bluuebunny/crossref_metadata_2025 huggingface dataset:
1034. “Four-Leaf Clover Sign” as a Rapid Identification of Coagulase-Negative Staphylococci Species by Gram Stain of Blood Culture
Authors: Matsuo Takahiro , Hayashi Kuniyoshi , Mori Nobuyoshi
Published: November 2018

Background

Gram-positive coccus (GPC) in cluster bacteremia is associated with high mortality and morbidity. Although laboratory technologists note morphological characteristics such as the size and number of cells help distinguish S. aureus and Coagulase-negative staphylococci (CoNS), there are few studies that explored the optimal findings to distinguish between them by Gram stain. Here, we analyze some findings in Gram stain contributing to identify S. aureus or CNS.

Methods

This study was conducted at St. Luke`s International Hospital from November 2016 and September 2017. Broths for which a Gram stain showed GPC cluster were included in our study. Two infectious diseases fellows examined direct Gram stains of blood culture within 24 hours of positivity. We defined the sign as follows: four-leaf clover (FLC) sign if four GPCs gather like four-leaf clover (Figure 1) and three-dimensional (3D) sign if GPCs resemble big grapes. They counted the number of fields that have FLC and 3D signs out of 10 fields per each slide. We performed logistic regression analysis to assess whether these signs are the contributable factors to identify SA or CNS. The predictive ability of these signs was evaluated on the basis of the sensitivity (Sen), specificity (Spe), positive predictive value (PPV), and negative predictive value (NPV) for CoNS with receiver operating curve (ROC) analysis.

Results

In total, 106 blood cultures in which a direct Gram stain showed GPC in cluster were examined. Cultures revealed 46 (43%) were SA and 66 (57%) were CoNS. A multivariate logistic analysis showed that FLC sign was statistically significant variable of CoNS with odds ratio (OR) 1.20 (95% CI 1.09–1.35, P < 0.05). In aerobic bottles, Sen, Spe, PPV, and NPV were 0.67, 0.91, 0.92, and 0.65, respectively (Table 1) and area under the curve (AUC) was 0.79 (95% CI 0.67–0.91) (Figure 2). Cut-off fields were 6.5 out of 20.

Conclusion

This is the first study to show FLC sign could be a rapid and useful finding of Gram stain to identify CoNS rather than SA in aerobic bottles. In the presence of FLC sign, clinicians should highly suspect of CoNS with PPV of 92% before the final identification.

Disclosures

All authors: No reported disclosures.
1035. Differentiation Between True Infection and Contamination of Coagulase-Negative Staphylococci by Developing a Prediction Rule
Authors: Fujino Takahisa , Matsuo Takahiro , Rahman Mahbubur , Mori Nobuyoshi
Published: November 2018

Background

Coagulase-negative staphylococci (CoNS) are one of the most common contaminant microorganisms isolated from blood cultures (BCs).

Methods

We conducted a retrospective cohort study at St Luke’s International Hospital from 2004 to 2017. We collected a total of 1,192 BCs due to CoNS. Of 1,192 BCs, 143 patients with polymicrobial infection and 112 patients who were <18 years old were excluded. We defined the true infection (TI) on the following criteria; (1) patients with persistent bacteremia due to CoNS, (2) BCs that were positive more than two sets, (3) patients with foreign body implanted 28 days before taking BCs. Chi-square test, Fisher’s exact test and Student’s t-test were used in univariate analysis and logistic regression analysis was used in multivariable analysis.

Results

Of 927 patients’ BCs data, 201 patients were defined as TI, and 726 patients were defined as contamination. BCs collection location (general ward), inpatient, malignant tumor, steroids or chemotherapy use 90 days before collection, presence of central venous catheter (CVC), mortality in 90 days after collection, time to positivity (TTP: 24–48 hours, and <24 hours) differed significantly between these two groups. Based on multivariable analysis, TTP: 24–48 hours (adjusted odds ratio [OR] 1.93, P = 0.019, 95% confidential interval [CI] 1.11–3.36), and <24 hours: (OR 4.83, P < 0.001, 95% CI 2.68–8.68), BCs collection location: general ward (OR 2.21, P < 0.001, 95% CI 1.58–3.10), and presence of CVC (OR 1.91, P < 0.001, 95% CI 1.37–2.66) were identified as independent risk factors of TI. Based on the estimates of OR, we assigned a score to each factors (Table 1). Area under the curve was 0.702 (95% CI 0.662–0.741) (Figure 1). ROC analysis showed that, if a patient’s score is 0 point, TI can be excluded with sensitivity: 98%. On the other hands, if a patient’s score is 7 points or more, TI can be diagnosed with specificity: 87%.

Conclusion

Time to positivity, location of blood collection, and the presence of CVC were associated with TI. The prediction rule developed in this study can be useful for clinicians for making decision whether to use antibiotics or not.

Disclosures

All authors: No reported disclosures.
1037. Effect of Oral Step-Down Therapy on Readmission Rates in Escherichia coli Bacteremia
Authors: Sessa Julia , Conn Kelly M , Avery Lisa
Published: November 2018

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.

Methods

This 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.

Results

Demographics 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).

