bluuebunny/crossref_metadata_2025 huggingface dataset:
2271. Bacteremia Due to Multi-Drug-Resistant Organisms Is an Independent Risk Factor for Death Among Patients Supported by Extracorporeal Membrane Oxygenation (ECMO)
Authors: Rivosecchi Ryan , Sappington Penny , Clarke Lloyd , Clancy Cornelius J , Nguyen Minh-Hong
Published: October 2019

Background

ECMO is a type of life-support for patients with refractory respiratory and/or cardiac failure. Our objective was to determine the incidence, resistance patterns and risk factors for development of blood stream infections (BSI) in patients receiving ECMO therapy.

Methods

This was a retrospective cohort study of a single intensive care unit. All patients receiving ECMO therapy between 7/1/13 and 4/28/18 were evaluated. Multidrug-resistant (MDR) pathogens were defined as non-susceptible to ≥1 agent in ≥3 antimicrobial classes, and vancomycin-resistant Enterococcus (VRE).

Results

471 patients received ECMO, accounting for 4,739 ECMO days. Thirty-six patients (7.6%) had ≥1 episode of BSI; 47 episodes occurred, resulting in 10 events per 1,000 ECMO days. The most common organisms were Enterobacteriaceae (26%), 33% of which were MDR. Staphylococcus aureus (17%), coagulase-negative Staphylococcus (17%), Enterococcus faecium (11%) and Candida spp. (6%) were also identified. Overall, 20% of BSI were due to MDR bacteria. Median duration of BSI was significantly longer for infections due to VRE (8.5 days), than other organisms (1 day; P = 0.0006). Duration of ECMO (P < 0.0001), continuous renal replacement therapy (P = 0.01), units of blood transfused (P = 0.0001) and end-stage lung disease (ESLD) awaiting transplant (P = 0.004) were risk factors for BSI. Duration of ECMO, units of blood transfused and ESLD were independent risk factors for BSI. VV vs. VA-ECMO or central vs. peripheral cannulation were not significant risk factors. By logistic regression, MDR bacterial BSI was associated with longer duration of ECMO (P = 0.001) and number of units of blood transfused (P = 0.01). 1-year mortality after initiation of ECMO was 48%. Independent risk factors for 1-year mortality were age (P < 0.0001) and BSI due to MDR bacteria (P = 0.049).

Conclusion

The rate of BSIs during ECMO is relatively low, but these infections are commonly caused by MDR bacteria and associated with high 1-year mortality. Clinicians should consider empiric antibiotic coverage for MDR bacteria in patients with BSI on prolonged ECMO, and in patients on ECMO who received multiple blood transfusions. Since MDR bacterial BSI is an independent risk factor for mortality, future research on preventive strategies are warranted in high-risk ECMO cohorts.

Disclosures

All authors: No reported disclosures.
2290. Carbapenem vs. Piperacillin–tazobactam Definitive Therapy for Patients with Bloodstream Infections Due to Ceftriaxone Not Susceptible Escherichia coli or Klebsiella species
Authors: MacVane Shawn H , Bhalodi Amira A , Spafford Kyle , Humphries Romney , Oppermann Niels
Published: October 2019

Background

Definitive therapy with piperacillin–tazobactam (TZP) for ceftriaxone (CRO)-resistant E. coli or K. pneumoniae bloodstream infections (BSI) has been shown to be inferior to carbapenem therapy in a randomized trial.

Methods

The Premier US database was queried for hospitalized patients with monomicrobial E. coli or Klebsiella spp BSI that were not susceptible (NS) to CRO between June 2015 and May 2018. Adults with index positive blood culture(s) drawn within the first 2 hospital days who were treated with active antibiotic therapy that continued for ≥3 consecutive days were included. We defined antibiotics administered on or prior to Day 3 as empirical therapy and all subsequent days as definitive therapy. Outcomes among patients who received definitive therapy with a carbapenem vs. TZP were evaluated.

Results

There were 954 patients (mean age, 67.6 years; 52.4% women) who met selection criteria and received active empirical therapy. 729/954 received carbapenem definitive therapy and 38/954 received TZP definitive therapy. Median Charlson Comorbidity Index scores were similar between carbapenem and TZP definitive therapy groups (6 vs. 5, P = 0.78). Crude 14-day in-hospital mortality for CRO-NS BSI due to E. coli or Klebsiella spp. was 4.4%. Definitive therapy with TZP (6/38; 15.8%) was associated with an increased likelihood of 14-day mortality relative to that of a carbapenem (22/729; 3.0%; P < 0.0001). The increased 14-day mortality observation was consistent in a multivariate cox proportional hazards model (adjusted hazard ratio, 5.70; 95% CI, 2.09 to 13.23; P = 0.002). Of patients who received carbapenem definitive therapy, 14-day mortality was 2.7% (19/693) if a carbapenem was part of empirical therapy and 8.3% (3/36; P = 0.06) if empirical therapy did not include a carbapenem. Median post-blood culture length of stay (7 vs. 6 days, P = 0.65) and hospital costs ($13,886 vs. $13,559, P = 0.62) were similar between carbapenem and TZP definitive therapy groups<./p>

Conclusion

In this large US database, definitive therapy with TZP was associated with an increased likelihood of 14-day mortality relative to that of definitive carbapenem therapy in patients with CRO-NS BSI due to E. coli or Klebsiella spp. These findings support recent clinical evidence in favor of definitive carbapenem therapy for CRO-NS BSI due to E. coli or Klebsiella spp.

