Pitt Bacteremia Score Research Articles

Clinical Data on Daptomycin plus Ceftaroline versus Standard of Care Monotherapy in the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia.

Vancomycin (VAN) and daptomycin (DAP) are approved as a monotherapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. A regimen of daptomycin plus ceftaroline (DAP+CPT) has shown promise in published case series of MRSA salvage therapy, but no comparative data exist to compare up-front DAP+CPT head-to-head therapy versus standard monotherapy as an initial treatment. In a pilot study, we evaluated 40 adult patients who were randomized to receive 6 to 8 mg/kg of body weight per day of DAP and 600 mg intravenous (i.v.) CPT every 8 h (q8h) (n = 17) or standard monotherapy (n = 23) with vancomycin (VAN; dosed to achieve serum trough concentrations of 15 to 20 mg/liter; n = 21) or 6 to 8 mg/kg/day DAP (n = 2). Serum drawn on the first day of bacteremia was sent to a reference laboratory post hoc for measurement of interleukin-10 (IL-10) concentrations and correlation to in-hospital mortality. Sources of bacteremia, median Pitt bacteremia scores, Charlson comorbidity indices, and median IL-10 serum concentrations were similar in both groups. Although the study was initially designed to examine bacteremia duration, we observed an unanticipated in-hospital mortality difference of 0% (0/17) for combination therapy and 26% (6/23) for monotherapy (P = 0.029), causing us to halt the study. Among patients with an IL-10 concentration of >5 pg/ml, 0% (0/14) died in the DAP+CPT group versus 26% (5/19) in the monotherapy group (P = 0.057). Here, we share the full results of this preliminary (but aborted) assessment of early DAP+CPT therapy versus standard monotherapy in MRSA bacteremia, hoping to encourage a more definitive clinical trial of its potential benefits against this leading cause of infection-associated mortality. (The clinical study discussed in this paper has been registered at ClinicalTrials.gov under identifier NCT02660346.).

Infections Caused by Carbapenemase-Producing Klebsiella pneumoniae: Microbiological Characteristics and Risk Factors.

The spread of carbapenemase-producing Klebsiella pneumoniae (CPKP) worldwide is a serious problem. This retrospective, matched case–control, parallel study in a tertiary teaching hospital analyzed the microbiological and clinical characteristics of CPKP infection, focusing on the risk factors for carbapenem resistance and patient mortality. The hospital department with the highest incidence of CPKP infections was the intensive care unit. All CPKP strains examined were positive for blakpc-2, and 84.8% of CPKP were ST11. Hypervirulent phenotype was identified in 22.7% of the patients with CPKP, with these strains displaying a high incidence of positivity for entB, ybtS, and iutA. Multivariate conditional logistic regression analysis demonstrated that Pitt bacteremia score >4, prior stomach tube, continuous renal replacement therapy (CRRT), and previous carbapenem exposure were associated with CPKP infection. Higher albumin concentration and use of cephalosporins after diagnosis were strong prognostic factors for crude 28-day mortality. Further, high APACHE II score, CRRT, use of carbapenems after diagnosis, and bacteremia were risk factors for crude in-hospital mortality. CPKP isolates showed clonal spread and were resistant to most antibiotics, resulting in higher financial burden. Critical illness was associated with increased mortality.

Utility of qSOFA score in identifying patients at risk for poor outcome in Staphylococcus aureus bacteremia

BackgroundThe prognostic capability of the quick Sequential Organ Failure Assessment (qSOFA) bedside scoring tool is uncertain in non-ICU patients with sepsis due to bacteremia given the low number of patients previously evaluated.MethodsWe performed a retrospective cohort study of adult hospitalized patients with Staphylococcus aureus bacteremia (SAB). Medical charts were reviewed to determine qSOFA score, systemic inflammatory response syndrome (SIRS) criteria, and Pitt bacteremia score (PBS) at initial presentation; their predictive values were compared for ICU admission within 48 h, ICU stay duration > 72 h, and 30-day mortality.ResultsFour hundred twenty-two patients were included; 22% had qSOFA score ≥2. Overall, mean age was 56y and 75% were male. More patients with qSOFA ≥2 had altered mentation (23% vs 5%, p < 0.0001), were infected with MRSA (42% vs 30%, p = 0.03), had endocarditis or pneumonia (29% vs 15%, p = 0.0028), and bacterial persistence ≥4d (34% vs 20%, p = 0.0039) compared to qSOFA <2 patients. Predictive performance based on AUROC was better (p < 0.0001) with qSOFA than SIRS criteria for all three outcomes, but similar to PBS ≥2. qSOFA≥2 was the strongest predictor for poor outcome by multivariable analysis and showed improved specificity but lower sensitivity than SIRS ≥2.ConclusionsqSOFA is a simple 3-variable bedside tool for use at the time of sepsis presentation that is more specific than SIRS and simpler to calculate than PBS in identifying septic patients at high risk for poor outcomes later confirmed to have S. aureus bacteremia.

A new simplified predictive model for mortality in methicillin-resistant Staphylococcus aureus bacteremia.

Adjustment for confounding is important in observational methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) studies due to the wide spectrum of disease severity and baseline health status that patients present with. The objectives of this study were to develop a simplified MRSAB-specific scoring model to estimate the risk of 30-day all-cause mortality and to compare its performance to the APACHE II and Pitt Bacteremia scores. Retrospective, singe-center, cohort study in adults with MRSAB 2008 to 2018. Independent predictors of mortality were identified through multivariable logistic regression. A scoring model was derived using a regression coefficient-based scoring method. Discriminatory ability was assessed using the c statistic. A total of 455 patients were included. Thirty-day mortality was 16.3%. The MRSAB score consisted of six variables: age, respiratory rate, Glasgow Coma scale, renal failure, hospital-acquired MRSAB, and infective endocarditis or lower respiratory tract infection source. The score demonstrated very good discrimination (c statistic 0.8662, 95% CI 0.824-0.909) and was superior to the APACHE II (P = 0.043) and the Pitt bacteremia (P < 0.001) scores. A weighted combination of six independent variables routinely measured in patients with MRSAB can be used to predict, with high discrimination, 30-day all-cause mortality. External validation is required before widespread use.

