bluuebunny/crossref_metadata_2025 huggingface dataset:
1369. Clinical Manifestations, Treatment, and Outcome of Nontuberculous Mycobacteria (NTM) Infection in Adult-Onset Immunodeficiency Associated with Anti-interferon-gamma Autoantibodies in King Chulalongkorn Memorial Hospital
Authors: Jutivorakool Kamonwan , Vanichanan Jakapat
Published: October 2019

Background

There is an increase of anti-interferon-γ autoantibodies syndromes because it is now well recognized, especially in the Southeast Asia region. One of the clinical features is an infection caused by nontuberculous mycobacteria (NTM). NTM infection in patients with anti-interferon-γ autoantibodies is usually severe, recurrent, and disseminated. In this study, we describe the clinical characteristics, treatment, and outcome of NTM infection in patients with anti-interferon-γ autoantibodies

Methods

A retrospective cohort study was conducted at the King Chulalongkorn Memorial Hospital, Bangkok, Thailand, during 2010–2018. Demographic, clinical, and microbiological data were collected and analyzed.

Results

A total of 45 patients were enrolled in this study. Twenty-nine patients were males, and 16 patients were females. The most common clinical manifestations were fever with lymphadenopathy. The median age of the study population was 55 years. The most common organ that was infected was the lymph node (91%). Sweet’s syndrome (68%) was the most common immunological skin reaction. The proportion of infection caused by rapid-growing NTM was more prevalent than slow-growing NTM. The most common NTM was Mycobacterium abscessus (44.4%). The most common co-pathogen identified in this study was Salmonella (37.8%). All patients had positive antibody to interferon-γin the serum which was detected by enzyme-linked immunosorbent assay (ELISA) and mean optical density was 3.28. Fifty-one percent of the patients received long-term antimycobacterial therapy due to chronic active infection, new infections and relapsed. 22.2% of the patients developed a new infection during treatment. However, 28.9% of patients were completely cured of the infection during the follow-up period. The overall mortality rate was 11.1%

Conclusion

Adult-onset immunodeficiency with anti-interferon-γ autoantibodies is a unique clinical syndrome that has been recognized in Thailand. Treatment of this disorder requires a long duration of the combination of antimycobacterial agents. Sweet’s syndrome is an indicator of recurrence/relapse of NTM infection during the clinical course. Long-term monitoring and immunomodulator are essential for the management of this condition.

Disclosures

All authors: No reported disclosures.
1384. Mycobacterium marinum Infection: 21 Years of Experience at a Tertiary-Care Hospital
Authors: Castillo Almeida Natalia E , Gurram Pooja , Abu Saleh Omar
Published: October 2019

Background

Mycobacterium marinum is a slow-growing, non-tuberculous mycobacterium responsible for skin and soft-tissue infections (SSTIs), tenosynovitis, and osteomyelitis (OM). We conducted a retrospective study describing the risk, clinical course, and outcome of M. marinum infection.

Methods

Adult patients with culture-confirmed M. marinum infections were identified from the mycology laboratory at Mayo Clinic, Rochester from January 1998 to December 2018. M. marinum infection was defined as uncomplicated (limited to SST) and complicated (tenosynovitis, OM, or disseminated).

Results

Forty-six cases of culture-confirmed infection with M. marinum were included (Table 1). Only 16 cases (35%) reported a water exposure and 22 (48%) involved finger and/or hand trauma. The median time to diagnosis was 3.6 months. Most patients (76%) presented with uncomplicated M. marinum infection with skin lesions mainly localized in the upper limb (Table 2). QuantiFERON and PPD were positive in 4 (8%) and 2 (4%) cases, respectively. Granulomatous inflammation and positive special stains were noted in 34 (74%) and 11 (24%) cases, respectively. Cases with complicated M. marinum infection had a longer duration of symptoms and length of treatment (P < 0.05) (Table 3). Prior to diagnosis, 63% of patients received at least one antibiotic for bacterial SSTIs. More than 50% of the patients diagnosed with M. marinum received a one drug regimen and 8% did not initiate therapy. Median treatment duration was 4.4 months. Twenty-six cases (56%) had susceptibilities performed and treatment modifications were made in 10 cases (38%). From the patients that started therapy, 73% completed therapy and 33% were lost to follow up. Cured was achieved in 87% of cases that completed therapy, 2 cases (6%) had a recurrence, and only one patient with active malignancy had a positive blood culture and died. Twelve (44%) and 10 cases (37%) were cured with one and two-drug regimens, respectively.