Disclosures

All authors: No reported disclosures.
2291. Evaluation of Multidrug-Resistant Pseudomonas aeruginosa Isolates in Patients Receiving Ceftolozane/tazobactam
Authors: Bodo Emily C , Caffrey Aisling , Lopes Vrishali , Cusumano Jaclyn A , Puzniak Laura A , McCann Eilish , LaPlante Kerry
Published: October 2019

Background

Multidrug-resistant (MDR) Pseudomonas aeruginosa is a challenging pathogen to treat. Ceftolozane/tazobactam (C/T) is a combination cephalosporin and β-lactamase inhibitor that has demonstrated activity against MDR P. aeruginosa, including carbapenem-resistant isolates. The objective of this study was to evaluate multidrug resistance in P. aeruginosa isolates obtained from patients treated with C/T across the Veterans Affairs (VA) Healthcare System nationally.

Methods

Hospitalized patients who received at least 1 dose of CT between January 2015 and April 2018 and had a positive P. aeruginosa culture were included in this retrospective study. Culture source and antimicrobial susceptibility reports were assessed for each P. aeruginosa isolate. Isolates were categorized as multidrug-resistant based on the Centers for Disease Control (CDC) definition. Resistance rates were categorized by source of culture.

Results

We identified 174 positive P. aeruginosa cultures among 154 patients who received at least one dose of C/T during the study period. The most common sources of isolates were lung (40% of patients), urine (21%), skin and soft tissue (15%), blood (14%), and bone/joint (14%). Most patients (98.1%) had isolates that were MDR, with high rates of carbapenem (84.4%), extended-spectrum cephalosporin (82.5%), and fluoroquinolone (79.9%) resistance. In this cohort, 50.6% of patients received at least one antibiotic prior to initiating C/T to which their clinical culture was not susceptible.

Conclusion

Antibiotic resistance was high in this cohort of patients with P. aeruginosa, and as a result, use of non-susceptible antibiotics occurred in 50.6% of patients before C/T was started. The high carbapenem resistance rates are of great clinical concern, but highlight an area of utilization for C/T given its activity against carbapenem-resistant P. aeruginosa.

Disclosures

All authors: No reported disclosures.
2299. A London Hospital’s Experience of Confirmed Measles Infections and Re-Infections Between 2009 and 2019
Authors: Sturdy Ann , Haque Tanzina , Griffiths Paul , Brown Kevin , Irish Dianne , Mahungu Tabitha
Published: October 2019

Background

2018 to 2019 has seen a global resurgence in measles cases, with the UK seeing an over 3-fold increase in cases in 2018 compared with 2017. In this context, our center saw a cluster of geographically linked measles cases presenting in the first quarter of 2019. We present this with comparative data of confirmed measles cases from our center over the preceding 10 years. Given the growing recognition of measles “re-infection” in fully vaccinated individuals, we also present our first confirmed cases of reinfection within this cohort.

Methods

Retrospective analysis of confirmed measles cases (positive Measles IgM or detectable Measles RNA) between 2009 and 2019. Laboratory and demographic data were obtained from electronic patient records.

Results

18 cases (of which 14 were adults) of measles (all genotype D8 of those tested) were confirmed in the first 4 months of 2019. 12 presented within a 14 day period from a geographically linked part of North London. There were 4 confirmed measles re-infections (detectable measles RNA on a buccal swab with either a high Measles IgG avidity or previous documented measles immunity). From the 10 year data, cases peaked in 2011 and 2016 consistent with national trends. Of the 89 cases identified, 60 (67%) were adults, who were over twice as likely to be admitted as children, had a longer median length of stay in hospital (2 days vs. 1.5 days) and were more likely to develop a hepatitis (1/10 pediatric cases vs. 26/48 adults, p ≤ 0.01)or other complications. The majority of adults (68%) were unsure of their vaccination status.

Conclusion

4 cases of 18 in the first 4 months of 2019 were confirmed re-infections. Re-infections in fully vaccinated individuals are described in the literature, typically presenting with a milder course; however, these are the first cases we have identified at our center. Overall, adult cases were more likely to be admitted to hospital and to have a complicated course compared with children. Vaccination history in adults was of limited clinical utility due to lack of reliable documentation and the potential for reinfection.

Disclosures

All authors: No reported disclosures.
123. Impact of Enterococcal Bacteremia on Clinical Outcomes in Patients with Liver Cirrhosis
Authors: Phe Kady , Won Isabel , Carlson Travis J , Ryan Russo Hannah , Yau Raymond
Published: October 2019

Background

Patients with liver cirrhosis are at an increased risk for bacterial infections due to bacteria overgrowth and dysregulation of the intestinal barrier function. These infectious complications are associated with significant morbidity and mortality. Currently, there is a paucity of literature evaluating the clinical outcomes of patients with enterococcal bacteremia and cirrhosis. We hypothesized that patients with cirrhosis and subsequent enterococcal bacteremia would have a higher odds of mortality.

Methods

This was a retrospective, case–control study including adult patients (>18 years) with liver cirrhosis and >1 positive blood culture with Enterococcus species (ENT) admitted from June 2013 through August 2018. These cases were then matched with cirrhotic patients without enterococcal bacteremia (NO ENT) in a 1:1 ratio based on the Model for End-Stage Liver Disease (MELD) score. The primary endpoint was all-cause inpatient mortality. Multivariable logistic regression was used to control for other patient covariates.