Clinical Characteristics and Antimicrobial Susceptibility Trends inCitrobacterBacteremia: An 11-Year Single-Center Experience

BackgroundRecently, Citrobacter freundii bacteremia outbreak in a neonatal intensive care unit has attracted public attention in Korea. However, Citrobacter bacteremia is uncommon and usually occurs in patients with underlying diseases such as malignancy and hepatobiliary diseases. Increase in resistance and emerging of multidrug resistance among Citrobacter species have gradually been reported. The aim of this study was to investigate the clinical characteristics and outcome of C. freundii and non-freundii bacteremia and antimicrobial susceptibility trends.Materials and MethodsWe reviewed the medical records of patients with Citrobacter bacteremia at St. Mary's Hospital, from 2007 to 2017.ResultsA total of 43 patients with a median age of 72 (24-93) years was identified and 90.7% of them had comorbidities. Twenty-nine (67.4%) patients had C. freundii bacteremia while 14 had non-freundii bacteremia (six of C. braakii, five of C. koseri, two of C. amalonaticus and one of C. youngae). A total of 26 (51.2%) patients had community-acquired infection and intra-abdominal infection including hepatobiliary tract was the most common portal of entry (24/43, 55.8%). Moreover, hepatobiliary tract was the leading primary site of nosocomial infection (9/17, 52.9%). Polymicrobial bacteremia was observed in 21 (48.8%) patients. The percentages of Citrobacter species susceptible to ampicillin, amikacin, aztreonam, cefazolin, cefoxitin, cefotaxime, cefepime, piperacillin-tazobactam, ciprofloxacin, and imipenem were 9.5%, 97.6%, 73.8%, 9.5%, 14.3%, 71.4%, 92.9%, 83.3%, 83.3% and 100%, respectively. The resistance rate did not increase during the study period. Of 39 patients treated with antibiotics, 36 (92.3%) received appropriate empirical antibiotics. Overall mortality was 18.6%. High Charlson comorbidity index and Pitt bacteremia score were significant risk factors for death in univariate analysis and showed trends in the multivariate analysis. No significant difference in clinical features and antimicrobial susceptibility rate was observed between C. freundii and non-freundii bacteremia.ConclusionCitrobacter bacteremia was predominant in the elderly with comorbidities, while no pediatric case was observed. Hepatobiliary tract is the leading primary focus of bacteremia both in community-acquired and nosocomial infection. The rate of susceptibility to antibiotics has not changed in the last 11 years.

Retrospective Study of Nephrotoxicity Rate among Adult Patients Receiving Colistin Compared to β-lactam Antibiotics.

ABSTRACTPurposePatients receiving colistin for carbapenem-resistant gram-negative bacteria (CR-GNB) infections generally have multiple risk factors for nephrotoxicity, so it might be possible that colistin may be erroneously blamed for the nephrotoxicity.Materials and methodsWe retrospectively analyzed case records of patients who received colistin and those who received antibiotics other than colistin [carbapenem or β-lactam–β-lactamases inhibitors (βL–βLI)] for gram-negative bacteremia. Those patients with preexisting renal failure and those who received antibiotics for <72 hours were excluded from the study. Nephrotoxicity was assessed using the risk of renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function, end-stage kidney disease (RIFLE) criteria.ResultsOut of the 222 patients, the colistin arm had 118 and the noncolistin arm had 104 patients. Even though the colistin arm had significantly higher number of sicker patients with neutropenia (40.7% vs 14.4%, p = 0.0001), mechanical ventilation (0.0001), having lines (0.0001), on inotropes (0.003), receiving other nephrotoxic drugs (0.0001), and higher Pitt score (p = 0.0001), there was no significant difference in the nephrotoxicity between the two arms (10.2% vs 9.6%, p = 0.89). Logistical regression showed a higher Pitt bacteremia score (p = 0.03) and a higher Charlson comorbidity index (p = 0.02), but not colistin administration (p = 0.32), were independently associated with nephrotoxicity.ConclusionAdministration of colistin was not associated with higher rates of nephrotoxicity than carbapenems or βL–βLI agents.How to cite this articleGhafur A, Bansal N, Devarajan V, Raja T, Easow J, Raja MA, et al. Retrospective Study of Nephrotoxicity Rate among Adult Patients Receiving Colistin Compared to β-lactam Antibiotics. IJCCM 2019;23(11):518–522.

Retrospective Observational Study from a Chinese Network of the Impact of Combination Therapy versus Monotherapy on Mortality from Carbapenem-Resistant Enterobacteriaceae Bacteremia.

Data for a total of 164 bloodstream infection cases due to carbapenem-resistant Enterobacteriaceae (CRE) from 2013 to 2017 were retrospectively collected from 36 tertiary hospitals in 19 provinces in China to evaluate the outcomes and risk factors for mortality by univariable and multivariable analysis. The most frequent infecting species was Klebsiella pneumoniae (69.5%, 114/164). The overall in-hospital and 14-day mortality rates were 32.9% (54/164) and 31.1% (42/135), respectively. Multivariable analysis revealed that septic shock (adjusted odds ratio [aOR], 6.339; 95% confidence interval [CI], 1.586 to 25.332; P = 0.009), the Pitt bacteremia score (aOR, 1.300; 95% CI, 1.009 to 1.676; P = 0.042), and the Charlson comorbidity index (aOR, 1.392; 95% CI, 1.104 to 1.755; P = 0.005) were independently associated with a hazard effect on mortality. Combination therapy, especially tigecycline-based combination therapy, resulted in relatively low rates of in-hospital mortality and failure in clearance of CRE infection. Survival analysis revealed that appropriate therapy was associated with a lower 14-day mortality rate than inappropriate therapy (including nonactive therapy; P = 0.022), that combination therapy was superior to monotherapy (P = 0.036), that metallo-β-lactamase producers were associated with a lower 14-day mortality than strains without carbapenemases or KPC-2 producers (P = 0.009), and that strains with MICs of >8 mg/liter for meropenem were associated with a higher 14-day mortality rate than those with MICs of ≤8 mg/liter (P = 0.037). Collectively, the severity of illness, meropenem MICs of >8 mg/liter, and carbapenemase-producing types were associated with the clinical outcome. Early detection of the carbapenemase type and initiation of appropriate combination therapy within 96 h might be helpful for improving survival.

