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1217. Molecular Epidemiology of Pseudomonas aeruginosa in Latin America: Clinical Isolates From Respiratory Tract Infection

Abstract Background Respiratory Tract Infection (RTI) caused by P. aeruginosa is a common infection among hospitalized patients, with increased levels of morbidity and mortality. This pathogen exhibits multiple resistance mechanisms to antibiotics. We analyzed the molecular epidemiology and activity of the main therapeutic options against P. aeruginosa isolated from RTI in Latin America (LATAM). Methods Isolates were collected from 36 sites in 10 countries during 2017-2019. Non-duplicate samples were consecutively collected. MICs were determined by broth microdilution and interpreted by CLSI criteria. A subset of imipenem non-susceptible isolates was selected for characterization of carbapenemase encoding genes via multiplex PCR and DNA sequencing. β-lactamase genes encoding ESBLs, carbapenemases, and plasmid-mediated AmpCs were investigated. Results A total of 2,044 P. aeruginosa were collected from RTI. Overall C/T [87.8% susceptible (S)] was the most active antimicrobial tested against P. aeruginosa isolates followed by amikacin (85.8% S) and imipenem/relebactam (IMI/REL; 82.5% S). Other antimicrobials had less than 80% susceptibility. C/T remained the most active agent including activity against imipenem and piperacillin/tazobactam non-susceptible isolates (Figure 1). 583 imipenem non-susceptible P. aeruginosa were selected for molecular analysis (Table 1). Thirty (5,1%) isolates were confirmed to be producers of serine-carbapenemases [GES-5 (6 isolates); KPC-2 (24 isolates)], while 83 (14.2%) were MBL producers. KPC-2 was found in Colombia (9), Chile (6), Puerto Rico (4), Guatemala (3), and Brazil (2). GES-5 was identified in Mexico (3), Argentina (2) and Brazil (1). VIM-2 was the most common MBL encoding gene identified. IMP variants were observed in Brazil (IMP-56, IMP-1), Ecuador (IMP-13), Mexico (IMP-18), Panama (IMP-18) and Puerto Rico (IMP-18). SPM-1 was only encountered in Brazil. The production of ESBLs was low in most LATAM countries, except for Guatemala (80%) (Figure 2). Figure 1. Activities of selected antimicrobial agents against 2,044 P. aeruginosa isolated from respiratory tract infections in Latin America (2017 to 2019). TABLE 1. Molecular analysis of imipenem non-susceptible P. aeruginosa isolates in Latin America (LATAM) from Respiratory Tract Infection (N=583). Figure 2. Carbapenemases identified in 583 imipenem non-susceptible P. aeruginosa isolated from patients with respiratory tract Infections in Latin America (LATAM). Conclusion CT, amikacin and IMI/REL showed good activity against RTI isolates and could represent effective treatment options for P. aeruginosa infections. The prevalence of carbapenemases-encoding genes varied geographically in LATAM. Disclosures Leandro Cardinal, PharmD, PhD, MSD (Employee) Cicera P. Marcelino, n/a, MSD (Employee) Aline Okuma, n/a, MSD (Employee)MSD Brazil (Employee) Gustavo Mizuno, PharmD, Merck Sharp Dohme (Employee) Felipe Tuon, PhD, Merck Sharp Dohme Brazil (Scientific Research Study Investigator) Ana C. Gales, MD, MSD (Board Member, Advisor or Review Panel member, Speaker’s Bureau)Pfizer (Board Member, Consultant, Advisor or Review Panel member, Speaker’s Bureau) Marina Della Negra, Medical Doctor, MSD Brazil (Employee) Thales Polis, Medical Doctor, MSD Brazil (Employee)


