From Co-Infections to Autoimmune Disease via Hyperactivated Innate Immunity: COVID-19 Autoimmune Coagulopathies, Autoimmune Myocarditis and Multisystem Inflammatory Syndrome in Children.

Neutrophilia and the production of neutrophil extracellular traps (NETs) are two of many measures of increased inflammation in severe COVID-19 that also accompany its autoimmune complications, including coagulopathies, myocarditis and multisystem inflammatory syndrome in children (MIS-C). This paper integrates currently disparate measures of innate hyperactivation in severe COVID-19 and its autoimmune complications, and relates these to SARS-CoV-2 activation of innate immunity. Aggregated data include activation of Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD) receptors, NOD leucine-rich repeat and pyrin-domain-containing receptors (NLRPs), retinoic acid-inducible gene I (RIG-I) and melanoma-differentiation-associated gene 5 (MDA-5). SARS-CoV-2 mainly activates the virus-associated innate receptors TLR3, TLR7, TLR8, NLRP3, RIG-1 and MDA-5. Severe COVID-19, however, is characterized by additional activation of TLR1, TLR2, TLR4, TLR5, TLR6, NOD1 and NOD2, which are primarily responsive to bacterial antigens. The innate activation patterns in autoimmune coagulopathies, myocarditis and Kawasaki disease, or MIS-C, mimic those of severe COVID-19 rather than SARS-CoV-2 alone suggesting that autoimmunity follows combined SARS-CoV-2-bacterial infections. Viral and bacterial receptors are known to synergize to produce the increased inflammation required to support autoimmune disease pathology. Additional studies demonstrate that anti-bacterial antibodies are also required to account for known autoantigen targets in COVID-19 autoimmune complications.

Bacterial co-infection and antibiotic stewardship in patients with COVID-19: a systematic review and meta-analysis.

INTRODUCTION: Understanding the proportion of patients with COVID-19 who have respiratory bacterial co-infections and the responsible pathogens is important for managing COVID-19 effectively while ensuring responsible antibiotic use. OBJECTIVE: To estimate the frequency of bacterial co-infection in COVID-19 hospitalized patients and of antibiotic prescribing during the early pandemic period and to appraise the use of antibiotic stewardship criteria. METHODS: Systematic review and meta-analysis was performed using major databases up to May 5, 2021. We included studies that reported proportion/prevalence of bacterial co-infection in hospitalized COVID-19 patients and use of antibiotics. Where available, data on duration and type of antibiotics, adverse events, and any information about antibiotic stewardship policies were also collected. RESULTS: We retrieved 6,798 studies and included 85 studies with data from more than 30,000 patients. The overall prevalence of bacterial co-infection was 11% (95% CI 8% to 16%; 70 studies). When only confirmed bacterial co-infections were included the prevalence was 4% (95% CI 3% to 6%; 20 studies). Overall antibiotic use was 60% (95% CI 52% to 68%; 52 studies). Empirical antibiotic use rate was 62% (95% CI 55% to 69%; 11 studies). Few studies described criteria for stopping antibiotics. CONCLUSION: There is currently insufficient evidence to support widespread empirical use of antibiotics in most hospitalised patients with COVID-19, as the overall proportion of bacterial co-infection is low. Furthermore, as the use of antibiotics during the study period appears to have been largely empirical, clinical guidelines to promote and support more targeted administration of antibiotics in patients admitted to hospital with COVID-19 are required.

Antibiotics Used for COVID-19 In-Patients from an Infectious Disease Ward.

