bluuebunny/crossref_metadata_2025 huggingface dataset:
2701. The Impact of Infant 13-valent Conjugate Pneumococcal Vaccination Program on Invasive Pneumococcal Disease in Children in British Columbia, Canada
Authors: Vadlamudi Nirma K , Patrick David , Hoang Linda , Marra Fawziah
Published: October 2019

Background

A significant reduction in invasive pneumococcal disease (IPD) has been reported following implementation of the 7-valent pneumococcal conjugate vaccine (PCV7) infant immunization program, but not much has been reported after introduction of the 13-valent vaccine (PCV13). This study represents the effect of PCV13 on IPD in British Columbia, Canada over a 14 year period (2002–2015).

Methods

Using provincial IPD laboratory surveillance data, we calculated the annual incidence following implementation of PCV7 (September 2004), and PCV13 (September 2010) in children less than 17 years of age. We also compared incidence rate ratios (IRR) against pre-PCV13 (2004–2010) and pre-PCV7 (2002–2003) baselines for overall and age-specific IPD rates using Poisson regression.

Results

A total of 697 cases were reported over the 14 year period. The overall annual incidence decreased from 10.9 cases per 100,000 population in 2002 to 4.64 cases per 100,000 population in 2015. While overall decline of IPD was 59% (IRR 0.41; 95% CI: 0.35–0.51) compared with baseline, this reduction was greatest after introduction of PCV7 (IRR 0.44; 95% CI: 0.37–0.53); the incremental change after introduction of PCV13 was non-significant (IRR 0.94; 95% CI: 0.78–1.13). The greatest reduction in IPD was in children <2 years of age (PCV13 vs baseline: IRR 0.19; 95% CI: 0.14–0.25), followed by children 3–5 years of age (PCV13 vs baseline: IRR 0.34; 95% CI: 0.21–0.56); no significant change was observed in 6–17 year olds.

Conclusion

While IPD rates have been significantly reduced since the introduction of the PCV vaccines, the impact of the additional 6 serotypes in the PCV13 vaccine is non-significant.

Disclosures

All authors: No reported disclosures.
2722. Effects of Sex, Age, and Race on Immunogenicity of MenB-FHbp, a Bivalent Meningococcal B Vaccine: A Pooled Evaluation of Clinical Trial Data
Authors: Beeslaar Johannes , Peyrani Paula , Maguire Jason , Eiden Joseph , Palmer Paul , Maansson Roger , Crowther Graham , Perez John L
Published: October 2019

Background

MenB-FHbp (bivalent rLP2086), a meningococcal serogroup B vaccine, is approved in several countries for adolescents and young adults. MenB-FHbp elicited robust immune responses and had an acceptable safety profile during an extensive clinical development program. Because immune responses to vaccines can vary by subject demographics, this subgroup analysis pooled data across 7 randomized MenB-FHbp clinical studies to evaluate potential differences in immunogenicity by sex, age, or race/ethnicity in a larger dataset relative to individual studies.

Methods

Data from subjects who received 120 µg MenB-FHbp at 0, 2, and 6 months and had valid immunogenicity results for 4 vaccine-heterologous test strains were included. Immune responses were evaluated by serum bactericidal assays using human complement (hSBA). Immunogenicity endpoints (assessed 1 month after dose 3) were percentages of subjects achieving ≥ 4-fold rise in hSBA titer against each strain, percentages achieving hSBA titers ≥ the lower limit of quantification (LLOQ) against each strain and against all 4 strains combined (composite response), geometric mean hSBA titers against each strain, and percentages achieving hSBA titers ≥ 1:4 (correlate of protection) against each strain.

Results

This analysis included 8026 subjects aged 10‒25 years (51.7% males, 80.7% adolescents aged 10‒18 years, 87.0% white, 9.3% black, 0.8% Asian, 3.0% other race). One month after dose 3, percentages of subjects achieving a ≥ 4-fold rise from baseline titer against each strain and achieving a composite response were similar across age and race (table). A marginally greater percentage of males vs. females achieved ≥ 4-fold rise in titer against each strain, but these differences were not considered clinically meaningful because of the high percentages of responders in both groups.

Conclusion

MenB-FHbp immunogenicity was similar across sex, age, and race in this pooled analysis, with high percentages of responders in all evaluated subgroups. The marginally lower response rates among females compared with males were not considered clinically meaningful. These findings support currently recommended MenB-FHbp vaccination practices without modification by sex, age, or race.

Funding: Pfizer

Disclosures

All authors: No reported disclosures.
165. Comparative Effectiveness of Oral Fluoroquinolones vs. β-Lactams for the Treatment of Patients with Enterobacteriaceae Bloodstream Infections
Authors: Bjork Lauren , Hopkins Teri , Yang Linda , Frei Christopher R , Jones Xavier , Cadena Jose , Walter Elizabeth
Published: October 2019

Background

Fluoroquinolones (FQ) are associated with unacceptable rates of adverse drug events (ADE) and drug resistance. Safe and effective alternative oral agents are needed for definitive treatment of Enterobacteriaceae bloodstream infections (BSI). This study aims to determine whether treatment failure rates were similar in patients who received FQ or β-lactams (BL) for stepdown treatment of Enterobacteriaceae BSI.