Associated factors and clinical outcomes of bloodstream infection due to extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae during febrile neutropenia

Patients with neutropenia are vulnerable to serious infections. During the last decade, increased prevalence of extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae has affected immunocompromised patients. We conducted a single-center case-control study to evaluate factors associated with ESBL-positive bacteremia among neutropenic patients, and its clinical impact. The study included adult patients with hematologic or oncologic diseases diagnosed with ESBL-positive and ESBL-negative Escherichia coli or Klebsiella pneumoniae bacteremia during febrile neutropenia between January 2010 and October 2017 at the Shaare Zedek Medical Center, Jerusalem, Israel. Analyses included risk factors for ESBL-positive bacteremia, appropriateness of empiric antibiotics, mortality, length of stay, and intensive care unit (ICU) admission. Univariate and multivariate models were constructed. The cohort (80 patients), consisted of 54 ESBL-negative and 26 ESBL-positive Gram-negative bacteremia. Multivariate analysis suggested ESBL-positive bacteremia to be associated with long-term central venous catheter (CVC) (odds ratio (OR), 8.7; 95% confidence interval (CI), 1.6-48.1; P=0.01], index culture obtained 48 h post-admission (OR, 3.6; 95% CI, 1-12.3; P=0.04), and exposure to previous antimicrobial therapy (OR, 12.6; 95% CI, 2.1-74; P<0.01). There were no significant differences between groups with regard to length of stay, ICU admission, or mortality rates. Mortality was associated with high Pitt bacteremia score but not inappropriate empirical therapy. Previous antimicrobial therapy, long-term CVC, and hospital-acquired bacteremia were associated with ESBL bacteremia. Neutropenic patients with ESBL bacteremia have increased morality due to other factors than ESBL status. These findings should be validated in other centers and with larger populations.

1180. Addition of Chronic Kidney Disease Status to Pitt Bacteremia Score Improves Prediction of Mortality in Patients With Carbapenem-Resistant Enterobacteriaceae Infections

BackgroundCarbapenem-resistant Enterobacteriaceae (CRE) infections are associated with high mortality. The Pitt Bacteremia Score (PBS) was developed and validated to predict mortality in bloodstream infections (BSI). The first goal of this analysis is to evaluate whether PBS also predicts mortality in non-BSI infections. Second, we determine whether adding chronic kidney disease (CKD) as a parameter to PBS improves prediction of mortality.MethodsThe Consortium on resistance against carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE-1) is a prospective multicenter consortium of hospitals. Each patient with CRE infection was included once at the time of the last positive culture episode. Infections were distinguished from colonization using established definitions. Relative risk regression was used to evaluate the association of PBS ≥4 and CKD with 14-day all-cause hospital mortality.ResultsFrom December 2011 to June 2016, 364 unique patients were included with the following infections: bloodstream (34%), respiratory (20%), urinary (30%), and wound (16%). Median PBS was 3 (IQR: 2–4); 45% of patients had PBS ≥4. CKD was present in 31% of patients with PBS ≥4 and 20% of patients with PBS <4. All-cause mortality within 14 days of the last positive culture episode was 20%. In multivariable analysis, PBS ≥4 was strongly associated with mortality in patients with bacteremia (PBS ≥4 adjusted RR = 6.1, 95% CI 2.5–14.6, CKD aRR = 1.5, 95% CI 0.9–2.3) and in patients with other infections (PBS ≥4 aRR = 14.0, 95% CI 4.3–44.6, CKD aRR = 1.6, 95% CI 1.0–2.7). Adding CKD as a parameter to the PBS improved mortality prediction, specifically in patients with PBS ≥4 (figure).ConclusionAs expected, PBS ≥4 was predictive of the 14-day risk of hospital mortality in this cohort of CRE bacteremic patients. In patients with other CRE infections, PBS ≥4 was also predictive of mortality. In this cohort, adding CKD to the PBS improved prediction of mortality patients with PBS ≥4.Figure: Risks and 95% confidence intervals for 14-day all-cause hospital mortality, by Pitt bacteremia score and chronic kidney disease (CKD) status.Disclosures S. S. Richter, bioMerieux: Grant Investigator, Research grant. BD Diagnostics: Grant Investigator, Research grant. Roche: Grant Investigator, Research grant. Hologic: Grant Investigator, Research grant. Diasorin: Grant Investigator, Research grant. Accelerate: Grant Investigator, Research grant. Biofire: Grant Investigator, Research grant. V. G. Fowler Jr., Merck: Consultant and Scientific Advisor, Consulting fee. Cerexa/Actavis/Allergan: Grant Investigator, Grant recipient. Pfizer: Consultant and Grant Investigator, Consulting fee and Grant recipient. Advanced Liquid Logics: Grant Investigator, Grant recipient. NIH: Grant Investigator, Grant recipient. MedImmune: Consultant and Grant Investigator, Consulting fee and Grant recipient. Basilea: Consultant and Grant Investigator, Consulting fee and Grant recipient.Karius: Grant Investigator, Grant recipient. Contrafect: Consultant and Grant Investigator, Consulting fee and Grant recipient. Regeneron: Grant Investigator, Grant recipient. Genentech: Consultant and Grant Investigator, Consulting fee and Grant recipient. Affinergy: Consultant and Grant Investigator, Consulting fee and Grant recipient. Locus: Grant Investigator, Grant recipient. Medical Surface, Inc.: Grant Investigator, Grant recipient. Theravance: Consultant, Consulting fee and Speaker honorarium. Green Cross: Consultant, Speaker honorarium. Grifols: Consultant, Consulting fee. xBiotech: Consultant, Consulting fee. Achaogen: Consultant, Consulting fee. Medicines Co: Consultant, Consulting fee. Novartis: Consultant, Consulting fee.Novadigm: Consultant, Consulting fee. Bayer: Consultant, Consulting fee. Cubist: Consultant, Consulting fee. Debiopharm: Consultant, Consulting fee. Durata: Consultant, Consulting fee. D. Van Duin, Shionogi: Scientific Advisor, Consulting fee. achaogen: Scientific Advisor, Consulting fee. Allergan: Scientific Advisor, Consulting fee. Astellas: Scientific Advisor, Consulting fee. Neumedicine: Consultant, Consulting fee. T2 Biosystems: Scientific Advisor, Consulting fee. Roche: Scientific Advisor, Consulting fee.