Background: although the prevalence of bacterial co-infections for COVID-19 patients is very low, most patients receive empirical antimicrobial therapy. Furthermore, broad spectrum antibiotics are preferred to narrow spectrum antibiotics. Methods: in order to estimate the excess of antibiotic prescriptions for patients with COVID-19, and to identify the factors that were correlated with the unjustified antibiotic usage, we conducted an observational (cohort) prospective study in patients hospitalized with COVID-19 at the National Institute for Infectious Diseases "Prof. Dr. Matei Bals", Bucharest, on an infectious disease ward, from November 2021 to January 2022. To evaluate the prevalence of bacterial co-infection in these patients, all positive microbiology results and concomitant suspected or confirmed bacterial co-infections, as documented by the treating doctor, were recorded. The patients were grouped in two categories: patients who received antibiotics and those who did not receive antibiotics, justified or not. Results: from the 205 patients enrolled in the study, 83 (40.4%) received antibiotics prior to being admitted to the hospital. 84 patients (41.0%) received antibiotics during their hospitalization; however, only 32 patients (15.6%) had signs and symptoms suggestive of an infection, 19 (9.3%) presented pulmonary consolidation on the computed tomography (CT) scan, 20 (9.7%) patients had leukocytosis, 29 (14.1%) had an increased procalcitonin level and only 22 (10.7%) patients had positive microbiological tests. It was observed that patients treated with antibiotics were older [70 (54−76) vs. 65 (52.5−71.5), p = 0.023, r = 0.159], had a higher Charlson index [4 (2−5) vs. 2 (1−4), p = 0.007, r = 0.189], had a severe/critical COVID-19 disease more frequently [61 (72.6%) vs. 38 (31.4%), p < 0.001, df = 3, X2 = 39.563] and required more oxygen [3 (0−6) vs. 0 (0−2), p < 0.001, r = 0.328]. Conclusion: empirical antibiotic treatment recommendation should be reserved for COVID-19 patients that also had other clinical or paraclinical changes, which suggest a bacterial infection. Further research is needed to better identify patients with bacterial co-infection that should receive antibiotic treatment.

Detection of staphylococcal pantone-valentine leukocidin (PVL) gene in covid-19 patients

Background: Millions of people throughout the world have been impacted by the 2019 pandemic coronavirus disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (COVID-19). Critical risk factors for the severity and fatality rates of COVID-19 are bacterial co-infection and subsequent bacterial infection. It is also necessary to take into account the antibiotic resistant as a result of overuse. We will review the secondary bacterial infections and bacterial co-infections in COVID-19 patients in this study, we aimed To isolate Staphylococcus aureus and investigate the role of Panton-Valentine Leukocidin (PVL) toxin in severity of infection in COVID-19 patients. Study the antibiogram of Staph, aureus. Methods: This study was conducted with 100 patients of Iraqi-Kut city in both sexes, aged 18-70 years, in cooperation with AL-Zahraa Teaching Hospital in day 10 of COVID-19 infection. Collected 100 sputum samples (50 mild and 50 as severe), during period from December 2020 to June 2021, It was looked at whether individuals with the coronavirus disease of 2019 (COVID-19) had additional respiratory pathogens coinfected with them. Detection of bacterial strains by use VITEK2 system, detection of PVL gene and mec A gene by real time per technique. Results: In this study, collected 100 sputum samples from COVID-19 patients, the results showed that the percentage of bacterial infection (63%), fungal infection (16%), no growth (21%). percentage of staphylococcus aureus was (17%);detection of PVL gene as positive results (29.4%). Conclusions: simultaneous PVL gene and VITEK2 system identification of respiratory infections in SARS-CoV-2 patients, mec In particular during the COVID-19 pandemic, a gene by molecular diagnosis assays is required for determining the causal agents of coinfection. © 2023, ResearchTrentz Academy Publishing Education Services. All rights reserved.

Profile of Co-Infection Prevalence and Antibiotics Use among COVID-19 Patients.