Methods

We conducted a retrospective cohort study comparing oral BL vs. FQ as definitive therapy for patients with BSI due to Escherichia coli, Klebsiella spp., or Proteus spp. Eligible patients were ≥18 years old with a monomicrobial BSI treated with a single definitive oral antibiotic. Patients with a total antibiotic treatment duration of <6 or >21 days were excluded. Groups were matched based on age and gender. The primary outcome was treatment failure defined as recurrence or all-cause mortality within 90 days with a 10% non-inferiority margin. Secondary outcomes were death or recurrence within 30 and 90 days, symptomatic urinary tract infection (UTI) or BSI within 30 days, and the safety outcome of antibiotic-related ADE.

Results

The average age was 68 years, with 94% males. In the BL group, 80% had a urinary source of infection vs. 69% of the FQ group. The majority of patients had source control (88% of BL group vs. 83% of FQ group). The most common pathogens were E. coli (66%) and K. pneumoniae (24%). Cefpodoxime (71%) and ciprofloxacin (85%) were the most commonly used oral antibiotics. The average duration of oral therapy was 9.2 vs. 9.6 days and total duration was 14.4 vs. 13.9 days in the BL vs. FQ group, respectively. The primary outcome occurred in 15.4% of the BL group vs. 12.3% of the FQ group (P = 0.8002, RR = 0.80, 95% CI = 0.33–1.90). No deaths were directly attributed to infection. Symptomatic UTI or BSI within 30 days occurred in 20% of BL patients vs. 21.5% of FQ patients (P = 1.0000, RR = 1.07, 95% CI = 0.55–2.11). Mortality or recurrence at 30 days were similar between groups (4.6% of BL group vs. 9.2% of FQ group, P = 0.4920, RR = 2.00, 95% CI = 0.52–7.66). One FQ patient experienced an antibiotic-related ADE (C. difficile infection).

Conclusion

BL are non-inferior to FQ and appear to be as effective for oral step-down treatment of Enterobacteriaceae BSI without the associated risks.

Disclosures

All authors: No reported disclosures.
168. Epidemiology, Risk Factors and Outcome of Bloodstream Infection Within the First Year After Kidney Transplantation
Authors: Siritip Napadol , Nongnuch Arkom , Dajsakdipon Thanate , Thongprayoon Charat , Cheungpasitporn Wisit , Bruminhent Jackrapong
Published: October 2019

Background

Bloodstream infections (BSIs) are an important cause of morbidity and mortality among kidney transplant (KT) recipients, especially within the first year. We investigated for an epidemiology, risk factors and outcome of this specific infection following KT.

Methods

We conducted a retrospective study of all adult KT recipients who developed BSI within the first year after KT from January to December 2016 at a large referral single transplant center in Bangkok, Thailand. The cumulative incidence of BSI after transplant was estimated with Kaplan–Meier methodology. Clinical characteristics, microbiological data, and outcome were extracted. Risk factors for BSI were assessed with multivariate Cox proportional hazards models.

Results

A total of 26 (15.2%) episodes of BSI occurred in 171 KT recipients, 58.5% of them were men and the mean ± SD age was 43 ± 12 years. The majority received deceased-donor allograft (58.5%) and induction therapy (59%). The Kaplan–Meier estimated for BSIs were 12.3% at 3 months, 13.5% at 6 months, and 15.2% at 12 months after KT. Gram-negative bacteria were responsible for 92% of BSI, with Escherichia coli was the most common causative pathogen (65%) and 71% of those produced extended-spectrum β-lactamases enzyme. The genitourinary tracts were the predominant source of BSIs (85%). In a multivariate analysis, the second kidney transplantation [HR, 4.55; 95% CI, 1.24–16.79 (P =0.02)] and receiving induction therapy [HR, 3.05; 95% CI, 1.15–8.10 (P<0.03)] were associated with BSI. One patient (4%) developed acute cellular rejection and one patient (4%) died from septic shock.

Conclusion

One-sixth of KT recipients could develop gram-negative bloodstream infection within the first year after KT especially those underwent the second transplantation or received induction therapy.

Disclosures

All authors: No reported disclosures.
2767. Variation in Incidence of Pediatric Herpes Zoster by First- and Second-Dose Varicella Vaccine Formulations
Authors: Weinmann Sheila , Irving Stephanie , Koppolu Padma , Naleway Allison , Belongia Edward , Hambidge Simon , Jackson Michael L , Klein Nicola , Lewin Bruno , Liles Elizabeth , Marin Mona , Smith Ning , Weintraub Eric , Chun Colleen
Published: October 2019

Background

Varicella (VAR) and measles-mumps-rubella (MMR) vaccines are recommended for children at ages 12–15 months and 4–6 years. These are administered as separate MMR and VAR vaccines (MMR+VAR) or as combined measles-mumps-rubella-varicella (MMRV) vaccine. Herpes zoster (HZ), caused by wild-type or vaccine-strain varicella-zoster virus, can occur in children after varicella vaccination. It is unknown whether HZ incidence after varicella vaccination varies by vaccine formulation or simultaneous receipt of MMR.

Methods

Using data from six integrated health systems, we examined HZ incidence among children who turned 12 months old during 2003–2008 and received varicella and MMR vaccines according to routine recommendations. All HZ cases ≥ 21 days after first varicella vaccination were identified using ICD-9 codes from inpatient, outpatient, emergency room encounters, and claims data, through 2014. HZ incidence was examined by vaccine formulation (MMR+VAR, MMRV, or VAR without same-day MMR) and doses received and compared using incidence rate ratios (IRR).