Conclusion

Step-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.
1044. Aztreonam (AZT) vs. Cephalosporin (CEP) Therapy for the Treatment of Gram-Negative Bacteremia
Authors: Shah Sunish , Krevolin Kyle , Bias Tiffany
Published: November 2018

Background

The IDSA recommends use of AZT in patients with a confirmed beta-lactam allergy for nosocomial Gram-negative infections. Despite this recommendation, there is limited data to suggest AZT is inferior to cephalosporins (CEP) for the treatment of Gram-negative infections. This study aims to evaluate clinical outcomes in bacteremic patients treated with either AZT or CEP therapy.

Methods

A single-center, retrospective chart review of adult patients with positive blood cultures for Escherichia coli, Klebsiella pneumoniae or Pseudomonas aeruginosa was conducted to compare clinical outcomes between those who received ≥ 48 hours of AZT or CEP therapy (cefepime or ceftriaxone). The following clinical outcomes were assessed: clinical cure, in-hospital mortality, post-infection length of stay (LOS), post-infection intensive care unit LOS, microbiologic cure and leukocytosis resolution.

Results

One-hundred and twenty-nine patients met criteria for evaluation: 41 received AZT and 88 received CEP therapy. At baseline, patients who received AZT were more likely to have renal dysfunction (34.1% vs. 18.2%, P = 0.046), receive synergistic antimicrobials (61% vs. 28.4%, P < 0.001) and had a longer pre-infection LOS (1 day [0–2] vs. 0 [0–1], P = 0.032) compared with those who received CEP. Although in-hospital mortality rates were similar between both groups (2.4% vs. 3.4%, P = 1.000), there was a statistically significant difference in clinical cure rates (70.7% vs. 90.9%, P = 0.003), post-infection length of stay (7 days [5–10] vs. 5 [4–8], P = 0.007), and time to clinical cure (2.8 days (1.6–5.8) vs. 2.0 (1.2–2.9), P = 0.018) in the AZT and CEP groups respectively. In a multivariate logistic regression model, patients who received AZT were significantly less likely to achieve clinical cure (OR=0.187, 95% CI (0.058–0.597). In a pre-determined subgroup analysis, clinical cure rates varied in E. coli (72% vs. 94.4%, P = 0.009), K. pneumoniae (70% vs. 90.5%, P = 0.296) and P. aeruginosa (66.7% vs. 76.9%, P = 1.000) in the AZT and CEP group respectively.

Conclusion

Patients who receive aztreonam for Gram-negative bacteremia may be more likely to experience clinical failure. Larger, prospective studies are warranted to confirm these findings.

Disclosures

All authors: No reported disclosures.
1045. A Multicenter Propensity Score-Adjusted Retrospective Study for Comparison of the Outcome of Treatment With Third-Generation Cephalosporin vs. Broad-Spectrum Antibiotics for Enterobacter Bacteremia
Authors: Hayano Satoshi , Yamamoto Shungo , Hase Ryota , Toguchi Akihiro , Otsuka Yoshihito , Hosokawa Naoto
Published: November 2018

Background

Enterobacter spp. can develop resistance during prolonged therapy with third-generation cephalosporins (3GC: ceftriaxone, cefotaxime, or ceftazidime) because of derepression of AmpC β-lactamase. However, the clinical significance of this phenomena remains undetermined. This study aims to assess the outcome of patients with 3GC-susceptible Enterobacter bacteremia (EB) who received definite therapy with 3GC or broad-spectrum antibiotics (BSA) using propensity score analysis.

Methods

In this retrospective, cohort study conducted at two tertiary care hospitals in Japan, we determined consecutive patients with EB identified from the laboratory databases between January 2010 and December 2017. We enrolled patients with 3GC-susceptible EB treated with 3GC or BSA (defined as fourth-generation cephalosporins, carbapenems, and piperacillin/tazobactam) as definitive therapy. The primary outcome was 28-day mortality. The secondary outcome was the emergence of antimicrobial-resistant strain during antimicrobial therapy. We compared outcomes using the propensity scores and inverse-probability-weighting (IPW) adjustment to decrease the confounding by indication.

Results

We identified 320 patients with EB; of these, 191 cases were eligible (86 treated with 3GC and 105 treated with BSA). All the measured covariates were well balanced after the IPW adjustment. We observed no significant differences in the unadjusted mortality [5.8% in the 3GC group vs. 13.3% in the BSA group; risk difference, −7.5%; 95% confidence interval (CI): −15.7–0.6; P = 0.09], and the IPW-adjusted mortality (5.1% vs. 9.4%; risk difference −4.3%; 95% CI: −12.2–3.5; P = 0.3) between the groups. The results of the propensity score-matched analysis and sensitivity analysis were similar. Furthermore, we did not observe the emergence of antimicrobial resistance during antimicrobial therapy in both groups.

Conclusion

Definitive therapy with 3GC for susceptible EB was not associated with an increased risk of the 28-day mortality after adjustment for potential confounders with the propensity score analysis or with the emergence of antimicrobial-resistant strain.

Disclosures

All authors: No reported disclosures.
1049. Outcome and Impact of Empirical Antimicrobial Treatment in Bacteraemia With Bacteroides Species; A Retrospective Cohort Study in a Region of Southern Sweden
Authors: Tham Johan , Kalin Karolina , Resman Fredrik , Holm Karin
Published: November 2018

Background

Anaerobic infections are an important cause of bacteremia and severe Infections. Due to increasing extended spectrum β-lactamase resistance (ESBL), the treatment recommendations for anaerobic infections in Sweden have changed during the past ten years. The effects of anaerobe resistance and outcome for patients with anaerobe infections is unclear.