Bacterial co-infection in COVID-19 patients significantly contributes to the worsening of the prognosis based on morbidity and mortality. Information on the co-infection profile in such patients could help to optimize treatment. The purpose of this study was to describe bacterial co-infections associated with microbiological, clinical, and laboratory data to reduce or avoid a secondary infection. A retrospective cohort study was conducted at Sant'Anna and San Sebastiano Hospital from January 2020 to December 2021. Bacterial co-infection was detected in 14.3% of the COVID-19-positive patients. The laboratory findings on admission showed significant alterations in the median D-dimer, C-reactive protein, interleukin-6, and lactate dehydrogenase values compared to normal values. All inflammatory markers were significantly elevated. The most common pathogens isolated from blood cultures were E. faecalis and S. aureus. Instead, the high prevalence of respiratory tract infections in the COVID-19 patients was caused by P. aeruginosa (41%). In our study, 220 (82.4%) of the COVID-19 patients received antimicrobial treatment. Aminoglycosides and ß-lactams/ß-lactamase inhibitors showed the highest resistance rates. Our results showed that older age, underlying conditions, and abnormal laboratory parameters can be risk factors for co-infection in COVID-19 patients. The antibiotic susceptibility profile of bacterial pathogen infection provides evidence on the importance, for the clinicians, to rationalize and individualize antibiotic usage.

Beyond Guidelines and Reports on Bacterial Co-/Superinfections in the Context of COVID-19: Why Uniformity Matters.

BACKGROUND: In the period following the declaration of the COVID-19 pandemic, more evidence became available on the epidemiology of bacterial co-/superinfections (bCSs) in hospitalized COVID-19 patients. Various European therapeutic guidelines were published, including guidance on rational antibiotic use. METHODS: In this letter to the editor, we provide an overview of the largest meta-analyses or prospective studies reporting on bCS rates in COVID-19 patients and discuss why the reader should interpret the results of those reports with care. Moreover, we compare different national and international COVID-19 therapeutic guidelines from countries of the European Union. Specific attention is paid to guidance dedicated to rational antibiotic use. RESULTS: We found a significant heterogeneity in studies reporting on the epidemiology of bCSs in COVID-19 patients. Moreover, European national and international guidelines differ strongly from each other, especially with regard to the content and extent of antibiotic guidance in hospitalized COVID-19 patients. CONCLUSION: A standardized way of reporting on bCSs and uniform European guidelines on rational antibiotic use in COVID-19 patients are crucial for antimicrobial stewardship teams to halt unnecessary antibiotic use in the COVID-19 setting.

First Case of Splenic Abscess Parvimonas micra and Bacteremia Porphyromonas gingivalis Coinfection.

We report a case of a 76-year-old Caucasian male with bacteremia caused by Porphyromonas gingivalis and splenic abscess caused by Parvimonas micra. This patient presented with nonspecific symptoms: fever, chills, body aches, and shortness of breath. He was treated with IV piperacillin-tazobactam that was later switched to ampicillin sodium/sulbactam sodium during his hospital course and underwent a splenectomy. He ultimately expired due to acute respiratory failure and cardiac arrest, secondary to post-surgical complications. To our knowledge, this is the first case of P. micra and P. gingivalis coinfection.

Negative predictive value of procalcitonin to rule out bacterial respiratory co-infection in critical covid-19 patients.

BACKGROUND: Procalcitonin (PCT) and C-Reactive Protein (CRP) are useful biomarkers to differentiate bacterial from viral or fungal infections, although the association between them and co-infection or mortality in COVID-19 remains unclear. METHODS: The study represents a retrospective cohort study of patients admitted for COVID-19 pneumonia to 84 ICUs from ten countries between (March 2020-January 2021). Primary outcome was to determine whether PCT or CRP at admission could predict community-acquired bacterial respiratory co-infection (BC) and its added clinical value by determining the best discriminating cut-off values. Secondary outcome was to investigate its association with mortality. To evaluate the main outcome, a binary logistic regression was performed. The area under the curve evaluated diagnostic performance for BC prediction. RESULTS: 4635 patients were included, 7.6% fulfilled BC diagnosis. PCT (0.25[IQR 0.1-0.7] versus 0.20[IQR 0.1-0.5]ng/mL, p<0.001) and CRP (14.8[IQR 8.2-23.8] versus 13.3 [7-21.7]mg/dL, p=0.01) were higher in BC group. Neither PCT nor CRP were independently associated with BC and both had a poor ability to predict BC (AUC for PCT 0.56, for CRP 0.54). Baseline values of PCT<0.3ng/mL, could be helpful to rule out BC (negative predictive value 91.1%) and PCT≥0.50ng/mL was associated with ICU mortality (OR 1.5,p<0.001). CONCLUSIONS: These biomarkers at ICU admission led to a poor ability to predict BC among patients with COVID-19 pneumonia. Baseline values of PCT<0.3ng/mL may be useful to rule out BC, providing clinicians a valuable tool to guide antibiotic stewardship and allowing the unjustified overuse of antibiotics observed during the pandemic, additionally PCT≥0.50ng/mL might predict worsening outcomes.

