Influence of Antibiotic Susceptibility Testing on Antibiotic Choice in Hospital-Acquired and Ventilator-Associated Pneumonia

Background: The survival of patients with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) is largely determined by the timely administration of effective antibiotic therapy. Guidelines for the treatment HAP and VAP recommend empiric treatment with broad-spectrum antibiotics and tailoring of antibiotic therapy once results of microbiological testing are available. Objective: We examined the influence of bacterial identification and antibiotic susceptibility testing on antibiotic therapy for patients with HAP or VAP. Methods: We used the US Veterans’ Health Administration (VHA) database to identify a retrospective cohort of patients diagnosed with HAP or VAP between fiscal year 2015 and 2018. We further analyzed patients who were started on empiric antibiotic therapy, for whom microbiological test results from a respiratory sample were available within 7 days and who were alive within 48 hours of sample collection. We used the antibiotic spectrum index (ASI) to compare antibiotics prescribed the day before and the day after availability of bacterial identification and antibiotic susceptibility testing results. Results: We identified 4,669 cases of HAP and VAP in 4,555 VHA patients. The median time from respiratory sample receipt in the laboratory to final result of bacterial identification and antibiotic susceptibility testing was 2.22 days (IQR, 1.31–3.38 days). The most common pathogen was Staphylococcus aureus (n = 994), with methicillin resistance in 58% of those isolates tested. The next most common pathogen was Pseudomonas spp (n = 946 isolates). The susceptibility of antipseudomonal antibiotics, when tested, was as follows: 64% to carbapenems, 74% to cephalosporins, 75% to β-lactam/β-lactamase inhibitors, 69% to fluoroquinolones, and 95% to amikacin. Lactose-fermenting gram-negative bacteria (296 Escherichia coli and 360 Klebsiella pneumoniae) were also common. Among the 3,094 cases who received empiric antibiotic therapy, 607 (20%) had antibiotics stopped the day after antibiotic susceptibility results became available, 920 (30%) had a decrease in ASI, 1,075 (35%) had no change in ASI, and 492 (16%) had an increase in ASI (Fig. 1). Among the 1,098 patients who were not started on empiric antibiotic therapy, only 154 (14%) were started on antibiotic therapy the day after antibiotic susceptibility results became available. Conclusions: Changes in antibiotic therapy occurred in at least two-thirds of cases the day after bacterial identification and antibiotic susceptibility results became available. These results highlight how respiratory cultures can inform the treatment and improve antibiotic stewardship for patients with HAP/VAP.Funding: This study was supported by Accelerate Diagnostics.Disclosures: None</jats:p

Similar Mortality in Patients with Invasive and Noninvasive Pneumonia Due to Group B <i>Streptococcus</i>

Background: Rates of invasive infections caused by caused group B Streptococcus (GBS) are increasing among adults. The burden of noninvasive GBS infections, including pneumonia, has not been well characterized. Here, we compare comorbidities and mortality associated with invasive and noninvasive pneumonia caused by GBS. Methods: Using the Veterans’ Health Administration national data warehouse, we studied a retrospective cohort review of veterans diagnosed with GBS pneumonia between 2008 and 2017. Invasive pneumonia was defined as blood cultures positive for GBS associated with an order for a chest x-ray and an International Classification of Disease (ICD) code for pneumonia. Noninvasive pneumonia was defined as a respiratory culture positive for GBS associated with both an order for a chest x-ray and an ICD code for pneumonia among patients with negative or without blood cultures. Patients with respiratory cultures positive for GBS without either an associated chest x-ray or ICD code for pneumonia were considered colonized. We compared demographics, comorbid conditions, and mortality among patients with invasive and noninvasive GBS pneumonia. Results: Between 2008 and 2017, we detected 706 cases of invasive GBS pneumonia, 1,244 cases of noninvasive GBS pneumonia, and 1,470 cases of respiratory colonization with GBS. Most patients were male (97%), with an average age of 69.0 years (SD, 12.0 years). The prevalence of several comorbid conditions differed between those with invasive and noninvasive disease: diabetes mellitus (61% and 46%, respectively); chronic pulmonary diseases (53% and 65%, respectively); chronic heart disease (58% and 44%, respectively), chronic kidney disease (43% and 27%, respectively). Mortality was similar among those with invasive and noninvasive GBS pneumonia at 30 days (17% and 18%, respectively) and at 1 year (38% and 43%, respectively) (Fig. 1). Conclusions: We identified important differences in underlying comorbid conditions between patients with invasive and noninvasive GBS pneumonia, which may give rise to differences in their clinical presentation. Overall mortality, however, was similar: more than one-third of patients with GBS pneumonia died within 1 year. These findings indicate that noninvasive GBS pneumonia is an important clinical entity.Funding: This study was supported by Pfizer.Disclosures: None</jats:p