Methods

A retrospective cohort study was conducted in patients with bacteraemia due to Bacteroides species in the Region of Skåne between 2011 and 2015. Data on patients were reviewed from medical and microbiological records and we determined the factors associated with 28-day mortality using a multivariate regression model.

Results

Data on 454 patients were reviewed from medical and microbiological records and 389 (median age, 76 years; male, 54%) met the inclusion criteria. The 28-day all-cause mortality rate was 19% (72/389). Inadequate empirical antibiotic therapy occurred among 182 (47%) patients, and we found a trend toward that inadequate antibiotic treatment increased the 28-day mortality (P = 0.055). The frequency of bacteraemia with Bacteroides increased during the period of time and Bacteroides fragilis was the most common bacteria, 55% (212/389). The resistance against piperacillin/tazobactam was higher than in many other studies and among the different Bacteroides isolates that were resistant to piperacillin/tazobactam, Bacteroides thetaiotamicron was the most prevalent with 60% (50/83) being resistant. Piperacillin/tazobactam was the frequently used antimicrobial agent against Bacteroides infections and the utilization was increasing. We did not find any resistance among the Bacteroides isolates against metronidazole and only three isolates were resistant against carbapenems.

Conclusion

Anaerobe resistance is an increasing issue and especially against the most common antibiotic treatment, piperacillin/tazobactam. Early recognition and appropriate treatment is important to avoid proliferation of these increasing bacteria since inadequate treatment increased the mortality.

Disclosures

All authors: No reported disclosures.
1051. Increased Mortality in Bacteremia by Enterobacter Species With Discordant Imipenem and Ertapenem Susceptibilities
Authors: Chou Andrew , Rossi Vittoria , Sucgang Richard , Hamill Richard , Zechiedrich Lynn , Trautner Barbara W
Published: November 2018

Background

Carbapenem-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.

Methods

We 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.

Results

We 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).

Conclusion

Bacteremia 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.

MIC: minimum inhibitory concentration; S: susceptible; I: intermediate; R: resistant;

Disclosures

B. W. Trautner, Paratek: Consultant, Consulting fee. Zambon: Consultant, Consulting fee and Research grant.
1053. Biofilm Production and Clinical Characteristics of S. maltophilia Causing Persistent or Relapsing Bacteremia
Authors: Kang Seung Ji , Oh Tae Hoon , Jung Younggon , Kim Seong Eun , Kim Uh Jin , Jang Hee-Chang , Park Kyung-Hwa , Jung Sook-In
Published: November 2018

Background

This study aimed to identify clinical or microbiological factors related to persistence or recurrence of Stenotrophomonas maltophilia bacteremia in adult patients.

Methods

S. maltophilia isolated from blood in two tertiary hospitals between 2011 and 2017 were investigated. Persistent bacteremia was defined as the consecutive blood culture positive for ≥5 days after initiation of appropriate antibiotics therapy. Relapse was defined as isolation of S. maltophilia from blood after completion of antibiotics treatment for the first episode of bacteremia. Biofilm formation was assessed in 96-well polystyrene plate with Trypticase Soy Broth using 0.5% crystal violet staining. The presence of smf-1 gene was detected by polymerase chain reaction.

Results

Of total 100 patients with S. maltophilia bacteremia, 10 of persistent, 8 of relapsing, and 46 of nonpersistent, nonrelapsing cases were investigated. The presence of indwelling urinary catheter (P = 0.011), nasogastric tube (P = 0.003), mechanical ventilator treatment (P = 0.001), and previous colonization of S. maltophilia (P = 0.016) were more frequently observed in patients with persistent bacteremia compared with nonpersistent, nonrelapsing bacteremia cases. In patients with relapsing bacteremia, hematologic malignancy (P = 0.022), neutropenia (P = 0.001), and concomitant isolation of S. maltophilia in clinical samples other than blood (P = 0.041) were more common than nonpersistent, nonrelapsing bacteremia patients. Catheter-related infection (37.0%) followed by pneumonia (28.3%) was the most common primary focus of nonpersistent, nonrelapsing bacteremia whereas pneumonia was the most frequent cause of bacteremia in both of persistent and relapsing cases (40.0% and 50.0%). Most of isolates (63 of 64) were susceptible to cotrimoxazole. The resistance to levofloxacin were comparable among isolates from persistent, relapsing and nonpersistent, nonrelapsing cases (10.0% vs. 12.5% vs. 15.2%, P = 0.988). Biofilm formation ability was not significantly different between three groups (optical density at 595, mean ± SD, 0.69 ± 0.34 vs. 0.78 ± 0.33 vs. 0.70 ± 0.33, P = 0.529). The smf-1 gene was found in all isolates.

Conclusion

More careful treatment approaches to patients with risk factors for S.maltophilia treatment failure should be warranted.

Disclosures

All authors: No reported disclosures.
1054. Biofilm Formation Among Escherichia coli Bloodstream Infection Isolates Is Associated With Source of Bacteremia and Bacterial Sequence Type
Authors: Chang Carolyn , Ruffin Felicia , Fowler Vance G , Thaden Joshua T
Published: November 2018

Background

The clinical impact of Escherichia coli biofilm formation is unknown.

