Georgia Emerging Infections Program Research Articles

Molecular and Epidemiological Investigation of Fluconazole-resistant Candida parapsilosis-Georgia, United States, 2021.

Reports of fluconazole-resistant Candida parapsilosis bloodstream infections are increasing. We describe a cluster of fluconazole-resistant C parapsilosis bloodstream infections identified in 2021 on routine surveillance by the Georgia Emerging Infections Program in conjunction with the Centers for Disease Control and Prevention. Whole-genome sequencing was used to analyze C parapsilosis bloodstream infections isolates. Epidemiological data were obtained from medical records. A social network analysis was conducted using Georgia Hospital Discharge Data. Twenty fluconazole-resistant isolates were identified in 2021, representing the largest proportion (34%) of fluconazole-resistant C parapsilosis bloodstream infections identified in Georgia since surveillance began in 2008. All resistant isolates were closely genetically related and contained the Y132F mutation in the ERG11 gene. Patients with fluconazole-resistant isolates were more likely to have resided at long-term acute care hospitals compared with patients with susceptible isolates (P = .01). There was a trend toward increased mechanical ventilation and prior azole use in patients with fluconazole-resistant isolates. Social network analysis revealed that patients with fluconazole-resistant isolates interfaced with a distinct set of healthcare facilities centered around 2 long-term acute care hospitals compared with patients with susceptible isolates. Whole-genome sequencing results showing that fluconazole-resistant C parapsilosis isolates from Georgia surveillance demonstrated low genetic diversity compared with susceptible isolates and their association with a facility network centered around 2 long-term acute care hospitals suggests clonal spread of fluconazole-resistant C parapsilosis. Further studies are needed to better understand the sudden emergence and transmission of fluconazole-resistant C parapsilosis.

1281. Ongoing Transmission of Clonal Strains of Invasive Nontypeable Haemophilus influenzae Disproportionately Affecting Persons with HIV in Metropolitan Atlanta, 2019—2022

Abstract Background Nontypeable Haemophilus influenzae (NTHi) is a genetically diverse pathogen that typically causes mucosal infections or invasive NTHi (iNTHi) disease in persons at the extremes of age. In 2017-2018, we reported a significant increase in incident iNTHi in Atlanta among virally-suppressed persons with HIV (PWH) and identified two clonal strains associated with septic arthritis/polyarthritis among Black men who have sex with men. Methods Surveillance data from the CDC-funded Georgia Emerging Infections Program was used to assess interim iNTHi epidemiology in adults ≥ 18 years old in metropolitan Atlanta, including the potential for continued transmission of clonal strains in adults 18-55 years old. Overall incidence of iNTHi and by HIV status from 2019-2022 was determined and compared with prior years; and demographic and clinical data were collected. Whole genome sequencing assessed genetic relatedness of isolates, which were categorized as belonging to cluster 1 or 2 (C1, C2) or non-clustered (NC). Results From 2019-2022 in Atlanta, there were 157 iNTHi cases in adults ≥ 18 years old (median age 56 [Q1-Q3 36-72] years, 59% male, 44% Black), including 29 in PWH. The iNTHi incidence among PWH in 2019-2022 was lower than in 2017-2018 (18.8 vs 41.7 cases per 100,000, respectively, p< 0.01), and higher than in 2008-2016 (9.6 per 100,000; p< 0.01) (Figure). Among iNTHi cases 18-55 years old (2019-2022), 94/95 had isolates available for cluster analysis: 7/94 (7%) and 18/94 (19%) were identified as C1 and C2, respectively. Characteristics of cases differed by clonal status (Table 1): among C1, C2, and NC cases, 6/7 (86%), 7/18 (39%), and 15/69 (22%) involved PWH, respectively; and septic arthritis was present in 1/7 (14%), 8/18 (44%), and zero, respectively. Table 2 provides detailed data on PWH with clonal strains. Conclusion Ongoing transmission of two clonal NTHi strains that are associated with a relatively high prevalence of joint involvement in invasive disease and disproportionately affect Black men and PWH was noted in Atlanta. The C2 clonal strain became more prevalent in 2022. Additional studies are needed to better understand modes of transmission, geographic distribution of clones, and to explore the unusual clinical manifestations to optimize prevention and treatment measures. Disclosures Lauren F. Collins, MD, MSc, Curio Science: Honoraria

Carbapenemase genes and mortality in patients with carbapenem-resistant Enterobacterales, Atlanta, Georgia, 2011–2020

Background: Carbapenemase genes in carbapenem-resistant Enterobacterales (CP-CRE) may be transmitted between patients and bacteria. Reported rates of carbapenemase genes vary widely, and it is unclear whether having a carbapenemase gene portends worse outcomes given that all patients with CRE infections have limited treatment options. Methods: Using active population- and laboratory-based active surveillance data collected by the US CDC-funded Georgia Emerging Infections Program from 2011 to 2020, we assessed the frequency of carbapenemase genes in a convenience sample of CRE isolates using whole-genome sequencing (WGS), and we investigated risk factors for carbapenemase positivity. Only the first isolate per patient in a 30-day period was included. We compared characteristics of patients with CP-CRE and non–CP-CRE. Using multivariable log binomial regression, we assessed the association of carbapenemase gene positivity and 90-day mortality. Results: Of 284 CRE isolates, 171 isolates (60.2%) possessed a carbapenemase gene (Table 1), and KPC-3 was the most common carbapenemase gene (80.7%), with only 7 isolates possessing NDM (Table 2). No isolates possessed >1 carbapenemase gene, and most isolates were from urine (82.4%) (Table 1). Carbapenemase gene positivity was associated with lower age, male sex, black race, infection with Klebsiella pneumoniae, polymicrobial infection, having an indwelling medical device, receiving chronic dialysis, and prior stay in a long-term acute-care hospital, long-term care facility, and/or prior hospitalization in the last year. The 90-day mortality rates were similar in patients with non–CP-CRE and CP-CRE: 24.8% versus 25.7% (P = .86). In multivariable analysis, carbapenemase gene presence was not associated with 90-day mortality (adjusted risk ratio, 0.82; 95% CI, 0.50–1.35) when adjusting for CCI, infection with Klebsiella pneumoniae, and chronic dialysis use. Conclusions: The frequency of CP-CRE among CRE was high in this study, but unlike prior studies, the 90-day mortality rates wer similar in patients with CP-CRE compared to non–CP-CRE. Our results provide novel associations (eg, lower age, male sex, infection with Klebsiella pneumoniae, and indwelling medical devices) that infection preventionists could use to target high-risk patients for screening or isolation prior to CP-CRE detection.Disclosure: None

Evaluating indwelling devices and other risk factors for mortality in invasive Carbapenem-resistant Enterobacterales infections in Georgia, 2012-2019.