466. Elevated Risk of Invasive Group B Streptococcal Infection Among Veterans with Poorly Controlled Diabetes Mellitus or at Extremes for Body Mass Index

Abstract Background Diabetes mellitus (DM) and obesity have been identified as risk factors for invasive Group B Streptococcal (GBS) infection in non-pregnant adults. We used data from the US Veterans Health Administration (VHA) to confirm these findings and determine if poor diabetic control (elevated hemoglobin A1C (HbA1c)) or extreme weight (body mass index (BMI)) impacted risk. Methods We examined the VHA Corporate Data Warehouse to identify veterans active in VHA between 2008 and 2017 with invasive GBS infection according to the US Centers for Disease Control and Prevention surveillance definitions. We used International Classification of Disease (ICD) codes to determine a diagnosis of DM and stratified veterans by the highest HbA1c and first BMI in a given year. Absent HbA1c among those with DM were recorded as such. For years without BMI, the most recent BMI was carried forward. Results Between 2008 and 2017, the rate of invasive GBS infection for veterans with HbA1C ≥9.5% ranged from 55 to 104 /100,000 person-years (Figure 1). Rates in the next-highest risk group (HbA1c 7.5%–9.4%) were 24 to 36/100,000 person-years. Veterans with a BMI ≥40 (extremely obese; n = 798) or ≤18.5 (underweight; n = 99) had similarly elevated rates of invasive GBS infection (26 to 37/100,000 and 15 to 33/100,000 person-years, respectively) while those with BMI of 18.5–40 ranged from 6 to 13/100,000 person-years (Figure 2). Among those with HbA1c ≥9.5%, the most common type of infection was osteomyelitis (500/1,182; 42%; Table 1). Pneumonia was most common among patients with a BMI, Table 2. Conclusion Our study confirms that DM and obesity are notable risk factors for invasive GBS infection among veterans. The risk is substantially increased in patients with poorly controlled DM and morbid obesity. The high rate of invasive GBS infections among the small proportion of underweight veterans may reflect long-standing type 1 DM or other chronic diseases. Effective interventions to reduce the burden of invasive GBS infection among veterans should target individuals with poorly controlled DM, morbid obesity and those markedly underweight. Disclosures All authors: No reported disclosures. </jats:sec

206. Variations in the frequency and impact of polymicrobial cultures in adults with invasive Group B Streptococcal (GBS) infection at the US Veterans Health Administration