Secondary Bacterial Infection and Clinical Characteristics in Patients With COVID-19 Admitted to Two Intensive Care Units of an Academic Hospital in Iran During the First Wave of the Pandemic.

Data on the prevalence of bacterial co-infections and secondary infection among adults with COVID-19 admitted to the intensive care unit (ICU) are rare. We aimed to determine the frequency of secondary bacterial infection, antibiotic use, and clinical characteristics in patients admitted to the ICU with severe SARS-CoV-2 pneumonia. This was a retrospective cohort study of adults with severe COVID-19 admitted to two ICUs from March 6 to September 7, 2020 in an academic medical center in Isfahan, Iran. To detect COVID-19, reverse transcription real-time polymerase chain reaction was performed and also typical pattern of CT scan was used for the diagnosis of COVID-19. Data collection included the age, gender, main symptoms, history of underlying disease, demographics, hospital stay, outcomes, and antibiotic regimen of the patient. Antimicrobial susceptibility testing was carried out according to the CLSI guidelines. During the study period, 553 patients were referred to the both ICUs for COVID-19 with severe pneumonia. Secondary bacterial infection was detected in 65 (11.9%) patients. The median age was 69.4 (range 21-95) years; 42 (63.6%) were men. Notably, 100% (n = 65) of the patients with superinfection were prescribed empirical antibiotics before first positive culture, predominantly meropenem (86.2%) with a median duration of 12 (range 2-32) days and levofloxacin (73.8%) with a median duration of nine (range 2-24) days. Most prevalent causative agents for secondary bacterial infection were Klebsiella pneumoniae (n = 44) and Acinetobacter baumannii (n = 33). Most patients with secondary bacterial infection showed extensive drug-resistance. The mortality among patients who acquired superinfections was 83% against an overall mortality of 38.1% in total admitted COVID-19 patients. We found a high prevalence of carbapenem-resistant Gram-negative bacilli in COVID-19 patients admitted to our ICUs, with a high proportion of K. pneumoniae followed by A. baumannii. These findings emphasize the importance of implementation of strict infection control measures and highlight the role of antimicrobial stewardship during a pandemic.

COVID-19 Autopsies Reveal Underreporting of SARS-CoV-2 Infection and Scarcity of Co-infections.

Coronavirus disease 2019 (COVID-19) mortality can be estimated based on reliable mortality data. Variable testing procedures and heterogeneous disease course suggest that a substantial number of COVID-19 deaths is undetected. To address this question, we screened an unselected autopsy cohort for the presence of SARS-CoV-2 and a panel of common respiratory pathogens. Lung tissues from 62 consecutive autopsies, conducted during the first and second COVID-19 pandemic waves in Switzerland, were analyzed for bacterial, viral and fungal respiratory pathogens including SARS-CoV-2. SARS-CoV-2 was detected in 28 lungs of 62 deceased patients (45%), although only 18 patients (29%) were reported to have COVID-19 at the time of death. In 23 patients (37% of all), the clinical cause of death and/or autopsy findings together with the presence of SARS-CoV-2 suggested death due to COVID-19. Our autopsy results reveal a 16% higher SARS-CoV-2 infection rate and an 8% higher SARS-CoV-2 related mortality rate than reported by clinicians before death. The majority of SARS-CoV-2 infected patients (75%) did not suffer from respiratory co-infections, as long as they were treated with antibiotics. In the lungs of 5 patients (8% of all), SARS-CoV-2 was found, yet without typical clinical and/or autopsy findings. Our findings suggest that underreporting of COVID-19 contributes substantially to excess mortality. The small percentage of co-infections in SARS-CoV-2 positive patients who died with typical COVID-19 symptoms strongly suggests that the majority of SARS-CoV-2 infected patients died from and not with the virus.