Results

Among 199,797 children, we identified 601 HZ cases. Crude HZ incidence after first-dose MMR+VAR (18.6 [95% CI 11.1–29.2] cases/100,000 person-years) was similar to the rate after first-dose MMRV (17.9 [95% CI 10.6–28.3] cases/100,000 person-years), but approximately double the rate among those with first-dose VAR without same-day MMR (7.5 [95% CI 3.1–15.0] cases/100,000 person-years); see Table 1. The IRR for HZ after first-dose MMR+VAR or MMRV, compared with VAR, was 2.5 (95% CI 1.4–4.4; P = 0.002). When examining any first or second dose formulation, crude HZ incidence was lower after the second varicella vaccine dose (13.9 cases/100,000 person-years), than in the period before the second dose (i.e., between first and second doses or after the first dose in children with only one dose; 21.8 cases/100,000 person-years, P < 0.0001). HZ incidence was also lower after two varicella vaccine doses in each of the three first-dose formulation groups.

Conclusion

HZ incidence among children varied by first-dose varicella vaccine formulation and number of varicella vaccine doses. Regardless of the first-dose varicella vaccine formulation, children who received two vaccine doses had lower HZ incidence after the second dose.

Disclosures

All authors: No reported disclosures.
2788. Case Report: Severe Community-Acquired Human Adenovirus 7 Infection in a Mother and Son
Authors: Bradford William , Priyank Kumar , Weber Devin , Pettengill Matthew
Published: October 2019

Background

We present the case of a 42-year-old male (Patient 1) with a history of morbid obesity and cirrhosis of unclear etiology who died of acute hypoxic respiratory failure and devastating encephalitis after community-acquired infection with human adenovirus 7 (HAdV7) in spite of antiviral treatment with Cidofovir. Patient 1’s course is outlined in Figure 1. During his stay, the patient’s mother (Patient 2) was also hospitalized in the same unit following a similar presentation with 10 days of flu-like symptoms that progressed to ARDS requiring intubation. Patient 2 recovered from her infection with no specific antiviral treatment.

Methods

N/A.

Results

These cases illustrate particularly fulminant presentations of HAdV7 infection and highlight the high pathogenicity of HAdV7 compared with other adenovirus subtypes. Severe lower respiratory tract HAdV7 infections have been reported most commonly as outbreaks of respiratory illness among military recruits and infants. A notable recent outbreak of HAdV-7d in New Jersey in 2016–2017 resulted in 12 confirmed cases with 4 deaths; however, all deaths occurred in patients with significant medical comorbidities.1 In a case particularly striking for its similarity to the one presented here, a healthy 44-year-old male along with his 68-year-old father were hospitalized with human adenovirus 7 days infection in Chicago in December 2014, with the son requiring ECMO for ARDS and the father briefly requiring ICU-level care.2

Conclusion

While our patient’s case is by no means unprecedented, it does represent an uncommon and potentially serious infection that points to need for continuing nosocomial testing efforts and deserves special attention in outbreak settings. In the future, perhaps use of the extant vaccine for human adenovirus serotypes 4 and 7 (currently licensed for military personnel3) could be expanded for use in civilian populations could be explored and potentially expanded for use in outbreak settings.

Disclosures

All authors: No reported disclosures.
2790. Respiratory Viral Testing and Antimicrobial De-escalation Among Hospitalized Patients at a Tertiary Care Facility, 2015–2016: A Matched Cohort Study Series
Authors: Ciccone Emily J , Kinlaw Alan C , Miller Melissa B , Weber David J , Juliano Jonathan J , Jhaveri Ravi , Willis Zachary
Published: October 2019

Background

The use of multiplex respiratory viral panels (RVP) is increasing. They have the potential to reduce unnecessary antibiotic use, but data are limited on their clinical effectiveness. Our objective was to estimate risk differences for antimicrobial de-escalation (discontinuation, intravenous to oral, or spectrum narrowing) between different sequences and results of RVP and rapid polymerase chain reaction (PCR) tests for influenza +/− respiratory syncytial virus.

Methods

We conducted a retrospective chart review of adults (age ≥18 years) admitted to a floor or stepdown unit at University of North Carolina Hospitals who had a respiratory viral test (RVT) within 48 hours of admission between September 2015 and April 2016. We estimated 3-day RDs for the relation between RVT and antimicrobial de-escalation. To control confounding and account for the 37-hour mean lag between PCR (faster) and RVP (slower) tests resulting, we leveraged the treatment decision design over a series of 1:1 matched cohort studies. Each targeted a clinically relevant scenario: (1) ordering RVP test (vs no RVP order) after learning PCR status; (2) learning RVP+ result (vs. no RVP result) after knowing PCR status; (3) learning RVP+ result (vs. RVP–) after knowing PCR–status; and (4) learning RVP+ result (vs. RVP–) given no prior PCR. For each subcohort, referent patients were matched to index patients by race, gender, RVT in prior month (y/n), age (±10 years), and season (±1.7 months).

Results

The overall cohort (n = 1,342) was 61% White, 29% African American, and 51% female. Median age was 56 years (IQR 39–69). Across all matched subcohorts (Figure 1), the matching success rate was 79–88% and referent frequency of antimicrobial de-escalation ranged 0.6%–1.9%. In scenario 1, ordering RVP results was associated with higher de-escalation (3-day RD 7.6%; 95% confidence intervals [CI] 3.2%, 12.1%). In scenarios 2–4, learning RVP+ results was associated with more frequent de-escalation (3-day RDs 14.8%, 13.8%, and 15.4%).

Conclusion

RVP testing and positive RVP results were associated with increased antimicrobial de-escalation, although de-escalation was overall infrequent. Future research should assess effect modification across subgroups and evaluate cost-effectiveness.