Conclusion

Most patients with M. marinum infection present as an uncomplicated infection in the upper limb. Classical exposure was only suspected in a third of the cases. Patients with complicated M. marinum infection had a prolonged duration of symptoms and lengthy treatment. Most patients were successfully treated with a one and two-drug regimen.

Disclosures

All authors: No reported disclosures.
1385. Mechanism-Based, In Vitro Inhibition of Mycobacterium abscessus: Assessing β-Lactam Therapy
Authors: Dousa Khalid M , Kurz Sebastian G , Bethel Christopher R , Barnes Melissa D , Taracilla Magdalena A , Selvaraju Suresh , Jacobs Michael R , Kreiswirth Barry , Kasperbauer Shannon H , Daley Charles L , Bonomo Robert A
Published: October 2019

Background

M. abscessus (Mab) is an emerging pathogen, a highly drug-resistant rapidly-growing nontuberculous mycobacteria. Mab L, D transpeptidases (LdtMab 1–5), D,D carboxypeptidase and BlaMab β-lactamase are important targets. Herein, we tested the susceptibility of ceftaroline (TAR) and imipenem (IMI) alone and in combinations with two diazabicyclooctanone β-lactamase inhibitors (BLI), relebactam (REL) and avibactam (AVI), against representative clinical isolates belonging to the Mab complex and assessed the mechanism of inhibition using mass spectrometry (QTOF-MS)

Methods

Minimum inhibitory concentrations (MICs) of TAR and IMI with or without AVI and REL and a TAR-IMI combination with and without REL were determined using microdilution. Approximately 5 x 105 colony-forming units (CFU) per milliliter were inoculated into Middlebrook 7H9 broth supplemented with 10% (vol/vol) oleic albumin dextrose catalase and 0.05% (vol/vol) Tween 80. AVI or REL were added at fixed concentration of 4 µg/mL to serial dilutions of TAR or IMI. For the TAR-IMI combinations, IMI at 1 µg/mL, and serial dilutions of TAR were used. Mab isolates were incubated with test agents at 30°C for 48 h, and MIC was defined as lowest antibiotic concentration that prevented visible bacterial growth. (QTOF-MS) was used to assess intermediates of BlaMab, LdtMab1 and LdtMab2 with TAR, IMI, AVI, and REL

Results

In-vitro susceptibility testing on representative clinical Mab strains (table). MIC90 was > 128 μg/mL for TAR and 8 μg/mL for IMI. Combination of TAR and IMI lowered MIC’s of all clinical isolates to <0.06 μg/mL. Addition of REL or AVI lowered TAR MICs but had minimal or no impact on IMI or TAR-IMI MICs. Mass spectrometry analyses of BlaMab, LdtMab (1–2) alone and incubated with IMI, TAR, REL and AVI (figure). BlaMab β-lactamase bound the AVI and REL, but acyl complexes with TAR or IMI were not detected. LdtMab (1–2) form stable acyl complexes with AVI, REL, TAR, and IMI.

Conclusion

Addition of IMI to TAR lowers MICs of TAR against Mab to therapeutically achievable concentrations. It would be welcome news for clinicians who are treating patients with highly resistant Mab infection that the combination of TAR and IMI is commercially available and thus might be considered as part of a rescue regimen.

Disclosures

All authors: No reported disclosures.
1397. Risk Factors of Unfavorable Clinical Outcomes in Patients with Brain Abscess and Subdural Empyema in Korea
Authors: Cho Yunsuk , Ahn Sangmin , Sohn Yujin , Lee Yongseop , Hyun Jonghoon , Ji Lee Woon , Ho Kim Jung , young Ahn Jin , Jin Jeong Su , su Ku Nam , yong Choi Jun , Yeom Joon-Sup , Seong Hye
Published: October 2019

Background

Brain abscess is a fatal neurological infection, despite reduction of mortality rate on account of medical improvement. Therefore, we investigated to identify risk factors for poor clinical outcomes of patients with brain abscess and subdural empyema in Korea.