Predictive model for bacterial co-infection in patients hospitalized for COVID-19: a multicenter observational cohort study.

OBJECTIVE: The aim of our study was to build a predictive model able to stratify the risk of bacterial co-infection at hospitalization in patients with COVID-19. METHODS: Multicenter observational study of adult patients hospitalized from February to December 2020 with confirmed COVID-19 diagnosis. Endpoint was microbiologically documented bacterial co-infection diagnosed within 72 h from hospitalization. The cohort was randomly split into derivation and validation cohort. To investigate risk factors for co-infection univariable and multivariable logistic regression analyses were performed. Predictive risk score was obtained assigning a point value corresponding to ß-coefficients to the variables in the multivariable model. ROC analysis in the validation cohort was used to estimate prediction accuracy. RESULTS: Overall, 1733 patients were analyzed: 61.4% males, median age 69 years (IQR 57-80), median Charlson 3 (IQR 2-6). Co-infection was diagnosed in 110 (6.3%) patients. Empirical antibiotics were started in 64.2 and 59.5% of patients with and without co-infection (p = 0.35). At multivariable analysis in the derivation cohort: WBC ≥ 7.7/mm3, PCT ≥ 0.2 ng/mL, and Charlson index ≥ 5 were risk factors for bacterial co-infection. A point was assigned to each variable obtaining a predictive score ranging from 0 to 5. In the validation cohort, ROC analysis showed AUC of 0.83 (95%CI 0.75-0.90). The optimal cut-point was ≥2 with sensitivity 70.0%, specificity 75.9%, positive predictive value 16.0% and negative predictive value 97.5%. According to individual risk score, patients were classified at low (point 0), intermediate (point 1), and high risk (point ≥ 2). CURB-65 ≥ 2 was further proposed to identify patients at intermediate risk who would benefit from early antibiotic coverage. CONCLUSIONS: Our score may be useful in stratifying bacterial co-infection risk in COVID-19 hospitalized patients, optimizing diagnostic testing and antibiotic use.

Elucidating the role of procalcitonin as a biomarker in hospitalized COVID-19 patients.

Our objectives were to evaluate the role of procalcitonin in identifying bacterial co-infections in hospitalized COVID-19 patients and quantify antibiotic prescribing during the 2020 pandemic surge. Hospitalized COVID-19 patients with both a procalcitonin test and blood or respiratory culture sent on admission were included in this retrospective study. Confirmed co-infection was determined by an infectious diseases specialist. In total, 819 patients were included; 335 (41%) had an elevated procalcitonin (>0.5 ng/mL) and of these, 42 (13%) had an initial bacterial co-infection. Positive predictive value of elevated procalcitonin for co-infection was 13% while the negative predictive value was 94%. Ninety-six percent of patients with an elevated procalcitonin received antibiotics (median 6 days of therapy), compared to 82% with low procalcitonin (median 4 days of therapy) (adjusted OR:3.3, P < 0.001). We observed elevated initial procalcitonin in many COVID patients without concurrent bacterial co-infections which potentially contributed to antibiotic over-prescribing.

Bacterial and fungal co-infection is a major barrier in COVID-19 patients: A specific management and therapeutic strategy is required.

