Distinctive features of ertapenem mono-resistant carbapenem-resistant Enterobacterales in the United States: A cohort study

Background Carbapenem-resistant Enterobacterales (CRE) are highly antibiotic-resistant bacteria. Whether CRE resistant only to ertapenem among carbapenems (ertapenem “mono-resistant”) represent a unique CRE subset with regards to risk factors, carbapenemase genes, and outcomes is unknown. Methods We analyzed surveillance data from nine CDC Emerging Infections Program (EIP) sites. A case was the first isolation of a carbapenem-resistant Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, K. oxytoca, K. pneumoniae, or K. variicola from a normally sterile site or urine in an EIP catchment area resident in 2016-2017. We compared risk factors, carbapenemase genes, antibiotic susceptibility, and mortality of ertapenem “mono-resistant” cases to “other” CRE cases (resistant to ≥1 carbapenem other than ertapenem), and analyzed risk factors for mortality. Results Of 2009 cases, 1249 (62.2%) were ertapenem mono-resistant and 760 (37.8%) were other CRE. Ertapenem mono-resistant CRE cases were more frequently ≥80 years old (29.1% vs. 19.5%, p<0.0001) and female (67.9% vs 59.0%, p<0.0001). Ertapenem mono-resistant isolates were more likely to be Enterobacter cloacae complex (48.4% vs. 15.4%, p<0.0001) but less likely to be isolated from a normally sterile site (7.1% vs. 11.7%, p<0.01) or have a carbapenemase gene (2.4% vs. 47.4%, p<0.0001). Ertapenem mono-resistance was not associated with 90-day mortality in logistic regression models. Carbapenemase-positive isolates were associated with mortality (odds ratio 1.93, 95% confidence interval 1.30-2.86). Conclusions Ertapenem mono-resistant CRE rarely have carbapenemase genes and have distinct clinical and microbiologic characteristics from other CRE. These findings may inform antibiotic choice and infection prevention practices, particularly when carbapenemase testing is not available.

943. Epidemiology of Actinomycosis in a Tertiary Care Cancer Center

Background Actinomyces are human commensals with significant pathogenic potential. The aim of this study was to determine the epidemiology of Actinomycosis in a tertiary care cancer center and identify species most commonly associated with invasive disease. Methods We retrospectively reviewed all patients referred to our institution with suspected or documented solid or hematological malignancies and positive cultures for Actinomyces species from July 2007 to June 2020 (13 years). Species identification was performed by VITEK® automated system (bioMerieux Inc.). Probable invasive actinomycosis was defined as cases with consistent clinical presentation, suggestive radiographic findings, and a positive culture from a nonsterile site, but lack of histopathological confirmation. Proven invasive actinomycosis was defined as the presence of consistent clinical symptoms, suggestive radiographic findings, a positive culture and histopathological confirmation, or cultures from sterile site without histopathological confirmation. Contaminants were considered positive cultures from sterile or non-sterile site without evidence of disease. Results Of 233 cases with positive cultures 194 (83.3%) were considered contaminants and 39 (16.7%) diagnostic of invasive actinomycosis. Of 39 cases of invasive actinomycosis, 64% were documented in patients with solid tumors, 13% in hematological malignancy and 23% among individuals without proven malignancy, 25 (64%) were probable and 14 (36%) proven. Of patients with proven/probable actinomycosis 27 (69%) had polymicrobial growth. Abdominopelvic was the most frequent site of invasive actinomycosis. A. odontolyticus was the most common species isolated (41%) followed by A. meyeri (28%) in patients with invasive disease, and A. odontolyticus (42%) among contaminants. Conclusion The majority of positive cultures for Actinomyces species were considered contaminants. In our cohort Invasive actinomycosis affected mainly patients with solid tumors. Abdominopelvic was the most common site of invasive disease. Species most commonly associated with invasive actinomycosis were A. odontolyticus followed by A. meyeri with A. israelii isolated less frequently. Disclosures All Authors: No reported disclosures

177. Distinctive Features of Ertapenem Mono-Resistant Carbapenem-Resistant Enterobacterales in the United States: A Cohort Study