Results

A total of 136 patients were identified during the study period (68 ENT and 68 NO ENT). The median length of stay was significantly longer in ENT patients (24.5 vs. 9 days, P < 0.001), while NO ENT patients were more likely to have renal dysfunction (55.9% vs. 83.8%, P < 0.001). All other baseline characteristics between the two groups were similar. Inpatient mortality was found to be significantly higher in ENT patients than NO ENT patients (51.5% vs. 29.4%, P = 0.009). In the multivariable analysis, risk factors found to be independently associated with mortality included enterococcal bacteremia (OR 3.96, 95% CI 1.61–9.73), MELD score (OR 1.11, 95% CI 1.05–1.19), and APACHE II score (OR 1.14, 95% CI 1.06–1.23).

Conclusion

Enterococcal bacteremia, MELD score, and APACHE II score were found to be independent risk factors for all-cause inpatient mortality in patients with liver cirrhosis. Future studies are needed to elucidate how treatment choice and bacterial characteristics might also influence patient outcomes.

Disclosures

All authors: No reported disclosures.
2302. A Meta-Analysis of Risk Factors for Herpes Zoster Infection
Authors: Parhar Kamalpreet K , Huang Bill , Vadlamudi Nirma K , Marra Fawziah
Published: October 2019

Background

The burden of herpes zoster (HZ) is significant worldwide, with millions affected and the incidence rising. Current literature has identified some risk factors for this disease; however, there is yet to be a comprehensive study that pools all evidence to provide estimates of risk. Therefore, The purpose of this study was to identify various risk factors, excluding immunosuppressive medication, that may predispose an individual to developing herpes zoster.

Methods

The literature search was conducted in MEDLINE, EMBASE, Cochrane Central, Cochrane Systematic Reviews, Web of Science, CAB Direct, yielding case–control, cohort and cross-sectional studies that were pooled from January 1966 to September 2018. Search terms included: zoster OR herpe*OR postherpe*OR shingle*AND riskOR immunosupp*OR stress OR trauma OR gender OR ethnicity OR race OR age OR diabetes OR asthma OR chronic obstructive pulmonary disease OR diabetes. Risk ratios for key risk factors were calculated via natural logarithms and pooled using random effects modeling.

Results

From a total of 4417 identified studies, 93 were included in analysis (n = 3826134 HZ cases). Immunosuppression through HIV/AIDS (RR 3.25; 95% CI 2.47–4.27) or malignancy (RR 2.17; 95% CI 1.86–2.53) significantly increased the risk of HZ compared with controls. Family history was also associated with a greater risk (RR 2.48; 95% CI 1.70–3.60), followed by physical trauma (RR 2.01; 95% CI 1.39–2.91) and older age (RR 1.68; 95% CI 1.41–2.01). A slightly smaller risk was seen those with psychological stress, females, and comorbidities such as diabetes, rheumatoid arthritis, cardiovascular diseases, renal disease, SLE, and IBD compared with controls (RR range: 2.08 to 1.25). We found that black race had lower rates of HZ development RR 0.69 (95% CI 0.56–0.85).

Conclusion

This study demonstrated patients with family history of HZ, older age, female sex, have particular comorbidities or are immunosuppressed have an elevated risk of herpes zoster. Patients with these characteristics are prime candidates for vaccination.

Disclosures

All authors: No reported disclosures.
2303. Chronic Hepatitis B Virus Infection and Risk of Herpes Zoster: A Cohort Study
Authors: Cheong Haesuk , Kim Bomi , Jeong Joo Eun , Chang YooSoo , Yoo Seungho
Published: October 2019

Background

No cohort studies have evaluated the effect of hepatitis B virus (HBV) infection on the risk of herpes zoster. We investigated the association of HBV infection with the development of herpes zoster.

Methods

We performed a cohort study of 224,691 non-cirrhotic adult men and women free of herpes zoster at baseline who underwent serologic testing for hepatitis B surface antigen (HBsAg) and were followed annually or biennially for a median of 4.2 years. Incident cases of herpes zoster were ascertained using the Korean Health Insurance and Review Agency (HIRA) database. A Cox proportional hazard model was used to estimate the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for incident herpes zoster according to HBsAg seropositivity status.

Results

During 830,073.4 person-years of follow-up, 11,061 cases of incident herpes zoster were identified. HBsAg seropositivity was inversely associated with the development of herpes zoster. After adjustment for possible confounders, the multivariable-adjusted hazard ratios (95% CI) for herpes zoster comparing HBsAg-positive to HBsAg-negative participants was 0.83 (0.75–0.93).

Conclusion

In a large cohort of Korean adults, HBsAg seropositivity was associated with lower risk of herpes zoster, suggesting that HBV seems to inhibit the reactivation of varicella-zoster virus.

Disclosures

All authors: No reported disclosures.
126. Cascade of Care for Opioid Use Disorder in Patients with Infective Endocarditis
Authors: Saldana Carlos S , Bal Gabriella , Shrestha Nabin K , Englund Kristin , Gordon Steven M
Published: October 2019

Background

The term “Cascade of Care” has been used to analyze care delivered by a health system for conditions such as HIV, hepatitis C, tuberculosis, and diabetes. It outlines sequential steps required to reach a specific outcome (i.e., viral suppression in the case of HIV). This allows to estimate the proportion of patients achieving each step and to identify gaps in care. Medication-assisted treatment (MAT) is integral in the treatment of patients with infective endocarditis (IE) and opioid use disorder (OUD). We propose a Cascade of Care aiming to identify fundamental milestones in the management of these patients.

Methods

A retrospective cohort study examined patients with IE in the setting of OUD hospitalized between July 1, 2007 and January 1, 2015 to the Cleveland Clinic. We identified 4 key steps along the treatment cascade of these patients and estimated the proportion of patients: (1) evaluated by an addiction treatment service, (2) prescribed MAT while in-patient, (3) prescribed MAT at discharge, and (4) continued MAT at least 90 days after discharge.