Methods

Adults with E. coli bloodstream infections (BSI) were prospectively enrolled from 2002 to 2015. All E. coli isolates were genotyped using Multilocus sequence typing (MLST) and underwent crystal violet biofilm formation assay quantified by absorbance at 540 nm (OD540) in triplicate. Associations between biofilm formation and patient/bacterial characteristics were characterized by t-tests and ANOVA tests.

Results

Ninety-eight percent (186) of the 189 isolates formed detectable biofilms. Bacterial sequence type (ST) was associated with biofilm formation (P < 0.001), as ST73 (average OD540 = 0.017) and ST393 (average OD540 = 0.016) had higher average biofilm formation while ST69 (average OD540 = 0.007) and ST405 (average OD540 = 0.002) had lower biofilm formation. E. coli isolates with non-multidrug-resistant (non-MDR) phenotype were associated with increased biofilm formation (MDR: average OD540 = 0.006; average non-MDR: OD540 = 0.01; P = 0.003). BSI isolates arising from pneumonia or urine/pyelonephritis were associated with the highest biofilm production (P = 0.04). No associations were identified between biofilm formation and route of infection, APACHE-II score, mortality, or complications of BSI.

Conclusion

In this prospective study of E. coli BSI isolates, biofilm formation was associated with ST, non-MDR phenotype, and BSI source.

Disclosures

All authors: No reported disclosures.
1056. Predicting Central Nervous System Complications in Staphylococcus aureus Bacteremia Using Clinical Scoring System
Authors: Kim Chung-Jong , Song Kyoung-Ho , Kang Chang Kyung , Choe Pyeong Gyun , Bae Ji Yun , Choi Hee Jung , Jung Younghee , Lee Seung Soon , Park Wan Beom , Bang Ji Hwan , Kim Eu Suk , Park Sang Won , Kim Nam Joong , Oh Myoung-Don , Kim Hong Bin ,   KIND Study Group
Published: November 2018

Background

Central nervous system (CNS) complications occurring in patients with Staphylococcus aureus bacteremia (SAB) are the most severe complications. In this study, we compared clinical data of SAB patients between cases with and without CNS complication and analyzed the risk factor of CNS complications.

Methods

Data from cases with SAB occurred during 5 years at four hospitals were collected. The presence of CNS complications was confirmed by brain MRI, CT, or lumbar puncture. We excluded the cases who already had CNS lesions such as trauma, brain tumor, or cerebrovascular accident. We also excluded the cases who were died or transfer out <7 days of bacteremia onset. Cases were divided into complication group or noncomplication group according to the presence of CNS complication. We compared the clinical profiles between the groups, and analyzed the risk factor of CNS complications by multivariate logistic regression analysis.

Results

A total of 1,085 cases of SAB patients were included. Among these, 43 (4%) cases were complication group (embolic infarct [n = 23], brain hemorrhage [n = 8], infarct with hemorrhage [n = 8], and brain abscess or meningitis [n = 4]), while 810 (74%) cases were noncomplication group. Two hundred and forty-one cases were excluded. The results of multivariate analysis were shown in table. When selecting by having less than three factors among SOFA > 5, methicillin-susceptible, endovascular infection (weight 2), presence of metastatic infection and community onset, it helps to exclude CNS complications (AUC of ROC curve = 0.77, P < 0.01, sensitivity; 67.5%, specificity: 75.5%, positive predictive value: 12.9%, negative predictive value 97.7%).

Conclusion

CNS complication could be excluded by using clinical variables

Disclosures

All authors: No reported disclosures.
1063. Impact of Rapid Organism Identification and a Standardized Algorithm on Antimicrobial Therapy in Patients With Bacteremia
Authors: Koutsari Christina , Gens Krista , Holt Jessica
Published: November 2018

Background

Bloodstream infection is associated with 12% to 32% mortality. The FilmArray® BCID panel is a multiplex polymerase chain reaction assay (PCR) that can rapidly identify the most common bacterial pathogens in the blood and three antimicrobial resistance genes. In April 2015, Abbott Northwestern Hospital (ANW) implemented the multiplex PCR panel and a pharmacist-driven process to assist with antibiotic tailoring. In August 2017, a standardized algorithm was approved providing first-line and second-line antimicrobial options for each microbial pathogen included in the multiplex PCR panel. The objective of this study was to compare the time from the multiplex PCR panel result to final appropriate antibiotic therapy (as defined by the standardized algorithm or when clinical decision was indicated) between pre- and post-algorithm implementation in hospitalized patients with bacteremia.

Methods

Retrospective chart review was performed in 93 randomly selected adult patients with ≥1 positive blood culture in November 2016–February 2017 (pre-algorithm) vs. 93 patients in November 2017–February 2018 (post-algorithm) at ANW.

Results

The two groups did not differ significantly in terms of age (average ~60 years), sex (45% female), intensive care unit admission on day 1 of bacteremia (~41%), infectious diseases (ID) consult within 72 hours of bacteremia (average 72%), bacteremia source, or etiologic bacteria. The median time to final appropriate antibiotic therapy in response to the multiplex PCR result was 19 hours (interquartile range, IQR 4–38 hours) pre-algorithm and 18 hours (IQR 4–31 hours) post-algorithm (P = 0.34).

Conclusion

The median time from the multiplex PCR result to final appropriate antibiotic therapy was ~19 hours pre- and post-algorithm. Previous studies showed a median of 21 hours to first appropriate de-escalation. Therefore, ANW performs very well in de-escalating antimicrobial therapy promptly. However, most of the rapidity in antibiotic change was driven by ID providers, who treated >70% of patients. Opportunities for improvement exist for non-ID providers in tailoring antimicrobial therapy and for pharmacists in engaging and providing recommendations in a timely manner.