Microbial co-infections are another primary concern in patients with coronavirus disease 2019 (COVID-19), yet it is an untouched area among researchers. Preliminary data and systematic reviews only show the type of pathogens responsible for that, but its pathophysiology is still unknown. Studies show that these microbial co-infections are hospital-acquired/nosocomial infections, and patients admitted to intensive care units with invasive mechanical ventilation are highly susceptible to it. Patients with COVID-19 had elevated inflammatory cytokines and a weakened cell-mediated immune response, with lower CD4+ T and CD8+ T cell counts, indicating vulnerability to various co-infections. Despite this, there are only a few studies that recommend the management of co-infections.

Evaluation of bacterial agents isolated from endotracheal aspirate cultures of Covid-19 general intensive care patients and their antibiotic resistance profiles compared to pre-pandemic conditions.

BACKGROUND: Early reports have shown that critically ill patients infected with SARS-CoV-2 have a high prevalence of nosocomial pneumonia, particularly ventilator-associated pneumonia (VAP). METHOD: In the present study, we determined the bacterial agents isolated from endotracheal aspirate (ETA) cultures of Covid-19 general intensive care patients and evaluated the antibiotic resistance profiles of common bacterial agents compared to the pre-pandemic period. RESULTS: While a total of 119 significant growths with polymicrobial growths were detected in the ETA cultures of 73 (7.5%) of 971 patients hospitalized in the intensive care unit before the pandemic, 87 significant growths were detected in the ETA cultures of 67 (11.1%) of 602 patients hospitalized in the Covid-19 intensive care unit (ICU) after the pandemic. While 61 (83.6%) of patients in the ICU died before the pandemic, 63 (94.0%) of patients in the Covid-19 ICU died after the pandemic. In terms of age, gender, and mortality, there was no significant difference between the two ICUs (p > 0.05). Before the pandemic, the mean length of stay in the ICU was 33.59 ± 32.89 days, and after the pandemic, it was 13.49 ± 8.03 days. This was a statistically significant difference (p < 0.05). Acinetobacter baumannii (28.5%), Klebsiella pneumoniae (22.6%), Pseudomonas aeruginosa (15.9%), Staphylococcus aureus (6.7%), Escherichia coli (7.5%), Candida spp. (5.0%) were the most prevalent causal microorganisms discovered in pre-pandemic ICU ETA samples, whereas A. baumannii (54.0%), K. pneumoniae (10.3%), P. aeruginosa (6.8%), E. faecium (8%), and Candida spp.(13.7%) were the most common causative microorganisms detected in Covid-19 ICU ETA samples. Except for tigecycline, antibiotic resistance rates in A. baumannii strains increased following the pandemic. Only tobramycin showed a significant difference in the increase of resistance among these antibiotics (p = 0.037). The rate of tigecycline resistance, on the other hand, was 17.6% before the pandemic and 2.2% afterward (p < 0.05). After the pandemic, increased resistance of K. pneumoniae strains to colistin, meropenem, ertapenem, amoxicillin-clavulanic acid, piperacillin-tazobactam, ciprofloxacin, tigecycline, and cefepime antibiotics was observed. However, these increases were not statistically significant. Except for imipenem, antibiotic resistance rates in P. aeruginosa strains increased following the pandemic. The increase in resistance of ceftazidime and levofloxacin was statistically significant (p < 0.05). CONCLUSION: As a result, the Covid-19 pandemic requires intensive care follow-ups at an earlier age and with a more mortal course. Although the length of stay in the intensive care unit has been shortened, it is observed that this situation is observed due to early mortality. In P. aeruginosa strains, a significant difference was detected in the resistance increase of the ceftazidime and levofloxacin (p < 0.05) and with the exception of tigecycline, antibiotic resistance rates in A. baumannii strains increased following the pandemic. Only tobramycin showed a significant difference in the increase of resistance among these antibiotics (p = 0.037). Secondary infections in patients create more difficult treatment processes due to both Covid-19 and increasing antibiotic resistance today.