Background Carbapenem-resistant Enterobacterales (CRE) are highly antibiotic-resistant bacteria. Whether CRE resistant only to ertapenem among carbapenems (ertapenem mono-resistant) represent a unique CRE subset with regards to risk factors, carbapenemase genes, and outcomes is unknown. Methods We analyzed laboratory- and population-based surveillance data from nine sites participating in CDC’s Emerging Infections Program (EIP). We defined an incident case as the first isolation of Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, K. oxytoca, K. pneumoniae, or K. variicola resistant to doripenem, ertapenem, imipenem, or meropenem (determined at clinical laboratory) from a normally sterile site or urine identified from a resident of the EIP catchment area in 2016-2017. We compared risk factors, carbapenemase genes (determined via polymerase chain reaction at CDC), and mortality of cases with ertapenem “mono-resistant” to “other” CRE (resistant to ≥ 1 carbapenem other than ertapenem). We additionally conducted survival analysis to determine the effect of ertapenem mono-resistant status and isolate source (sterile vs. urine) on survival. Results Of 2009 cases, 1249 (62.2%) were ertapenem mono-resistant and 760 (37.8%) were other CRE (Figure 1). Ertapenem mono-resistant CRE cases were more frequently ≥ 80 years old (29.1% vs. 19.5%, p< 0.0001), female (67.9% vs 59.0%, p< 0.0001), and white (62.6% vs. 45.1%, p< 0.0001). Ertapenem mono-resistant isolates were more likely than other CRE to be Enterobacter cloacae complex (48.4% vs. 15.4%, p< 0.0001) but less likely to be isolated from a normally sterile site (7.1% vs. 11.7%, p< 0.01) or have a carbapenemase gene (2.4% vs. 47.4%, p< 0.0001) (Figure 2). Ertapenem mono-resistance was not associated with difference in 90-day mortality (unadjusted odds ratio [OR] 0.82, 95% confidence interval [CI] 0.63-1.06) in logistic models or survival analysis (Figure 3). Figure 1. Flow diagram of carbapenem-resistant Enterobacterales cases included in analysis, 2017-2018. CRE, carbapenem-resistant Enterobacterales; MIC, minimum inhibitory concentration. Ertapenem mono-resistant CRE are only resistant to ertapenem (among carbapenems). Other CRE are resistant to ≥1 carbapenem other than ertapenem. We excluded isolates that (1) had no interpretable MICs for any carbapenem, (2) were only tested against ertapenem, (3) had unknown death status, or (4) were not associated with patient’s first incident case. Figure 2. Proportion of ertapenem mono-resistant carbapenem-resistant Enterobacterales (CRE) vs. other CRE isolates with specific carbapenemase genes. KPC, Klebsiella pneumoniae carbapenemase; NDM, New Delhi metallo-ß-lactamase; OXA, oxacillinase. Ertapenem mono-resistant carbapenem-resistant Enterobacterales (CRE) are only resistant to ertapenem (among carbapenems). Other CRE are resistant to ≥1 carbapenem other than ertapenem. Testing via reverse transcriptase polymerase chain reaction. Figure 3. Survival analysis comparing patients with carbapenem-resistant Enterobacterales (CRE) that are ertapenem mono-resistant to other CRE (i.e., resistant to ≥1 carbapenem other than ertapenem), either total (A) or stratified by isolate site (B). Ertapenem mono-resistant) isolates were not associated with decreased mortality, and sterile isolate source (i.e., non-urinary isolates) was associated with increased mortality regardless of ertapenem mono-resistance. Conclusion Ertapenem mono-resistant CRE rarely have carbapenemase genes and have distinct clinical and microbiologic characteristics compared to other CRE. These findings may inform antibiotic choice particularly when testing for carbapenemases is not readily available. Disclosures All Authors: No reported disclosures

Performances of automated digital imaging of Gram-stained slides with on-screen reading against manual microscopy

The objective of this study was to evaluate the performances of the automated digital imaging of Gram-stained slides against manual microscopy. Four hundred forty-three identified Gram-stained slides were included in this study. When both methods agreed, we considered the results as correct, and no further examination was carried out. Whenever the methods gave discrepant results, we reviewed the digital images and the glass slides by manual microscopy to avoid incorrectly read smears. The final result was a consensus of multiple independent reader interpretations. Among the 443 slides analyzed in this study, 101 (22.8%) showed discrepant results between the compared methods. The rates of discrepant results according to the specimen types were 5.7% (9/157) for positive blood cultures, 42% (60/142) for respiratory tract specimens, and 22% (32/144) for sterile site specimens. After a subsequent review of the discrepant slides, the final rate of discrepancies dropped to 7.0% (31/443). The overall agreement between the compared methods and the culture results reached 78% (345/443) and 79% (349/443) for manual microscopy and automated digital imaging, respectively. According to culture results, the specificity for automated digital imaging and manual microscopy were 90.8% and 87.7% respectively. In contrast, sensitivity was 84.1% for the two compared methods. The discrepant results were mostly encountered with microorganism morphologies of rare occurrence. The results reported in this study emphasize that on-screen reading is challenging, since the recognition of morphologies on-screen can appear different as compared to routine manual microscopy. Monitoring of Gram stain errors, which is facilitated by automated digital imaging, remains crucial for the quality control of reported Gram stain results.

