292. Antibiotic Use Is Increased in Patients with Acute Respiratory Distress Syndrome (ARDS) Requiring Extracorporeal Membrane Oxygenation (ECMO) due to COVID-19 Compared with Influenza

Background During the COVID-19 pandemic, >50% of hospitalized patients (pts) received an antimicrobial. ECMO is increasingly used in COVID-19 pts with severe ARDS. ECMO has been used for ARDS due to influenza at our center in prior years. Pts on ECMO are at high risk for infections. We compared the rates of antibiotic (Ab) and antifungal (AF) use in pts on ECMO for COVID-19 vs influenza ARDS. Methods This was a retrospective review of pts on ECMO for COVID-19 (2020-2021) or influenza (2013-2019). Antimicrobials (Abs and AFs) were categorized as anti-MRSA, anti-pseudomonal β-lactams (AP-BL), carbapenems, and new broader spectrum β-lactams. We calculated total Ab and AF utilization, adjusted for ECMO duration. Results Seventy-one pts (36 COVID-19 and 35 influenza) were included. COVID-19 pts had longer ECMO duration (median: 25 vs 11 days, p=.03). 100% and 97% of pts with COVID-19 and influenza received ≥1 Ab, respectively, and 42% and 33% an AF, respectively. COVID-19 pts received longer duration of Abs (26 vs 10 days, p< 0.001) and but not AF. COVID-19 group (gp) were more likely to receive anti-MRSA Ab (69% vs 33%, p=.004); otherwise, there were no differences between gps in types of Abs used. When adjusted for ECMO days, COVID-19 gp received higher median number of Abs (1.23 vs 1, p=.06). Specifically, COVID-19 gp received higher median number of anti-MRSA Ab (0.2 vs 0, p=.007) and AP-BL (0.44 vs 0.28, p=.08). There was no difference in Ab-free days between gps, though the proportion of Ab-free days was lower (0.2 vs 0.36) in COVID-19 pts (p=.08). More COVID-19 pts had pathogens recovered from clinical cultures, especially S. aureus and Enterobacterales (Figure). Pathogens recovered from clinical cultures Patients recovered from clinical cultures of patients with COVID-19 and Influenza ARDS requiring ECMO Conclusion Among pts on ECMO, those with COVID-19 received significantly longer courses of Abs than those with influenza, even after adjusting for longer durations of ECMO. Differences were driven by receipt of anti-MRSA and AP-BLs. Recovery of pathogenic bacteria was greater in COVID-19 pts than influenza pts. Given difficulties in distinguishing pneumonia from airway colonization among ARDS pts on ECMO, development of diagnostic criteria for pt care, rational antimicrobial stewardship and further research are needed. Disclosures Cornelius J. Clancy, MD, Merck (Grant/Research Support)

Interrupting the Conversation: Implications for Crosstalk Between Viral and Bacterial Infections in the Asthmatic Airway

Asthma is a heterogeneous, chronic respiratory disease affecting 300 million people and is thought to be driven by different inflammatory endotypes influenced by a myriad of genetic and environmental factors. The complexity of asthma has rendered it challenging to develop preventative and disease modifying therapies and it remains an unmet clinical need. Whilst many factors have been implicated in asthma pathogenesis and exacerbations, evidence indicates a prominent role for respiratory viruses. However, advances in culture-independent detection methods and extensive microbial profiling of the lung, have also demonstrated a role for respiratory bacteria in asthma. In particular, airway colonization by the Proteobacteria species Nontypeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) is associated with increased risk of developing recurrent wheeze and asthma in early life, poor clinical outcomes in established adult asthma and the development of more severe inflammatory phenotypes. Furthermore, emerging evidence indicates that bacterial-viral interactions may influence exacerbation risk and disease severity, highlighting the need to consider the impact chronic airway colonization by respiratory bacteria has on influencing host responses to viral infection. In this review, we first outline the currently understood role of viral and bacterial infections in precipitating asthma exacerbations and discuss the underappreciated potential impact of bacteria-virus crosstalk in modulating host responses. We discuss the mechanisms by which early life infection may predispose to asthma development. Finally, we consider how infection and persistent airway colonization may drive different asthma phenotypes, with a view to identifying pathophysiological mechanisms that may prove tractable to new treatment modalities.

Invasive Candidiasis with Cavitary Lung Lesion in a Post-Covid-19 Diabetic Patient- A Case Report

There have been reported several complications after corona virus disease-2019 (COVID-19). Superinfections, especially secondary fungal diseases are now on rise in post-COVID-19 patients. Candida usually reflects airway colonization and true Candida pneumonia is rare, but can occur after hematologic dissemination from other body sites, such as the skin, gastrointestinal and genitourinary tract. Diabetes mellitus (DM) is an independent risk factor for both severe COVID-19 and increased susceptibility to fungal infections. We describe a case of invasive candidiasis in a 72-year-old post-COVID-19 diabetic male, who presented with cough, fever and cavitary lesion in lung seen on contrast-enhanced computed tomography (CECT) Chest. The patient’s sputum and blood cultures were positive for Candida.