1061. Comparison of the Acute Physiology and Chronic Health Evaluation (APACHE) II Score and the Pitt Bacteremia Score to Predict Mortality in Methicillin-Resistant Staphylococcus aureus Bacteremia

BackgroundMethicillin-resistant Staphylococcus aureus bloodstream infection (MRSA BSI) is associated with high morbidity and mortality. The prediction of outcomes may have a profound impact on clinical decision making and risk stratification. The Acute Physiology and Chronic Health Evaluation (APACHE) II Score and the Pitt Bacteremia Score (PBS) have been repeatedly described as independent predictors of mortality in MRSA BSI. The APACHE II is complex to calculate and many of the variables may not be pertinent to MRSA BSI. The PBS is a simple score using readily assessable variables. The comparative predictive performance of the two models in MRSA BSI has not been evaluated.MethodsRetrospective, observational, singe-center cohort study in adults with MRSA BSI between 2008 and 2018. Patients who did not receive active therapy ≤72 hours of index culture were excluded. APACHE II and PBS were calculated using the worst physiological values recorded ≤24 hours of blood culture collection. Discriminatory ability for 30-day mortality was assessed using the c-statistic and was compared using the Hanley and McNeil method. The best cut-off point in each scoring system was determined using the Youden Index (J).ResultsA total of 455 patients were included. The median (IQR) PBS and APACHE II were 2 (0, 3) and 18 (11, 23), respectively. All-cause 30-day mortality was 16.3%. The c-statistic (95% CI) for the APACHE II vs. PBS in the overall cohort and stratified by ICU status were: 0.813 (0.763, 0.863) vs. 0.717 (0.653, 0.782), P = 0.0035; ICU 0.729 (0.610, 0.848) vs. 0.570 (0.442, 0.699), P = 0.026; and non-ICU 0.821 (0.761, 0.881) vs. 0.700 (0.614, 0.786),P = 0.0046, respectively. The APACHE II with the maximum J value was 21; sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for 30-day mortality were 81.08%, 72.97%, 36.81%, and 95.21%, respectively. The PBS with the maximum J value was 3; sensitivity, specificity, PPV, and NPV were 66.22%, 72.18%, 31.61%, and 91.67%, respectively.ConclusionThe APACHE II was superior to the PBS in predicting 30-mortality in patients with MRSA BSI in the overall cohort and stratified by ICU status at BSI onset. Future research to develop a more practical scoring model with high discriminatory power is needed.Disclosures M. J. Rybak, Allergan: Consultant, Grant Investigator and Speaker’s Bureau, Research grant and Research support. Achaogen: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Bayer: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Melinta: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Merck: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Theravance: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Sunovian: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Zavante: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. NIAID: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support.

1643. Pharmacodynamics (PD) of Daptomycin (DAP) in Combination Therapy for Enterococcal Bloodstream Infection (BSI)

BackgroundDAP is frequently employed in combination with a second antibiotic for enterococcal BSI. We previously observed that a free drug area under the curve to MIC ratio (fAUC/MIC) >27.43 was predictive of survival when DAP was administered as monotherapy. The extent to which combination therapy affects DAP PD remains unexplored.MethodsThis study pooled data from 7 published trials assessing outcomes in DAP treated enterococcal BSI. fAUC/MIC was calculated using a published population pharmacokinetic model based on creatinine clearance, 90% protein binding, and baseline DAP MIC for each patient that received ≥72 hours of DAP as part of a combination antibiotic regimen. The fAUC/MIC threshold predictive of 30-day survival was determined by classification and regression tree analysis and confirmed by multivariable logistic regression. To control for comorbidities, the threshold was examined in the low-acuity patients only (APACHE-II score <21, Charlson co-morbidity index <5, or Pitt bacteremia score <4). Monte Carlo simulation was performed to determine the probability of target attainment (PTA) over a range of MICs.ResultsIn total, 240 adults were included and 137 (57.1%) were alive at 30 days. A majority of patients (62.8%) were immunosuppressed. Combination therapy with DAP plus a β-lactam was observed in 187 (77.9%) patients and with a β-lactam and 1 other active agent in 34 (14.2%) patients. Low-acuity patients (n = 135) were more likely to survive when fAUC/MIC >12.3 was achieved (63.2% versus 20.0%, P = 0.015). This difference remained significant when controlling for BSI source and immunosuppression (P = 0.017). The PTA for a 6 mg/kg/day dose was 95.2% at MIC=2 mg/L and 43.0% at MIC=4 mg/L; PTA for a 12 mg/kg/day dose was 95.2% at 4 mg/L.ConclusionCompared with our previous observations for DAP monotherapy against enterococcal BSI, a lower DAP PD exposure was required when administered with at least one additional antibiotic. For combination therapy with DAP, a fAUC/MIC >12.3 was associated with 30-day survival. As part of an active combination therapy regimen, DAP 6 mg/kg/day was appropriate for treatment of BSI caused by enterococci with MICs ≤2 mg/L, while 12 mg/kg/day was optimal for isolates with MICs of 4 mg/L.Disclosures J. L. Kuti, Merck & Co., Inc.: Consultant and Grant Investigator, Consulting fee and Research support. Pfizer, Inc.: Consultant, Consulting fee. Theravance Biopharma: Grant Investigator, Research support. Shionogi, Inc.: Grant Investigator, Research support. Allergan: Scientific Advisor and Speaker’s Bureau, Research support. C. Arias, Merck & Co., Inc.: Grant Investigator, Research support. MeMed: Grant Investigator, Research support. Allergan: Grant Investigator, Research support. N. S. Britt, Merck & Co., Inc.: Grant Investigator, Research support. Gilead Sciences, Inc.: Grant Investigator, Research support.