Subcutaneous abscess caused by Streptococcus pneumoniae serotype 28F in an infant: a case report

Background Invasive pneumococcal disease (IPD) is defined by the detection of Streptococcus pneumoniae on culture from samples obtained from a normally sterile site. Pneumococcal conjugate vaccines (PCV) have been developed for the prevention of IPD that is caused by highly virulent serotypes. Despite the effective reduction of IPD caused by vaccine serotypes after the introduction of PCV, there has been a rapid increase in the incidence of IPD caused by non-vaccine serotypes, and serotype replacement has become a global issue. Case presentation We report a previously healthy 4-month-old girl presenting with a large subcutaneous abscess caused by S. pneumoniae, identified as non-vaccine serotype 28F. The patient had received routine vaccination, including PCV vaccination. After the incision and drainage of the subcutaneous abscess, the patient was treated with antibiotics. She was discharged on Day 7 of hospitalization without any residual sequelae. Conclusions Subcutaneous abscess is a common pediatric skin and soft tissue infection, whereas pneumococcal subcutaneous abscesses are quite rare. As the pneumococcal serotype 28F caused a subcutaneous abscess, this serotype possibly has a high virulence. The incidence of IPD caused by non-vaccine serotypes, such as 28F, is expected to increase in the future. The consolidation of international data on pneumococcal serotypes is important for the development of novel PCV.

Meningococcal Surveillance Australia Reporting period 1 April to 30 June 2020

The reference laboratories of the National Neisseria Network, Australia report laboratory data on invasive meningococcal disease (IMD) cases confirmed by laboratory testing using culture- and non-culture-based techniques for the Australian Meningococcal Surveillance Programme. Culture-positive cases, where Neisseria meningitidis is grown from a normally sterile site or skin lesions, and non-culture-based diagnoses (nucleic acid amplification testing), are defined as IMD by the Public Health Laboratory Network definitions. Data contained in quarterly reports are restricted to a description of the numbers of cases by jurisdiction and serogroup, where known. Some minor corrections to data in Table 1 may be made in subsequent reports if additional data are received. A full analysis of laboratory-confirmed cases of IMD in each calendar year is contained in the AMSP annual report published in Communicable Diseases Intelligence.

Characteristics Associated with Death in Patients with Carbapenem-Resistant Acinetobacter baumannii, United States, 2012–2017

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is an important cause of healthcare-associated infections with limited treatment options and high mortality. To describe risk factors for mortality, we evaluated characteristics associated with 30-day mortality in patients with CRAB identified through the Emerging Infections Program (EIP). Methods: From January 2012 through December 2017, 8 EIP sites (CO, GA, MD, MN, NM, NY, OR, TN) participated in active, laboratory-, and population-based surveillance for CRAB. An incident case was defined as patient’s first isolation in a 30-day period of A. baumannii complex from sterile sites or urine with resistance to ≥1 carbapenem (excluding ertapenem). Medical records were abstracted. Patients were matched to state vital records to assess mortality within 30 days of incident culture collection. We developed 2 multivariable logistic regression models (1 for sterile site cases and 1 for urine cases) to evaluate characteristics associated with 30-day mortality. Results: We identified 744 patients contributing 863 cases, of which 185 of 863 cases (21.4%) died within 30 days of culture, including 113 of 257 cases (44.0%) isolated from a sterile site and 72 of 606 cases (11.9%) isolated from urine. Among 628 hospitalized cases, death occurred in 159 cases (25.3%). Among hospitalized fatal cases, death occurred after hospital discharge in 27 of 57 urine cases (47.4%) and 21 of 102 cases from sterile sites (20.6%). Among sterile site cases, female sex, intensive care unit (ICU) stay after culture, location in a healthcare facility, including a long-term care facility (LTCF), 3 days before culture, and diagnosis of septic shock were associated with increased odds of death in the model (Fig. 1). In urine cases, age 40–54 or ≥75 years, ICU stay after culture, presence of an indwelling device other than a urinary catheter or central line (eg, endotracheal tube), location in a LTCF 3 days before culture, diagnosis of septic shock, and Charlson comorbidity score ≥3 were associated with increased odds of mortality (Fig. 2). Conclusion: Overall 30-day mortality was high among patients with CRAB, including patients with CRAB isolated from urine. A substantial fraction of mortality occurred after discharge, especially among patients with urine cases. Although there were some differences in characteristics associated with mortality in patients with CRAB isolated from sterile sites versus urine, LTCF exposure and severe illness were associated with mortality in both patient groups. CRAB was associated with major mortality in these patients with evidence of healthcare experience and complex illness. More work is needed to determine whether prevention of CRAB infections would improve outcomes.Funding: NoneDisclosures: None