Disclosures

All authors: No reported disclosures.
184. Channeling Alexander Fleming: Efficacy of Penicillin (PCN) to Treat Staphylococcus aureus (SA) Bacteremia
Authors: Mathews Samantha K , Zuckerman Richard A , Calderwood Michael S , Martin Isabella W , Parsonnet Jeffrey
Published: October 2019

Background

Up to 20% of SA isolates in the United States are penicillin-susceptible (PSSA); however, treatment with penicillin has been discouraged because of concern that routine testing may miss strains that have the capacity to produce clinically significant ß-lactamase in vivo. We performed a retrospective analysis to determine whether PCN therapy for the treatment of PSSA bacteremia was of comparable efficacy and safety to standard therapies.

Methods

We identified all episodes of SA bacteremia (March 18, 2010–July 23, 2018). SA penicillin susceptibility testing in our lab was performed by broth microdilution followed by nitrocefin ß-lactamase testing per CLSI guidelines on these isolates. A retrospective chart review was performed and our primary outcome was a composite endpoint of clinical success (no change in PSSA therapy due to persistent or worsening signs and symptoms, no PSSA bacteremia recurrence or persistence, and no infection‐related mortality). Microbiologic failure was defined as either failure to clear bacteremia/infection or recurrence after completion of therapy. Patients were followed until last contact with our medical system, the only tertiary center in the region. We compared our rates of success, mortality, and adverse drug reaction to historical SA bacteremia controls from the literature.

Results

PSSA accounted for 13% (130/971) of SA bloodstream episodes. Nineteen patients with PSSA (15%) were treated with PCN and 79% (15/19) achieved the primary endpoint of clinical success. Of the 4 patients who did not achieve the endpoint, 2 developed rash and were switched to a different antibiotic and 2 died from complications of sepsis. One of the patients died after clearing blood cultures but had DIC and a catastrophic intracranial hemorrhage, the other died of overwhelming sepsis after 4 days (2 days nafcillin, 2 days PCN) with continued bacteremia. Thus, our only microbiologic failure was due to early death from sepsis. Rates of success, mortality and drug reaction were similar to prior reports of alternative standard therapies (Table 1).

Conclusion

PCN is a viable treatment option for PSSA bacteremia as identified by routine laboratory testing. Further study will include characterizing the presence of ß-lactamase in these patient’s isolates.

Disclosures

All authors: No reported disclosures.
189. A Case Series of Elizabethkingia meningosepticum Bacteremia in the Cancer Population
Authors: Hyun Lee Dae , Mehra Ishita , Chandrasekhar Sanjay , Mirza Abu-Sayeef , Shenoy Rahul , Topham Annie , Nanjappa Sowmya , Greene John
Published: October 2019

Background

Elizabethkingia meningosepticum (E. meningosepticum) is a ubiquitous microorganism previously known as Chryseobacterium meningosepticum. It is emerging as a pathogen responsible for bacteremia in immunocompromised patients such as cancer patients especially those with a history of prolonged hospital stay and frequent instrumentations.

Methods

A retrospective chart review of all cases over 10 years in Moffitt Cancer Center showed a total of three patients with E. meningosepticum infection.

Results

First patient (history of multiple myeloma) underwent endoscopy complicated by aspiration pneumonia and blood culture positive for E. meningosepticum infection. He was treated with ciprofloxacin, cefoxitin, minocycline and metronidazole and was discharged in stable conditions after 10 days. The second patient (current acute myelogenous leukemia) had neutropenic fever in the setting of recent chest port infection. Blood culture from chest port showed E. meningosepticum and was treated with ciprofloxacin, meropenem and minocycline successfully. The third patient (history of esophageal adenocarcinoma and acute myelogenous leukemia) had history of recent pneumonia and cellulitis who came in with recurrent neutropenic fever. Blood culture was positive for E. meningosepticum and was treated with ciprofloxacin and minocycline. However, the infection was complicated by multiorgan failure and required tracheostomy. As these three cases illustrate, E. meningosepticum bacteremia has high 28- day mortality rate (41%).

Conclusion

Early identification of the pathogen along with empiric treatment with a fluoroquinolone and/or minocycline is indicated to reduce morbidity and mortality.

Disclosures

All authors: No reported disclosures.
192. Augmenting Utility of Rapid Diagnostic Testing in Treatment of Gram-Negative Bacteremia with Stewardship Intervention
Authors: Gerges Jessica , Raja Karan , Patel Mitesh , Patel Ruben , Chen Brandon , Philips Mona
Published: October 2019

Background

Rapid diagnostic tests (RDT) can identify pathogens in bloodstream infections (BSI) in less than 24 hours. Our institution utilizes an RDT for blood cultures (BCx) that can detect various organisms and resistance determinants. A retrospective evaluation conducted in our institution calculated the negative predictive values (NPV) of various Gram-negative pathogens and susceptibility to target antimicrobials in the absence of detected resistance markers. Resultant NPV >90% for E. coli and K. pneumoniae to ceftriaxone support use of RDT with stewardship intervention for more rapid de-escalation of antimicrobial therapy in patients with resistance marker-negative BSI.

Methods

In our facility, all positive BCx are processed through RDT. In the post-intervention group, pharmacists monitored RDT results and provided recommendations. Our IRB-approved, prospective study assessed time to antimicrobial de-escalation in treatment of resistance marker-negative E. coli and K. pneumoniae BSI before (January 1 to December 31, 2018) and after Stewardship intervention (January 1 to March 31, 2019). Secondary outcomes included days of therapy (DOT) of target narrow-spectrum β-lactams, carbapenems, and non-carbapenem anti-pseudomonal (NCAP) β-lactams, length of stay (LOS), and treatment failure. Data were analyzed using the Fisher exact or Chi-square and t-test for categorical and continuous data, respectively.