1037. Effect of Oral Step-Down Therapy on Readmission Rates in Escherichia coli Bacteremia

Background Escherichia coli is the most common cause of community-acquired bloodstream infections. Fluoroquinolones (FQ) and trimethoprim/sulfamethoxazole (TS) are preferred for oral step-down therapy due to high bioavailability. Antimicrobial stewardship programs commonly restrict FQ use, promoting consideration of non-FQ agents for treatment of sensitive organisms. We hypothesized that oral β-lactams would be non-inferior to FQ and TS with a primary outcome of 30-day all-cause readmission.MethodsThis was a retrospective non-inferiority study that reviewed electronic health records for patients with E. coli bacteremia from January 1, 2016 to December 31, 2017. Exclusion criteria included hospital acquired infections, death during hospitalization and concomitant infections. Patient demographics, Pitt Bacteremia Score, Charleston Comorbidity Index, antibiotic regimen (IV/PO), and readmission were collected. Patients were divided into two groups, oral FQ/TS verses β-lactams. A pretrial noninferiority margin for the primary outcome was set at 3%. Secondary outcomes included 30-day infection and E. coli readmission. Significant risk factors for readmission were entered into a multiple logistic regression model in a forward stepwise approach using SPSS.ResultsDemographics were similar between groups, 57 patients received FQ/TS and 151 received β-lactams. The 30-day-all cause readmission rate was 15.8% and 29.1%, respectively (absolute risk difference 13.3%, CI: 1–25).β-lactams were found to be inferior to FQ/TS for 30-day all-cause readmission. readmission occurred in 5.3% of patients in the FQ/TS group verses 14.6% of patients in the β-lactam group (P = 0.07). E.coli accounted for 100% of the infection-related readmissions in the FQ/ST group and 70% in the β-lactam group. Patients who received a β-lactam antibiotic were more likely to be readmitted then those patients treated with FQ/TS (odds ratio: 2.25, CI: 0.95–5.30, P = 0.06).ConclusionStep-down therapy to oral β-lactams resulted in higher rates of 30-day all-cause and infection-related readmissions in patients with E. coli bacteremia.Disclosures All authors: No reported disclosures.

1227. Development of a Clinical Prediction Model for Mortality in Methicillin-Resistant Staphylococcus aureus Bacteremia

BackgroundMethicillin-resistant Staphylococcus aureus bloodstream infection (MRSA BSI) is associated with high mortality despite advances in medical care. Mortality prediction may have a profound impact on clinical decision making and risk stratification. Widely used scoring systems such as the Acute Physiology and Chronic Health Evaluation (APACHE) II Score and the Pitt Bacteremia Score were derived in the general critical care and Gram-negative BSI populations, respectively and may be less precise in MRSA BSI. We sought to develop a predictive model (PM) for 30-day mortality in patients with MRSA BSI based on characteristics readily assessable at initial evaluation.MethodsRetrospective, singe-center, cohort study in adults with MRSA BSI 2008 to 2018. Patients who did not receive active therapy within 72 hours of index culture were excluded. Independent baseline demographic, clinical and infection predictors of 30-day mortality were identified through multivariable logistic regression analysis with bootstrap resampling and coefficient shrinkage. The PM was derived using a regression coefficient-based scoring method. PM discriminatory ability was assessed using the c-statistic. The optimal threshold score was determined using the Youden Index (J).ResultsA total of 455 patients were included and 30-day mortality was 16.3%. The PM consisted of five variables and a potential total score of 33. Points were assigned as follows: age (9 points ≥90 years, 6 points 80–89 years, 5 points 70–79 years, 0 points <70 years); Glasgow Coma Scale (8 points ≤9, 5 points 10–13, 0 points ≥14); 7 points infective endocarditis or pneumonia; 5 points serum creatinine ≥ 3.5 dl/L; and four points respiratory rate <10 or >24. The PM c-statistic was 0.860 (95% CI 0.818, 0.902). The PM score with the maximum J value was 13. Thirty-day mortality was 5.2% vs. 44.5% for PM score <13 vs. ≥13 points, respectively (P < 0.001). The sensitivity, specificity, positive predictive value (PV), negative PV, and accuracy using a threshold of 13 points were 77.0%, 81.4%, 44.5%, 94.8%, and 80.7%, respectively.ConclusionOur findings demonstrate a weighted combination of five independent variables readily assessable at initial evaluation can be used to predict, with high discrimination, 30-d mortality in MRSA BSI. External validation is required before wide-spread clinical use.Disclosures M. J. Rybak, Allergan: Consultant, Grant Investigator and Speaker’s Bureau, Research grant and Research support. Achaogen: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Bayer: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Melinta: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Merck: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research supportTheravance: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Sunovian: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Zavante: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. NIAID: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support.

