Identification of priority pathogens for aetiological diagnosis in adults with community-acquired pneumonia in China: a multicentre prospective study.

BACKGROUND: Community-acquired pneumonia (CAP) is a major public health challenge worldwide. However, the aetiological and disease severity-related pathogens associated with CAP in adults in China are not well established based on the detection of both viral and bacterial agents. METHODS: A multicentre, prospective study was conducted involving 10 hospitals located in nine geographical regions in China from 2014 to 2019. Sputum or bronchoalveolar lavage fluid (BALF) samples were collected from each recruited CAP patient. Multiplex real-time PCR and bacteria culture methods were used to detect respiratory pathogens. The association between detected pathogens and CAP severity was evaluated. RESULTS: Among the 3,403 recruited eligible patients, 462 (13.58%) had severe CAP, and the in-hospital mortality rate was 1.94% (66/3,403). At least one pathogen was detected in 2,054 (60.36%) patients, with two or more pathogens were co-detected in 725 patients. The ten major pathogens detected were Mycoplasma pneumoniae (11.05%), Haemophilus influenzae (10.67%), Klebsiella pneumoniae (10.43%), influenza A virus (9.49%), human rhinovirus (9.02%), Streptococcus pneumoniae (7.43%), Staphylococcus aureus (4.50%), adenovirus (2.94%), respiratory syncytial viruses (2.35%), and Legionella pneumophila (1.03%), which accounted for 76.06-92.52% of all positive detection results across sampling sites. Klebsiella pneumoniae (p < 0.001) and influenza viruses (p = 0.005) were more frequently detected in older patients, whereas Mycoplasma pneumoniae was more frequently detected in younger patients (p < 0.001). Infections with Klebsiella pneumoniae, Staphylococcus aureus, influenza viruses and respiratory syncytial viruses were risk factors for severe CAP. CONCLUSIONS: The major respiratory pathogens causing CAP in adults in China were different from those in USA and European countries, which were consistent across different geographical regions over study years. Given the detection rate of pathogens and their association with severe CAP, we propose to include the ten major pathogens as priorities for clinical pathogen screening in China.

Clinical Features of COVID-19 and Differentiation from Other Causes of CAP.

Community-acquired pneumonia (CAP) is a significant cause of morbidity and mortality, one of the most common reasons for infection-related death worldwide. Causes of CAP include numerous viral, bacterial, and fungal pathogens, though frequently no specific organism is found. Beginning in 2019, the COVID-19 pandemic has caused incredible morbidity and mortality. COVID-19 has many features typical of CAP such as fever, respiratory distress, and cough, and can be difficult to distinguish from other types of CAP. Here, we highlight unique clinical features of COVID-19 pneumonia such as olfactory and gustatory dysfunction, lymphopenia, and distinct imaging appearance.

Fall of viral and bacterial pneumonia hospitalizations following COVID-19 pandemic mitigation strategies: a central Italian Region retrospective study.

Community-Acquired Pneumonia (CAP) represents one of the first causes of hospitalization and death in the elderly all over the world and weighs heavily on public health system. Since the beginning of the COVID-19 (CoronaVirus Disease-19) pandemic, everybody's behavior was forced to change, as the result of a global lockdown strategy and the obligation of using personal protection equipment (PPE). We aimed to evaluate how the mitigation strategies adopted to fight SARS-CoV-2 (Severe Acute Respiratory Coronavirus Syndrome 2) infection have influenced hospitalizations due to CAP in two different Local Health Boards (LHBs) of central Italy. We considered two main periods of observation: before and after the national start of lockdown, in two Abruzzo's LHBs. We analyzed 19,558 hospital discharge records of bacterial and viral CAP. Excluding SARS-CoV2 infection, a significant decrease in CAP hospitalizations was observed. Through the analysis of Diagnosis Related Group (DRG) values, we highlighted a significant saving of founds for the Regional Health Service. The enactment of social distancing measures to contain COVID-19 spread, brought down admissions for bacterial and viral pneumonia. Our study emphasizes that costs for hospitalizations due to CAP could be drastically reduced by mask wearing and social distancing.

Seroprevalence of community-acquired atypical bacterial pneumonia among adult COVID-19 patients from a single center in Al Madinah Al Munawarah, Saudi Arabia: A retrospective cohort study.