Results

Of 273 patients with IE in the setting of OUD, 134 (49%) were evaluated by an addiction treatment service; 45 (17%) were prescribed MAT while in-patient; only 22 (8%) were prescribed MAT at discharge. At 90 days following discharge, there was evidence of continuing MAT for all 22 patients (8%).

Conclusion

Describing the process of addiction treatment for patients with IE and OUD in the format of a cascade of care provides a powerful quantitative method to identify gaps in care and can be used as a resource to implement interventions to address losses. We found only 8% of these patients continued MAT in the community after discharge. This study provides an estimate of how compromised the potential benefits from medical and surgical treatment for IE are by the lack of an effective approach to OUD after hospital discharge.

Disclosures

All authors: No reported disclosures.
2332. Low Serum Vitamin D Levels Are Related to Life-Threatening Respiratory Syncytial Virus Infection in Previously Healthy Infants
Authors: Martin Ferolla Fausto , Walter Yfran Eduardo , Gabriela Ballerini Maria , Toledano Analia , Caratozzolo Ana , Clara Giordano Ana , Carrizo Barbara , Feldman Florencia , Anselmino Cecilia , Chiormi Agustina , Visingardi Gabriela , Retta Alejandra , Reyero Mariana , Dastugue Monica , Mascardi Normando , Neira Pablo , Ropelato Gabriela , Marta Contrini Maria , Luis Lopez Eduardo
Published: October 2019

Background

Serum 25-hydroxy-vitamin D (VD) effects on lung growth and immune system modulation might affect respiratory infections outcomes. Data are controversial regarding the role of VD status in the severity of Respiratory Syncytial Virus (RSV) infection. The aim of this study was to assess serum VD levels and its association with life-threatening disease (LTD) in previously healthy infants infected with RSV.

Methods

Prospective cohort study including previously healthy infants <12 months, hospitalized with a first RSV infection in 2017–2018. Viral load (VL) was assessed by qRT–PCR in nasopharyngeal aspirates and serum VD levels measured by ECLIA, in samples obtained on admission. VD deficiency was defined as levels <20 ng/mL, VD insufficiency 20–29 ng/mL, and LTD as need of intensive care and mechanical or noninvasive ventilation

Results

98 patients, mean age 4.5 months (±3.1), 55 (56.1%) male. VD status: 18 (18.4%) with deficiency, 32 (32.6%) with insufficiency; 14 (77.8%) patients with deficiency had not received VD supplementation. There was no relationship between VD deficiency and anemia (P = 0.28) or age (P = 0.27). LTD was observed in 17 infants, with no significant differences in socioeconomic, pregnancy and infant variables compared with other RSV cases. Patients with LTD had significantly lower levels of VD (17.5 ng/mL [IQR 15.2–26.3] vs. 31.8 ng/mL [IQR 23.5–52.1, P < 0.001)], Figure 1. 15 patients, 88.2% of all infants with VD levels ≤29 ng/mL developed LTD compared with a study population frequency of LTD of 17.3%. Multivariable regression analysis including breastfeeding confirmed VD deficiency as a risk factor for LTD (aOR 14.3, 95% CI 3.9–51.5, P < 0.001). Normal VD values conferred protection (aOR 0.1, 95% CI 0.02–0.49, P = 0.004). VD levels inversely correlated with days of hypoxemia (P = 0.007); VD deficiency increased the risk of requiring O2 supplementation >7 days (aOR 8.5, P < 0.001). VL did not correlate with VD levels (P = 0.696), length of stay (P = 0.378), days of hypoxemia (P = 0.681). VL was not associated with LTD (P = 0.42).

Conclusion

Vitamin D deficiency was a risk factor for LTD in previously healthy infants with RSV infection. Viral titers did not correlate with VD levels. These findings provide additional evidence for the development of low-cost preventive and therapeutic strategies.

Disclosures

All authors: No reported disclosures.
127. Novel Treatment Approach for Left Ventricular Assist Device-related Infections
Authors: Yalcin Yunus C , Verkaik Nelianne , Bax Hannelore I , Croughs Peter D , Bogers Ad J J C , Caliskan Kadir
Published: October 2019

Background

Left ventricular assist device (LVAD) implantation has become an effective treatment option for patients with severe heart failure. However, infections remain a substantial risk. Therefore, the aim of this study was to gain insight in the incidence and outcome of LVAD infections in our center and develop an up-to-date flowchart for the management of LVAD-related infections.

Methods

A retrospective study was performed which included all patients with an LVAD implanted between 2006 until 2019, along with a rigorous review of the current literature. Clinical records and microbiological laboratory results of all patients were reviewed. In view of local infectious complications, a flowchart was developed for the contemporary management of LVAD-related infections (Figure 1).

Results

Overall, 106 patients (median age 54 years [IQR 47–60], 78% male) were included, of whom 92 (87%) as bridge-to-transplantation/decision and 14 (13%) as destination therapy. LVAD-related infections occurred in n = 30 (28%) of the patients. The median time until first infection was 308 days [IQR 115–528], and the median duration of hospital stay was 16 days [IQR 4–29]. Eighty percent of LVAD-related infections were driveline-related. The most common causative pathogen was Staphylococcus aureus, which was present in almost half of the cases (40%). Patients who experienced infections were younger (46 [IQR 37–57] vs. 56 [IQR 52–62]; P < 0.001).The survival rate at 3 years was 76% in the infected vs. 94% not infected patients; P = 0.037). A secondary infection occurred in 10 patients (33%). At 3 years of follow-up, 31 patients were successfully transplanted. Six patients with deep S. aureus driveline infections were treated according to the standardized protocol of whom 2 with suppressive therapy by cephalexin, with clinical success so far.