1799. Impact of Real-Time Electronic Notifications to Pharmacists of Rapid Diagnostic Blood Culture Results

BackgroundRapid diagnostic tests that utilize multiplex PCR technology provide faster time to pathogen identification, but maximizing the impact on outcomes is dependent upon who is available to respond to test results. In June 2017, pharmacists began receiving in-basket notifications of positive results from the institution’s FilmArray BCID assay. The objective of this study was to determine the impact on antibiotic utilization associated with this method of communicating results.MethodsThis was a retrospective, observational, before-and-after study at an academic medical center with an established stewardship program. Inclusion criteria: Adult patients age ≥18 admitted to an ICU or oncology unit with ≥1 positive blood culture containing a gram-positive organism identified by FilmArray BCID. Patients with polymicrobial infection, concomitant infection caused by a different organism, antibiotics started before admission, or death prior to organism identification were excluded. Data were collected during a 4-month period before (PRE) and a 4-month period after (POST) implementation of in-basket notifications. Stewardship metrics and other outcome measures were compared between the two groups. Pharmacists received no targeted stewardship training on how to respond to results.ResultsNinety-two patients met study criteria (49 PRE and 43 POST). Patients were age 62 ± 16, male (55%), and 77 (84%) were located in an ICU. Median Charlson Comorbidity Index was 4 and Pitt Bacteremia Score was 1. Sixty-seven patients were considered to have noncontaminant bloodstream infection. Median results for these patients are listed in the table. Patients with contaminants (n = 25) had 3.5 and 7 antibiotic-free days in the PRE and POST groups, respectively (P = 0.34).ConclusionIn-basket notifications did not significantly improve antibiotic utilization or clinical outcomes. Active interventions and antimicrobial stewardship initiatives are needed in combination with rapid diagnostic tests.PRE (n = 35)POST (n = 32) P-valueTime to active therapy (hours)0.853.20.33Time to optimal abx (hours)47.444.40.43Time to de-escalation (hours)48.446.80.24Defined daily doses10.410.40.81Days of therapy13110.70In-hospital mortality, n (%)9 (26)8 (25)0.98Length of stay from positive culture (days)9.67.90.94Disclosures All authors: No reported disclosures.

1072. Streamlining to Oral β-Lactam vs. Fluoroquinolone as Definitive Therapy for Enterobacteriaceae Bacteremia

BackgroundOral treatment strategies for Enterobacteriaceae bacteremia (EB) are controversial, with both β-lactams (BL) and fluoroquinolones (FQ) used in clinical practice. FQ may be preferred for their high bioavailability, but other oral antibiotics are needed due to concerns of resistance and adverse effects. As an effort to facilitate antibiotic stewardship, BL should be explored as an additional oral option for EB treatment.MethodsThis retrospective study compared clinical characteristics and outcomes in patients with EB treated with BL vs. FQ as definitive oral therapy between January 2013 and July 2017. Adult patients diagnosed with their first incidence of EB and transitioned from IV antibiotics to either study antibiotic class were included. Primary and secondary outcomes assessed recurrence, collateral damage, readmission, and all-cause mortality.ResultsA total of 173 patients were included (BL n = 59, FQ n = 114). Median age was 70 years, Pitt bacteremia score was 2 (range 0–7), and Charlson Comorbidity Index was 5 (0–12); all were comparable between groups. Urinary source of infection was most common (57%). The majority of oral BL courses used cefpodoxime (63%). More patients in FQ vs. BL had a prior transplant (9% vs. 0%, P = 0.05), presence of abscess (11% vs. 0%, P = 0.01), and Infectious Diseases consultation (63% vs. 34%, P = 0.0001). Onset of EB in an intensive care unit was more common in BL vs. FQ (24% vs. 10%, P = 0.01). Median duration of IV and oral therapy was 5 vs. 4 days, P = 0.22 and 11 vs. 12 days, P = 0.17 in BL and FQ, respectively. Recurrence within 90 days was 7% in BL and 4% in FQ, P = 0.49 (adjusted OR 1.44, 95% CI 0.31–6.66; P = 0.64). Multivariate analysis identified liver cirrhosis (OR 16.89, 95% CI 1.06–268.32; P = 0.05) as an independent predictor of recurrence within 90 days. All secondary outcomes were similar between BL vs. FQ: superinfection within 90 days (10% vs. 9%, P = 0.76), C. difficile infection within 90 days (3% vs. 1%, P = 0.27), 30-day readmission (15% vs. 20%, P = 0.43), all-cause 30-day mortality (0% vs. 3%, P = 0.55).ConclusionIn our cohort of patients with EB, clinical outcomes were similar between those treated with oral BL compared with FQ. Oral BL may be considered for definitive treatment of EB, although further investigation in larger studies is needed.Disclosures All authors: No reported disclosures.

