Respiratory Bacterial and Fungal Superinfections During the Third Surge of the COVID-19 Pandemic in Iran.

Objective: We characterized bacterial and fungal superinfection and evaluated the antimicrobial resistance profile against the most common superinfection-causing pathogens (Klebsiella pneumoniae, Acinetobacter baumannii, and Staphylococcus aureus). Methods: In a cross-sectional study, 192 respiratory samples were collected from patients with and without SARS-COV-2 admitted to a teaching hospital in Tehran. Superinfection proportions and the antibiotic resistance profile were assessed and compared with demographic, comorbidities, and other clinical factors. Results: Superinfection rate was 60% among COVID-19 patients (p = 0.629). Intensive care unit admission (p = 0.017), mortality rate (p ≤ 0.001), and antiviral and corticosteroid therapy (p ≤ 0.001) were significantly more common among patients with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). The most common superinfections were caused by K. pneumoniae (42.7%, 82/192), A. baumannii (14.6%, 28/192), and S. aureus (13%, 25/192). A. baumannii isolates exhibited greater antibiotic resistance. Forty-four percent (11/25) of S. aureus isolates were cefoxitin resistant and also confirmed as methicillin-resistant S. aureus by PCR. Conclusion: The rise of difficult-to-treat infections with a high burden of antibiotic resistance, coupled with an increase in mortality rate of SARS-COV-2 superinfected individuals, illustrates the impact of the COVID-19 pandemic on antimicrobial resistance. Post-pandemic antimicrobial resistance crisis management requires precise microbiological diagnosis, drug susceptibility testing, and prescription of antimicrobials appropriate for the patient's condition.

What happened during COVID-19 in African ICUs? An observational study of pulmonary co-infections, superinfections, and mortality in Morocco.

BACKGROUND: There is a growing literature showing that critically ill COVID-19 patients have an increased risk of pulmonary co-infections and superinfections. However, studies in developing countries, especially African countries, are lacking. The objective was to describe the prevalence of bacterial co-infections and superinfections in critically ill adults with severe COVID-19 pneumonia in Morocco, the micro-organisms involved, and the impact of these infections on survival. METHODS: This retrospective study included severe COVID-19 patients admitted to the intensive care unit (ICU) between April 2020 and April 2021. The diagnosis of pulmonary co-infections and superinfections was based on the identification of pathogens from lower respiratory tract samples. Co-infection was defined as the identification of a respiratory pathogen, diagnosed concurrently with SARS-Cov2 pneumonia. Superinfections include hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). A multivariate regression analysis was performed to identify factors independently associated with mortality. RESULTS: Data from 155 patients were analyzed. The median age was 68 years [62-72] with 87% of patients being male. A large proportion of patients (68%) received antibiotics before ICU admission. Regarding ventilatory management, the majority of patients (88%) underwent non-invasive ventilation (NIV). Sixty-five patients (42%) were placed under invasive mechanical ventilation, mostly after failure of NIV. The prevalence of co-infections, HAP and VAP was respectively 4%, 12% and 40% (64 VAP/1000 ventilation days). The most isolated pathogens were Enterobacterales for HAP and Acinetobacter sp. for VAP. The proportion of extra-drug resistant (XDR) bacteria was 78% for Acinetobacter sp. and 24% for Enterobacterales. Overall ICU mortality in this cohort was 64.5%. Patients with superinfection showed a higher risk of death (OR = 6.4, 95% CI: 1.8-22; p = 0.004). CONCLUSIONS: In this single-ICU Moroccan COVID-19 cohort, bacterial co-infections were relatively uncommon. Conversely, high rates of superinfections were observed, with an increased frequency of antimicrobial resistance. Patients with superinfections showed a higher risk of death.

Bacterial/fungal infection in hospitalized patients with COVID-19 in a tertiary hospital in the Community of Castilla y León, Spain.