Conclusion

LVAD infections occur frequently and lead to prolonged periods of hospital admissions and death. The lack of standardized treatment regimens complicates the treatment of LVAD-related infections. A comprehensive flowchart to treat future LVAD-related infections in a protocolized fashion was developed, based on our single-center experience. While the preliminary results look promising, more follow-up time of the treated patients is needed.

Disclosures

All authors: No reported disclosures.
2346. Cost Savings Associated with Implementation of Clinical Decision Support for Clostridiodes difficile Testing
Authors: Hoegg Cindy L , Williams Katie L , Shelov Eric , Metjian Talene A , Maria Cardenas Ana , Kelsen Judith , Hayes Molly , Lori Handy K
Published: October 2019

Background

Clinical decision support for Clostridioides difficile infection (CDI) diagnostics reduces inappropriate testing, leading to decreased need for isolation and antibiotic use. Our institution utilized manual discontinuation by laboratory staff of CDI testing for inappropriate specimens, including formed stool and age < 1 year. We aimed to assess the financial impact of instituting a CDI best practice alert at a quaternary care children’s hospital.

Methods

A multidisciplinary team mapped inappropriate testing criteria identified from literature review with discrete fields in our electronic health record (EHR, EpicCare) to design an alert. The exclusion criteria identified included: (1) age < 1 year; (2) positive C. difficile test within past 14 days; (3) less than or equal to 3 unformed stools in past 24 hours; (4) current receipt of CDI-directed therapy; or (5) laxative use or barium exposure in prior 48 hours. 6 months of data prior to implementation were reviewed to estimate impact of the alert. At implementation, any exclusion criteria detected in the EHR at the time of order entry triggered an alert to deter CDI testing. Cost estimates for averted tests (Quick Check Complete Assay/Illumigene) included cost of test ($50), cost of isolation/personal protective equipment ($159/day), and cost of treatment with oral vancomycin in false-positives ($2250/treatment course).

Results

In a 6-month pre-implementation period, 586 tests for CDI were ordered; of which, 23% were identified by our criteria as inappropriate. During the first 3 months of alert implementation, 256 tests were ordered, of which 105 (41%) caused the alert to fire. Of those, 56 tests were not ordered, for a 22% reduction in testing. Laboratory staff continued to manually stop tests not meeting criteria, such as patient age <1 year when possible. Based on avoidance of testing, use of PPE, and 10 day antibiotic treatment for false-positives (assumed 25% by literature review), this translated to cost savings of $69,916, and an annual cost savings of $279,664.

Conclusion

Implementation of an alert for select patients using a bioinformatics algorithm reduced inappropriate CDI testing. Clinical decision support for CDI can lead to substantial cost savings for both antibiotic use and isolation precautions.

Disclosures

All authors: No reported disclosures.
2352. Clinician Assessment of Pretest Probability for Clostridioides difficile Infection and Disease Severity While Using Multiplex, Syndromic Molecular Panel in Patients Presenting with Diarrhea
Authors: Throneberry S Kyle , Lopansri Bert K , Grisel Nancy A
Published: October 2019

Background

The role of nucleic acid amplification tests (NAAT) for diagnosing Clostridioides difficile (CD) infection remains controversial. Adding CD to multiplex molecular panels (GIPCR) that detects multiple GI pathogens of community origin, has the potential to introduce confusion leading to delayed diagnosis and unnecessary antibiotic use especially if pretest probability is not considered.

Methods

We conducted a retrospective study to determine the frequency at which clinicians characterize pretest probability and disease severity in adult patients with diarrhea who tested positive for CD by GIPCR (BioFire, Inc.) from July 1, 2017 to October 16, 2018. We excluded immunocompromised patients. Routine testing includes reflex to GDH and toxin A/B detection when GIPCR is positive for CD. Charts were reviewed and clinical suspicion (PTP) was assigned as high, medium, low, or not done. Disease severity was classified as mild, moderate and severe. Exposure to systemic antibiotic within 90 days prior to testing and stool frequency was also captured.

Results

In total, 447 patients were included in the analysis: 110 (24.6%) were positive for both GDH and Toxin (G+/T+), 158 (35.3%) were G+/T−, 179 (40%) were G−/T−, and 149 (33%) were not classified. Toxin positivity was highest in the setting of high PTP (67%) (figure). In contrast, toxin was negative in most cases when suspicion for CDI was low or not characterized (81%). For medium suspicion, only 36% were T+. Antibiotic exposure prior to testing was observed in 203 (45%) of the cases. More G+/T+ patients received antibiotics (63%) before testing and 66% of G−/T− did not receive antecedent antibiotics. Clinicians did not characterize frequency of diarrhea in 261 (58%) of the patients tested and 95% of cases did not undergo severity classification. When documented, 24% of tested patients had < 3 diarrheal episodes/day (Table 1). Most cases where multiple pathogens were detected were T− (84.5%) and G−/T− (44%) (Table 2).

Conclusion

Overall, characterization of diarrheal illness was poor and PTP was frequently omitted. A large proportion of GIPCR results positive for CD (40%) were negative for both GDH and Toxin. CD results in molecular testing with syndromic panels should be interpreted with caution.