423. Ten-Year Experience of Burkholderia pseudomallei Infections in a Singapore Tertiary Hospital

Background Burkholderia pseudomallei is endemic in the tropics and associated with high mortality. We performed a retrospective study analyzing the clinical and microbiologic features of melioidosis, and predictors of mortality.MethodsPatients with culture-positive melioidosis from 2006 to 2016 were identified from microbiologic records. Clinical data including demographics, treatment, and outcomes were extracted from medical records. Categorical variables were compared using χ2 test or Fisher exact test while continuous variables were compared using Student’s t-test or Mann–Whitney U test.ResultsForty-three cases of melioidosis were identified. Presentations included fever (41.9%), respiratory symptoms (20.9%), and joint swelling (9.3%). 76.7% were bacteremic and 69.7% were culture-positive from a nonblood source. Mean time from presentation to positive microbiological data was 5.1 ± 6.4 days. Infection sites included pulmonary (62.8%), spleen (27.9%), skin/soft tissue (25.6%), and bone/joint (25.3%). Antibiotic susceptibility were as follows: ceftazidime (97.5%), imipenem (100.0%), trimethoprim–sulfamethoxazole (92.1%), amoxicillin–clavulanate (94.7%), and doxycycline (94.7%). Mean time from presentation to melioid-active coverage was 6.8 ± 9.1 days. Thirty-day all-cause mortality occurred in nine patients (from first positive culture); one patient died within 5 months. Univariable analysis associations with 30-day all-cause mortality were: intensive care unit (ICU) admission (OR 26.3, 95% CI 4.0–173.1, P < 0.01), mechanical ventilation (OR 15.0, 95% CI 2.6–85.0, P < 0.01), higher median Pitt Bacteremia Score (PBS) (4.0 vs. 2.0; P < 0.01), receipt of ceftazidime (vs. a carbapenem) as primary induction antibiotic therapy (OR 0.2, 95% CI 0.03–0.91, P = 0.047) and not receiving melioidosis-active induction intravenous antibiotics (P = 0.04). Multivariable analysis found mechanical ventilation to be an independent predictor for 30-day mortality (P = 0.003, OR 18.8, 95% CI 2.7–130.9).ConclusionICU admission, a high PBS, and in particular, receipt of mechanical ventilation may help identify patients with high mortality risk. Delays in melioid-active therapy were not uncommon. Prompt recognition of melioidosis and early institution of active therapy, especially in the critically ill, may reduce mortality.Disclosures All authors: No reported disclosures.

1021. Repeat Infective Endocarditis (rIE) in Persons Who Inject Drugs (PWID)

BackgroundInjection drug use (IDU) is a major risk factor for infective endocarditis (IE). Rates of IE have recently increased in the US concurrent with the opioid crisis. Although IDU-related IE is well described, few data exist on repeat IE (rIE) in persons who inject drugs (PWID).MethodsPatients ≥18 years old seen at Wake Forest Baptist Medical Center from 2004–2017 with an ICD-9 or -10 diagnosis of IE who met Duke criteria for IE and who self-reported IDU in the 3 months prior to admission were identified. The subset of PWID who developed rIE, defined as another episode of IE at least 10 weeks after the diagnosis of the first episode, was then reviewed.ResultsOf the 94 PWID with IE, 22 (23.4%) experienced rIE (19 re-infections, three relapses). All patients were Caucasian, 50% were male, and 68.2% lived in rural areas; the median age was 30. All 22 patients resumed IDU after their first episode of IE. The mean duration from completion of antibiotics for the prior IE episode to admission with rIE was 257.5 days; the episode of rIE occurred within 1 year in 17 patients (77.3%). On repeat admission, those with rIE had a Pitt bacteremia score of 3.0 and an APACHE II score of 13.1. Fever and bacteremia persisted for an average of 5.6 days and 2.6 days, respectively. S. aureus was the cause of rIE in 54.5% of patients and the tricuspid valve (TV) was involved in 77.3% of cases. Valve surgery occurred in 22.7% of patients. Mean length of stay was 25.3 days and mean duration of antibiotic therapy was 32.1 days. Seven patients (31.8%) died during the rIE hospitalization and another died within 12 months after discharge resulting in a 1-year mortality of 36.3%. Compared with their first episode of IE, rIE patients had higher admission Pitt bacteremia (3.0 vs. 1.5, P = 0.07) and APACHE II scores (13.1 vs. 9.5, P = 0.18), fewer S. aureus infections (54.5% vs. 95.4%, P = 0.01), similar TV involvement (77.3% vs. 72.7%, P = 1), and less frequent surgery (22.7% vs. 59.1%, P = 0.06).ConclusionrIE is common in PWID with most episodes occurring within 1 year of the initial episode. Reinfection is more frequent than relapse. The microbiology of rIE is more varied than first episode IE in PWID with S. aureus being less frequently isolated. Illness severity is high, hospitalizations are prolonged, and 1-year mortality is significant. More effective strategies for preventing rIE in PWID are needed.Disclosures J. Peacock, Pfizer: Shareholder, Owns common stock in Pfizer which was inherited and held in a trust.

1064. Clinical Outcomes of Daptomycin in Combination With Ceftaroline or Anti-Staphylococcal Penicillins for Patients With Persistent MRSA Bacteremia

BackgroundDaptomycin-β-lactam (DAP-BL) combinations demonstrate in vitro synergy against MRSA; however, the clinical efficacy of combo is limited. Our objective was to compare the outcomes of patients with persistent MRSA bacteremia treated with DAP-BL combinations.MethodsRetrospective, cohort study of hospitalized patients receiving DAP with ceftaroline (CPT) or oxacillin (OXA) between March 2012 and February 2018. Patients with persistent MRSA bacteremia despite ≥4 days of vancomycin therapy were included. Clinical success was defined as resolution of signs and symptoms of infection, microbiological eradication and in hospital survival.ResultsThirty-two patients included. Forty-four percent were male, median age was 61 (range: 26–78), and the median Charlson score was 2 (range: 0–11). Sixteen percent were IVDU. Sources of bacteremia included endocarditis (31%), bone/joint (31%), skin soft tissue (28%), and catheter (25%); 53% had more than one source. At the onset of combo therapy, median Pitt Bacteremia score was 1 (0–7). ID was consulted in all patients. Twenty-three and nine patients received DAP in combo with CPT or OXA, respectively. Baseline demographics, underlying disease, and clinical characteristics were comparable between groups. Patients receiving DAP-CPT had higher median Pitt Bacteremia scores (2 vs. 1; P = 0.04) and shorter median durations of prior vancomycin (8 vs. 10 days; P = 0.02) than did patients receiving DAP-OXA. Source control was pursued equally between groups. Median time to clearance of bacteremia following combo therapy was 3 (0–24) vs. 2 (−1–16) days in the DAP-CPT and DAP-OXA groups, respectively (P = 0.45). Corresponding rates of clinical success (43% vs. 56%) and microbiologic eradication (78% for both) did not vary between groups (figure). In hospital mortality occurred in 39% of patients receiving DAP-CPT and 0% of patients receiving DAP-OXA (P = 0.03). Adverse events occurred in 35% and 44% of patients, respectively.ConclusionWe have demonstrated high rates of microbiologic eradication and reasonable clinical success rates with DAP-BL combination therapy. Patients receiving DAP-CPT had higher severity of illness at baseline, which paralleled with higher mortality. These data provide compelling evidence for future studies designed to determine the optimal BL in combination with DAP for persistent MRSA bacteremia. Disclosures R. K. Shields, Allergan: Grant Investigator, Research grant. Pfizer: Consultant and Scientific Advisor, Speaker honorarium. Shionogi: Scientific Advisor, Consulting fee. Roche: Grant Investigator, Research grant. Venatorx: Grant Investigator, Research grant. Medicines Company: Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Accelerate Diagnostics: Scientific Advisor, Consulting fee.