OBJECTIVES: To investigate the seroprevalence of the community-acquired bacterial that causes atypical pneumonia among confirmed severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) patients. METHODS: In this cohort study, we retrospectively investigated the seroprevalence of Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila among randomly selected 189 confirmed COVID-19 patients at their time of hospital presentation via commercial immunoglobulin M (IgM) antibodies against these bacteria. We also carried out quantitative measurements of procalcitonin in patients' serum. RESULTS: The seropositivity for L. pneumophila was 12.6%, with significant distribution among patientsolder than 50 years (χ2 test, p=0.009), while those of M. pneumoniae was 6.3% and C. pneumoniae was 2.1%, indicating an overall co-infection rate of 21% among COVID-19 patients. No significant difference (χ2 test, p=0.628) in the distribution of bacterial co-infections existed between male and female patients. Procalcitonin positivity was confirmed amongst 5% of co-infected patients. CONCLUSION: Our study documented the seroprevalence of community-acquired bacteria co-infection among COVID-19 patients. In this study, procalcitonin was an inconclusive biomarker for non-severe bacterial co-infections among COVID-19 patients. Consideration and proper detection of community-acquired bacterial co-infection may minimize misdiagnosis during the current pandemic and positively reflect disease management and prognosis.

Bacterial Pneumonia and Respiratory Culture Utilization among Hospitalized Patients with and without COVID-19 in a New York City Hospital.

COVID-19 is associated with prolonged hospitalization and a high risk of intubation, which raises concern for bacterial coinfection and antimicrobial resistance. Previous research has shown a wide range of bacterial pneumonia rates for COVID-19 patients in a variety of clinical and demographic settings, but none have compared hospitalized COVID-19 patients to patients testing negative for severe acute respiratory syndrome coronavirus (SARS-CoV-2) in similar care settings. We performed a retrospective cohort study on hospitalized patients with COVID-19 testing from March 10th, 2020 to December 31st, 2020. A total of 19,219 patients were included, of which 3,796 tested positive for SARS-CoV-2. We found a 2.6-fold increase (P < 0.001) in respiratory culture ordering in COVID-19 patients. On a per-patient basis, COVID-19 patients were 1.5-fold more likely than non-COVID patients to have positive respiratory cultures (46.8% versus 30.9%, P < 0.001), which was primarily driven by patients requiring intubation. Among patients with pneumonia, a significantly higher proportion of COVID-19 patients had ventilator-associated pneumonia (VAP) relative to non-COVID patients (86.3% versus 70.8%, P < 0.001), but a lower proportion had community-acquired (11.2% vs 25.5%, P < 0.01) pneumonia. There was also a significantly higher proportion of respiratory cultures positive for methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae, and antibiotic-resistant organisms in COVID-19 patients. Increased rates of respiratory culture ordering for COVID-19 patients therefore appear to be clinically justified for patients requiring intubation, but further research is needed to understand how SARS-CoV-2 increases the risk of VAP.

Severe Recurrent Bacterial Pneumonia Among Children Living With HIV.

BACKGROUND: Bacterial pneumonia imparts a major morbidity and mortality burden on children living with HIV, yet effective prevention and treatment options are underutilized. We explored clinical factors associated with severe recurrent bacterial pneumonia among children living with HIV. METHODS: Children enrolled in the TREAT Asia Pediatric HIV Observational Database were included if they started antiretroviral therapy (ART) on or after January 1st, 2008. Factors associated with severe recurrent bacterial pneumonia were assessed using competing-risk regression. RESULTS: A total of 3,944 children were included in the analysis; 136 cases of severe recurrent bacterial pneumonia were reported at a rate of 6.5 [95% confidence interval (CI): 5.5-7.7] events per 1,000 patient-years. Clinical factors associated with severe recurrent bacterial pneumonia were younger age [adjusted subdistribution hazard ratio (aHR): 4.4 for <5 years versus ≥10 years, 95% CI: 2.2-8.4, P < 0.001], lower weight-for-age z-score (aHR: 1.5 for <-3.0 versus >-2.0, 95% CI: 1.1-2.3, P = 0.024), pre-ART diagnosis of severe recurrent bacterial pneumonia (aHR: 4.0 versus no pre-ART diagnosis, 95% CI: 2.7-5.8, P < 0.001), past diagnosis of symptomatic lymphoid interstitial pneumonitis or chronic HIV-associated lung disease, including bronchiectasis (aHR: 4.8 versus no past diagnosis, 95% CI: 2.8-8.4, P < 0.001), low CD4% (aHR: 3.5 for <10% versus ≥25%, 95% CI: 1.9-6.4, P < 0.001) and detectable HIV viral load (aHR: 2.6 versus undetectable, 95% CI: 1.2-5.9, P = 0.018). CONCLUSIONS: Children <10-years-old and those with low weight-for-age, a history of respiratory illness, low CD4% or poorly controlled HIV are likely to gain the greatest benefit from targeted prevention and treatment programs to reduce the burden of bacterial pneumonia in children living with HIV.