Abstract Background GBS, a colonizer of human skin, genitourinary and gastrointestinal tracts, is responsible for increasing rates of invasive infection among non-pregnant adults in the United States. GBS is often isolated with other bacteria; however, the clinical significance of polymicrobial cultures in patients with invasive GBS infection is unknown. Our aim was to characterize polymicrobial cultures in patients with invasive GBS infection and explore their impact on mortality at 30 days. Methods Within the VHA Corporate Data Warehouse, we identified veterans active in VHA between 2008–2017 with invasive GBS infection according to CDC’s surveillance definitions. Reports of cultures from blood, bone and sterile fluid with GBS were assessed for the presence of other bacteria.We used International Classification of Disease (ICD) codes to define the type of invasive GBS infection. We compared 30-day all-cause mortality between patients with cultures that identified only GBS (monomicrobial cases) and patients with cultures that identified GBS and other bacteria (polymicrobial cases). Results Of 4780 incident cases of invasive GBS infection identified between 2008–2017, 1204 (25%) were polymicrobial. The proportion of polymicrobial cases varied by type of invasive GBS infection, ranging from 58% in osteomyelitis to 10–15%in meningitis, endocarditis, skin and soft-tissue infections, and septic arthritis (table). Staphylococcus aureuswas found in 516 (43%) of polymicrobial cases;there were variations in the bacteria isolated by type of infection (figure). Overall, there was no difference in 30-day mortality between polymicrobial and monomicrobial cases of invasive GBS infection (both 8%). However, when compared with monomicrobial cases, 30-day mortality was doubled in polymicrobial cases of pneumonia and bacteremia (15% vs. 31% and 11% vs. 22%, respectively). Conclusion The frequency, composition and mortality of polymicrobial cases vary according to the type of invasive GBS infection. Polymicrobial infection could be an important determinant of outcome in certain invasive GBS infections. The effect of polymicrobial infection involving GBS, relative to age, severity of illness and underlying comorbidities, needs further exploration. Disclosures All authors: No reported disclosures. </jats:sec

220. Characteristics and Outcomes of Veterans with Invasive Group B Streptococcal Infection Vary with the Type of Syndrome

Abstract Background Surveillance from the US Center for Disease Control and Prevention (CDC) has detected an increase in the prevalence of invasive Group B streptococcus (GBS) infections between 2008 and 2016 among non-pregnant adults. Here, we use data from the US Veterans Health Administration (VHA) to assess the underlying clinical characteristics and outcomes associated with specific types of invasive GBS infection among veterans. Methods We used the VA Corporate Data Warehouse to identify patients with invasive GBS infection diagnosed between 2008–2017 using CDC’s surveillance definitions. Data on the microbiological source of infection (e.g., GBS in cultures from blood, bone or sterile fluids) and associated International Classification of Disease (ICD) codes were used to classify the type of invasive infection. We determined associated co-morbid conditions and 30-day all-cause mortality for incident cases. Results Between 2008 and 2017, there were 4780 incident cases of invasive GBS infection in veterans with a mean age of 66.6 years (±11.7) and30-day all-cause mortality of 8%. The most common syndrome was osteomyelitis (23%, N = 1078) with 30-day mortality of 1%. Other common infections, such as bacteremia (20%; N = 972), skin and soft-tissue infections (18%, 853), and pneumonia (14%, N = 664), had higher mortality (13%, 4% and 17%, respectively; Figure). In patients with GBS peritonitis, present in 3% (N = 138) incidence cases, 46% had chronic liver disease with a 30-day mortality of 28%. Diabetes mellitus (DM) occurred in 66% of patients with any invasive GBS infection and in 86% of patients with GBS osteomyelitis. Chronic heart, kidney, or lung disease affected &gt;25% of patients (table). Conclusion Invasive GBS infection is a burden for veterans with DM and other high-risk conditions, with some types of infections associated with substantial mortality. Osteomyelitis, the most common type of infection, was associated with lower mortality compared with other invasive GBS infections. DM and chronic lung, kidney and heart disease are common among veterans with invasive GBS infection. Disclosures All authors: No reported disclosures. </jats:sec