Carbapenem-resistant Enterobacterales (CRE) infections are a public health threat due to the risk of transmission between patients and high associated mortality. We sought to identify risk factors for mortality in patients with invasive CRE infections and to specifically evaluate whether there was an association between indwelling medical devices and 90-day mortality. Retrospective observational cohort study of patients infected with CRE in the eight-county metropolitan Atlanta area between 2012 and 2019. Patients with invasive CRE infections were identified via the Georgia Emerging Infections Program's active, population- and laboratory-based surveillance system and linked with the Georgia Vital Statistics database. We used bivariate analysis to identify risk factors for mortality and completed log binomial multivariable regression to estimate risk ratios (RR) for the association between indwelling devices and mortality. In total, 154 invasive CRE infections were identified, with indwelling devices present in most patients (87.7%) around the time of infection. Admission to an intensive care unit was found to be associated with 90-day mortality (adjusted RR [aRR] 1.55, 95% CI 1.07, 2.24); however, the presence of any indwelling device was not associated with increased risk of 90-day mortality in multivariable analysis (aRR 1.22, 95% CI 0.55, 2.73). Having at least two indwelling devices was associated with increased mortality (aRR 1.79, 95% CI 1.05, 3.05). Indwelling devices were prevalent in our cohort but were not consistently associated with an increased risk of mortality. Further studies are needed to examine this relationship and the role of device removal.

416. Evaluating Indwelling Devices and Mortality in Invasive Carbapenem-Resistant Enterobacterales Infections, Atlanta, GA, 2012–2019.

Abstract Background Carbapenem-resistant Enterobacterales (CRE) infections pose a grave public health threat due to the potentially silent transmission leading to outbreaks, limited therapeutic options and high mortality. We sought to identify risk factors for mortality in patients with invasive CRE infections and describe the association between indwelling medical devices and 90-day mortality. Methods The Georgia Emerging Infections Program performs active population and laboratory based surveillance for CRE in the Atlanta, Georgia metropolitan area. Using this data we created a retrospective observational cohort of patients with invasive CRE infections between 2012 and 2019. Invasive infections were defined as resistant isolates obtained from a normally sterile site (Table 1). Indwelling medical devices, including central venous catheters (CVCs), were present within two calendar days prior to infection. We completed bivariate analyses examining the relationship between covariates and mortality. Multivariable log binomial regression was used to estimate adjusted risk ratios (aRR) for the association of covariates and all-cause 90-day mortality. Sub-group analyses were completed evaluating only those patients with CVCs and those with at least two indwelling devices. Table 1.Definition of Carbapenem-resistant Enterobacterales Abbreviations: MIC – minimum inhibitory concentration Results There were 154 invasive CRE infections (Table 2) with 87.7% having at least one indwelling device and an overall mortality of 23.4%. Intensive care unit (ICU) admission, having at least two indwelling devices, and requiring chronic dialysis were associated with mortality on bivariate analysis. The presence of any indwelling device (aRR 1.02, 95% CI 0.36, 2.89) or specifically a CVC (aRR 1.13, 95% CI 0.54, 2.37) were not associated with increased risk of 90-day mortality in unadjusted or multivariable analysis (Table 3). Having at least two indwelling devices was associated with increased risk of mortality (aRR 2.48, 95% CI: 1.02, 5.99) (Table 3). Characteristics of Patients with Invasive CRE Infections in Atlanta, Georgia 2012-2019 Race: 6 unknowns, Ethnicity: 28 unknowns Other race: American Indian or Alaska Native, Asian, Native Hawaiian or Pacific Islander Other sites of infection: deep tissue, sterile fluid, or other sterile site Other indwelling devices: endotracheal or nasotracheal tube, nephrostomy tube, nasogastric tube, other * 1 missing **16 patients never admitted to the hospital and 2 with missing data Risk Ratios for Invasive Devices and Mortality Including Subgroup Analyses 1 Adjusted for indwelling device, Charlson comorbidity score, intensive care admission, previous stay at LTACH 2 Adjusted for central venous catheter, Charlson comorbidity score, intensive care admission, previous stay at LTACH 3 Adjusted for at least two indwelling devices, Charlson comorbidity score, previous stay at LTACH Abbreviations: LTACH - Long Term Acute Care hospital Conclusion In patients with invasive CRE infections, indwelling medical device use was frequent but only associated with mortality in patients with multiple devices. Stewardship of medical devices may be an important target for intervention in this population. Disclosures All Authors: No reported disclosures.

Clinical and Genomic Epidemiology of mcr-9-Carrying Carbapenem-Resistant Enterobacterales Isolates in Metropolitan Atlanta, 2012 to 2017.

ABSTRACTColistin is a last-resort antibiotic for multidrug-resistant Gram-negative infections. Recently, the ninth allele of the mobile colistin resistance (mcr) gene family, designated mcr-9, was reported. However, its clinical and public health significance remains unclear. We queried genomes of carbapenem-resistant Enterobacterales (CRE) for mcr-9 from a convenience sample of clinical isolates collected between 2012 and 2017 through the Georgia Emerging Infections Program, a population- and laboratory-based surveillance program. Isolates underwent phenotypic characterization and whole-genome sequencing. Phenotypic characteristics, genomic features, and clinical outcomes of mcr-9-positive and -negative CRE cases were then compared. Among 235 sequenced CRE genomes, 13 (6%) were found to harbor mcr-9, all of which were Enterobacter cloacae complex. The median MIC and rates of heteroresistance and inducible resistance to colistin were similar between mcr-9-positive and -negative isolates. However, rates of resistance were higher among mcr-9-positive isolates across most antibiotic classes. All cases had significant health care exposures. The 90-day mortality was similarly high in both mcr-9-positive (31%) and -negative (7%) CRE cases. Nucleotide identity and phylogenetic analysis did not reveal geotemporal clustering. mcr-9-positive isolates had a significantly higher number of median [range] antimicrobial resistance (AMR) genes (16 [4 to 22] versus 6 [2 to 15]; P < 0.001) than did mcr-9-negative isolates. Pangenome tests confirmed a significant association of mcr-9 detection with mobile genetic element and heavy metal resistance genes. Overall, the presence of mcr-9 was not associated with significant changes in colistin resistance or clinical outcomes, but continued genomic surveillance to monitor for emergence of AMR genes is warranted.IMPORTANCE Colistin is a last-resort antibiotic for multidrug-resistant Gram-negative infections. A recently described allele of the mobile colistin resistance (mcr) gene family, designated mcr-9, has been widely reported among Enterobacterales species. However, its clinical and public health significance remains unclear. We compared characteristics and outcomes of mcr-9-positive and -negative CRE cases. All cases were acquired in the health care setting and associated with a high rate of mortality. The presence of mcr-9 was not associated with significant changes in colistin resistance, heteroresistance, or inducible resistance but was associated with resistance to other antimicrobials and antimicrobial resistance (AMR), virulence, and heavy metal resistance (HMR) genes. Overall, the presence of mcr-9 was not associated with significant phenotypic changes or clinical outcomes. However, given the increase in AMR and HMR gene content and potential clinical impact, continued genomic surveillance of multidrug-resistant organisms to monitor for emergence of AMR genes is warranted.