Disclosures

All authors: No reported disclosures.
2362. Back to the Future: The Impact of Multi-Step Algorithm C. difficile Testing at a Large Tertiary Medical Center
Authors: Bork Jacqueline , Claeys Kimberly C , Johnson J Kristie , Jones Jennifer , Obiekwe Uzoamaka , Lusby Martha , Heil Emily , Leekha Surbhi
Published: October 2019

Background

Antibiotic stewardship and infection control programs rely on C. difficile infection (CDI) test results to measure CDI incidence in the hospital setting. C. difficile carriage is common and distinguishing infection from colonization is difficult with the highly sensitive nucleic acid amplification testing (NAAT) commonly used. Current guidelines recommend a multi-step algorithm for testing. The impact on patient outcomes and CDI metrics are largely unknown.

Methods

This was a pre-post study at the University of Maryland Medical Center, evaluating the impact of a CDI testing strategy (introduced October 2018) that simultaneously reported NAAT and confirmatory enzyme immunoassay (EIA) when used with existing best practice alerts for appropriate testing. Pre-intervention (November 2017–September 2018) and post intervention (October 2018–March 2019) periods were compared for mean CDI incidence (CDI per 10,000 admissions) defined by: (1) positive NAAT, (2) reported CDI (last positive test), and (3) treated CDI (receiving oral vancomycin). Both community and hospital-onset cases were included. The NAAT CDI incidence was used as the pre-intervention comparison for all 3 measures. In addition, oral vancomycin days of therapy (DOT) per 1,000 patient-days (PD) was compared. Pre–post comparisons of mean CDI incidence and mean DOT rates were done using Student t-test.

Results

There were 3,237 samples tested (2,269 pre and 968 post-intervention) with 376 NAAT positive (262 pre and 114 post-intervention). Of the 99 tests with reflex EIA, there were 74 discordant tests (NAAT +/EIA -) with 35 (47%) treated for CDI. Mean NAAT CDI incidence pre-intervention was 54 per 10,000 admissions. Post-intervention mean CDI incidence decreased as follows: 45 NAAT CDI per 10,000 admissions (P = 0.13), 15 reported CDI per 1000 admissions (P < 0.0001), and 28 treated CDI per 10,000 admissions (P = 0.0007). Oral vancomycin DOT per 1,000 PD decreased from 16 to 9 (P = 0.0002).

Conclusion

C. difficile NAAT testing with confirmatory EIA, in combination with best practice alert, decreased reported and treated cases of CDI, which may distinguish infection vs. colonization and avoid unnecessary treatment, beyond that achieved with alerts that improve appropriate patient selection for testing.

Disclosures

All authors: No reported disclosures.
2374. Healthcare Resource Use, Costs, and Recurrences in Patients with Clostridioides difficile Infection: A Real-world Data Analysis
Authors: Nelson Winnie , Stong Laura , Sacks Naomi , Portelli Alexandria , Healey Bridget , Lang Kathleen , Dahdal David N
Published: October 2019

Background

Clostridioides difficile infection (CDI), especially recurrent CDI (rCDI), is associated with high morbidity and resource use and imposes a significant burden on the US healthcare system. The objective of this study was to evaluate the burden of rCDI on healthcare resource utilization.

Methods

A retrospective study analyzed commercial claims data from patients aged 18–64 years old in the IQVIA PharMetrics Plus™ database. CDI episodes required an inpatient stay with CDI diagnosis code (ICD-9-CM 008.45; ICD-10-CM A04.7, A04.71, A04.72), or an outpatient medical claim with CDI diagnosis code plus a CDI treatment, and index episodes occurred from January 1, 2010 to June 30, 2017. Only patients who were observable 6 months before and 12 months after the index CDI episode were included. Each CDI episode was followed by a 14-day claim-free period after the end of treatment. rCDI was defined as another CDI episode within an 8-week window immediately after the claim-free period. Number of CDI and rCDI episodes, healthcare resource use, and costs were calculated over 12-month follow-up and stratified by number of rCDI episodes. Costs were adjusted to 2018 dollars.

Results

46,571 patients with an index CDI episode were included, with 3,129 (6.7%) who had 1 rCDI, 472 (1.0%) who had 2 rCDI, and 134 (0.3%) who had 3+ rCDI episodes. Mean age was 47.4 years, and 62.4% were female. In the 12-month follow-up, the mean (SD) numbers of inpatient visits were 1.4 (2.1) for those with no rCDI, 2.7 (3.4) for those with 1 rCDI, 3.7 (3.9) for those with 2 rCDI, and 5.8 (6.0) for those with 3+ rCDI episodes. Emergency department (ED) visits had a similar trend, with mean (SD) number of visits of 1.5 (3.5), 2.5 (6.0), 3.7 (7.0), and 4.6 (13), respectively for the four study groups. All-cause costs after the index CDI were $71,980 for those with no rCDI, $131,953 for those with 1 rCDI, $180,574 for those with 2 rCDI, and $207,733 for those with 3+ rCDI.

Conclusion

CDI and rCDI are associated with substantial healthcare resource utilization and direct medical costs. During the 12 months after an index CDI episode, the number of inpatient admissions and ED visits increased substantially for patients with an rCDI episode. Direct medical costs for patients with rCDI also increased with number of recurrences.

Disclosures

All authors: No reported disclosures.
2383. Epidemiological and Clinical Features of Clostridioides difficile Infections in Pediatric Oncology and Transplant Patients
Authors: Barbar Ruba , Hakim Hana , Hayden Randall , Hayden Randall
Published: October 2019

Background

Clostridioides difficile infection (CDI) is the most common cause of healthcare-associated diarrhea-causing significant morbidity and mortality in adults. The epidemiology and clinical course of CDI in children, especially with cancer are poorly defined. We aim to describe the clinical, epidemiological features and outcomes of CDI, and identify risk factors for recurrence in a pediatric oncology center

Methods

This is a retrospective cohort study of CDI in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients in 2016 and 2017. CDI cases were identified by electronic medical record search for positive C. difficile PCR tests. CDI episodes were classified as incident, duplicate or recurrent and community-onset (CO), hospital-onset (HO), or community-onset healthcare facility associated (COHCFA) using National Healthcare Safety Network surveillance definitions. Demographics, underlying diagnosis, CDI characteristics, drug exposure, and outcomes were analyzed. Risk factors for CDI recurrence were assessed by logistic regression.