2190. Influence of Microbiological Culture Results on Antibiotic Choice for Veterans with Hospital-Acquired Pneumonia

Abstract Background Respiratory specimens help inform the treatment of hospital-acquired pneumonia (HAP), permitting clinicians to ensure effective and, ideally, narrow-spectrum antibiotic therapy. Here, we examine changes in antibiotic regimens to treat HAP based on the antibiotic susceptibility of pathogens recovered from respiratory samples. Methods At a single Veterans Affairs (VA) Medical Center, we identified veterans hospitalized between October 2014 and September 2018 with HAP, defined as a clinical respiratory sample obtained &gt;48 hours after admission and corresponding clinical signs and symptoms. Exclusion criteria were death, transfer to hospice care or discharge within 48 hours of sample collection or admission from an outside hospital. For each specimen, we assessed timestamps for collection, Gram stain, identification of organisms and results of susceptibility testing. We used the antibiotic spectrum index (ASI) to assess changes in antibiotics given to patients during hospitalization and at discharge. Results Between October 2014 and September 2018, 70 veterans met our inclusion criteria and experienced 73 episodes of HAP. Their mean age was 66.2 years (±9 years) and 47 (67%) had chronic pulmonary disease. All-cause mortality at 30-days after specimen collection was 14%. The median time from specimen collection to Gram stain result was 0.8 days (interquartile range (IQR) 0.1–1.9) and to antibiotic susceptibility results was 2.4 days (IQR 1.5–3.3). The most common bacteria recovered were Enterobacteriaceae (20 isolates), Pseudomonas aeruginosa (11 isolates), Streptococcus spp. and Staphylococcus aureus (8 isolates each); colonization with Candida spp. was frequent (26 isolates). Vancomycin and piperacillin–tazobactam were the most common antibiotics on day 0 (24%, 22%, respectively) and day 3 (21%, 13%, respectively). Compared with the day of sample collection (day 0), the ASI score was lower at day 3 in 23 (32%) and higher in 21 (29%) cases. Conclusion The high proportion of escalation and de-escalation of antibiotics suggests that results of bacteria identification and susceptibility testing influence therapeutic decisions, emphasizing the importance of obtaining respiratory samples to inform treatment of HAP and improve antibiotic stewardship. Disclosures All authors: No reported disclosures. </jats:sec

Evaluating the Appropriate Use Criteria for Coronary Revascularization in Stable Ischemic Heart Disease Using Randomized Data From the ISCHEMIA Trial

BACKGROUND: The appropriate use criteria for revascularization of stable ischemic heart disease have not been evaluated using randomized data. Using data from the randomized ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches; July 2012 to January 2018, 37 countries), the health status benefits of an invasive strategy over a conservative one were examined within appropriate use criteria scenarios. METHODS: Among 1833 participants mapped to 36 appropriate use criteria scenarios, symptom status was assessed using the Seattle Angina Questionnaire-7 at 1 year for each scenario and for each of the 6 patient characteristics used to define the scenarios. Coronary anatomy and SYNTAX(Synergy between percutaneous coronary intervention with Taxus and cardiac surgery) scores were measured using coronary computed tomography angiography. Treatment effects are expressed as an odds ratio for a better health status outcome with an invasive versus conservative treatment strategy using Bayesian hierarchical proportional odds models. Differences in the primary clinical outcome were similarly examined. RESULTS: The mean age was 63 years, 81% were male, and 71% were White. Diabetes was present in 28% and multivessel disease in 51%. Most clinical scenarios favored invasive for better 1-year health status. The benefit of an invasive strategy on Seattle Angina Questionnaire angina frequency scores was reduced for asymptomatic patients (odds ratio [95% credible interval], 1.16 [0.66-1.71] versus 2.26 [1.75-2.80]), as well as for those on no antianginal medications. Diabetes, number of diseased vessels, proximal left anterior descending coronary artery location, and SYNTAX score did not effectively identify patients with better health status after invasive treatment, and minimal differences in clinical events were observed. CONCLUSIONS: Applying the randomization scheme from the ISCHEMIA trial to appropriate clinical scenarios revealed baseline symptoms and antianginal therapy to be the primary drivers of health status benefits from invasive management. Consideration should be given to reducing the patient characteristics collected to generate appropriateness ratings to improve the feasibility of future data collection

Initial invasive or conservative strategy for stable coronary disease

BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, 121.8 percentage points; 95% CI, 124.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used