787. Clinical and Genomic Epidemiology of mcr-9 Containing Carbapenem-resistant Enterobacterales Isolates in Metropolitan Atlanta, 2012-2017

BackgroundColistin is a last-resort antibiotic for multidrug resistant gram-negative infections. Recently, a new allele of the mobile colistin resistance (mcr) gene family designated mcr-9, has been reported. However, its clinical and phenotypic significance remains unclear.MethodsThe Centers for Diseases Control and Prevention-funded Georgia Emerging Infections Program (EIP) performs population- and laboratory- based surveillance for CRE isolated from sterile sites or urine in metropolitan Atlanta, GA including standardized chart abstraction. We queried genomes of carbapenem-resistant Enterobacterales (CRE) for mcr-9 from a convenience sample of Georgia EIP clinical isolates between 2012-2017. Isolates underwent phenotypic characterization by broth microdilution and population analysis profiling. Nine available E. cloacae (two mcr-9 positive, seven mcr-9 negative) genomes from the National Institutes of Health were included in downstream genomic analysis. Fastq files underwent de novo assembly, annotation and AMR and virulence gene prediction, pan-genome association analysis, pairwise comparisons of average nucleotide identity and phylogenetic tree construction based on core genes. We compared characteristics and outcomes of mcr-9 positive and negative CRE cases.ResultsAmong 449 sequenced CRE genomes, thirteen (2.9%) were found to harbor mcr-9, all of which were E. cloacae. Fourteen mcr-9 negative E. cloacae (n=14) were included as a comparative group. E. cloacae was most commonly isolated from the urine (22/24, 86%), and none were community associated. The median colistin MIC, rates of heteroresistance and inducible resistance were similar between mcr-9 positive and negative isolates (Table 1). 90-day mortality was high in both mcr-9 positive (31%) and negative (7% cases (p=0.28, Table 1). Phylogenetic analysis revealed no geo-temporal clustering (Figure 1). Plasmid-associated genes were significantly associated with the presence of mcr-9 (p< 0.001). Phylogeny and average nucleotide identity heatmap of mcr-9 positive and mcr-9 negative E. cloacae. Figure Legend 1: Phylogeny and average nucleotide identity heatmap of mcr-9 positive (n=13) and mcr-9 negative (n=14) E. cloacae from Georgia Emerging Infection program in addition to 9 available E. cloacae (two mcr-9 positive, seven mcr-9 negative) from the National Institutes of Health. A phylogenetic tree based on a core gene alignment containing 1,904 genes defined using Roary v3.13.0. was generated using IQtree v2.0.3. A maximum likelihood tree was generated by running 1,000 bootstrap replicates under the generalized time-reversible model of evolution. The tree was visualized and annotated using Interactive Tree of Life (iTOL) v4. Pairwise comparisons of average nucleotide identity on the assembled genomes were performed with the Mashmap method using fastANI v1.32. Abbreviations: GA EIP: Georgia Emerging Infection Program, NIH: National Institutes of Health,Table 1: Carbapenem-resistant E. cloacae clinical and microbiological characteristics ConclusionThe presence of mcr-9 was not associated with significant changes in colistin resistance or clinical outcomes.Disclosures All Authors: No reported disclosures

1219. Unfavorable Clinical Outcomes with Polymyxins Compared to Ceftolozane/Tazobactam for the Treatment of Carbapenem-Resistant Pseudomonas aeruginosa

BackgroundPatients with carbapenem-resistant Pseudomonas aeruginosa (CRPA) have high in-hospital mortality rates. It is unknown if patients with CRPA treated with ceftolozane/tazobactam (C/T) have improved clinical outcomes compared to those treated with polymyxins. MethodsThe CDC-funded, Georgia Emerging Infections Program performed active population- and laboratory-based surveillance for CRPA isolated from sterile sites, urine, lower respiratory tract and wounds in metropolitan Atlanta, GA from 8/1/2016–7/31/2018. We reviewed charts of adults without cystic fibrosis who were hospitalized within 1 week of CRPA culture. Using a desirability of outcome ranking (DOOR) analysis which incorporates both benefits and risks into a single outcome, we estimated the probability that a patient treated first with C/T would have a more desirable clinical outcome at 30-days than a patient treated with polymyxins (polymyxin B or colistin). We adjusted for confounding using inverse probability of treatment weighting (IPTW) based on culture source and need for dialysis at baseline. A partial credit analysis allowed for variable weighting of DOOR ranks and calculation of differences in mean partial credit scores. ResultsAmong 710 cases from 18 different hospitals, we identified 73 patients treated for CRPA infections with polymyxins (n=31) or C/T (n=42). Most patients were male (64%) and Black (80%), and those receiving polymyxins were more likely to have required dialysis at baseline (35% vs. 14%, p=0.03) (Table 1). At 30 days after culture, 34 (47%) were alive with no adverse events, 21 (29%) were alive with ≥ 1 adverse event, and 18 (25%) had died. Patients first treated with C/T had a lower 30-day mortality rate than those treated with polymyxins (14% vs 39%, p=0.03). Additionally, those receiving C/T had better overall clinical outcomes, with an adjusted DOOR probability of having an improved outcome of 67% (95% CI 53%–80%) compared to those receiving polymyxins (Figure 1). Partial credit analyses indicated consistent results across different patient values of survival with adverse events (Figure 2). Figure 1: Inverse probability of treatment weighting-adjusted desirability of outcome ranking (DOOR) distributions by treatment group, accounting for adverse events and survival status that occurred up to 30 days after CRPA culture. 1. Percentages are adjusted using inverse probability of treatment weighting, controlling for culture source and need for dialysis at baseline 2. Adverse events measured included: acute kidney injury, discharge to higher acuity location than previous residence, or being hospitalized 30 days after cultureFigure 2: Inverse probability of treatment weighting-adjusted partial credit analysis. This displays the difference (ceftolozane/tazobactam minus polymyxin) in mean partial credit scores (black line) and associated 95% confidence bands (gray lines) as a function of the partial credit score assigned to an individual having at least one adverse event (range 0 – 100%). A score of 100% is assigned to patients alive with no adverse events and a score of 0% is assigned to patients who die. A difference in mean partial credit scores of approximately zero suggests there was no difference observed between treatment groups.ConclusionThese findings support the recent Infectious Diseases Society of America guidance favoring C/T over polymyxins for treatment of CRPA infections.Disclosures David van Duin, MD, PhD, Entasis (Advisor or Review Panel member)genentech (Advisor or Review Panel member)Karius (Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Pfizer (Consultant, Advisor or Review Panel member)Qpex (Advisor or Review Panel member)Shionogi (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)Utility (Advisor or Review Panel member) Scott R. Evans, PhD, Abbvie (Consultant)Advantagene (Consultant)Alexion (Consultant)Amgen (Consultant)AstraZeneca (Consultant)Atricure (Consultant)Breast International Group (Consultant)Cardinal Health (Consultant)Clover (Consultant)FHI Clinical (Consultant)Genentech (Consultant)Gilead (Consultant)Horizon (Consultant)International Drug Development Institute (Consultant)Lung Biotech (Consultant)Microbiotix (Consultant)Neovasc (Consultant)Nobel Pharma (Consultant)Novartis (Consultant)Nuvelution (Consultant)Pfizer (Consultant)Rakuten (Consultant)Roche (Consultant)Roivant (Consultant)SAB Biopharm (Consultant)Shire (Consultant)Stryker (Consultant)SVB Leerink (Consultant)Takeda (Consultant)Teva (Consultant)Tracon (Consultant)Vir (Consultant)