INTRODUCTION: Bacterial/fungal coinfection and superinfections contribute to the increased morbi-mortality of viral respiratory infections (RIs). The main objective of this study was to determine the incidence of these infections in hospitalized patients with COVID-19. METHOD: Retrospective observational study of all patients admitted for COVID-19 and bacterial/fungal infections at the Hospital Clínico Universitario of Valladolid, Spain (March 1-May 31, 2020). Demographic, clinical and microbiological data were compared based on Intensive Care Unit (ICU) admission and predictors of mortality by were identified using multivariate logistic regression analyses. RESULTS: Of the 712 COVID-19 patients, 113 (16%) presented bacterial/fungal coinfections or superinfections. Their median age was 73 years (IQR 57-89) and 59% were men. The profiles of ICU patients (44%) included male, SARS-CoV-2 pneumonia, leukocytosis, elevated inteleukin-6, with interferon ß-1b and tocilizumab and superinfection (p < 0.05). Coinfections were diagnosed in 5% (39/712) patients. Most common pathogens of respiratory coinfection (18) were Streptococcus pneumoniae (6) and Staphylococcus aureus (6). Superinfections were detected in 11% (80/712) patients. Urinary (53) and RI (39) constituted the majority of superinfections Acinetobacter baumannii multidrug-resistant was the main agent of IR and bacteremia. An outbreak of A. baumannii contributed to this result. Three patients were considered to have probable pulmonary aspergillosis. Mortality was higher in UCI patients (50% vs. 29%, p = 0.028). The predictive factors of mortality included being a male with various comorbidities, SARS-CoV-2 pneumonia, bacteremia and superinfections from A. baumannii. CONCLUSION: The outbreak of A. baumannii was a determining factor in the increases of the incidence of infection and the morbi-mortality of ICU patients.

The prevalence of early- and late-onset bacterial, viral, and fungal respiratory superinfections in invasively ventilated COVID-19 patients.

The role of respiratory superinfections in patients with coronavirus disease 2019 (COVID-19) pneumonia remains unclear. We investigated the prevalence of early- and late-onset superinfections in invasively ventilated patients with COVID-19 pneumonia admitted to our department of intensive care medicine between March 2020 and November 2020. Of the 102 cases, 74 (72.5%) received invasive ventilation and were tested for viral, bacterial, and fungal pathogens on Days 0-7, 8-14, and 15-21 after the initiation of mechanical ventilation. Approximately 45% developed one or more respiratory superinfections. There was a clear correlation between the duration of invasive ventilation and the prevalence of coinfecting pathogens. Male patients with obesity and those suffering from chronic obstructive pulmonary disease and/or diabetes mellitus had a significantly higher probability to develop a respiratory superinfection. The prevalence of viral coinfections was high, with a predominance of the herpes simplex virus (HSV), followed by cytomegalovirus. No respiratory viruses or intracellular bacteria were detected in our cohort. We observed a high coincidence between Aspergillus fumigatus and HSV infection. Gram-negative bacteria were the most frequent pathogen group. Klebsiella aerogenes was detected early after intubation, while Klebsiella pneumoniae and Pseudomonas aeruginosa were related to a prolonged respiratory weaning.

Bacterial superinfection in adults with COVID-19 hospitalized in two clinics in Medellín-Colombia, 2020.

COVID-19 represents high morbidity and mortality, its complications and lethality have increased due to bacterial superinfections. We aimed to determine the prevalence of bacterial superinfection in adults with COVID-19, hospitalized in two clinics in Medellín-Colombia during 2020, and its distribution according to sociodemographic and clinical conditions. A cross sectional study was made with 399 patients diagnosed with COVID-19 by RT-PCR. We determined the prevalence of bacterial superinfection and its factors associated with crude and adjusted prevalence ratios by a generalized linear model. The prevalence of superinfection was 49.6%, with 16 agents identified, the most frequent were Klebsiella (pneumoniae and oxytoca) and Staphylococcus aureus. In the multivariate adjustment, the variables with the strongest association with bacterial superinfection were lung disease, encephalopathy, mechanical ventilation, hospital stay, and steroid treatment. A high prevalence of bacterial superinfections, a high number of agents, and multiple associated factors were found. Among these stood out comorbidities, complications, days of hospitalization, mechanical ventilation, and steroid treatment. These results are vital to identifying priority clinical groups, improving the care of simultaneous infections with COVID-19 in people with the risk factors exposed in the population studied, and identifying bacteria of public health interest.