Methods

A retrospective analysis was conducted among patients treated for brain abscess or subdural empyema over a period of 11 years between May 2005 and July 2016 in a tertiary hospital, Seoul, South Korea. Based on medical records, we reviewed the clinical findings, therapeutic modalities and prognostic factors of brain abscess or subdural empyema. A multivariate analysis was performed to evaluate the independent risk factors of poor clinical outcomes. Unfavorable clinical outcomes were defined as death or neurologic deficit.

Results

In total, 121 patients were enrolled in this study. 79 (65.2%) were males and the mean age was 55.3 years. The common symptoms at presentation included a focal neurological deficit (52.8%), a reduced Glasgow coma scale (47%), headache (49.5%) and fever (22.3%). Gram-positive cocci were most frequently isolated as the causative microorganism. The most common location of brain abscess was the frontal lobe (32.5%), followed by parietal (18.7%) and temporal lobe (11.38%) and a subdural empyema (8.26%). 28-day mortality was 2.47% (3/121), and 43.8% (53/121) had long-term disability. In multivariate analysis, reduced GCS, headache at presentation and high blood urea nitrogen were independently associated with unfavorable clinical outcomes.

Conclusion

In this study, reduced GCS, headache at presentation and high blood urea nitrogen were significant risk factors for unfavorable clinical outcomes in patients with brain abscess and subdural empyema.

Disclosures

All authors: No reported disclosures.
1398. Clinical Performance of Film Array Meningitis/Encephalitis Multiplex PCR Panel in CNS Infection
Authors: Ananthanarayanan Rajalakshmi , Sasidharan Aswathy , Chandran Sarath
Published: October 2019

Background

Rapid identification of pathogen is important in the management of meningoencephalitis. A fully-automated multiplex PCR, the FilmArray (FA) meningitis/encephalitis (ME) panel, detects 14 pathogens simultaneously in an hour. As there is not much data on this, we undertook this study to understand its performance.

Methods

A retrospective analysis was done on patients, both adult and pediatric, admitted with meningitis/encephalitis syndrome between December 2016 and 2018 and who underwent the FA–ME panel (BioFire Diagnostics, USA) multiplex PCR test on CSF. The performance of the FA- ME panel was compared with that of routine tests done on CSF which is cell count, biochemistry, gram stain, bacterial culture, and other relevant tests.

Results

FA- ME panel was done in 259 patients and it detected pathogen in 61 (23.6%) patients with ME syndrome. Viruses accounted for 70.4%, bacteria 24.5%, and 2 patients had 2 organisms in a single sample (enterovirus and H. influenzae on both occasions). Enterovirus was the commonest accounting for 29 cases, followed by varicella in 11, pneumococci in 9. HHV 6, H. influenzae, Strep agalactiae and Listeria were the rest. Enterovirus meningitis showed seasonal prevalence; 24 out of 29 cases occurred during October till December. CSF bacterial culture yield was low, positive only in 8 (3%) cases and matched with FA ME panel in one sample which grew pneumococci; 7 other cultures grew either Gram-negative pathogens, rare organisms/ contaminants not included in FA ME panel. CNS tuberculosis was diagnosed in 6, 7 patients had aseptic meningitis due to tropical infections, 5 of which were dengue fever, 2 were scrub typhus. Overall, 191 patients (73.7%) were treated as CNS infection through FA ME panel were negative in 130 of these, rest had alternative diagnosis. Antibiotic de-escalation was better in the group with positive FA ME panel result.

Conclusion

FA-ME panel has better diagnostic yield compared with culture (26.3% vs. 3%). Viruses were commoner and majority were enteroviruses showing seasonal prevalence. Those bacteria that grew in CSF culture but not identified by FA ME panel were Gram-negative or unusual pathogens. Additional tests need to be used when considering post-traumatic or nosocomial meningitis, tuberculosis, and tropical infections.

Disclosures

All authors: No reported disclosures.
1415. Use of Adjunctive Steroids in Adults with Encephalitis
Authors: Allana Ambreen , Samannodi Mohammed , Hansen Michael , Hasbun Rodrigo
Published: October 2019

Background

To describe the use and the impact on clinical outcomes of adjunctive steroids in adults with encephalitis.

Methods

We conducted a retrospective observational study of 230 adults (age >17 years) who met the international consortium definition for encephalitis. An adverse clinical outcome was defined as a Glasgow outcome score of 1–4. The study took place at three tertiary care hospitals in Houston TX, between August 2008 and September 2017.