Results

Of the 12,893 evaluated RDT results in the pre-intervention group and 2,238 post intervention, 41 and 12 patients met inclusion criteria, respectively. Baseline characteristics were similar in both groups. Time to de-escalation to a target agent was decreased by 24 hours after stewardship intervention (50 v 74.6 hours) (P = 0.14). There were no statistically significant differences in DOTs for target agents (5.19 v 5.25 DOT; P = 0.48), carbapenems (1.29 v 1.08 DOT; P = 0.41), or NCAP β-lactams (1.73 v 2.33; P = 0.25). Treatment failure (2 in each group; P = 0.17) and LOS (10.9 v 11.9 days; P = 0.4) were similar between groups. Protocol compliance and intervention acceptance rate was approximately 60%.

Conclusion

Appreciation of NPVs and utilization of stewardship intervention allowed for early de-escalation of empiric therapy in patients with resistance marker-negative E. coli and K. pneumoniae bacteremia.

Disclosures

All authors: No reported disclosures.
203. Correlating Cardiac PET Results with Intra-Operative Findings in Infectious Endocarditis
Authors: El-Dalati Sami , Weinberg Richard , Murthy Venkatesh , Owczarczyk Anna , Riddell Jamie , Cinti Sandro , Fagan Christopher
Published: October 2019

Background

Care for patients with infectious endocarditis is complicated by delays in diagnosis and relatively low sensitivity of existing diagnostic algorithms, particularly the Duke Criteria. In recent years, cardiac positron emission tomography (PET) has been identified as a useful tool in detecting occult endocardial infections. Multiple prospective studies have demonstrated that when incorporated with conventional imaging modalities cardiac PET can improve the sensitivity of the Duke Criteria by 27–38 percent. These studies used as their gold standard for diagnosis the consensus opinion of an endocarditis team and were characterized by a relatively low percentage of patients who underwent surgery. We reviewed 4 years of surgically managed IE cases at a tertiary care center where cardiac PET was used to aid diagnosis.

Methods

Between July 1, 2014 and December 31, 2018 we retrospectively reviewed 68 surgically managed cases of endocarditis. Cases were identified using ICD-9 and ICD-10 codes of patients who underwent surgical valve replacement for endocarditis as well as all patients who had cardiac PET scans to rule out endocarditis. Variables including PET results, operative findings, valve culture, pathology and PCR testing were recorded.

Results

14 patients were identified who underwent cardiac PET prior to their surgical intervention. 9 cases were classified as possible endocarditis by Duke Criteria and 10 involved prosthetic valves. 12/14 scans were interpreted as suggestive of or consistent with endocarditis. Twelve positive PETs were associated with either operative findings of infection and/or positive PCR testing on the excised valve (positive predictive value: 100%). The 2 patients with negative scans were found to have noninfectious vegetations intra-operatively, negative valve cultures and negative pathology.

Conclusion

Cardiac PET correlates closely with intra-operative findings in patients with endocarditis. In patients with suspected endocarditis it may help guide surgical decision making. Cardiac PET should be considered for addition to the Modified Duke’s Criteria similar to the European Society of Cardiology guidelines.

Disclosures

All authors: No reported disclosures.
207. High Severity and Mortality Due to Methicillin-Susceptible Staphylococcus aureus Infections in a Colombian Hospital
Authors: Ordonez Diaz Karen M , Baron Laura M , Garcia Juan M , Cristancho Edilberto , Alzate John , Carvajal Lina P , Echeverri Aura M , Rincon Sandra , Reyes Jinnethe , Arias Cesar A
Published: October 2019

Background

Methicillin-susceptible Staphylococcus aureus (MSSA) infections are considered less severe than those caused by methicillin-resistant S. aureus. However, we have observed an important increase in severe cases of invasive MSSA infections in a hospital in Pereira, Colombia. Here, we characterize the clinical outcomes and epidemiology of these infections.

Methods

We included adult and pediatric patients hospitalized between February 2018 and April 2019 presenting with invasive infections caused by MSSA. All isolates were sent to a central laboratory to confirm identification. We determined cefazolin MICs at standard (105 CFU/mL) and high inoculum (107 CFU/mL) by broth microdilution and a rapid test to detect cefazolin inoculum effect (CIE). The CIE was defined as an increase of MIC to ≥16 µg/mL when tested at high inoculum. Clinical data (demographics, intensive care unit (ICU) admission, therapy and mortality) were obtained from medical records.

Results

A total of 60 patients were included in the study and 41.6% were women. Most (63.3%) infections were hospital-associated. Bacteremia was the most frequent type of infection (71.6%). The mean duration of hospital stay was 24.5 days (IQR, 14–44). 61.6% of patients were admitted to the ICU with a mean length of stay of 14 days (IQR, 7–30). Mortality at 30 days was 28.3% (17 out of 60 patients) and was slightly higher (30.2%) in patients with bacteremia. Early mortality (48 h) was 10% (n = 6). Most patients (75%) received β-lactams (28.8% cefazolin and 84% oxacillin). 18 patients (33%) had isolates that exhibited the CIE but most (n = 11) received oxacillin. Among 17 patients who died, 35% had received antibiotics other than β-lactams (5 vancomycin, 1 ampicillin-sulbactam) and two did not received any therapy due to rapid death. The mean duration of antibiotic therapy was 11 days. Source control was deemed appropriate in 65% of the cases.