Population-Based Surveillance of Pneumococcal Infections in Children with Sickle Cell Disease before and after Prevnar 7® and Prevnar 13® Licensure: Implications for Expanded Vaccination

Before prophylactic antibiotic use, approximately 1/10 children <5 years old with sickle cell disease (SCD) developed invasive pneumococcal disease (IPD) with a high risk of meningitis and death. Although the emergence of penicillin-resistance in IPD threatened benefits of penicillin prophylaxis, after licensure of the 7-valent pneumococcal polysaccharide vaccine (PCV7) in 2000, IPD rates in children with SCD decreased by over 2/3. In 2010, PCV13 (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 19A, 19F, 18C, 23F) was licensed in children, and in 2021, two additional conjugated vaccines were approved for use in adults: PCV15 (VAXNEUVANCE®, PCV13+: 22F, 33F) and PCV20 (PREVNAR20®, PCV13+: 8, 10A, 11A, 12F, 15B, 22F, 33F). IPD rates in children with SCD over 24 years in Atlanta were evaluated to describe trends in age of infection, frequency of antibiotic resistance, non-vaccine IPD serotype distribution after vaccine licensures, and estimates for serotype coverage by newer vaccines. IPD among children with SCD, ages 0 to 4 years and 5 to 9 years, residing in the Metropolitan area of Atlanta, Georgia, USA, from 1/1/1994 through 7/31/2018, were compared to the general population. The Centers for Disease Control and Prevention (CDC)-funded Georgia Emerging Infections Program (GA EIP) Active Bacterial Core Surveillance network included initially 8 counties in 1994 and from 1997 onward, 20 counties (total populations of approximately 3.8 and 5.1 million, respectively). Two registries of patients with SCD seen at least once at one of 3 pediatric hospitals serving the region were merged and matched with GA EIP data. The serotyping and antibiotic susceptibility testing were conducted at the CDC. The study was approved by the Emory University Institutional Review Board. Data from 3 periods: pre PCV period (94-99), PCV7 period (00-09) and PCV13 period (10-18) were analyzed. Compared to the pre PCV period, overall, IPD rates decreased in children with SCD vs 91% in the RP for 0-4 years; and 80% in children with SCD vs 78% in the RP for 5-9 years (table1). The difference in IPD rates between patients with SCD and the general population increased over time: pre PCV period, relative risk (RR)=24.22 (95 % Confidence Interval [CI] 17.43,32.88), P<.001; PCV 7 period, RR=32.17 (95 %CI 22.17,45.37), P<.001; PCV 13 period, RR=39.18 (95 %CI 22.35,64.69) P<.001. Meningitis and deaths from IPD decreased significantly in all populations examined but remained significantly higher in patients with SCD compared to RP (table 2). The mean age at IPD diagnosis for the 3 periods examined increased both in SCD and in the RP. For those with SCD (n=50), pre-PCV7 period mean age was :2.7 standard deviation (+/-) 2.3 years; for the PCV 13 period: n=19; 3.7 years +/-2.2 years p= 0.0877; for the RP: Pre-PCV period: n=1025; 1.3 +/-1.6 years; PCV 13 period: n=213; 2.2 +/-2.3 years. Overall absolute IPD rates declined for all age groups examined (table 1). Prior to PCV7 licensure, IPD in patients with SCD were significantly less likely to be penicillin susceptible (MIC <0.06 µg/mL) compared to the RP: 41.9% (18/43) vs 60.0% (476/793) RR=0.70 (95% CI 0.49,1.00), p=0.025. This difference was no longer present after PCV licensure (PCV 13 period , SCD 52.9% [9/17], vs RP 48.6% [70/144]). Non PCV serotypes IPD rates increased after PCV7 licensure but remained stable after PCV13 licensure; 16% of non PCV13 serotypes during all time periods are included in PCV15, whereas PCV20 may cover between 29% and 50% depending on related serotypes cross protection (table3). Although significantly less frequent compared with pre-PCV-era, IPD can be severe in patients with SCD. Increase in IPD age was seen in both SCD and RP. Lower rates of penicillin non-susceptibility may may reflect lower exposure to penicillin prophylaxis. Newer vaccines may offer expanded coverage for children with SCD. Ongoing surveillance will help determine their effect. Vaccines that cover all serotypes are needed. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Mortality in patients with carbapenem-resistant Pseudomonas aeruginosa with and without susceptibility to traditional antipseudomonal β-lactams.