Results

A total of 230 adults with encephalitis were enrolled, out of which 121 (52.6%) received steroids. Adjunctive steroids were given more frequently to those with focal neurological deficits (P = 0.013), had a positive cerebrospinal fluid (CSF) HSV PCR (P = 0.013), required mechanical ventilation (MV) (P = 0.011), required intensive care unit (ICU) admission (P < 0.001), had white matter abnormalities (P = 0.014) or had cerebral edema on the brain magnetic resonance imaging (MRI) (P = 0.003). An adverse outcome was seen in 139 (60.7%) of patients. Predictors for adverse outcomes included a Glasgow coma score (GCS) < 8, fever, seizures, ICU admission, and presence of edema on brain MRI. The use of adjunctive steroids did not impact clinical outcomes (P = 0.521). Independent prognostic factors on logistic regression analysis were edema on brain MRI (7.780 [1.717–35.263] P = 0.008), GCS < 8 (6.339 [1.992–20.168] P = 0.002), and fever (2.601 [1.342–5.038] P = 0.005).

Conclusion

Adults with encephalitis continues to be associated with significant adverse clinical outcomes in the majority of patients. Adjunctive steroids are used in the sicker patients and it is not associated with improved clinical outcomes.

Disclosures

All authors: No reported disclosures.
1420. Successful Treatment of Acute Osteomyelitis with Once-Weekly Oritavancin
Authors: Van Hise Nicholas W , Chundi Vishnu , Didwania Vishal , Anderson Michael , Van Hise Allyssa , Petrak Russell M
Published: October 2019

Background

Osteomyelitis is a complex infection with high morbidity and without standard treatment guidelines. Intravenous therapy is the standard of care, often requiring multiple daily antibiotic doses in an infusion center or home setting. Many of these infections are gram-positive and therefore are commonly treated with vancomycin or daptomycin. Oritavancin, a lipoglycopeptide antibiotic was FDA-approved in 2014 as a single dose regimen for treatment of ABSSSI and may be useful for the treatment of osteomyelitis where once-weekly therapy presents logistical advantages over vancomycin.

Methods

This was a retrospective case series of patients treated with four to six weekly doses of oritavancin at 20 infusion centers in 6 states under the care of 37 infectious diseases physicians. Patients were administered oritavancin between January 1, 2016 and December 31, 2018. Post therapy evaluation was completed by an ID PharmD utilizing a standardized set of questions. This study has been approved by an IRB.

Results

One-hundred 34 patients received oritavancin during the study period, all for acute osteomyelitis. All patients received baseline diagnostic imaging with MRI, along with clinical evaluation from a Metro Infectious Disease Consultants physician throughout their care. Cultures showing staph aureus, either MSSA or MRSA, were present in 120/134 (89.5%) of patients with MRSA encompassing the majority of patients 96/120 (80%). Patients were dosed with 1200 mg initially, and 800 mg weekly thereafter. At the end of therapy, clinical cure or improvement was achieved in one-hundred eighteen patients (88%). Follow-up was obtained through phone calls with all patients at 3 months and 6 months post-therapy in one-hundred thirty patients. Persistent or relapsing infection was diagnosed in patients 13/120 patients (10.8%). Nine patients were readmitted, but none for osteomyelitis or adverse drug reactions. Adverse reactions were reported in 5 patients (3.7%) including hypoglycemia (3) and tachycardia (2) in which 2 went to the emergency room, but were not admitted.

Conclusion

The use of oritavancin for gram-positive infections resulted in clinical cure or improvement in the majority of patients treated, offering a convenient and effective therapeutic option for the treatment of osteomyelitis.

Disclosures

All authors: No reported disclosures.
1423. Antibiotic Utilization and Outcomes in Patients with Sacral Osteomyelitis and Decubitus Ulcers
Authors: Carpenter Byrge Kelly , Bailey Amanda , Harris Bryan , Talbot Thomas , Wright Patty , Bloch Karen
Published: October 2019

Background

Osteomyelitis is a common complication of advanced stage pressure ulcers and known to be associated with increased mortality, length of stay (LOS), and treatment costs. However, limited data and lack of guidelines regarding appropriate diagnosis and treatment result in variability in management. We sought to investigate whether microbiology data are associated with reduced antibiotic utilization in patients with osteomyelitis secondary to decubitus ulcers.