Conclusion

An increase in severe invasive infections caused by MSSA was observed in our hospital with a high proportion of patients requiring ICU care. A significant proportion of patients received inappropriate treatment. Due to the aggressive nature of invasive MSSA infections, efforts to optimize appropriate therapy for these infections are urgently needed in Colombia.

Disclosures

All authors: No reported disclosures.
232. Genomic Evidence for Dissemination of Mycobacterium marinum in an HIV Patient with Multifocal Cutaneous Disease
Authors: Dulanto Chiang Augusto , Khil Pavel P , Manion Maura , Sereti Irini , Zelazny Adrian , Dekker John P
Published: October 2019

Background

Hematogenous dissemination has been proposed to explain multifocal cutaneous disease caused by Mycobacterium marinum in certain patients. Treatment duration for disseminated disease is often months longer than for skin infection alone. However, distinguishing multiple independent inoculation events from dissemination has relied primarily on clinical judgement. Additionally, whether temperature-sensitive non-tuberculous mycobacteria such as M. marinum are indeed capable of invading the vascular space at core body temperature is debated. Here we used whole-genome sequencing (WGS) of serial isolates from a single patient with multifocal cutaneous M. marinum infection to distinguish dissemination of a clonal strain from multiple inoculation events.

Methods

A 35-year-old male with HIV (CD4 of 66 cells/µL) presented with a two-month history of a non-healing M. marinum wound on his left elbow (isolate MM0). This was followed a month later after initiation of antiretroviral therapy by a second M. marinum lesion on the right heel (MM1) without history of repeat inoculation, and increased swelling and erythema of the wound on the left arm (MM2) consistent with paradoxical immune reconstitution inflammatory syndrome. A PacBio genome was generated for MM0 and short read Illumina genomes were generated for MM1 and MM2.

Results

All isolates were found to be closely related, with MM1 and MM2 distinguished from MM0 by one and five single-nucleotide variants (SNVs), respectively. Given the substantial genetic heterogeneity among environmental M. marinum strains, such close relatedness of these isolates suggests common origin, and provides strong evidence for dissemination of a clonal strain in this patient. The SNVs included a frameshift mutation in the purT gene, which encodes a formate-dependent phosphoribosylglycinamide formyltransferase involved in de novo purine synthesis, and missense mutations in atsA and the DNA methylase hsdM. All isolates grew at 35°C, compared with the optimal growth temperature of 30°C typically observed for M. marinum, suggesting thermotolerance permissive for dissemination.

Conclusion

These results demonstrate the potential role of WGS for providing supportive evidence of disseminated infection with M. marinum.

Disclosures

All authors: No reported disclosures.
249. Limited Diagnostic Utility of Extended Aerobic Blood Culture Incubation for Fungal Pathogen Detection
Authors: Bourassa Lori , Kates Olivia , Liu Catherine
Published: October 2019

Background

Blood cultures are an important diagnostic tool for the detection of fungemia. At our institution, fungal blood cultures consist of aerobic blood culture with incubation extended from the standard 5 days to 14 days. Orders for fungal blood cultures exist in multiple electronic order sets for selected populations, including oncology and bone marrow transplant services.

Methods

To determine the yield of fungal blood cultures at our institution, a 570-bed tertiary-care referral center, we extracted all fungal blood culture results over a 4.5-year period (January 1, 2014–May 15, 2018) from a Laboratory Information System.

Results

Of the 21,657 fungal blood cultures performed, only 202 (0.9%) demonstrated growth and 189 (0.9%) grew fungal organisms. The majority (90%, n = 182/202) of positive fungal blood cultures grew a Candida or other yeast species. 96% (n = 174/182) of the fungal cultures that grew yeast would have been detected with standard bacterial blood culture. Eight of these cultures became positive during the extended hold period and grew a Candida species. All 8 cultures were collected from patients who had previous positive cultures for the same Candida species detected by standard incubation. Five fungal blood cultures from 4 patients turned positive after 5 days of incubation. Among these, two additional fungal pathogens were identified including 2 cases of Lomentospora prolificans and 2 cases of Fusarium. In both cases of L. prolificans and one case of Fusarium, the patients had previous positive blood cultures that detected the same organism with standard incubation. One patient with Fusarium had no previous positive blood cultures, but had multiple tissue cultures positive for Fusarium. The remaining cultures that turned positive after 5 days of incubation contained bacterial organisms, a number of which were considered clinically insignificant (e.g., Cutibacterium species).

Conclusion

These data suggest that extended incubation of aerobic blood culture bottles has limited diagnostic utility beyond standard bacterial blood culture for detection of fungemia. Fungal blood cultures represent an opportunity for improved diagnostic test stewardship, and use should be restricted to selected situations in consultation with Infectious Diseases or Laboratory Medicine.

Disclosures

All authors: No reported disclosures.
251. Implementation of the Sōna Coccidioides Antibody Lateral Flow Assay in the Clinical Laboratory Proves to Reduce Cost and Decrease Turnaround Time When Compared with Send out Immunodiffusion and Complement Fixation Testing
Authors: Candelaria Wesley J
Published: October 2019

Background

Coccidioidomycosis (Valley fever) is an airborne, invasive fungal infection endemic to Arizona, California, Mexico, and Central and South America. The dominant method of diagnosis is serology, which includes complement fixation (CF), immunodiffusion (ID), and enzyme immunoassay (EIA). These serological assays require highly trained personnel and are time consuming, with turnaround times (TAT) that range anywhere from 5 days to 2+ weeks. Due to costs of send outs and long TAT, Valley fever presents a diagnostic challenge to physicians and laboratorians. IMMY developed the sōna Coccidioides Antibody Lateral Flow Assay (LFA), a rapid and simple diagnostic assay that detects anti-Coccidioides antibodies in patient serum in 30 minutes.