BackgroundCarbapenem-resistant Pseudomonas aeruginosa (CRPA) isolates can frequently retain susceptibility to traditional antipseudomonal β-lactams including cefepime, ceftazidime and piperacillin/tazobactam.ObjectivesThis observational study aimed to determine the proportion of CRPA isolates that were susceptible to all tested other traditional antipseudomonal β-lactams (S-CRPA) and assess whether patients with S-CRPA had improved 30 day mortality compared with patients with NS-CRPA (non-susceptible to cefepime, ceftazidime or piperacillin/tazobactam).MethodsPatients with CRPA isolated from normally sterile sites, urine, lower respiratory tracts and wounds were identified using active population- and laboratory-based surveillance through the Georgia Emerging Infections Program from August 2016 to July 2018 in Atlanta, GA, USA. Only unique patients who were hospitalized at the time of, or within 1 week of, culture were included. We excluded patients with cystic fibrosis. Multivariable logistic regression estimated the association between S-CRPA and 30 day mortality.ResultsAmong 635 adults hospitalized with CRPA, 219 (34%) had S-CRPA. Patients with S-CRPA were more likely to be white (50% versus 38%, P = 0.01) and live in a private residence prior to culture (44% versus 28%, P < 0.01), and less likely to have required ICU care within the prior week (23% versus 36%, P < 0.01) compared with patients with NS-CRPA. Compared with those with NS-CRPA, patients with S-CRPA had an increased 30 day mortality (18% versus 15%, adjusted OR 1.9; 95% CI 1.2–3.1).ConclusionsS-CRPA was associated with higher 30 day mortality than NS-CRPA in hospitalized patients. The reason for this observed increase in mortality deserves further investigation.

912. Beyond the Usual Suspects in Invasive Mold Infections: Public Health Surveillance Identifies Clinical Diversity

BackgroundInvasive mold infections (IMI) such as aspergillosis and mucormycosis are often fatal among immunocompromised patients and cause high-profile outbreaks. Public health surveillance for IMI is challenging; most epidemiologic studies are limited to transplant and cancer patients at greatest risk of IMI. The established Mycoses Study Group (MSG) case definition is useful for clinical trials but lacks sensitivity. To address these challenges, we created IMI surveillance within the Georgia Emerging Infections Program. Here, we describe cases identified through this system, using both the MSG criteria and a novel, more sensitive surveillance case definition.MethodsTo identify potential IMI cases, we captured 2,363 positive fungal laboratory results, including cultures, histopathology, and galactomannan tests, within a 60-day window at three large Atlanta hospitals during April 2018–March 2019. We excluded yeast and dimorphic fungi, hair and nail specimens, and cystic fibrosis patients. Potential cases underwent chart review and were classified by 2 physicians as proven, probable, or non-case according to MSG criteria. Cases that partially met MSG probable criteria and included antifungal treatment were classified as surveillance cases; definitions were mutually exclusive (Fig 1). ResultsOf 120 potential IMI cases, 46 (38%) met an IMI case definition: 8 proven, 9 probable, and 29 surveillance cases (Fig 2). Of cases, 14 (30%) involved transplant or cancer in the previous year; 8 of these were proven or probable cases. IMI presented primarily as sinusitis among proven cases (50%), and pulmonary infections among probable (56%) and surveillance (45%) cases. Most surveillance cases were caused by Aspergillus spp. (72%) and accounted for all 5 cutaneous IMI (fig 3). Over 80% of cases vs. 10% of non-cases had antifungal treatment. ConclusionOf IMI cases identified, nearly two thirds had evidence of infection but did not meet an MSG case definition. MSG captured over half of transplant and cancer-associated cases, but these were uncommon overall, revealing most IMI lack classical risk factors. A more sensitive surveillance case definition can capture a broader spectrum of IMI patients receiving antifungal treatment to help guide clinical and public health interventions.Disclosures All Authors: No reported disclosures

1425. Impact of Social Determinants on Racial Differences in Carbapenem-Resistant Enterobacteriaceae Incidence, Atlanta, 2012-2018

BackgroundPublic health prioritizes addressing social determinants of health to promote health equity. We hypothesized that social determinants of health, including poverty, are associated with racial disparity in the incidence of carbapenem-resistant Enterobacteriaceae (CRE).MethodsThe Georgia Emerging Infections Program conducted CDC-funded, active population-based CRE surveillance in metropolitan Atlanta (2017 population: 3.9 million) from 2012-2018. CRE cases were defined as Atlanta residents with a urine or normally sterile specimen growing E. coli, Klebsiella spp., or Enterobacter spp. resistant to ≥ 1 carbapenems (excluding ertapenem) and all third generation cephalosporins tested. Poverty, education and insurance levels by census tract of residence were obtained from the US Census Bureau’s 2017 American Community Survey. Race and end-stage renal disease (ESRD) were determined from chart review, and primary care provider (PCP) shortage area was obtained from the Health Resources and Services Administration. Age-adjusted incidence rate ratios were individually calculated using direct age standardization. Covariates were considered for inclusion in a multivariable Poisson regression model for the expected rate of CRE.ResultsAdjusting for age, CRE incidence was three times higher in blacks than whites. Higher CRE incidence was also observed among cases assigned > 40% below poverty level, > 15% below high school education, > 10% uninsured, and in a PCP shortage area (Table 1). CRE incidence was 58 times higher among ESRD cases than non-ESRD cases. In the multivariable model (Figure 1) addition of education, poverty or ESRD (p< 0.001), but not PCP access (p = 0.61) and insurance status (p=0.19), significantly reduced the racial difference in CRE incidence compared to race and age alone. Although controlling for age and either education, poverty level or ESRD reduced CRE among blacks, CRE incidence in blacks remained double that of whites.Figure 1. Comparison of race CRE incidence rate ratio adjusting for age alone (red line) to adjusting for age and individual social determinants (blue bars)” Table 1. Social Determinants Distribution and Age-Adjusted CRE Incidence Rate Ratio (N = 378) ConclusionPoverty level, ESRD and education only partially account for the racial differences seen in CRE incidence. While ESRD suggests a possible biologic component, persistent racial differences indicate the need for targeted public health interventions to address social determinants of health.Disclosures All Authors: No reported disclosures

Evaluating Facility Characteristics and Connectivity Metrics as Predictors of Clostridioides difficile Rates in Nursing Homes, Atlanta, GA