Utilisation of antimicrobials used to treat bacterial pneumonia in principal referral hospitals during the COVID-19 pandemic, Australia, 2020.

BACKGROUND: Concerns have been raised internationally, regarding possible increased antimicrobial use during the COVID-19 pandemic and the potential impact on antimicrobial resistance. This analysis aimed to investigate hospital usage rates of broad-spectrum antibacterial agents used to treat community-acquired pneumonia (CAP) and/or hospital-acquired pneumonia (HAP) in Australian principal referral hospitals during 2020. Secondly, usage rates in Victoria were compared with equivalent national rates. METHODS: Monthly antimicrobial dispensing data for all 31 Australian principal referral hospitals were analysed for the period January 2019 to December 2020. Grams of antimicrobial agents used were converted into the World Health Organization (WHO) assigned metric 'Defined Daily Dose' (DDD). Using the hospital activity metric Occupied Bed Days (OBD), a standardised usage density rate was calculated (in units of DDD / 1,000 OBD). RESULTS: The typical expected seasonal trend in aggregate usage rates, for antibacterials used in the treatment of CAP, was not evident in 2020. Overall usage of doxycycline, azithromycin, amoxicillin and cefuroxime decreased in principal referral hospitals compared to 2019. Aggregated monthly usage rates for broad-spectrum agents used to treat HAP increased nationally, on average, by 5.0% in 2020 compared to 2019. Victoria's second COVID-19 wave (July-October 2020) coincided with higher usage rates of antibacterials used for CAP. CONCLUSION: Public health interventions introduced to limit the spread of SARS-CoV-2 infections may have had unintended benefits on other respiratory infection rates. The drop in hospital usage of antibacterials typically used to treat CAP suggests that the number of cases of pneumonia acquired in the community requiring hospitalisation was markedly reduced in 2020.

Viral and Bacterial Co-Infections in the Lungs: Dangerous Liaisons.

Respiratory tract infections constitute a significant public health problem, with a therapeutic arsenal that remains relatively limited and that is threatened by the emergence of antiviral and/or antibiotic resistance. Viral-bacterial co-infections are very often associated with the severity of these respiratory infections and have been explored mainly in the context of bacterial superinfections following primary influenza infection. This review summarizes our current knowledge of the mechanisms underlying these co-infections between respiratory viruses (influenza viruses, RSV, and SARS-CoV-2) and bacteria, at both the physiological and immunological levels. This review also explores the importance of the microbiome and the pathological context in the evolution of these respiratory tract co-infections and presents the different in vitro and in vivo experimental models available. A better understanding of the complex functional interactions between viruses/bacteria and host cells will allow the development of new, specific, and more effective diagnostic and therapeutic approaches.

Body Mass Index and Mortality in Coronavirus Disease 2019 and Other Diseases: A Cohort Study in 35,506 ICU Patients.

OBJECTIVES: Obesity is a risk factor for severe coronavirus disease 2019 and might play a role in its pathophysiology. It is unknown whether body mass index is related to clinical outcome following ICU admission, as observed in various other categories of critically ill patients. We investigated the relationship between body mass index and inhospital mortality in critically ill coronavirus disease 2019 patients and in cohorts of ICU patients with non-severe acute respiratory syndrome coronavirus 2 viral pneumonia, bacterial pneumonia, and multiple trauma. DESIGN: Multicenter observational cohort study. SETTING: Eighty-two Dutch ICUs participating in the Dutch National Intensive Care Evaluation quality registry. PATIENTS: Thirty-five-thousand five-hundred six critically ill patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics and clinical outcomes were compared between four cohorts (coronavirus disease 2019, nonsevere acute respiratory syndrome coronavirus 2 viral pneumonia, bacterial pneumonia, and multiple trauma patients) and between body mass index categories within cohorts. Adjusted analyses of the relationship between body mass index and inhospital mortality within each cohort were performed using multivariable logistic regression. Coronavirus disease 2019 patients were more likely male, had a higher body mass index, lower Pao2/Fio2 ratio, and were more likely mechanically ventilated during the first 24 hours in the ICU compared with the other cohorts. Coronavirus disease 2019 patients had longer ICU and hospital length of stay, and higher inhospital mortality. Odds ratios for inhospital mortality for patients with body mass index greater than or equal to 35 kg/m2 compared with normal weight in the coronavirus disease 2019, nonsevere acute respiratory syndrome coronavirus 2 viral pneumonia, bacterial pneumonia, and trauma cohorts were 1.15 (0.79-1.67), 0.64 (0.43-0.95), 0.73 (0.61-0.87), and 0.81 (0.57-1.15), respectively. CONCLUSIONS: The obesity paradox, which is the inverse association between body mass index and mortality in critically ill patients, is not present in ICU patients with coronavirus disease 2019-related respiratory failure, in contrast to nonsevere acute respiratory syndrome coronavirus 2 viral and bacterial respiratory infections.