Methods

This retrospective cohort study included hospitalized patients from 2007 to 2015 with an advanced stage (IV or unstageable) sacral decubitus ulcer and clinical concern for osteomyelitis. The exposure group was those who underwent tissue culture (superficial swab, deep bedside or surgical tissue, or bone biopsy). The primary outcome was antibiotic days of therapy (DOT). Additional secondary outcomes including clinical characteristics at presentation, LOS, readmission rates, and antibiotic-related complications were evaluated using Fisher’s exact or Wilcoxon-Mann–Whitney test for continuous variables.

Results

A total of 220 cases of advanced-stage decubitus ulcer with clinical concern for osteomyelitis were identified. Data abstracted from 40 cases show that tissue cultures were obtained in 22 (55%). Bacterial growth was identified from 100% of samples sent for culture. Antibiotic use prior to admission was the most significant predictor of failure to obtain tissue cultures (P = 0.0002). MRI was performed in 15% of abstracted cases, with radiographic evidence of osteomyelitis noted in 100%. Bone biopsy was performed in 4 cases; bone pathology was not sent in any of these instances. Median antibiotic DOT was 84 days in both groups.

Conclusion

In cases of sacral osteomyelitis secondary to decubitus ulcers, antibiotic use prior to admission was inversely related to the likelihood of obtaining a tissue culture. When tissue cultures were obtained, they were uniformly positive; however, in our preliminary analysis of 40 cases, this did not appear to influence antibiotic utilization as determined by DOT. Bone biopsy was rarely performed, and when done, was not sent for pathology despite this being recognized as the gold standard in the diagnosis of osteomyelitis.

Disclosures

All authors: No reported disclosures.
1435. Urinary Tract Infections Due to Extended-Spectrum Β-Lactamase-Producing Bacteria in Hospitalized Children: Demographics, Risk Factors, Clinical Characteristics, Imaging and Treatment
Authors: Bukhari Areej , Villacis Nunez Diana S , Etinger Veronica , Clemente Melissa , Gruber Joshua , Lozano Michell M , Iskowitz Seth , Marin Ruiz Beatriz F , Sedor Alanna , Houssay Magdalena , Rockwell Mikaela , Calderon Rebeca , Laufer Marcelo
Published: October 2019

Background

Urinary tract infections (UTIs) are a common cause for hospitalization in children. Inadequate treatment can lead to long-term renal damage. AAP guidelines recommend third-generation cephalosporins as empiric therapy. However, the incidence of community-acquired multiresistant, extended-spectrum β-lactamase (ESBL)-producing pathogens is rising. More research is needed to evaluate risk factors and management of ESBL UTI in children.

Methods

A case–control retrospective study was conducted at a tertiary care children’s hospital from July 2014 to December 2017. Hospitalized, non-ICU patients aged 0–18 years with UTI and urine culture positive for potentially ESBL-producing organisms were retrieved. Of the 1301 cultures reviewed, 106 cases (UTI+ESBL) were identified and 208 controls (UTI+non-ESBL) were randomly selected. We compared demographics, risk factors, clinical characteristics and treatment between both groups.

Results

Both groups had similar demographics, except for a higher median age for ESBL patients (3 vs. 0 years). ESBL patients were significantly more likely (P < 0.001) to have recent antibiotic use, history of UTI, urinary tract anomalies or non-renal comorbidities. Both groups had similar clinical presentations and laboratory results. ESBL patients had more VCUGs performed (59.4% vs. 38%), but the prevalence of high-grade VUR was similar in both groups. ESBL patients had longer course of IV antibiotics and length of stay (mean 6 vs. 3 days). Although 59.4% of ESBL patients received inappropriate initial antibiotics based on culture susceptibilities, 77.4% of these patients clinically improved with initial therapy.

Conclusion

Our results support previous studies demonstrating that prior antibiotic use, history of UTI, urinary tract anomalies or non-renal comorbidities are risk factors for ESBL UTI. When these are encountered, the suspicion for ESBL should be higher and may guide antibiotic therapy pending culture results. Given the similar prevalence of high-grade VUR in both groups, the presence of ESBL UTI alone should not be an indication to obtain a VCUG. Finally, a subgroup of patients with ESBL UTI might be clinically responsive to third-generation cephalosporins, despite in vitro resistance.