Background: Nursing home (NH) residents are at high risk for Clostridioides difficile infection (CDI) due to older age, frequent antibiotic exposure, and previous healthcare exposure. Incidence of CDI attributed to NHs is not well established, but it is hypothesized to be related to the magnitude of transfers. We evaluated the relationship between NH CDI incidence and facility characteristics to explain variability in rates in Atlanta, Georgia. Methods: Incident C. difficile cases from 2016 to 2018 were identified through the Georgia Emerging Infections Program (funded by the Centers for Disease Control and Prevention), which conducts active population-based surveillance in the 8-county metro Atlanta area. An incident case was defined as an NH resident with a toxin-positive stool specimen (without a positive test within 8 weeks). Sampled (1 to 3 on age and gender) incident cases were attributed to a NH if a patient was an NH resident within 4 days of specimen collection. Facility characteristics (beds, resident days, admissions, and average length of stay [ALOS]) were obtained from NH cost reports, and facility-specific connectivity metrics were calculated (indegree and betweenness) from 2016 Medicare claims data. Case counts were aggregated to estimate yearly incidence and correlated with facility characteristics and location within the healthcare network using the Spearman correlation. A negative binomial model was used to assess residual variability in NH CDI incidence. Results: In total, 386 incident CDI cases were attributed to 64 NHs (range, 0–27). Approximately half (54.7%) resided in the NH at the time of specimen collection; however, 33.7% were in inpatient units (≤4 days of admission), and 10.9% were in an emergency room (ER). The frequency of NH CDI cases correlated strongly with admissions (r = .70; P &lt; .01), inversely with ALOS (r = −0.53; P &lt; .01), and moderately with resident days (r = .38; P &lt; .01). After accounting for admissions, incidence (per 1,000 admissions) still varied (Fig. 1) (median 14; range, 0–34). The inverse association with ALOS decreased and incidence no longer correlated with the remaining facility characteristics or location within the healthcare transfer network (P &gt; .05, all comparisons). However, there was residual correlation with connectivity metrics (indegree r = 0.26; P = .04). Conclusions: Our data suggest that attributing CDI to NHs requires the inclusion of hospital and ER-based specimen collection. NH CDI incidence appears highest among facilities with a low ALOS and a high number of admissions; incidence rates calculated per 1,000 admissions may best account for infection risk inherent early in a resident’s stay. Residual variability attributed to connectivity to the healthcare network was of borderline significance and should be further explored in the NH setting.Funding: NoneDisclosures: Scott Fridkin, consulting fee, vaccine industry (spouse)

The Incidence, Characteristics, and Outcomes of Community and Hospital-Associated S. aureus Disease in Fulton County, Georgia

Background: Due to reliance on hospital discharge data for case identification, the burden of noninvasive and community-acquired S. aureus disease is often underestimated. To determine the full burden of S. aureus infections, we utilized population-based surveillance in a large urban county. Methods: The Georgia Emerging Infections Program (GA EIP) conducted CDC-funded, population-based surveillance by finding cases of S. aureus infections in 8 counties around Atlanta in 2017. Cases were residents with S. aureus isolated from either a normally sterile site in a 30-day period (invasive cases) or another site in a 14-day period (noninvasive cases). Medical records (all invasive and 1:4 sample of noninvasive cases) among Fulton County residents were abstracted for clinical, treatment, and outcome data. Cases treated were mapped to standard therapeutic site codes. Noninvasive specimens were reviewed and attributed to an invasive case if both occurred within 2 weeks. Incidence rates were calculated using 2017 census population and using a weight-adjusted cohort to account for sampling. Results: In total, 1,186 noninvasive (1:4 sample) and 529 invasive cases of S. aureus in Fulton county were reviewed. Only 35 of 1,186 (2.9%) noninvasive cases were temporally linked to invasive cases, resulting in 5,133 cases after extrapolation (529 invasive, 4,604 noninvasive). All invasive cases and 3,776 of 4,604 noninvasive cases (82%) were treated (4,305 total). Treatment was highest in skin (90%) and abscess (97%), lowest in urine (62%) and sputum (60%), and consisted of antibacterial agents alone (65%) or in addition to drainage procedures (35%). Overall, 41% of all cases were hospitalized, 12% required ICU admission, and 2.7% died, almost exclusively with bloodstream and pulmonary infections. Attribution of noninvasive infection was most often outside healthcare settings (87%); only 341 (7.9%) were hospital-onset cases; however, 34% of cases had had healthcare exposure in the preceding year, most often inpatient hospitalization (75%) or recent surgery (35%). Estimated countywide incidence was 414 per 100,000 (130 for MRSA and 284 for MSSA), invasive infection was 50 per 100,000. Among treated cases, 57% were SSTI, and the proportion of cases caused by MRSA was ~33% but varied slightly by therapeutic site (Fig. 1). Conclusions: The incidence of treated S. aureus infection in our large urban county is estimated to be 414 per 100,000 persons, which exceeds previously estimated rates based on hospital discharge data. Only 12% of treated infections were invasive, and &lt;1 in 10 were hospital onset. Also, two-thirds of treated disease cases were MSSA; most were SSTIs.Funding: Proprietary Organization: Pfizer.Disclosures: Scott Fridkin, consulting fee - vaccine industry (spouse).

Racial Differences in Incidence of Staphylococcus aureus Joint Infections in Metropolitan Atlanta, 2016–2018

Background:Staphylococcus aureus is the leading cause of joint infections. These infections may arise in native or prosthetic joints. Previous analysis of population-based surveillance has documented racial differences in incidence of invasive S. aureus bloodstream infections. We hypothesized that racial differences in incidence would not persist among of S. aureus joint infections. Methods: We utilized data from the Georgia Emerging Infections Program (GA EIP), which conducts CDC-funded active, population-based surveillance for iSA within the 8-county area of Atlanta. Cases were defined as residents of the surveillance area with S. aureus isolated during 2016–2018 from joint fluid or tissue, and cultures within a 30-day period after the initial culture date were considered a single case. Age- and race-specific incidence were calculated using US census data; incidence rate ratios (RR) and adjusted rate ratios (aRR) were calculated using the Mantel-Hanzel method. Results: Between 2016 and 2018, 500 iSA joint infections were identified (iMRSA, 28.2% and iMSSA, 71.8%): 34.4% occurred in black patients and 65.6% occurred in white patients. Also, 90 cases (18%) had a bloodstream infection (BSI) within 30 days of the joint infection. Incidence of iSA joint infections dropped 22% from 9.4 per 100,000 in 2016 to 7.5 per 100,000 in 2018 (RR, 0.79; 95% CI, 0.7–0.9). Adjusting for year, incidence was 40% lower among blacks than whites (RR, 0.6,; 95% CI, 0.5–0.7); this finding was attributed to blacks having 60% lower incidence of iMSSA joint infections compared to whites (aRR, 0.4; 95% CI, 0.3–0.5) but similar MRSA incidence (aRR, 1.2; 95% CI, 0.8–1.6). The highest incidence was observed among whites aged &gt;65 years with iMSSA infections (30.2 per 100,000) (Fig. 1). Among cases with a full chart review (n = 138), surgery in the prior 90 days was uncommon (n = 42, 30.4%), and a preceding major orthopedic procedure was even more rare (n = 13, 9.4%). Antecedent therapeutic injections and arthroscopic procedures are under investigation. Conclusions: Unlike S. aureus bacteremia, where previous analysis demonstrates higher incidences among blacks predominantly due to MRSA, our data demonstrate that the incidence of S. aureus joint infections is higher in whites, predominantly due to MSSA. Investigations in differential practices regarding orthopedic illness and injury should be pursued.Funding: NoneDisclosures: Scott Fridkin reports that his spouse receives consulting fees from the vaccine industry.