Disclosures

All authors: No reported disclosures.
1068. Evaluation of Cefazolin vs. Anti-Staphylococcal Penicillins for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections in Acutely-Ill Adult Patients: Results of a Systematic Review and Meta-Analysis
Authors: Lee Benjamin J , Constantino-Corpuz Janie K , Apolinario Kristel , Wang Sheila K , Nadler Barbara , Scheetz Marc H , Rhodes Nathaniel J
Published: November 2018

Background

Anti-staphylococcal penicillins (ASPs) have been regarded as first-line in the treatment of serious MSSA bloodstream infections (BSI) with cefazolin considered an alternative. Recent studies have suggested that infection outcomes between cefazolin and ASPs may be similar. The objective of this study was to compare the clinical efficacy and tolerability of cefazolin to ASPs for MSSA BSI.

Methods

A systematic review and meta-analysis was conducted. Articles were identified via PubMed, Web of Science, and the Cochrane Library. Studies written in English comparing cefazolin to ASPs for MSSA BSI in adult patients were included. Study quality was assessed using the Cochrane Risk of Bias Assessment Tool and the Newcastle-Ottawa Scale for prospective and retrospective studies, respectively. All review stages were independently conducted by two reviewers, with a third reviewer adjudicating any discrepancies. The fixed- or random-effects model was utilized, as appropriate. A planned subgroup analysis was conducted between high (>15%) vs. low (<14.9%) mortality probability as defined by logit functions applied at the study level.

Results

Nine studies were identified. Pooled data extracted from 1,726 cefazolin- and 2,716 ASP-patients indicated that cefazolin was associated with a significant reduction in treatment failure (OR: 0.70; 95% CI: 0.61–0.82; P < 0.001; I2 = 14%) and crude, all-cause mortality (OR: 0.69; 95% CI: 0.59–0.81; P < 0.001; I2 = 18%) compared with ASPs. Within a subset of studies (n = 6) demonstrating low mortality probability (<14.9%), cefazolin therapy remained protective against failure (OR: 0.70; P < 0.001; I2 = 39%) and mortality (OR: 0.70; P < 0.001; I2 = 35%). Within the high mortality probability (>15%) subset, no significant differences for failure or mortality were noted. The risk of adverse events was higher with ASPs (OR: 2.58; 95% CI: 1.00–6.64; P = 0.05).

Conclusion

Cefazolin was associated with significantly lower rates of failure, mortality, and treatment-related adverse events when compared with ASPs among less severely ill patients. Prospective, randomized controlled trials are needed to establish the role of these agents in serious MSSA BSI.

Disclosures

All authors: No reported disclosures.
1071. Impact of Standard vs. Prolonged Courses of Antibiotics for the Treatment of Uncomplicated Staphylococcus aureus Bacteremia (SAB) in Patients With Hematologic Malignancies
Authors: Cheung Edna , McKenzie Matt G , Colon Lydia Benitez , Kaye Keith S , Petty Lindsay , Martin Emily T , Marini Bernard L , Perissinotti Anthony J , Eschenauer Gregory , Alaniz Cesar , Wallace Katie L , Patel Twisha S
Published: November 2018

Background

The optimal treatment duration for uncomplicated SAB (U-SAB) is unknown in patients with hematologic malignancies. The goal of this study was to evaluate the impact of antibiotic duration on outcomes in patients with hematologic malignancies and U-SAB.

Methods

This was a multicenter, retrospective cohort study of adult patients with hematologic malignancies and U-SAB treated with standard (2 weeks) or prolonged (>2 weeks) antibiotic therapy. U-SAB was defined as defervescence and culture clearance within 96 hours of index culture and the absence of: endocarditis, implanted prostheses, metastatic sites of infection, and bone/joint involvement. Patients with SAB therapy <10 days and those with inadequate source control were excluded. The primary outcome was a composite global clinical cure: absence of relapse SAB, absence of SAB progression, and survival at 60 days following index SAB.

Results

Of 89 included patients, 51% received a standard antibiotic duration for U-SAB. The median age of the entire cohort was 56 and majority was male (60%). Neutropenia was present at index culture in 53% of patients, and acute leukemia (48%) and lymphoma (26%) were the most common underlying malignancies. Other baseline characteristics were similar between the two groups except more patients in the standard duration group had relapsed/refractory malignancy (51% vs. 25%, P = 0.016), central-line source (71% vs. 48%, P = 0.032), and antibiotic prophylaxis prior to index SAB (42% vs. 18%, P = 0.021). Median duration of treatment in the standard group was 15 days vs. 28 days in the prolonged duration group. No differences in global clinical cure and other clinical outcomes were seen between groups (Figure 1). On multivariable logistic regression analysis, only relapsed/refractory malignancy was identified as an independent predictor of global clinical failure (odds ratio, OR, 9.43; 95% confidence interval, CI, 1.17–76.9; P = 0.035). Duration of treatment was not associated with global clinical cure (OR, 2.92; 95% CI, 0.51–16.7; P = 0.23).

Conclusion

No differences in clinical outcomes were seen in patients with active hematologic malignancies who received 2 weeks vs. >2 weeks of antibiotic therapy for the treatment of U-SAB, although confirmation of our findings in a larger study is warranted.