Hafnia alvei Pneumonia: A Rare Cause of Infection in a Patient with COVID-19.

Herein, we describe a case report of a critically ill patient, a 48-year-old man without comorbidities admitted to the hospital with a serious type 1 (hypoxemic) respiratory insufficiency and confirmed diagnosis of COVID-19. After 5 days with invasive mechanical ventilation, the patient developed a bacterial co-infection, namely a pneumonia by Hafnia alvei, requiring the last line of respiratory support: extracorporeal membrane oxygenation (ECMO). Subsequently, his clinical situation gradually stabilized, until he was discharged from the hospital on day 61, being accompanied in ambulatory consultation by the physical medicine and pulmonology department during the post-COVID-19 recovery. H. alvei is a Gram-negative bacterium that is rarely isolated from human specimens and is rarely considered to be pathogenic. However, COVID-19 disease can cause substantial organ dysfunction and can be associated with bacterial secondary infections which can favor the emergence of rare infectious diseases by uncommon microorganisms.

Bacterial coinfections and secondary infections in COVID-19 patients from a tertiary care hospital of northern India: Time to adhere to culture-based practices.

OBJECTIVE: Bacterial co-pathogens are common in various viral respiratory tract infections, leading to increased disease severity and mortality. Still, they are understudied during large outbreaks and pandemics. This study was conducted to highlight the overall burden of these infections in COVID-19 patients admitted to our tertiary care hospital, along with their antibiotic susceptibility patterns. MATERIAL AND METHODS: During the six-month study period, clinical samples (blood samples, respiratory samples, and sterile body fluids, including cerebrospinal fluid [CSF]) of COVID-19 patients with suspected bacterial coinfections (at presentation) or secondary infections (after 48 hours of hospitalization) were received and processed for the same. RESULTS: Clinical samples of 814 COVID-19 patients were received for bacterial culture and susceptibility. Out of the total patient sample, 75% had already received empirical antibiotics before the samples were sent for analysis. Overall, 17.9% of cultures were positive for bacterial infections. Out of the total patients with bacterial infection, 74% (108/146) of patients had secondary bacterial infections (after 48 hours of hospitalization) and 26% (38/146) had bacterial coinfections (at the time of admission). Out of the 143 total isolates obtained, the majority (86%) were gram-negative organisms, of which Acinetobacter species was the commonest organism (35.6%), followed by Klebsiella pneumoniae (18.1%). The majority (50.7%) of the pathogenic organisms reported were multidrug resistant. CONCLUSION: The overall rate of secondary bacterial infections (SBIs) in our study was lower (7.9%) than reported by other studies. A rational approach would be to adhere to the practice of initiating culture-based guidance for antibiotics and to restrict unnecessary empirical antimicrobial therapy.

Antimicrobial prescription in severe COVID-19 and CAP: a matched case-control study.

BACKGROUND: In severe coronavirus diseases 2019 (COVID-19), a high and potentially excessive use of antimicrobials for suspected bacterial co-infection and intensive care unit (ICU)-acquired infections has been repeatedly reported. OBJECTIVES: To compare an ICU cohort of community-acquired pneumonia (CAP) with a cohort of severe COVID-19 pertaining to co-infections, ICU-acquired infections and associated antimicrobial consumption. METHODS: We retrospectively compared a cohort of CAP patients with a cohort of COVID-19 patients matched according to organ failure, ICU length of stay (LOS) and ventilation days. Patient data such as demographics, infection focus, probability and severity, ICU severity scores and ICU and in-hospital mortality, days of antimicrobial therapy (DOT) and number of antimicrobial prescriptions, using an incremental scale, were registered and analysed. The total number of cultures (sputum, urinary, blood cultures) was collected and corrected for ICU LOS. FINDINGS: CAP patients (n = 148) were matched to COVID-19 patients (n = 74). Significantly less sputum cultures (68.2% versus 18.9%, P < 0.05) and bronchoalveolar lavages (BAL) (73.7% versus 36.5%, P < 0.05) were performed in COVID-19 patients. Six (8.1%) COVID-19 patients were diagnosed with a co-infection. Respectively, 58 of 148 (39.2%) CAP and 38 of 74 (51.4%) COVID-19 patients (P = 0.09) developed ICU-acquired infections. Antimicrobial distribution, both in the number of prescriptions and DOT, was similar in both cohorts. CONCLUSIONS: We found a low rate of microbiologically confirmed bacterial co-infection and a high rate of ICU-acquired infections in COVID-19 patients. Infection probabilities, antimicrobial prescriptions and DOT were comparable with a matched CAP cohort.