Two original observations concerning bacterial infections in COVID-19 patients hospitalized in intensive care units during the first wave of the epidemic in France.

Among 197 COVID-19 patients hospitalized in ICU, 88 (44.7%) experienced at least one bacterial infection, with pneumonia (39.1%) and bloodstream infections (15,7%) being the most frequent. Unusual findings include frequent suspicion of bacterial translocations originating from the digestive tract as well as bacterial persistence in the lungs despite adequate therapy.

State-of-the-art review of secondary pulmonary infections in patients with COVID-19 pneumonia.

BACKGROUND: The incidence of secondary pulmonary infections is not well described in hospitalized COVID-19 patients. Understanding the incidence of secondary pulmonary infections and the associated bacterial and fungal microorganisms identified can improve patient outcomes. OBJECTIVE: This narrative review aims to determine the incidence of secondary bacterial and fungal pulmonary infections in hospitalized COVID-19 patients, and describe the bacterial and fungal microorganisms identified. METHOD: We perform a literature search and select articles with confirmed diagnoses of secondary bacterial and fungal pulmonary infections that occur 48 h after admission, using respiratory tract cultures in hospitalized adult COVID-19 patients. We exclude articles involving co-infections defined as infections diagnosed at the time of admission by non-SARS-CoV-2 viruses, bacteria, and fungal microorganisms. RESULTS: The incidence of secondary pulmonary infections is low at 16% (4.8-42.8%) for bacterial infections and lower for fungal infections at 6.3% (0.9-33.3%) in hospitalized COVID-19 patients. Secondary pulmonary infections are predominantly seen in critically ill hospitalized COVID-19 patients. The most common bacterial microorganisms identified in the respiratory tract cultures are Pseudomonas aeruginosa, Klebsiella species, Staphylococcus aureus, Escherichia coli, and Stenotrophomonas maltophilia. Aspergillus fumigatus is the most common microorganism identified to cause secondary fungal pulmonary infections. Other rare opportunistic infection reported such as PJP is mostly confined to small case series and case reports. The overall time to diagnose secondary bacterial and fungal pulmonary infections is 10 days (2-21 days) from initial hospitalization and 9 days (4-18 days) after ICU admission. The use of antibiotics is high at 60-100% involving the studies included in our review. CONCLUSION: The widespread use of empirical antibiotics during the current pandemic may contribute to the development of multidrug-resistant microorganisms, and antimicrobial stewardship programs are required for minimizing and de-escalating antibiotics. Due to the variation in definition across most studies, a large, well-designed study is required to determine the incidence, risk factors, and outcomes of secondary pulmonary infections in hospitalized COVID-19 patients.

Ventilator-associated bacterial pneumonia in coronavirus 2019 disease, a retrospective monocentric cohort study.