Results

One hundred-eighty patients developed 305 CDI episodes; 233 (78%) were incident, 65 (22%) recurrent, and 7 duplicate and removed from the analysis. Recurrence occurred after 51 incident episodes (Table 1). Median age (range) was 5.7 (0.5–25.5) years. Underlying diagnoses were leukemia/lymphoma (56%) and solid/brain tumors (42%). 87 (29%) received HSCT. Almost all patients received antibiotics 4 weeks prior to CDI. 14% received laxatives 72 hours prior to CDI. 50% of patients were neutropenic. The median (range) duration of diarrhea was 10.0 (1–77). Thirty patients (15%) were hospitalized due to CDI, for a median (range) of 3 (1–49) days. 16% had a delay in chemotherapy due to CDI. There was no ICU admissions nor death due to CDI. None of the evaluated variables was identified as a significant risk factor for CDI recurrence by logistic regression (Table 3).

Conclusion

CDI in pediatric oncology and transplant patients ran a generally mild course, associated with chemotherapy delay and hospitalization in a small fraction, and no attributable ICU admission nor death. CDI recurred in less than a quarter of patients. Risk factors for CDI recurrence were not identified.

Disclosures

Randall Hayden, MD, Abbott Molecular: Advisory Board; Quidel: Advisory Board; Roche Diagnostics: Advisory Board
2410. Molecular Characteristics of Environmental Clostridioides difficile From a Large Texas Hospital
Authors: Begum Khurshida , Alam M Jahangir , McPherson Jacob , Costa Gabriela , Miranda Julie M , Lancaster Chris , Garey Kevin W
Published: October 2019

Background

Clostridioides difficile is an anaerobic spore-forming, toxin-producing Gram-positive bacillus listed by the CDC as an “urgent threat” pathogen. Epidemiologic studies using whole-genome sequencing (WGS) have found that genetically distinct lineages infections occur in hospitalized patients, in addition to the fact that C. difficile spores persist on hospital surfaces after disinfection. The purposes of this study were to isolate and characterize C. difficile from the environment of a large Texas hospital.

Methods

We collected 330 swab samples of hospital environmental surfaces using sterile cotton gauze. The samples were then anaerobically enriched in brain heart infusion broth for 48–72 hours and plated onto cycloserine–cefoxitin fructose agar (CCFA). Suspected colonies were then genetically characterized using PCR (for tcdA, tcdB, cdtA, cdtB and tpi genes) and genotyped using fluorescent PCR ribotyping techniques.

Results

A total of 90/330 (27.3%) environmental samples were culture positive for C. difficile, of which 75/90 (82.1%) tested were toxigenic C. difficile by the presence of tcdA, tcdB, cdtA or cdtB. A total of 16 distinct ribotypes were identified from 41 C. difficile isolates tested using a fluorescent-ribotyping method. The predominant ribotypes isolated were F078–126 (8/41), F002 (5/41), F106 (4/41), F255 (4/41), and F014-020 (3/41).

Conclusion

We found a diversity of C. difficile strain types in various hospital high-touch surface environment in addition to ribotype F027 and F078, suggesting the hospital environment a reservoir and significant source C. difficile infections.

Disclosures

All authors: No reported disclosures.
2417. Feasibility and Safety of Using a Probiotic Comprised of Lactobacillus acidophilus CL1285, L. casei LBC80R and L. rhamnosus CLR2 for C. difficile Infection Prevention Among Antibiotic Users: 15-Years of Prospective Results from a Single-Center
Authors: Maziade Pierre-Jean , Lussier Daniel , Dubé Francoise
Published: October 2019

Background

Hospitals use multiple concurrent prevention strategies to curb nosocomial C. difficile infection, but there are limited data on the long-term feasibility or safety of using a probiotic. Pierre-Le Gardeur Hospital, Québec, has been administering a probiotic comprised of Lactobacillus acidophilus CL1285, L. casei LBC80R and L. rhamnosus CLR2 since 2004 with documented results through March 31, 2014. Here we present an update for the past 5 years.

Methods

Several nosocomial infection prevention practices were running concurrently at the hospital. Adult inpatients treated with antibiotics from April 1, 2014 to March 31, 2019 were eligible to receive the probiotic. The hospital pharmacy ensured that each patient took the probiotic capsules (Bio-K+® 50 Billion) daily from the initiation of antibiotic use. Confirmed nosocomial cases of C. difficile infection were recorded and reported to the provincial public health agency. The rate of nosocomial CDI for this hospital was compared with other non-University affiliated hospitals in the health region with more than 110 beds and fewer than 45% of patients age 65 and older, and, to all other hospitals in the health system.

Results

Cumulatively over the past 15 years, more than sixty thousand antibiotic-treated adult inpatients took the probiotic daily during antibiotic use. Among 13 comparable hospitals, Pierre-Le Gardeur Hospital had the lowest rate of nosocomial CDI in 2014–2015, 2015–2016, 2016–2017, 2017–2018 and on average had the lowest rate for 2013–2018 (1.1 CDI cases per 10,000 patient-days). Compared with all hospitals in the Province of Quebec health system, N = 95, the hospital had the lowest nosocomial CDI rate on average for 2013–2018. No cases of Lactobacillus bacteremia were detected.