Are Patients Preferentially Receiving Oral Vancomycin for Clostridioides difficile Infection in 2018? A Population Perspective

Background: Historically, metronidazole was first-line therapy for Clostridioides difficile infection (CDI). In February 2018, the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) updated clinical practice guidelines for CDI. The new guidelines recommend oral vancomycin or fidaxomicin for treatment of initial episode of CDI in adults. We examined the changes in treatment of CDI during 2018 across all types of healthcare settings in metropolitan Atlanta. Methods: Cases were identified through the Georgia Emerging Infections program (funded by the Centers for Disease Control and Prevention), which conducts active population-based surveillance in an 8-county area including Atlanta, Georgia (population, 4,126,399). An incident case was a resident of the catchment area with a positive C. difficile toxin test and no additional positive test in the previous 8 weeks. Recurrent CDI was defined as &gt;1 incident CDI episode in 1 year. Clinical and treatment data were abstracted on a random 33% sample of adult (&gt;17 years) cases. Definitive treatment categories were defined as the single antibiotic agent, metronidazole or vancomycin, used to complete a course. We examined the effect of time of infection, location of treatment, and number of CDI episodes on the use of metronidazole only. Results: We analyzed treatment information for 831 adult sampled cases. Overall, cases were treated at 29 hospitals (568 cases), 4 nursing homes (6 cases), and 101 outpatient providers (257 cases). The mean age was 60 (IQR, 34–86), and 111 (13.4%) had recurrent infection. Moreover, ∼28% of first-incident CDI episodes, 8% of second episodes, and 6% of third episodes were treated with metronidazole only. Compared to facility-based providers, outpatient providers were more likely to treat initial CDI episodes with metronidazole only (44% vs 21%; relative risk [RR], 2.1; 95% CI, 1.7–2.7). Treatment changed over time from 56% metronidazole only in January to 10% in December (Fig. 1). First-incident cases in the first quarter of 2018 were more likely to be treated with metronidazole only compared to those in the fourth quarter (RR, 2.76; 95% CI, 1.91–3.97). Conclusions: Preferential use of vancomycin for initial CDI episodes increased throughout 2018 but remained &lt;100%. CDI episodes treated in the outpatient setting and nonrecurrent episodes were more likely to be treated with metronidazole only. Additional studies on persistent barriers to prescribing oral vancomycin, such as cost, are warranted.Funding: NoneDisclosures: Scott Fridkin reports that his spouse receives a consulting fee from the vaccine industry.

Carbapenem-Resistant Enterobacteriaceae Resistant Only to Ertapenem: An Epidemiologically Distinct Cohort, Atlanta, 2016–2018

Background: Carbapenem-resistant Enterobacteriaceae (CRE), particularly carbapenemase-producing (CP) CRE, pose a major public health threat. In 2016, the phenotypic definition of CRE expanded to include ertapenem resistance to improve sensitivity for detecting CP-CRE. We compared characteristics of CRE resistant to ertapenem only (CRE-EO) to CRE resistant to ≥1 other carbapenem (CRE-O). Methods: The Georgia Emerging Infections Program performs active, population-based CRE surveillance in metropolitan Atlanta. CRE cases were defined as any Escherichia coli, Klebsiella pneumoniae, K. oxytoca, K. variicola, Enterobacter cloacae complex, or Enterobacter aerogenes resistant to ≥1 carbapenem by the clinical laboratory and isolated from urine or a sterile site between 2016 and 2018. Data were extracted from retrospective chart review and 90-day mortality from Georgia vital statistics for 2016–2017. Polymerase chain reaction (PCR) for carbapenemase genes was performed on a convenience sample of isolates by the CDC or Georgia Public Health Laboratory. We compared characteristics of CRE-EO cases to CRE-O cases using χ2 tests or t tests. Results: Among 927 CRE isolates, 553 (60%) were CRE-EO. CRE-EO were less frequently isolated from blood (5% vs 12%; P &lt; .01) and less commonly K. pneumoniae (21% vs 58%; P &lt; .01) than CRE-O. CRE-EO cases were more often women (65% vs 50%; P &lt; .01), had a lower Charlson comorbidity index (mean ± SD, 2.4±2.3 vs 3.0±2.6; P &lt; .01), and were less commonly at a long-term care facility (24% vs 31%) or hospital (15% vs 21%; P &lt; .01) in the 4 days prior to the CRE culture. CRE-EO were more susceptible to all antibiotics tested at the clinical laboratory (P &lt; .01) except for tigecycline (P = 1.0) (Table 1). Of the 300 (32%) isolates tested for carbapenemase genes, 98 (33%) were positive (7% CRE-EO vs 62% CRE-O; P &lt; .01). Of the CP isolates, we identified blaKPC in 93 cases (95%), blaNDM in 3 cases (3%), blaOXA-48-like in 2 cases (2%). CRE-EO cases had lower 90-day mortality (13% vs 21%; P &lt; .01). Conclusions: CRE-EO are epidemiologically distinct from CRE-O and are less likely to harbor carbapenemase genes. CRE-EO may require less intensive infection prevention interventions and have more therapeutic options.Funding: NoneDisclosures: None

Reductions in Positive Clostridioides difficile Events Reportable to NHSN With Adoption of Reflex EIA Testing in 13 Atlanta Hospitals