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CUNY School of Public Health, New York, New York ; 4 CUNY, New York, New York Session: P-71. Public Health Background. Severe bacterial infections (SBI) associated with intravenous drug use have been increasing in frequency in the U.S. over the last decade. This mixed methods study aims to identify the risk factors associated with SBI in hospitalized individuals with recent injection drug use.
Methods. We conducted 34 quantitative and 15 qualitative interviews between August 2020 and June 2021 at Bellevue Hospital in New York City. Eligible participants were (1) >/= 18 year of age, (2) admitted with a SBI, and (3) reported injection drug use within the 90 days prior to admission. Quantitative and qualitative data was obtained using a quantitative survey and in-depth, semi structured interviews of participants respectively. Analysis was performed to examine trends and explore common themes potentially contributing factors to SBI.
Results. Of the 34 participants included, the median age was 37.5, 85% were male, 53% white, and 65% reported being homeless within the past 3 months. Endocarditis was the most common primary diagnosis (65%). Median length of hospital stay was 24 days and 35% required ICU level care during admission. A causative microorganism was identified in 85% of participants and 50% had Staphylococcus aureus as the sole organism. Discharges against medical advice occurred in 35%. Daily injection drug use in prior 30 days was 95% with a median of 10 injections per day. In the 30 days prior to admission, 50% reported an increase in injection frequency, 80% reported reusing needles and/or syringes, 75% reused cookers, 65% reused cottons. Analysis of qualitative interview data revealed high risk injection behaviors. Participants were not practicing and unaware of strategies to reduce their risk of drug injection-related SBI. Prior hospitalizations for SBI did not impact on this knowledge deficit on what constitutes bacterial infection risk and how to prevent it.

Conclusion.
Study findings highlight the complexity of the injection drug use process and the potential social and physiological pathways leading to SBI. Multiple domains at the structural, network, and individual level that impact drug injection practices and provide context by which these factors predispose and lead to physiological tissue damage and the development of SBI among PWID.

Session: P-72. Resistance Mechanisms
Background. Meropenem-vaborbactam (MVB) is an important addition to the armamentarium to treat infections caused by carbapenem-resistant Enterobacterales (CREs). Carbapenemase-negative (CN) CRE isolates have been reported, but the activity of newer agents against these isolates is still not well understood. We evaluated the activity of MVB against CN-CRE collected during 6 years of surveillance in US hospitals.
Methods. A total of 27,968 Enterobacterales isolates collected in US hospitals from 2014-2019 were susceptibility tested by reference broth microdilution methods. Results were interpreted using CLSI 2020 breakpoints. CRE isolates were submitted to PCR/sequencing (2014)(2015) or whole genome sequencing (WGS; 2016-2019) for characterization of carbapenemase genes. Isolates from 2016-2019 were evaluated for other beta-lactam resistance mechanisms.
Results. Among 357 (1.3% of all isolates) CRE isolates identified during 6 years of surveillance, 48 (13.4% of the CRE) isolates did not produce known carbapenemases. The CN-CRE collection included 7 bacterial, species, or species complex. The top four most common species in the collection were K. pneumoniae (16 isolates) followed by E. cloacae (9), E. coli (8), and K. aerogenes (8). MVB was the most active agent tested against these isolates, inhibiting 47/48 (97.9%) of the isolates tested. The only isolate displaying a resistant MIC for MVB was a P. mirabilis (MIC, 16 mg/L) collected in 2015. Meropenem alone inhibited only 2.1% of the isolates. Other beta-lactams inhibited 4.2 to 14.6% of the isolates. Among non-beta-lactam comparator agents, tigecycline and amikacin inhibited 93.8 and 91.7% of the isolates, respectively, when applying CLSI or US FDA breakpoints. A total of 89.6% of the isolates had intermediate colistin MIC values. Among the 27 isolates collected from 2016-2019 that were submitted to WGS, 15 harbored CTX-M encoding genes. K. aerogenes and E. cloacae isolates (3 each) overexpressed AmpC. OmpC/K36 was disrupted in 20 isolates and OmpF/K35 was disrupted in 8 isolates.
Conclusion. MVB displayed good activity against CN-CRE isolates from US hospitals. This combination agent could be a good option to treat infections caused by these isolates.