrophages. Finally, we identified that PCV2 capsid protein (Cap) directly inhibits JMJD3 transcription to restrain expression of interferon regulatory factor (IRF4) that controls M2 macrophage polarization. Consequently, sustained infection of PCV2 facilitates bacterial infection in vitro. In summary, these findings showed that PCV2 infection functionally modulated M1 macrophage polarization via targeting canonical signals and epigenetic histone modification, which contributes to bacterial coinfection and virial pathogenesis.

Procalcitonin Predicts Intensive Care Unit Admission and Mortality in Patients With A COVID-19 Infection in The Emergency Department

IntroductionPatients with a severe COVID-19 infection often require admission at an intensive care unit (ICU) when they develop acute respiratory distress syndrome (ARDS). Hyperinflammation plays an important role in the development of ARDS in COVID-19. Procalcitonin (PCT) is a biomarker which may be a predictor of hyperinflammation. When patients with COVID-19 are in the emergency department (ED), PCT could be a predictor of severe COVID-19 infection. The goal of this study is to investigate the predictive value of PCT on severe COVID-19 infections in the ED. MethodsThis was a retrospective cohort study including patients with confirmed COVID-19 infection who visited the ED of Erasmus Medical Center in Rotterdam, the Netherlands, between March and December 2020. The primary endpoint was a severe COVID-19 infection, which was defined as patients who required ICU admission, in-hospital mortality and 30-day mortality after hospital discharge. PCT levels were measured during the ED visit. We used logistic regression to calculate the odds ratio (OR) of PCT on a severe COVID-19 infection, adjusting for bacterial coinfections, age, gender and comorbidities. ResultsA total of 332 patients were included in the final analysis of this study, of which 105 patients reached the composite endpoint of a severe COVID-19 infection. PCT showed an unadjusted OR of 4.19 (CI: 2.52-7.69) on a severe COVID-19 infection. Corrected for bacterial coinfection, the OR of PCT was 4.05 (2.45 – 7.41). Adjusted for gender, bacterial coinfection, age and comorbidities, PCT was still an independent predictor of severe COVID-19 infection with an adjusted OR of 3.82 (CI: 2.26-7.48).ConclusionPCT is a predictor of severe COVID-19 infections in patients with a COVID-19 infection in the ED. The routine measurement of PCT in patients with a COVID-19 infection in the ED may assist physicians in the clinical decision making process regarding ICU disposition when PCT levels are elevated.