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Background Invasive aspergillosis (IA) causes significant morbidity and mortality in lung transplant (LTx) recipients. Antifungal resistance in Aspergillus species is on the rise globally with specific concern in Europe related to the TR34/L98H mutation in the cyp51A enzyme that induces pan-azole resistance. Azole exposure is a known risk factor for development of resistant Aspergillus, but this is less well described in LTx population. Methods We reviewed the electronic medical records of LTx patients with respiratory cultures positive for Aspergillus species known to be inherently resistant or any Aspergillus species tested to be resistant to one or more triazole from 2010 to 2019. For available isolates, Sanger sequencing was performed on cyp51A with primers targeting the promoter region and 3 known hotspot areas. Results Twenty eight patients met inclusion criteria and 2.7% (28/1026) Aspergillus isolates were azole-resistant during study period (Figure 1). Median time from LTx to resistant Aspergillus growth was 196 days (range 14 - 3146). There was a cluster of positive cultures within 1-year post-Tx period (13/28). Azole exposure varied, from 7 to 2443 days (median 128). There was no change in incidence over the study period. The most common species was Aspergillus calidoustus (Figure 2). Twenty cases were deemed colonization, vs 5 probable IFI and 3 proven IFI. Mortality of IFI with resistant Aspergillus was 38% (3/8), higher than azole-susceptible IA (p=0.05). Twelve isolates were available for sequencing; none carried TR34/L98H mutation. There was wide variation in mutations, ranging from 1 to 12 point mutations in the cyp51 enzyme, many of them SNPs previously described as engendering an azole resistant phenotype (Figure 3). Aspergillosis-free Survival by Resistant and Susceptible Isolates Development of azole-resistant aspergillus colonization/infection was rare relative to common occurrence of colonization/infection with susceptible isolates in the lung transplant recipient population Azole Resistant Aspergillus Species Isolated from Lung Transplant Recipients The most commonly isolated species were A. calidoustus and ustus. Only 4/28 isolates were A. fumigatus. Azole Resistant Aspergillus Genotypic Analysis Sequenced isolates showed wide variability in point mutations. M220V, G54, and G448 were the only mutations observed more than once. 3 isolates were wild type. Conclusion Azole resistant Aspergillus infections remain an uncommon problem in LTx. The majority of isolates were deemed colonization, but mortality was high when IFI was present. Most isolates had mutations within the hot spot regions of cyp51A known to induce azole resistance. There were no TR34/L98H mutants found in our patient population. Disclosures Minh-Hong Nguyen, MD, Merck (Grant/Research Support)

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)