Methods

We tested the sōna Coccidioides antibody LFA using 315 patient specimens and compared cost-analysis and TAT to a send out reference lab’s ID and CF assays.

Results

In this study, we found that after implementing the sōna Coccidioides Antibody LFA as a screening test, the cost of send-outs reduced by 84%, and the cost of all testing reduced by 68%. The TAT for sending out testing averaged 5–10 days, whereas the sōna Coccidioides Antibody LFA averaged a total TAT of <24 hours.

Conclusion

The sōna Coccidioides Antibody LFA offers a rapid, simple, and inexpensive method for accurately detecting antibodies against Coccidioides spp. in patient serum.

Disclosures

All authors: No reported disclosures.
258. False Negative Rate of T2Candida Assay in Blood Culture Positive Candidemia
Authors: McCarty Todd , Leal Sixto M , Lee Rachael A , White Cameron , Pappas Peter
Published: October 2019

Background

The T2Candida (T2C) assay is an FDA-approved, non-culture-based rapid diagnostic that utilizes PCR and magnetic resonance technology to detect candidemia in a whole blood specimen. T2C can detect the 5 most common pathogenic species: C. albicans, C. tropicalis, C. parapsilosis, C. krusei, and C. glabrata. The sensitivity of T2C is reported to be 88–94%, varying by the species, based on the original clinical trial from 2015. Only 6 patients with candidemia were included in the study, so it was supplemented with samples spiked with known quantities of Candida spp. In this study, we sought to evaluate the sensitivity of T2C with routine usage in a tertiary-care academic hospital.

Methods

All patients with a blood culture (BC) positive for Candida spp. during the years 2016 through 2018 were identified. Repeat positive cultures of the same species within 30 days of the initial culture were excluded. We then reviewed the medical records of those patients with a T2C collected ±12 hours from the time of the BC collection. Data collection included demographics, time to antifungal therapy, time to culture reported positive, impact of false negative T2C on antifungal therapy, and 30-day mortality.

Results

There were 281 episodes of candidemia (designated as a positive blood culture) in the study period. Forty-four of these episodes had a T2C collected within the specified timeframe (Figure 1). Overall, there were 17 false-negative T2C, reflecting a sensitivity of 61% (27/44). Excluding species not detected by T2C, the sensitivity was 71% (21/38). Of the false-negative group, antifungal therapy was impacted in 8 patients: delayed initiation in 6 patients (1–4 days) and treatment interruption in 2 patients (1 dose each). Demographics, time to treatment, time to culture positivity, and 30-day mortality were similar in the two groups (Table 1).

Conclusion

In spite of the test being readily available and increasingly used, only 44/281 (16%) of patients with a positive BC had a T2C ordered concurrently. Our experience shows a much lower sensitivity than the clinical trial, in part due to species not detected by T2C. Considering only those organisms on the T2C panel, the false-negative rate was 29%. Impact on treatment was limited to half of the false-negative patients with no difference in mortality.

Disclosures

All authors: No reported disclosures.
262. Assessment of Serum Galactomannan Test Results of Pediatric Patients with Hematologic Malignancies According to Different Threshold Levels and Consecutive Positivity in Terms of Invasive Aspergillosis Diagnosis: Cross-Sectional Research in a Tertiary Care Hospital
Authors: Çağlar İlknur , Özkerim Duygu , Tahta Neryal , Düzgöl Mine , Bayram Nuri , Demirağ Bengü , Hilkay Karapınar Tuba , Sorguç Yelda , Gözmen Salih , Dursun Vecihe , Oymak Yeşim , Vergin Canan , devrim İlker
Published: October 2019

Background

The aim of this study was to evaluate the diagnostic utility of serum galactomannan (GM) test by investigating the impact of positivity according to different threshold levels and consecutiveness in terms of invasive aspergillosis (IA) in pediatric hematology-oncology patients.

Methods

Positive GM test results between January 2015 and August 2017 were reviewed, retrospectively. The children with hematological malignancies and GM positivity were included in the study and grouped according to the presence of IA. Impact of single and consecutive (3-day interval) GM positivity on IA diagnosis were evaluated according to different galactomannan index (GMI) threshold values of >0.5, >0.7, >1.0, and >1.5.

Results

There were 104 positive GM results from 70 patients. Forty-one patients (58.6%) had no clinical evidence of IA and categorized as the non-IA group. Invasive aspergillosis diagnosis was identified in 29 (41.4%) of the patients; 2 of them were proven and 27 were probable. Demographic characteristics and clinical findings of the patients were reviewed in Tables 1 and 2. According to different cutoff GMI values, the number of positive results was 104 for >0.5, 76 for >0.7, 57 for >1.0 and 32 for >1.5. The PPVs were low at a single GMI of >0.5 (39.4%) and reached to 50.0% with single GMI of >1.0. There was not a statistically significant difference between IA and non-IA groups in terms of different thresholds of a single GM positivity (P > 0.05) (Table 3). The number of two consecutive positive results was 34 for GMI of >0.5, 20 for GMI of >0.7, 13 for GMI of >1.0 and 4 for GMI of >1.5. In the IA group, GM positivity of consecutive results was significantly higher than non-IA group (P < 0.05). The PPVs of two consecutive positive results for GMI >0.5, GMI >0.7, GMI >1.0, and GMI >1.5 were 58.8%, 65.0%, 84.6%, and 100.0%, respectively. The effect of the GMI increase between two consecutive GM results on IA diagnosis (GM2-GM1 >0.5) was also evaluated and the PPV was found 53.8% without a statistical significance between two groups (Table 4).