Disclosures

All authors: No reported disclosures.
1087. Aortic Graft Infections Caused by Propionibacterium acnes at the Minneapolis Veterans Affairs Health Care System (MVAHCS) 2007–2017
Authors: El Rafei Abdelghani , Drekonja Dimitri M
Published: November 2018

Background

Propionibacterium acnes is a Gram-positive microaerophilic bacterium and part of the human skin flora. The ability of P. acnes to cause infections has been recognized, particularly in the presence of hardware. We aimed to define the frequency of P. acnes infections, with a focus on aortic graft infection.

Methods

We used microbiology laboratory records at the Minneapolis Veterans Affairs Health Care System to identify all P. acnes cultures from January 2007 to January 2017. We retrospectively reviewed all adult (≥18 years) patient’s medical records to identify associated infectious syndromes. Case definitions by the management of Aortic Graft Infection Collaboration were used to classify aortic graft infection cases.

Results

We identified 328 positive P. acnes cultures during the study period. P. acnes was classified as a pathogen in 48 (15%), a pathogen of undetermined significance in 70 (21%), and a contaminant in 210 (64%) cases. We identified three cases aortic graft infection which accounted for (2.5%) of infections caused by P. acnes. Median age (range) at presentation was 74 years (67–83). Symptoms included pain (n = 3), fever (n = 2), and altered mental status (n = 1). None were hypotensive. All patients had at least one revision for endoleak prior to presentation. Median time from symptom onset to diagnosis was 120 days (78–140). Microbiological diagnosis was obtained by blood cultures, percutaneous peri-graft tissue aspiration, and operative culture in each patient, respectively. Infection was complicated by metastatic abscess in one patient. All cultures grew on Day 7. All patients were treated with IV ceftriaxone, and two were transitioned to life-long oral suppressive antibiotic therapy. Two patients had complete removal of infected material. No relapse was documented and survival was 100% at 1 year follow-up.

Conclusion

Aortic graft infection is an uncommon subset of infections caused P. acnes. Clinical course is indolent and diagnosis is delayed due to nonspecific clinical presentation. In contrast to endovascular graft infection caused by other organisms, mortality is low when treated with appropriate antibiotic therapy and removal of infected material. The current laboratory practice of holding blood cultures for 5 days may need to be altered when P. acnes is a potential cause of infection.

Disclosures

All authors: No reported disclosures.
1089. Analytical Performance of an Ultrasensitive Immunoassay for Detection of Clostridium difficile Toxins in Stool
Authors: Bartolome Amelita , Almazan Anna , Abusali Salina , Tam Stanley , Lee Eric , Changavi Amogh , Trinh Wendy , Chau Kent , Estis Joel , Noland Brian , Bishop Jeffrey
Published: November 2018

Background

Clostridium difficile infection (CDI) is the main cause for nosocomial diarrhea. Currently available assays for the diagnosis of CDI show deficits in sensitivity, specificity, and/or turnaround time. The Singulex Clarity® C. diff toxins A/B assay, in development for the Singulex Clarity® system, was designed to provide an accurate and automated detection of C. difficile toxins A (TcdA) and B (TcdB) in stool. Here, the analytical performance of the assay is reported.

Methods

Limits of detection (LoD) for TcdA and TcdB in stool and buffer was determined, and a preliminary cutoff, as compared with cell cytotoxicity neutralization assay (CCNA), was established. Analytical reactivity against 38 toxigenic and nontoxigenic C. difficile strains of eight different toxinotypes was determined. Cross-reactivity against 53 other gastrointestinal pathogens and potential interference by 11 endogenous and exogenous substances were determined. Reproducibility was tested with triplicate samples (n = 85), and stability was evaluated in samples stored at room temperature, refrigerated, and frozen conditions, and subjected to three freeze-thaw cycles.

Results

The LoDs for TcdA and TcdB were 0.8 and 0.3 pg/mL in buffer, and 2.0 and 0.7 pg/mL in stool, respectively. Using a preliminary cutoff, the assay demonstrated 96.3% sensitivity and 96.1% specificity compared with CCNA. The Singulex Clarity® C. diff toxins A/B assay detected toxins from all tested strains and toxinotypes. No cross-reactivity or interference were detected. The repeatability was 99%, and samples for C. difficile toxin testing were stable up to 8 hours in room temperature, 1 week in 2–8°C, 6 months in −70°C, and up to three freeze–thaw cycles.

Conclusion

The Singulex Clarity C. diff toxins A/B assay (in development) can detect TcdA and TcdB at very low concentrations and it has high sensitivity and specificity compared with CCNA. The assay demonstrates reactivity to common C. difficile strains, does not show cross-reactivity to common gastrointestinal pathogens, is robust against common interferents, allows for toxin detection in both fresh and frozen stool samples and up to three freeze–thaw cycles, and provides results with high reproducibility.