Conclusion

The overall infection prevention strategy has been highly effective, resulting in a consistently low rate of nosocomial CDI. We found that it is feasible to administer this probiotic to antibiotic-treated inpatients with few restrictions. No Lactobacillus infections were observed from any of the three strains of bacteria for this probiotic when given to more than sixty thousand adult inpatients.

Disclosures

All authors: No reported disclosures.
2421. Efficacy of Secondary Prophylaxis with Oral Vancomycin in Preventing Recurrent Clostridioides difficile Infections in Patients Receiving Systemic Antibiotics
Authors: Pillinger Kelly E , Lew Jason K , Conn Kelly M , Shulder Stephanie
Published: October 2019

Background

One of the major challenges in Clostridioides difficile infection (CDI) is preventing recurrence, particularly in the setting of risk factors, such as systemic antibiotics that impact the gut microbiome. There are little data to demonstrate the impact of secondary prophylaxis with oral vancomycin and due to the lack of evidence, the IDSA guidelines do not make a recommendation.

Methods

This was a multi-site, retrospective cohort study of adult inpatients within the University of Rochester Medical Center who received either a high- or medium-risk systemic antibiotic between July 1, 2013 and September 30, 2018 and had a positive C. difficile test within one year prior to admission. The primary endpoint was incidence of recurrent CDI within 90 days from the start of antibiotics in patients who received oral vancomycin prophylaxis (OVP) vs. those who did not receive prophylaxis (control).

Results

Of 425 patients screened, 153 patients were included in the control and 78 patients in the OVP group. The OVP group was more likely to be immunosuppressed (P < 0.001), have increased hospital length of stay (P < 0.001), receive a proton pump inhibitor (P = 0.049), have a prior episode of CDI within the previous 90 days (P < 0.001), and have > 1 prior episode of CDI (P = 0.038). The control group was more likely to have received metronidazole for the most recent CDI episode (P < 0.001), likely reflecting mild-moderate severity. Recurrent CDI within 90 days was 10.3% in the OVP group compared with 17.6% in the control (P = 0.175). A subgroup analysis of the patients with recurrent CDI found the time to recurrence from initiation of systemic antibiotics was similar in the OVP group compared with control (43 vs 30 days, P = 0.223).

Conclusion

While there was not a statistically significant difference in recurrent CDI within 90 days, the OVP group had numerous risk factors that made these patients at higher risk for recurrence compared with the control group. This may be clinically important and certain risk factors, such as timing of previous CDI episode, could be used to guide which patients should receive OVP. Prospective studies are needed to better elucidate the role of OVP and better define the patients that may benefit the most.

Disclosures

All authors: No reported disclosures.
135. Clinical and Microbiologic Analysis of Risk Factors for Mortality in Patients with Carbapenem-Resistant Acinetobacter baumannii Bacteremia
Authors: Cho Eunbeen , Son Hyo-Ju , Bae Seongman , Seo Hyeonji , Yang Eunmi , Sung Heungsup , Kim Mi-Na , Jung Jiwon , Jae Kim Min , Kim Sung-Han , Lee Sang-Oh , Hee Woo Jun , Soo Kim Yang , Pil Chong Yong
Published: October 2019

Background

Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is an emerging clinical issue and shows high mortality rates. There are a few studies that have evaluated the microbiologic risk factors for mortality in CRAB bacteremia. Aim of this study is to identify the clinical and microbiologic risk factors for mortality in CRAB bacteremia.

Methods

Adult patients with monomicrobial CRAB bacteremia at a 2,700-bed tertiary hospital between December 2012 and December 2018 were retrospectively enrolled in the study. Risk factors for 30-day mortality were evaluated through a detailed clinical and microbiological analysis of study patients. All isolates collected on the first day of bacteremia were subjected to colistin susceptibility testing by broth microdilution and genotyping by multilocus sequence typing (MLST).

Results

A total of 164 patients were enrolled and 90 (55%) died within 30 days. Of the 164 patients, 111 (68%) were male and median age was 66.5 years. The most common MLST genotype was ST191 (80 isolates, 49%), followed by ST451 (14%) and ST784 (13%), and 12 (7%) isolates were resistant to colistin (MIC ≥4 mg/L). Deceased patients were more likely to have hematologic malignancy, neutropenia, pneumonia, and primary bacteremia; less likely to have solid tumor, catheter-related infection, and biliary tract infection; more likely to have a high Pitt bacteremia score; and less likely to receive appropriate antibiotic treatment, colistin, and combination therapy with colistin and tigecycline, compared with surviving patients (Table 1). Genotype, colistin MIC, and colistin resistance were not associated with mortality (Figure 1 and 2). In multivariable analysis, neutropenia (aOR, 3.25; 95% CI, 1.18–8.95), catheter-related infection (aOR, 0.33; 95% CI, 0.11–0.99), biliary tract infection (aOR, 0.20; 95% CI, 0.04–0.99), a high Pitt bacteremia score (aOR,1.42; 95% CI, 1.20–1.67), and combination therapy with colistin and tigecycline (aOR, 0.36; 95% CI, 0.14–0.92) were independent risk factors for mortality (Table 2).

Conclusion

Clinical factors such as the site of infection, severity of bacteremia, and specific combination therapy rather than microbiologic factors contributed to mortality in CRAB bacteremia. Appropriate combination therapy may help improving outcomes in CRAB bacteremia.

Disclosures

All authors: No reported disclosures.