Conclusion

When evaluated with consecutive GM positivity, the GM assay would have higher PPVs independently from the GMI cutoff value chosen. Since it may be more effective on IA diagnosis, consecutive sampling should be performed in pediatric patients at high risk.

Disclosures

All authors: No reported disclosures.
265. Clinical Epidemiology of Invasive Fungal Infection with Aspergillus and Mucor Species in a Tertiary Children’s Hospital
Authors: Oikonomopoulou Zacharoula , Patel Sameer , Toia Jacquie , Muller William
Published: October 2019

Background

Patients undergoing hematopoietic stem cell transplantation and patients with hematologic malignancies are at increased risk for acquiring invasive fungal infection (IFI) due to immune system impairment from chemotherapy. Affected patients require prolonged antifungal therapy with the risk of associated toxicity and extended hospitalization due to delay of accurate diagnosis. There is a lack of effective serologic biomarkers and hesitancy to proceed with tissue diagnosis due to thrombocytopenia or other associated risks. Mortality in oncology patients with invasive mycoses is high, with pediatric mortality rates of 30–40% at 12 weeks following diagnosis.

Methods

All patients that were admitted to Lurie Children’s Hospital between January 2014 and December 2018 and received voriconazole, ambisome, posaconazole and isavuconazole were identified. The following data were retrospectively collected: CT chest and sinus, (1,3)-β-d-Glucan and Aspergillus galactomannan, ANC and ALC at diagnosis, blood next-generation sequencing, tissue 18s rRNA, fungal culture, duration of neutropenia and lymphopenia, site of infection, time between underlying diagnosis and development of IFI, surgical intervention and associated mortality.

Results

A total of 94 unique patients that received voriconazole were identified. There were 8 proven cases of invasive Aspergillus infection the past 5 years, 50% male, mean age 14 years. Only 25% of patients had positive serum Aspergillus galactomannan and 37.5% had positive β-d-Glucan. Seven cases were due to Aspergillus fumigatus and one case was due to Aspergillus flavus. There were 9 patients with mucormycosis and all but one were culture positive. Three patients with Mucor had mold identification in blood next-generation sequencing prior to surgery. Mucor associated mortality was 22.2%.

Conclusion

The majority of pediatric patients with invasive aspergillosis did not have characteristic chest CT imaging findings and serum Aspergillus galactomannan was usually negative.The was no associated mortality in invasive Aspergillus cases, whereas the mortality rate of invasive mucormycosis was 22.2%. Although we have a small sample size, this is significantly lower compared with published literature.

Disclosures

All authors: No reported disclosures.
304. Hepatocellular Carcinoma Occurs Frequently and Early After Treatment in HCV Genotype 3 Infected Persons Treated with DAA Regimens
Authors: Un Nabi Tayyab Ghias , Rasool Shafqat , Nasir Bilal , Butt Adeel A
Published: October 2019

Background

Treatment of HCV with directly acting antiviral agents (DAAs) is associated with a significant reduction in cardiovascular, metabolic and cancer risk. However, there are conflicting data regarding the risk of hepatocellular carcinoma (HCC) after DAA treatment. Risk of HCC in HCV genotype 3 infected persons after DAA therapy is not well known.

Methods

We prospectively studied HCV-infected persons initiated on treatment between October 2014 and March 2017 at two centers in Pakistan. All persons were free of HCC at study initiation. The occurrence of HCC was confirmed based on radiologic findings on a triphasic CT on 64 slice MDCT scanner. The treatment regimen was at the discretion of clinical care providers, taking into account the national guidelines and patient preferences. Patients were followed for 24 weeks after the completion of therapy. Informed consent was obtained from all participants.

Results

A total of 662 persons were initiated on treatment. Median age (IQR) was 50 (41, 57) years and 48.8% were male. At baseline, 49.4% were cirrhotic with 90% of cirrhotics having compensated cirrhosis. 91% were genotype 3 and SVR was attained in 91.9%. Treatment regimens used were: Sofosbuvir (SOF)/ribavirin (RBV)/pegylated interferon (PEG-IFN), 25.2%; SOF/RBV, 62.4%; SOF/RBV/daclatasavir (DCL), 10.6%; SOF/DCL, 2.0%. Incident HCC was detected in 42 patients (12.8%) in the six month period after treatment completion, and was exclusively observed in those with cirrhosis. In multivariable Cox regression analysis, SVR was associated with a reduction in HCC risk (HR, 95% CI: 0.35, 0.14,0.85) while SOF/RBV/DCL regimen (compared with SOF/RBV/PEG-IFN) was associated with an increased risk of HCC (HR, 95% CI: 17.32, 2.14,140.36). In K-M plots by treatment regimen, those treated with SOF/RBV, SOF/RBV/DCL, or SOF/DCL regimens had shorter HCC-free survival compared with those treated with a SOF/RBV/PEG-IFN regimen. (See figure)

Conclusion

In a predominantly genotype 3 cohort, incident HCC occurs commonly and early after treatment completion, and exclusively in those with pretreatment cirrhosis. SVR reduces but does not completely eliminate the risk of HCC. Treating HCV-infected persons before the development of cirrhosis may reduce future risk of HCC.

Disclosures

All authors: No reported disclosures.