INTRODUCTION: Severe coronavirus 2019 disease (CoViD-19) may lead to respiratory failure and mechanical ventilation. Therefore, ventilator associated pneumonia (VAP) may complicate the course of the disease. The aim of the current article was to investigate possible predictive factors for bacterial VAP on a retrospective manner, in a cohort of mechanically ventilated CoViD-19 patients. Additionally, determinant factors of lethality were analyzed. METHODS: Medical records of patients hospitalized in the intensive care units (ICU) at the university hospital UZ Brussel during the epidemic were reviewed. VAP was defined following the National Healthcare Safety Network 2017 criteria. Univariate and multivariate logistic regressions analyses were performed. RESULTS: Among the 39 patients included in the study, 54% were diagnosed with bacterial VAP. Case fatality rate was 44%, but 59% of the deceased patients had a do-not-resuscitate status. Multivariate logistic regression for prediction of VAP showed significant differences in duration of ICU hospitalization and in minimal lung compliance. Additional analyses were performed on CoViD-19 patients who were affected by bacterial respiratory superinfection. The responsible pathogens correspond to the commonly found bacteria in VAP. However, 71% of the isolated germs were multi-drug resistant and bacteraemia was reported in 38%. Multivariate analyses for prediction of lethality found significant difference in SOFA score. CONCLUSIONS: Mechanically ventilated CoViD-19 patients might frequently develop VAP. Longer ICU hospitalization was associated with pulmonary superinfection in the current cohort. Moreover, decreased minimal lung compliance was correlated to VAP and higher SOFA score at VAP diagnosis was associated with lethality.

Recognition and management of respiratory co-infection and secondary bacterial pneumonia in patients with COVID-19.

In COVID-19, respiratory infection with SARS-CoV-2 plus another virus (viral co-infection) or with SARS-CoV-2 plus a bacterial pathogen (combined viral and bacterial pneumonia) has been described. Secondary bacterial pneumonia can follow the initial phase of viral respiratory infection or occur during the recovery phase. No obvious pattern or guidelines exist for viral co-infection, combined viral and bacterial pneumonia, or secondary bacterial pneumonia in COVID-19. Based on existing clinical data and experience with similar viruses such as influenza and SARS-CoV, the management approach in COVID-19 should, ideally, take into consideration the overall presentation and the trajectory of illness.

Pneumonia in children admitted to the national referral hospital in Bhutan: A prospective cohort study.

OBJECTIVES: The study aim was to describe the etiological profile and clinical characteristics of pneumonia among children hospitalized in Thimphu, Bhutan. METHODS: This prospective study enrolled children aged 2-59 months admitted to the Jigme Dorji Wangchuck National Referral Hospital with World Health Organization (WHO)-defined clinical pneumonia. Demographic and clinico-radiological data were collected through questionnaires, physical examination, and chest radiography. Blood samples and nasopharyngeal washing were collected for microbiological analysis including culture and molecular methods. RESULTS: From July 2017 to June 2018, 189 children were enrolled, of which 53.4% were infants. Pneumonia-related admissions were less frequent over the winter. Chest radiographies were obtained in 149 children; endpoints included pneumonia in 39 cases (26.2%), other infiltrates in 31 (20.8%), and were normal in 79 children (53.0%). Non-contaminated bacterial growth was detected in 8/152 (5.3%) blood cultures, with only two cases of Streptococcus pneumoniae. Viral detection in upper respiratory secretions was common, with at least one virus detected in 103/115 (89.6%). The three most-commonly isolated viruses were respiratory syncytial virus (52/115; 45.2%), rhinovirus (42/115; 36.5%), and human parainfluenza virus (19/115; 16.5%). A third of patients with viral infections showed mixed infections. Case fatality rate was 3.2% (6/189). CONCLUSION: Respiratory viral infections predominated among this cohort of WHO-defined clinical pneumonia cases, whereas bacterial aetiologies were uncommon, highlighting the epidemiologic transition that Bhutan seems to have reached.

Bacterial co-infections with SARS-CoV-2.

The pandemic coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has affected millions of people worldwide. To date, there are no proven effective therapies for this virus. Efforts made to develop antiviral strategies for the treatment of COVID-19 are underway. Respiratory viral infections, such as influenza, predispose patients to co-infections and these lead to increased disease severity and mortality. Numerous types of antibiotics such as azithromycin have been employed for the prevention and treatment of bacterial co-infection and secondary bacterial infections in patients with a viral respiratory infection (e.g., SARS-CoV-2). Although antibiotics do not directly affect SARS-CoV-2, viral respiratory infections often result in bacterial pneumonia. It is possible that some patients die from bacterial co-infection rather than virus itself. To date, a considerable number of bacterial strains have been resistant to various antibiotics such as azithromycin, and the overuse could render those or other antibiotics even less effective. Therefore, bacterial co-infection and secondary bacterial infection are considered critical risk factors for the severity and mortality rates of COVID-19. Also, the antibiotic-resistant as a result of overusing must be considered. In this review, we will summarize the bacterial co-infection and secondary bacterial infection in some featured respiratory viral infections, especially COVID-19.