Disclosures

All authors: No reported disclosures.
1440. Prevalence and Regional Variation of in ESBLs and CRE Enterobacteriaceae (ENT) among Adult, Hospitalized Patients with ENT on a Urine Culture: A Multicenter Evaluation
Authors: Lodise Thomas , Gupta Vikas , Yu Kalvin , Gupta Kalpana , Early Maureen , Ye Gang , Schranz Jennifer , Gelone Steven P
Published: October 2019

Background

Despite increased public health awareness of ESBLs and CRE, limited data exist regarding the true frequency of these resistant bacteria in urine cultures collected from adult patients in US hospitals. This study sought to quantify the prevalence and rates of ESBLs and CRE from urine cultures in adult hospitalized patients with ENT.

Methods

All hospitalized adults with a urine culture (first urine isolate of a species per 30-day period) from 377 hospitals in 2018 were evaluated (BD Insights Research Database, Becton, Dickinson & Company). ESBL was defined as an ENT that was ESBL-positive per commercial panels or intermediate or resistant (non-susceptible, [NS]) to a third-generation cephalosporin; CRE was defined as an ENT that was NS to imipenem, meropenem, doripenem or ertapenem. Urine isolates were classified as community-onset (CO: < 3 days of an inpatient admission and no previous admission within 14 days) or hospital-onset (HO: ≥ 3 days post-admission or within 14 days of discharge) period. Prevalence and rates per 100 admissions were calculated overall, by onset location (CO vs. HO), and by US Department of Health and Human Services (HHS) geographic region.

Results

In 2018, there were 193,476 non-duplicate ENT urine isolates across 4,623,333 admissions; 63.6% were E. coli (EC), 19.5% were K. pneumoniae/oxytoca (KPO), and 8.7% were P. mirabilis (PM). Overall, 12.6% were ESBL and 0.9% were CRE. Rate per 100 admissions was 0.484 and 0.037 for ESBL and CRE, respectively. Among CO, 11.8% were ESBLs and ESBL rates per 100 admissions were 0.358; 0.7% were CRE and CRE rates per 100 admissions was 0.024. Among HO, 15.7% were ESBLs and ESBL rates per 100 admissions was 0.126; 1.5% were CRE and CRE rates per 100 admissions was 0.013. Regional differences in both ESBL and CRE ENT were noted (table).

Conclusion

The prevalence of ESBLs/CRE among adult hospitalized patients with ENT in a urine culture was 13% and 1%, respectively. The % ESBL/CRE was higher among patients HO urine isolates whereas ESBL/CRE rates per 100 admissions were higher among patients with CO urine isolates. Considerable geographic variations were observed. Region and site of onset differences in ESBL/CRE epidemiology should be considered when making empiric antibiotic treatment decisions.

Disclosures

All authors: No reported disclosures.
1450. Risk Factors for Antibiotic Resistance of Escherichia coli Urinary Isolates in Outpatients
Authors: Frisbie Lauren , Weissman Scott , Kapoor Hema , A. D’Angeli Marisa , Salm Ann , Rabinowitz Peter
Published: October 2019

Background

Antibiotic-resistant E. coli infections represent a major cause of morbidity and mortality, and pose a challenge to antibiotic stewardship. Patient age has been suggested as a key determinant of resistance patterns in studies based in the United States and Europe, although local antibiotic use patterns may affect this relationship. We analyzed results from clinical antibiotic susceptibility tests performed at a large reference laboratory to further examine the association of age with E. coli urinary tract resistance patterns in WA State.

Methods

We analyzed 5 years of E. coli antibiotic susceptibility data for outpatient urinary tract infections in WA State from a national clinical reference laboratory. We included only the first isolate recorded for each patient and calculated crude rates of resistance to antibiotics for the age groups of 50 years. In a multivariate logistic model, we tested the effect of patient age, year of antimicrobial susceptibility test submission, and sex on antibiotic resistance.

Results

Univariate analyses indicated that resistance rates differed significantly across patient age groups for ciprofloxacin and nitrofurantoin. Among females, resistance rates also differed significantly across patients age groups for amoxicillin-clavulanate and gentamicin. Logistic regression using data from male patients found the odds of resistance to be significantly greater in older individuals for ciprofloxacin (OR 2.59) and lower in older individuals for amoxicillin-clavulanate (OR 0.56). For females, logistic regression found the odds of resistance to be significantly greater for older individuals for amoxicillin-clavulanate (OR 1.43), ciprofloxacin (OR 3.04), ceftriaxone (OR 2.58), nitrofurantoin (OR 2.20), and gentamicin (OR 1.62).