Characterization of Ceftazidime-Avibactam-Resistant Carbapenem-Resistant Enterobacteriaceae, United States, 2015–2017

Background: Carbapenem-resistant Enterobacteriaceae (CRE) are a major public health problem. Ceftazidime-avibactam (CZA) is a treatment option for CRE approved in 2015; however, it does not have activity against isolates with metallo-β-lactamases (MBLs). Emerging resistance to CZA is a cause for concern. Our objective was to describe the microbiologic and epidemiologic characteristics of CZA-resistant (CZA-R) CRE. Methods: From 2015 to 2017, 9 states participated in laboratory- and population-based surveillance for carbapenem-resistant Escherichia coli, Klebsiella pneumoniae, K. oxytoca, K. aerogenes, and Enterobacter cloacae complex isolates from a normally sterile site or urine. A convenience sample of isolates from this surveillance were sent to the CDC for antimicrobial susceptibility testing (AST) using reference broth microdilution (BMD) including an MBL screen, species confirmation with MALDI-TOF, and real-time PCR to detect blaKPC, blaNDM, and blaOXA-48–like genes. Additional AST by BMD was performed on CZA-R isolates using meropenem-vaborbactam (MEV), imipenem-relebactam (IMR), plazomicin (PLZ), and eravacycline (ERV). Epidemiologic data were obtained from a medical record review. Community-associated cases were defined as having no healthcare exposures in the year prior to culture, no devices in place 2 days prior to culture, and culture collected before calendar day 3 after hospital admission. Data were analyzed in 3 groups: CRE that were CZA-susceptible (CZA-S), CZA-R that were due to blaNDM, and CZA-R without blaNDM. Results: Among 606 confirmed CRE tested with CZA, 33 (5.4%) were CZA-R. Of the CZA-R isolates, 16 (48.5%) harbored a blaNDM gene, of which 2 coharbored blaNDM and blaOXA-48-like genes; 9 (27.3%) harbored only a blaKPC gene. Of the 17 CZA-R isolates without blaNDM, all were MBL screen negative. CZA-R due to blaNDM were more frequently community-associated (43.8%) than CZA-S or CZA-R without blaNDM (11.0% and 5.9%, respectively); a higher percentage of CZA-R cases due to blaNDM also had recent international travel (25%) compared to the other groups (1.8% and 5.9%, respectively). CZA-R without blaNDM were more susceptible to MEV (76%), IMR (71%), PLZ (88%), and ERV (65%) compared to CZA-R due to blaNDM (19%, 6%, 56%, and 44%, respectively). Conclusions: The emergence of CZA-R isolates without blaNDM are concerning; however, these isolates are more susceptible to newer antimicrobials than those with blaNDM. In addition to high rates of resistance to newer antimicrobials, isolates with blaNDM are more frequently community-associated than other CRE. This underscores the need for more aggressive measures to stop the spread of CRE.Funding: NoneDisclosures: None

Carbapenem-Resistant Acinetobacter baumannii Incidence Trends Identified Through the Emerging Infections Program, 2012–2018