COVID-19 versus influenza A/B supeRInfectionS in the IntenSive care unit (CRISIS): Protocol for a Danish nationwide cohort study.

BACKGROUND: Superinfection following viral infection is a known complication, which may lead to longer hospitalisation and worse outcome. Empirical antibiotic therapy may prevent bacterial superinfections, but may also lead to overuse, adverse effects and development of resistant pathogens. Knowledge about the incidence of superinfections in intensive care unit (ICU) patients with severe Coronavirus Disease 2019 (COVID-19) is limited. METHODS: We will conduct a nationwide cohort study comparing the incidence of superinfections in patients with severe COVID-19 admitted to the ICU compared with ICU patients with influenza A/B in Denmark. We will include approximately 1000 patients in each group from the time period of 1 October 2014 to 30 April 2019 and from 10 March 2020 to 1 March 2021 for patients with influenza and COVID-19, respectively. The primary outcome is any superinfection within 90 days of admission to the ICU. We will use logistic regression analysis comparing COVID-19 with influenza A/B after adjustment for relevant predefined confounders. Secondarily, we will use unadjusted and adjusted logistic regression analyses to assess six potential risk factors (sex, age, cancer [including haematological], immunosuppression and use of life support on day 1 in the ICU) for superinfections and compare outcomes in patients with COVID-19 with/without superinfections, and present descriptive data regarding the superinfections. CONCLUSION: This study will provide important knowledge about superinfections in ICU patients with severe COVID-19.

Trichosporon asahii superinfections in critically ill COVID-19 patients overexposed to antimicrobials and corticosteroids.

OBJECTIVES: To investigate the occurrence of Trichosporon asahii fungemia among critically ill COVID-19 patients. METHODS: From 1 July to 30 September 2020, cases of T asahii fungemia (TAF) in a Brazilian COVID-19 referral centre were investigated. The epidemiology and clinical courses were detailed, along with a mycological investigation that included molecular species identification, haplotype diversity analysis and antifungal susceptibility testing. RESULTS: Five critically ill COVID-19 patients developed TAF in the period. All five patients had common risk conditions for TAF: central venous catheter at fungemia, previous exposure to broad-spectrum antibiotics, prior echinocandin therapy and previous prolonged corticosteroid therapy. The average time of intensive care unit hospitalisation previous to the TAF episode was 23 days. All but one patient had voriconazole therapy, and TAF 30-day mortality was 80%. The five T asahii strains from the COVID-19 patients belonged to 4 different haplotypes, mitigating the possibility of skin origin and cross-transmission linking the 5 reported episodes. The antifungal susceptibility testing revealed low minimal inhibitory concentrations for azole derivatives. CONCLUSIONS: Judicious prescription of antibiotics, corticosteroids and antifungals needs to be discussed in critically ill COVID-19 patients to prevent infections by hard-to-treat fungi like T asahii.

Prevalence and outcomes of co-infection and superinfection with SARS-CoV-2 and other pathogens: A systematic review and meta-analysis.