A Case of Phage Therapy against Pandrug-Resistant Achromobacter xylosoxidans in a 12-Year-Old Lung-Transplanted Cystic Fibrosis Patient

Bacteriophages are a promising therapeutic strategy among cystic fibrosis and lung-transplanted patients, considering the high frequency of colonization/infection caused by pandrug-resistant bacteria. However, little clinical data are available regarding the use of phages for infections with Achromobacter xylosoxidans. A 12-year-old lung-transplanted cystic fibrosis patient received two rounds of phage therapy because of persistent lung infection with pandrug-resistant A. xylosoxidans. Clinical tolerance was perfect, but initial bronchoalveolar lavage (BAL) still grew A. xylosoxidans. The patient’s respiratory condition slowly improved and oxygen therapy was stopped. Low-grade airway colonization by A. xylosoxidans persisted for months before samples turned negative. No re-colonisation occurred more than two years after phage therapy was performed and imipenem treatment was stopped. Whole genome sequencing indicated that the eight A. xylosoxidans isolates, collected during phage therapy, belonged to four delineated strains, whereby one had a stop mutation in a gene for a phage receptor. The dynamics of lung colonisation were documented by means of strain-specific qPCRs on different BALs. We report the first case of phage therapy for A. xylosoxidans lung infection in a lung-transplanted patient. The dynamics of airway colonization was more complex than deduced from bacterial culture, involving phage susceptible as well as phage resistant strains.

Antenatal Infections and Respiratory Outcome in Preterm Infants

Fetal exposure to infection and inflammation can result in accelerated lung maturation and simultaneously altered lung development. This alteration is characterized by reduced alveolar and vascular formation that is one of the hallmarks of the changes observed in animal models and in infants with bronchopulmonary dysplasia (BPD). These opposite effects on maturation and on lung development can explain the reduced severity of respiratory distress syndrome (RDS) but increased incidence of BPD observed in infants exposed to antenatal infections. This also explains why infants born to mothers with chorioamnionitis or colonized with ureaplasma urealitycum have an increased risk of lung injury and BPD. Despite the negative effects of infection on lung development, there is no clear evidence that antibiotic therapy improves the respiratory course in these infants. While the administration of azithromycin to ureaplasma colonized infants is effective in eradicating airway colonization, the effect on BPD is inconclusive. One of the few interventions that have been shown to improve respiratory outcome and reduce BPD in infants with severe RDS is the modulation of inflammation by the administration of systemic or intratracheal steroids early after birth. Key Points

Early life bacterial airway colonization, local immune mediator response and risk of otitis media

Introduction. Acute otitis media (AOM) is the most common bacterial infection in early childhood, but the underlying mechanisms making some children more susceptible are poorly understood. Aim. To examine the associations between bacterial airway colonization in early life and the risk of AOM and tympanostomy tube insertion (TTI), and whether such associations are modulated by an insufficient local immune mediator response to bacterial colonization. Methodology. Bacterial cultures from hypopharyngeal samples were obtained at 1 week, 1 month and 3 months of age in the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) cohort comprising 700 children. Twenty immune mediators were quantified from airway mucosal lining fluid sampled at 1 month. AOM symptoms were registered in a daily diary until 3 years. Information on TTI in the first 3 years was obtained from national registers. Results. Children colonized with Streptococcus pneumoniae at 1 month of age had increased incidence of AOM [aIRR 2.43 (1.14–5.21)] and children colonized with Moraxella catarrhalis at 1 month or Haemophilus influenzae at 3 months had an increased risk of TTI [aHR 1.45 (1.00–2.10) and 1.73 (1.10–2.71)]. There were no associations between the local immune mediator response to colonization and risk of AOM or TTI. Conclusion. Pathogenic bacterial airway colonization in early life was found to be associated with an increased risk of otitis media, albeit not consistently. These associations were independent of the local immune response to colonization.

Bacterial Colonization within the First Six Weeks of Life and Pulmonary Outcome in Preterm Infants <1000 g

Bronchopulmonary dysplasia (BPD) is a multifactorial disease mainly provoked by pre- and postnatal infections, mechanical ventilation, and oxygen toxicity. In severely affected premature infants requiring mechanical ventilation, association of bacterial colonization of the lung and BPD was recently disclosed. To analyze the impact of bacterial colonization of the upper airway and gastrointestinal tract on moderate/severe BPD, we retrospectively analyzed nasopharyngeal and anal swabs taken weekly during the first 6 weeks of life at a single center in n = 102 preterm infants <1000 g. Colonization mostly occurred between weeks 2 and 6 and displayed a high diversity requiring categorization. Analyses of deviance considering all relevant confounders revealed statistical significance solely for upper airway colonization with bacteria with pathogenic potential and moderate/severe BPD (p = 0.0043) while no link could be established to the Gram response or the gastrointestinal tract. Our data highlight that specific colonization of the upper airway poses a risk to the immature lung. These data are not surprising taking into account the tremendous impact of microbial axes on health and disease across ages. We suggest that studies on upper airway colonization using predefined categories represent a feasible approach to investigate the impact on the pulmonary outcome in ventilated and non-ventilated preterm infants.