1051. Increased Mortality in Bacteremia by Enterobacter Species With Discordant Imipenem and Ertapenem Susceptibilities

BackgroundCarbapenem-resistant Enterobacteriaceae (CRE) that are resistant only to one carbapenem have been reported, but the frequency of discordance between ertapenem and imipenem/meropenem is not known for Enterobacter species. We investigated the occurrence of discordant carbapenem susceptibilities in Enterobacter species bacteremia and the potential association with increased mortality.MethodsWe examined all cases of Enterobacter species bacteremia from January 2012 to December 2016 at the Michael E. DeBakey VA Medical Center in Houston, Texas, USA. Clinical and microbiological data were independently extracted by two investigators. Antibiotic susceptibility testing results were interpreted according to current CLSI breakpoints.ResultsWe found 14/67 (20.9%) isolates had discordance between ertapenem and imipenem susceptibilities. Eight isolates were ertapenem susceptible/imipenem nonsusceptible and six isolates were ertapenem nonsusceptible/imipenem susceptible (table). Bacteremia cleared in 94.5% (52/55) of all patients who had follow-up cultures, including infection by all (13/13) isolates with discordant carbapenem susceptibilities tested. Thirty-day mortality was statistically higher in infection by isolates with discordant carbapenem susceptibilities than by isolates that were susceptible to all tested carbapenems (10% vs. 36%; P = 0.03, Fisher’s exact test). In-hospital mortality was also higher in the discordant cohort as well (12% vs. 36%; P = 0.04, Fisher’s exact test). Acute severity of illness at bacteremia onset did not differ between the groups (median Pitt bacteremia score 2 vs. 3; P = 0.11, Wilcoxon rank-sum test).ConclusionBacteremia by Enterobacter species with discordant ertapenem and imipenem/meropenem susceptibilities is a relevant clinical issue, occurring in 20.9% of Enterobacter species bacteremias at our institution, and the discordance is associated with increased mortality. Whether such species can be safely treated with one carbapenem but not another is worth further investigation.Ertapenem MIC (μg/mL)Imipenem MIC (μg/mL)Number of Isolates≤0.5 (S)2 (I)81 (I)≤1 (S)22 (R)≤1(S)22 (R)0.5 (S)14 (R)≤1(S)1MIC: minimum inhibitory concentration; S: susceptible; I: intermediate; R: resistant;Disclosures B. W. Trautner, Paratek: Consultant, Consulting fee. Zambon: Consultant, Consulting fee and Research grant.

2446. Clinical Spectrum and Outcomes of Colistin-Resistant Carbapenem-Resistant Enterobacteriaceae

BackgroundColistin is considered as one of the last resort of antibiotics against carbapenem-resistant enterobacteriaceae. During the last decade, increased use of colistin or polymyxins due to the increasing prevalence of carbapenem-resistant Gram-negative bacteria has unfortunately led to the emergence of colistin-resistant strains. There are no defined antibiotic regimens for colistin-resistant strains which makes the treatment of these organisms extremely challenging. We therefore report the clinical spectrum and outcomes of infections due to colistin-resistant carbapenem-resistant Enterobacteriaceae (Co-CRE) as well as the factors associated with acquisition of co-CRE.MethodsWe conducted a retrospective cross-sectional study from January 2013 till December 2017 on patients admitted to a tertiary care hospital in Karachi, Pakistan. Statistical analysis was done using SPSS 19.ResultsForty patients with Co-CRE were identified of which 29 (72.5%) were males. Median age was 54.5 years. The most common organism isolated was Klebsiella in 22 (55%) followed by Providencia in 5 (12.5%) patients. Most common source of infection was the lung in 12 (30%) followed by urine in 11 (27.5%) patients. Similarly, the most common cause of bacteremia was pneumonia followed by intra-abdominal infections (50% and 37.5% of bacteremia cases, respectively). Twenty-eight (70%) patients had prior cultures with multi-drug-resistant organisms and 36 (90%) had used antibiotics in the past. A quarter (10) patients had pan resistant co-CRE strains while of the remaining strains 66% were sensitive to Fosfomycin. All patients received Colistin-based regimen in combination with 2 or 3 of the following: carbapenem, Fosfomycin, Amikacin, co-triamoxazole, and tigecycline. Complete clinical cure was achieved in only 50% of patients whereas microbiological eradication was achieved in 75%. Higher PITT bacteremia score, solid-organ transplant, and acute kidney injury were associated with mortality in patients with co-CRE.ConclusionInfections with co-CRE was seen in patients with prior nosocomial exposures and led to poor outcomes, despite combination treatment guided by susceptibilities.Disclosures All authors: No reported disclosures.