Background: US hospitals are required to report C. difficile infections (CDIs) to the NHSN as a performance measure tied to payment penalties for poor scores. Currently, only the charted CDI test results performed last in reflex testing scenarios are reported to the NHSN (CDI events). We describe the reduction in NHSN CDI events from the addition of a reflex toxin enzyme immunoassay (EIA) after a positive nucleic acid amplification test (NAAT) in teaching and nonteaching hospitals, and we estimate the impact on standardized infection ratios (SIR). Methods: Reporting of all CDI test results, by test method, occurred during April 2018–July 2019 to the Georgia Emerging Infections program (funded by the Centers for Disease Control and Prevention), which conducts active population-based surveillance in an 8-county Atlanta area (population, 4 million). Among facilities starting reflex EIA testing, results were aggregated by test method during months of reflex testing to calculate facility-specific reduction in NHSN CDI events (% reduction; 1-[no. EIA+/no. NAAT+]). Differences in percent reduction between facilities by characteristic were compared using the Kruskal-Wallis test. We simulated expected changes in the SIR for a range of reductions, assuming equal effect on both community-onset (CO) and hospital-onset (HO) tests. Each facility’s historical NHSN CDI events prior to reflex testing were used to estimate changes to facility-specific SIRs by reducing values by the corresponding facility’s percent reduction. Results: Overall, 13 acute-care hospitals (bed size, 52–633; ICU bed size, 6–105) started reflex testing during the study period (mean, 7 months, 15,800 admissions, 66,400 patient days), resulting in 550 +NAAT tests reflexing to 180 +EIA tests (pooled mean 58% reduction). Percent reduction varied (mean, 67%; range, 42%–81%) but did not differ between larger (≥217 beds) and smaller hospitals (61 vs 50% reduction; P &gt; .05) or by outsourced versus inhouse testing (65% vs 54% reduction; P &gt; .05). Simulations identified a threshold reduction at which point effect on HO counteract the effects on CO events enough to reduce the SIR; thresholds for nonteaching and teaching were 26% and 32% reduction, respectively (Fig. 1). The estimated reductions in facility-specific SIRs using measured percent reductions on historic NHSN CDI events closely paralleled the simulation, and the mean estimated change in SIR was −46% (range, −12% to −71%) (Fig. 1). Conclusions: Although the magnitude of the effect varied, all 13 facilities experienced dramatic reductions in CDI events reportable to NHSN due to reflex testing; applying these reductions to historical NHSN data illustrates anticipated reductions in their facility-specific SIRs due to this testing change.Funding: NoneDisclosures: Scott Fridkin, consulting fee, vaccine industry (various) (spouse)

Molecular Epidemiology and Outcomes of Patients with Carbapenem-Resistant Enterobacteriaceae Bacteriuria, Atlanta 2012–2015

Background: Carbapenem-resistant Enterobacteriaceae (CRE) represent a significant antibiotic resistance threat, in part because carbapenemase genes can spread on mobile genetic elements. Here, we describe the molecular epidemiology and outcomes of patients with CRE bacteriuria from the same city in a nonoutbreak setting. Methods: The Georgia Emerging Infections Program performs active, population-based CRE surveillance in Atlanta. We studied a cohort of patients with CRE (resistant to all tested third-generation cephalosporins and ≥1 carbapenem, excluding ertapenem) first identified in urine, and not in a prior or simultaneous sterile site, between 2012 and 2015. Whole-genome sequencing (WGS) was performed on a convenience sample. We obtained epidemiologic and outcome data through chart review and Georgia Vital Statistics records (90-day mortality). Using WGS, we created a core-genome alignment-based phylogenetic tree of the Klebsiella pneumoniae isolates and calculated the SNP difference between each sample. Using SAS version 9.4 software, we performed the Fisher exact test and univariable odds ratios (OR) with 95% CI to compare patient isolates with and without a carbapenemase gene. Results: Among 81 patients included, the median age was 68 (IQR, 57–74) years, and most were female (58%), black (60%), and resided in a long-term care facility 4 days prior to culture isolation (53%). Organisms isolated were K. pneumoniae (84%), Escherichia coli (7%), Enterobacter cloacae (7%), and Klebsiella oxytoca (1%). WGS identified at least 1 β-lactamase gene in 91% of the isolates; 85% contained a carbapenemase gene, the most frequent of which was blaKPC-3 (94%). Patients with CRE containing a carbapenemase gene were more likely to be black (OR, 3.7; 95% CI, 1.0–13.8) and to have K. pneumoniae (OR, 8.9; 95% CI, 2.2–35.0). Using a core-genome alignment of 3,708 genes (~63% of the complete genome), we identified a median of 67 (IQR, 23–3,881) SNP differences between each K. pneumoniae isolate. A phylogenetic tree identified clustering around carbapenemase gene and multilocus sequence type (84% were ST 258) but not based on referring laboratory or county of residence (Fig. 1). Although 7% of patients developed an invasive CRE infection within 1 year and 21% died within 90 days, having a carbapenemase gene was not associated with these outcomes. Conclusions: Molecular sequencing of a convenience sample of CRE bacteriuria support K. pneumoniae ST258 harboring blaKPC-3 being distributed throughout the Atlanta area, across the healthcare continuum. Overall mortality was high in this population, but the presence of carbapenemase genes was not associated with worse outcomes.Funding: NoneDisclosures: NoneDisclosures: NoneFunding: None

1714. Testing a Novel Clinical Surveillance Case Definition for Invasive Mold Infections

BackgroundInvasive mold infections (IMI) such as aspergillosis and mucormycosis are often fatal among immunosuppressed patients and have caused high-profile outbreaks. Surveillance for IMI is challenging because distinguishing a case from colonization or contamination is complex. The established case definition, Mycoses Study Group (MSG) criteria, lacks sensitivity. Because the need for surveillance remains, we designed a pilot IMI surveillance system within the Georgia Emerging Infections Program. Here, we describe cases identified through this system, using both the MSG criteria and a novel, more sensitive clinical case definition.MethodsTo identify potential IMI cases, we captured fungal cultures positive for mold, histopathology specimens with evidence of fungal tissue invasion, and positive galactomannan results within a 60-day window at three large hospitals in Atlanta during March 2017–2018. We excluded dimorphic fungi and hair and nail specimens. Of 194 potential cases, we selected 24 for complete medical chart review. Two physicians classified cases as proven, probable, or non-case according to MSG criteria. Cases that partially met MSG probable criteria and included antifungal treatment were classified as clinical cases; definitions were mutually exclusive (Figure 1).ResultsOf 24 potential IMI cases, 16 (66%) met an IMI case definition, including 5 proven, 2 probable and 9 clinical cases. Inter-rater agreement was 92%., Most (5/7) MSG cases involved Aspergillus and were more likely to have cancer, a transplant, or other immunosuppression compared with clinical cases (Figure 2 and 3). Clinical cases included conditions not specified in MSG criteria, including burns (1), wounds (1) or eye (4) infections. MSG and clinical cases more often had antifungal treatment (16/16 vs. 1/8) or died (4/16 vs. 0/8) compared with non-cases.ConclusionIn this preliminary analysis of potential IMI cases, most represented true invasive infections, indicating effective exclusion of most colonization. Most of the 16 cases were classified as clinical, however, and would have been missed in a system relying on the MSG criteria alone. Results suggest that a less-specific clinical case definition incorporating antifungal treatment may improve the sensitivity and utility of IMI surveillance. Disclosures All authors: No reported disclosures.