Disclosures

A. Bartolome, Singulex, Inc.: Employee, Salary. A. Almazan, Singulex, Inc.: Employee, Salary. S. Abusali, Singulex, Inc.: Employee, Salary. S. Tam, Singulex, Inc.: Employee, Salary. E. Lee, Singulex, Inc.: Employee, Salary. A. Changavi, Singulex, Inc.: Employee, Salary. W. Trinh, Singulex, Inc.: Employee, Salary. K. Chau, Singulex, Inc.: Employee, Salary. J. Estis, Singulex, Inc.: Employee, Salary. B. Noland, Singulex, Inc.: Employee, Salary. J. Bishop, Singulex, Inc.: Employee, Salary.
1093. Single Molecule Counting Technology for Ultrasensitive Quantification of Clostridium difficile Toxins A and B
Authors: Katzenbach Phoebe , Dave Gipshu , Mukherjee Ali , Todd John , Bishop Jeffrey , Sandlund Johanna , Estis Joel
Published: November 2018

Background

Clostridium difficile, a spore-forming, anaerobic, Gram-positive bacterium, is the leading cause of nosocomial diarrhea. C. difficile infection (CDI) is mediated by two toxins, A (TcdA) and B (TcdB), and the role of each toxin in CDI pathogenesis remains unclear. Many assays used in CDI diagnostics, such as most NAATs and cell cytotoxicity neutralization assay (CCNA), detect presence of only tcdB or TcdB. In this study, an ultrasensitive immunoassay (UIA) powered by Single Molecule Counting technology was used for quantification of TcdA and TcdB, to assess toxin dynamics in CDI.

Methods

Banked samples from 46 patients with suspected CDI were tested with PCR (BD MAX™ Cdiff Assay) and CCNA, and TcdA and TcdB were quantified using the UIA (tested in triplicate). The limits of detection (LoDs) for the TcdA and TcdB assays are 0.04 and 0.12 pg/mL, respectively.

Results

There were 21 PCR+/CCNA+ and 25 PCR−/CCNA− samples. Both toxins were measured above LoD in all PCR+/CCNA+ samples, ranging up to 100,000 pg/mL. The average CV for the PCR+/CCNA+ samples was 9%. The median TcdA concentrations in PCR−/CCNA− and PCR+/CCNA+ samples were 0.19 pg/mL (IQR 0.12–0.67) and 3,301 pg/mL (125–8,737), respectively. The median TcdB concentrations in PCR−/CCNA− and PCR+/CCNA+ samples were 0.12 pg/mL (0.12–0.21) and 2,690 pg/mL (145–30,307), respectively. In the PCR+/CCNA+ samples, TcdA was one or more logs higher than TcdB in two samples, one or more logs lower than TcdB in six samples, and within one log of TcdB in 13 samples. In one sample (4.8% of PCR+/CCNA+ samples), TcdA was at moderately high concentration while TcdB was below a provisional cutoff, indicating that only TcdA was expressed. There was a significant correlation between TcdA and TcdB (Spearman r = 0.753).

Conclusion

The UIA allows for toxin quantification over a concentration range of ≥5 logs, suggesting that the quantitative TcdA and TcdB assays could be of value in CDI characterization and clinical decision making. The TcdA/TcdB ratio varied, and toxin quantification could be a useful tool in further understanding their individual roles in CDI. The TcdA concentration was not lower than TcdB (trended higher), indicating that detection of tcdB or TcdB alone may not be sufficient for accurate CDI diagnostics.

Disclosures

P. Katzenbach, Singulex, Inc.: Employee, Salary. G. Dave, Singulex, Inc.: Employee, Salary. A. Mukherjee, Singulex, Inc.: Employee, Salary. J. Todd, Singulex, Inc.: Employee, Salary. J. Bishop, Singulex, Inc.: Employee, Salary. J. Sandlund, Singulex, Inc.: Employee, Salary. J. Estis, Singulex, Inc.: Employee, Salary.
1099. Antibiotic Prescriptions for Acute Gastroenteritis during Office and Emergency Department Visits–United States, 2006–2015
Authors: Collins Jennifer P , Watkins Louise Francois , King Laura M , Bartoces Monina , Fleming-Dutra Katherine , Friedman Cindy
Published: November 2018

Background

Acute gastroenteritis (AGE) is a major cause of office and emergency department (ED) visits in the United States. Most patients can be managed with supportive care alone, although some require antibiotics. Limiting unnecessary antibiotic use can minimize side effects and the development of resistance. We used national data to assess antibiotic prescribing for AGE to target areas for stewardship efforts.

Methods

We used the 2006–2015 National Hospital Ambulatory Medical Care Survey of EDs and National Ambulatory Medical Care Survey to describe antibiotic prescribing for AGE. An AGE visit was defined as one with a new problem (<3 months) as the main visit indication and an ICD-9 code for bacterial or viral gastrointestinal infection or AGE symptoms (nausea, vomiting, and/or diarrhea). We excluded visits with ICD-9 codes for Clostridium difficile or an infection usually requiring antibiotics (e.g., pneumonia). We calculated national annual percentage estimates based on weights of sampled visits and used an α level of 0.01, recommended for these data.

Results

Of the 12,191 sampled AGE visits, 13% (99% CI: 11–15%) resulted in antibiotic prescriptions, equating to an estimated 1.3 million AGE visits with antibiotic prescriptions annually. Antibiotics were more likely to be prescribed in office AGE visits (16%, 99% CI: 12–20%) compared with ED AGE visits (11%, 99% CI: 9–12%; P < 0.01). Among AGE visits with antibiotic prescriptions, the most frequently prescribed were fluoroquinolones (29%, 99% CI: 21–36%), metronidazole (18%, 99% CI: 13–24%), and penicillins (18%, 99% CI: 11–24%). Antibiotics were prescribed for 25% (99% CI: 8–42%) of visits for bacterial AGE, 16% (99% CI: 12–21%) for diarrhea without nausea or vomiting, and 11% (99% CI: 8–15%) for nausea, vomiting, or both without diarrhea. Among AGE visits with fever (T ≥ 100.9oF) at the visit, 21% (99% CI: 11–31%) resulted in antibiotic prescriptions.