Procalcitonin to Guide Antibacterial Prescribing in Patients Hospitalised with COVID-19.

Antibacterial prescribing in patients presenting with COVID-19 remains discordant to rates of bacterial co-infection. Implementing diagnostic tests to exclude bacterial infection may aid reduction in antibacterial prescribing. (1) Method: A retrospective observational analysis was undertaken of all hospitalised patients with COVID-19 across a single-site NHS acute Trust (London, UK) from 1 December 2020 to 28 February 2021. Electronic patient records were used to identify patients, clinical data, and outcomes. Procalcitonin (PCT) serum assays, where available on admission, were analysed against electronic prescribing records for antibacterial prescribing to determine relationships with a negative PCT result (<25 mg/L) and antibacterial course length. (2) Results: Antibacterial agents were initiated on admission in 310/624 (49.7%) of patients presenting with COVID-19. A total of 33/74 (44.5%) patients with a negative PCT on admission had their treatment stopped within 24 h. A total of 6/49 (12.2%) patients were started on antibacterials, but a positive PCT saw their treatment stopped. Microbiologically confirmed bacterial infection was low (19/594; 3.2%) and no correlation was seen between PCT and culture positivity (p = 1). Lower mortality (15.6% vs. 31.4%; p = 0.049), length of hospital stay (7.9 days vs. 10.1 days; p = 0.044), and intensive care unit (ICU) admission (13.9% vs. 40.8%; p = 0.001) was noted among patients with low PCT. (3) Conclusions: This retrospective analysis of community acquired COVID-19 patients demonstrates the potential role of PCT in excluding bacterial co-infection. A negative PCT on admission correlates with shorter antimicrobial courses, early cessation of therapy, and predicts lower frequency of ICU admission. Low PCT may support decision making in cessation of antibacterials at the 48-72 h review.

Informing antimicrobial management in the context of COVID-19: understanding the longitudinal dynamics of C-reactive protein and procalcitonin.

BACKGROUND: To characterise the longitudinal dynamics of C-reactive protein (CRP) and Procalcitonin (PCT) in a cohort of hospitalised patients with COVID-19 and support antimicrobial decision-making. METHODS: Longitudinal CRP and PCT concentrations and trajectories of 237 hospitalised patients with COVID-19 were modelled. The dataset comprised of 2,021 data points for CRP and 284 points for PCT. Pairwise comparisons were performed between: (i) those with or without significant bacterial growth from cultures, and (ii) those who survived or died in hospital. RESULTS: CRP concentrations were higher over time in COVID-19 patients with positive microbiology (day 9: 236 vs 123 mg/L, p < 0.0001) and in those who died (day 8: 226 vs 152 mg/L, p < 0.0001) but only after day 7 of COVID-related symptom onset. Failure for CRP to reduce in the first week of hospital admission was associated with significantly higher odds of death. PCT concentrations were higher in patients with COVID-19 and positive microbiology or in those who died, although these differences were not statistically significant. CONCLUSIONS: Both the absolute CRP concentration and the trajectory during the first week of hospital admission are important factors predicting microbiology culture positivity and outcome in patients hospitalised with COVID-19. Further work is needed to describe the role of PCT for co-infection. Understanding relationships of these biomarkers can support development of risk models and inform optimal antimicrobial strategies.