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a serious threat to patient safety due to limited treatment options and propensity to spread in healthcare settings. Using Emerging Infections Program (EIP) data, we describe changes in CRAB incidence and epidemiology. Methods: During January 2012 to December 2018, 9 sites (Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee) participated in active laboratory- and population-based surveillance. An incident case was defined as the first isolation of A. baumannii complex, in a 30-day period, resistant to ≥1 carbapenem (excluding ertapenem) from a normally sterile site or urine of a surveillance area resident. Cases were considered hospital-onset (HO) if the culture was collected >3 days after hospital admission; all others were community-onset (CO). Cases were classified as device-associated (DA) if the patient had 1 or more medical devices (ie, urinary catheter, central venous catheter (CVC), endotracheal/nasotracheal tube, tracheostomy, or another indwelling device) present in the 2 days prior to culture collection. Temporal trends were estimated using generalized linear models adjusted for age, race, sex, and EIP site. Results: Overall, 984 incident CRAB cases were identified, representing 849 patients. Among these patients, 291 (34%) were women, 510 (61%) were nonwhite, and the median age was 62 years (mean, 59; range, 0–102). Among the cases, 226 (23%) were HO; 758 (77%) were CO; and 793 (81%) were DA. Overall incidence rates in 2012 and 2018 were 1.58 (95% CI, 1.29–1.90) and 0.60 (95% CI, 0.40–0.67) per 100,000 population, respectively. There was a 15% annual decrease in incidence (adjusted rate ratio [aRR] 0.85; 95% CI: 0.82-0.88, P < .0001). Decreases were observed among sterile site (aRR 0.88; 95% CI, 0.84–0.93) and urine cases (aRR 0.83; 95% CI, 0.80–0.87). Annual decreases occurred for HO cases (aRR, 0.78; 95% CI, 0.73–0.85) and CO cases (aRR, 0.86; 95% CI, 0.83–0.9). The DA cases decreased 16% annually overall (aRR, 0.84; 95% CI, 0.81–0.88). Decreases among cases in patients with CVC (aRR, 0.85; 95% CI, 0.80–0.90) and urinary catheters (aRR, 0.84; 95% CI, 0.80–0.88) were smaller than what was seen in patients with other indwelling devices (aRR, 0.81; 95% CI, 0.77–0.86). Discussion: Overall, from 2012 to 2018, the incidence of CRAB decreased >60%. Decreases were observed in all case groups, regardless of source, infection onset location, or types of devices. Smaller annual decreases in rates of CO-CRAB than HO-CRAB suggest that there may be opportunities to accelerate prevention outside the hospital to further reduce the incidence of these difficult-to-treat infections.Funding: NoneDisclosures: None

934. Diagnostic Utility of Blood (1- >3)-β-D-Glucan Testing in Patients with HIV in Arkansas

Background Blood (1- &gt; 3)-β-D-Glucan (BDG) is a sensitive marker for Pneumocystis jirovecii pneumonia (PJP) in patients with AIDS (PWA). However, other fungal infections, including progressive disseminated histoplasmosis (PDH), cause high levels of BDG. At our hospital, PDH is a common diagnosis in PWA with fever and respiratory complaints, making it difficult to differentiate PJP from PDH based on clinical features alone. The objective of this study was to assess BDG as a diagnostic test for PJP in Arkansas where histoplasmosis is endemic. Methods We performed a retrospective review of patients with confirmed PJP and confirmed PDH who had BDG testing between 2014-2020. Positive cytological or histological evidence of P. jirovecii in bronchoalveolar lavage (BAL) or lung biopsy, or positive PCR on sputum or BAL confirmed PJP. Identification of Histoplasma capsulatum in culture of blood or other normally sterile site, histology showing typical yeast forms, or a positive urine H. capsulatum antigen assay (MiraVista Diagnostics) confirmed PDH. The Fungitell Assay determined BDG levels as follows: negative, &lt; 60 pg/mL; indeterminate, 60-79 pg/mL, and positive &gt; 80 pg/mL. Values below 31 pg/mL and those above 500 pg/mL were censored at 30 and 500, respectively. Respiratory symptoms were defined as the presence of cough, shortness of breath, or dyspnea on exertion. Results 53 episodes of PDH occurred in 46 patients. 42 were accompanied by a BDG result. Of these, 38 (90%) were positive; 3 (7%) were negative; and 1 (2%) was indeterminate. 44 (83%) of the PDH episodes were associated with respiratory symptoms. 36 of these had a BDG result. 34 (94%) were positive; 1 (3%) was negative; and 1 (3%) was indeterminate. 44 episodes of PJP occurred in 40 patients. All had a BDG result. 43 (98%) were positive.10 (23%) episodes of PJP were accompanied by a concomitant infection. The mean BDG level was significantly higher in the PJP group compared to those with PDH and respiratory symptoms (P=.002). However, values overlapped substantially, and BDG positivity was not significantly more frequent in the PJP group (P=.586). Box-and-Whisker Display of (1-&gt;3)-β-D-Glucan Results Conclusion In Arkansas, BDG positivity is not a reliable marker of PJP because it cannot distinguish between PJP and PDH. Attributing an elevated BDG to PJP without additional evaluation risks misdiagnosis. Disclosures All Authors: No reported disclosures