Conclusion

Patients treated for AGE in office settings were significantly more likely to receive prescriptions for antibiotics compared with those seen in an ED, despite likely lower acuity. Antibiotic prescribing was also high for visits for nausea or vomiting, conditions that usually do not require antibiotics. Antimicrobial stewardship for AGE is needed, especially in office settings.

Disclosures

All authors: No reported disclosures.
1107. The MAAGE Study: Health Care Utilization for the Treatment of Medically Attended Acute Gastroenteritis
Authors: Mattison Claire P , Groom Holly , Donald Judy , Salas S Bianca , Marsh Zachary , Burke Rachel M , Schmidt Mark A , Hall Aron J , Naleway Allison L
Published: November 2018

Background

Acute gastroenteritis (AGE) exacts a substantial disease burden across the age spectrum, although healthcare utilization for AGE is not well characterized. Through active surveillance of medically attended acute gastroenteritis (MAAGE) encounters within a large, integrated healthcare delivery system, we analyzed demographic patterns of healthcare utilization among AGE patients.

Methods

From April 1, 2014 to September 30, 2016, we collected information on all MAAGE encounters in Kaiser Permanente Northwest (KPNW) patients through daily abstraction from electronic health records using ICD-9/-10 codes. For each patient, a MAAGE episode was defined as all MAAGE encounters <30 days apart.

Results

There were 109,493 MAAGE encounters among 39,451 patients. Patients were 60.4% female and 39.6% male; 10.3% were <5 years old, 9.7% were 5–17, 31.1% were 18–44, 25.4% were 45–64, and 23.5% were ≥65. Among those with known race, 87.2% were white; 4.1% were Asian, 3.6% were black, and 5.1% were other or multiple races. Prevalence of any chronic comorbid condition was 52.9%.

Of 52,107 MAAGE episodes, 81.0% first presented as outpatients; this was most common in those aged <5 (92.1%) and decreased with age to 75.0% in those ≥65. First presenting remotely (email or telephone) ranged from 4.0% in those aged <5 to 19.3% in those ≥65; 52.7% of episodes first presenting remotely had no subsequent visits. Few episodes first presented to an emergency department (3.8% in <5 year olds to 6.6% in 18–44 year olds) or inpatient setting (0.1% in <5 year olds to 1.7% in ≥65 year olds).

Most MAAGE episodes comprised of one encounter (median: 1.0, mean: 2.1). The number of encounters per episode was lowest in those <5 years old (median: 1.0, mean: 1.5) and highest in those ≥65 (median: 2.0, mean: 2.5). Most deaths within 30 days from the start of an episode (131/161) were in those ≥65; there were none in those <5, 1 in those 5–17, 5 in those 18–44, and 24 in those 45–64.

Conclusion

We found that the number of encounters per MAAGE episode increased with age and that outpatient and remote encounters are important settings for the initial clinical management of MAAGE in all ages. These data can help to better quantify the economic burden of AGE and guide appropriate delivery of healthcare services.

Disclosures

All authors: No reported disclosures.
1112. Detection of Enteric Viruses in Children With Acute Gastroenteritis
Authors: Hamdan Lubna , Batarseh Einas , Piya Bhinnata , Stewart Laura , Fonnesbeck Chris , Chappell James D , Payne Daniel C , Hall Aron J , Dunn John , Wikswo Mary E , Halasa Natasha
Published: November 2018

Background

Acute gastroenteritis (AGE) is a major cause of morbidity in children. Viral pathogens are the most common infectious agents. Differences in illness characteristics of AGE with and without virus detection are poorly defined. We compared AGE illness characteristics between children with and without any-virus detected, and with single vs. multiple viruses detected.

Methods

Children between 15 days and 17 years with AGE defined as diarrhea (>3 loose stools/24 hours) or any vomiting within 10 days duration were enrolled in Vanderbilt Children’s Hospital inpatient, ED, and outpatient settings from December 2012 to November 2015. Stool specimens were tested by RT-qPCR for norovirus, sapovirus, and astrovirus and by ELISA (VP6 antigen [Rotaclone®]) for rotavirus.

Results

Of 3,705 children enrolled, 2,892 (78%) specimens were collected. A single virus was detected in 1,109 (38%) stools [51% norovirus, 20% rotavirus, 21% sapovirus, and 8% astrovirus], viral co-detections were found in 115 (4%) stools, and 1,665 (58%) had no detected viruses. Table 1 compares children with and without any-virus detected. Children with a single-virus detected were older than those with >1 virus detected (1.8 vs. 1.5 years [P < 0.05]) with no other significant differences.

Conclusion

Children with any-virus detected had more severe symptoms, higher MVS, and more frequently reported sick contacts compared with no-virus detected. Children with no-virus detected were more likely to present with fever and higher temperatures, which may be due to bacterial organisms. These data highlight the importance of infection-prevention precautions in the community and the need for additional testing to define the etiologic spectrum of AGE in children.

Disclosures

N. Halasa, sanofi pasteur: Investigator, Research support. GSK: Consultant, Consulting fee. Moderna: Consultant, Consulting fee.