INTRODUCTION: The recovery of other pathogens in patients with SARS-CoV-2 infection has been reported, either at the time of a SARS-CoV-2 infection diagnosis (co-infection) or subsequently (superinfection). However, data on the prevalence, microbiology, and outcomes of co-infection and superinfection are limited. The purpose of this study was to examine the occurrence of co-infections and superinfections and their outcomes among patients with SARS-CoV-2 infection. PATIENTS AND METHODS: We searched literature databases for studies published from October 1, 2019, through February 8, 2021. We included studies that reported clinical features and outcomes of co-infection or superinfection of SARS-CoV-2 and other pathogens in hospitalized and non-hospitalized patients. We followed PRISMA guidelines, and we registered the protocol with PROSPERO as: CRD42020189763. RESULTS: Of 6639 articles screened, 118 were included in the random effects meta-analysis. The pooled prevalence of co-infection was 19% (95% confidence interval [CI]: 14%-25%, I2 = 98%) and that of superinfection was 24% (95% CI: 19%-30%). Pooled prevalence of pathogen type stratified by co- or superinfection were: viral co-infections, 10% (95% CI: 6%-14%); viral superinfections, 4% (95% CI: 0%-10%); bacterial co-infections, 8% (95% CI: 5%-11%); bacterial superinfections, 20% (95% CI: 13%-28%); fungal co-infections, 4% (95% CI: 2%-7%); and fungal superinfections, 8% (95% CI: 4%-13%). Patients with a co-infection or superinfection had higher odds of dying than those who only had SARS-CoV-2 infection (odds ratio = 3.31, 95% CI: 1.82-5.99). Compared to those with co-infections, patients with superinfections had a higher prevalence of mechanical ventilation (45% [95% CI: 33%-58%] vs. 10% [95% CI: 5%-16%]), but patients with co-infections had a greater average length of hospital stay than those with superinfections (mean = 29.0 days, standard deviation [SD] = 6.7 vs. mean = 16 days, SD = 6.2, respectively). CONCLUSIONS: Our study showed that as many as 19% of patients with COVID-19 have co-infections and 24% have superinfections. The presence of either co-infection or superinfection was associated with poor outcomes, including increased mortality. Our findings support the need for diagnostic testing to identify and treat co-occurring respiratory infections among patients with SARS-CoV-2 infection.

Bacterial pulmonary superinfections are associated with longer duration of ventilation in critically ill COVID-19 patients.

The impact of secondary bacterial infections (superinfections) in coronavirus disease 2019 (COVID-19) is not well understood. In this prospective, monocentric cohort study, we aim to investigate the impact of superinfections in COVID-19 patients with acute respiratory distress syndrome. Patients are assessed for concomitant microbial infections by longitudinal analysis of tracheobronchial secretions, bronchoalveolar lavages, and blood cultures. In 45 critically ill patients, we identify 19 patients with superinfections (42.2%). Superinfections are detected on day 10 after intensive care admission. The proportion of participants alive and off invasive mechanical ventilation at study day 28 (ventilator-free days [VFDs] at 28 days) is substantially lower in patients with superinfection (subhazard ratio 0.37; 95% confidence interval [CI] 0.15-0.90; p = 0.028). Patients with pulmonary superinfections have a higher incidence of bacteremia, virus reactivations, yeast colonization, and required intensive care treatment for a longer time. Superinfections are frequent and associated with reduced VFDs at 28 days despite a high rate of empirical antibiotic therapy.

Incidence of co-infections and superinfections in hospitalized patients with COVID-19: a retrospective cohort study.

OBJECTIVES: To describe the burden, epidemiology and outcomes of co-infections and superinfections occurring in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: We performed an observational cohort study of all consecutive patients admitted for ≥48 hours to the Hospital Clinic of Barcelona for COVID-19 (28 February to 22 April 2020) who were discharged or dead. We describe demographic, epidemiologic, laboratory and microbiologic results, as well as outcome data retrieved from electronic health records. RESULTS: Of a total of 989 consecutive patients with COVID-19, 72 (7.2%) had 88 other microbiologically confirmed infections: 74 were bacterial, seven fungal and seven viral. Community-acquired co-infection at COVID-19 diagnosis was uncommon (31/989, 3.1%) and mainly caused by Streptococcus pneumoniae and Staphylococcus aureus. A total of 51 hospital-acquired bacterial superinfections, mostly caused by Pseudomonas aeruginosa and Escherichia coli, were diagnosed in 43 patients (4.7%), with a mean (SD) time from hospital admission to superinfection diagnosis of 10.6 (6.6) days. Overall mortality was 9.8% (97/989). Patients with community-acquired co-infections and hospital-acquired superinfections had worse outcomes. CONCLUSIONS: Co-infection at COVID-19 diagnosis is uncommon. Few patients developed superinfections during hospitalization. These findings are different compared to those of other viral pandemics. As it relates to hospitalized patients with COVID-19, such findings could prove essential in defining the role of empiric antimicrobial therapy or stewardship strategies.