Conclusion

In WA State, the distribution of antibiotic resistance in E. coli urinary isolates varies with age, sex and the antibiotic of interest. Greater and more timely use of databases of susceptibility testing of clinical isolates from outpatient settings can allow for the creation of age-specific antibiograms to guide and improve stewardship.

Disclosures

All authors: No reported disclosures.
1452. Is Carbapenem-Sparing Therapy as Effective as Carbapenems Against Extended-Spectrum β-Lactamase Producing Enterobacteriaceae in UTI?
Authors: Hyun Jonghoon , Lee Yongseop , Seong Hye , Ho Kim Jung , su Ku Nam , yong Choi Jun , Yeom Joon-Sup , Jin Jeong Su
Published: October 2019

Background

With the emergence of carbapenem-resistant strains of Enterobacteriaceae, non-carbapenem antibiotics are suggested as the alternative treatment of extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae infection. In this study, efficacy of non-carbapenem antibiotics on acute pyelonephritis (APN) with ESBL-producing Enterobacteriaceae was compared with that of carbapenems.

Methods

The medical records of patients who had diagnosed to have acute pyelonephritis with ESBL-producing Enterobacteriaceae on their urine culture, from January 2011 to December 2018, were reviewed retrospectively. Patients were classified as carbapenem and non-carbapenem group according to the definitive antibiotics they had treated with.

Results

Total number of patients was 141, including 112 (79.4%) who had received carbapenem, and 29 (20.6%) received non-carbapenem as definitive therapy against to APN with ESBL-producing Enterobacteriaceae. The duration of hospitalization was shorter for non-carbapenem group (median 9.93 days) than for carbapenem group (median 14.39 days) (P < 0.001). The duration of negative conversion of culture was shorter for carbapenem group (median 40.73 hours) than for non-carbapenem group (median 56.79 hours). There was no significant difference in time to febrile period and duration of definitive therapy between two groups.

Conclusion

Non-carbapenem therapy against APN with ESBL-producing Enterobacteriaceae has no significant difference in clinical outcome compared with carbapenem therapy.

Disclosures

All authors: No reported disclosures.
1454. Cephalosporins and Quinolones Account for 95 Percent of Oral Antibiotic Treatment for Uncomplicated Cystitis in Japan
Authors: Kusama Yoshiki , Ishikane Masahiro , Kihara Tomomi , Ohmagari Norio
Published: October 2019

Background

Uncomplicated cystitis (UC) imposes a large burden on antimicrobial use due to its high morbidity. IDSA/ESCMID guidelines recommend nitrofurantoin, sulfamethoxazole/trimethoprim (SMX/TMP), fosfomycin trometamol, and pivmecillinam for treating UC, but only SMX/TMP and fosfomycin calcium (FOM-C) are available in Japan. Therefore, we examined the antibiotics use to treat UC in Japan.

Methods

We obtained data from the JMDC Inc. claims database, which includes data of corporate employees and their family members. We extracted all records of oral antibiotic prescriptions for the treatment of acute cystitis (ICD-10 code: N300) between 2013 and 2016, and excluded prescriptions for male individuals and inpatients because they were considered to have complicated cystitis. Prescriptions for durations >7 days were also excluded because they were potentially prophylactic. Furthermore, we defined treatment failure as cases that required re-prescription within 13 days after the first prescription and estimated the treatment failure rate (TFR) of each antibiotic.

Results

Cephalosporins and quinolones accounted for 41.5% and 53.2% of the total number of antibiotic prescriptions (48,678). SMX/TMP and FOM-C only accounted for 0.7% and 0.8%. Third-generation cephalosporins accounted for 93.8% of total cephalosporins. TFR was less than 10% across almost all antibiotic categories, with the only exception being FOM-C.

Conclusion

Cephalosporins and quinolones accounted for 94.7% of oral antibiotic treatment for UC in Japan between 2013 and 2016. To avoid spreading antimicrobial resistance, approval of new antibiotics with good efficacy or an official recommendation for the use of narrower-spectrum antibiotics for treating UC may be required.

Disclosures

All authors: No reported disclosures.
1455. Epidemiology, Empiric Treatment, and Outcomes Among Hospitalized Patients With Complicated Urinary Tract Infections in the United States, 2013–2018
Authors: Zilberberg Marya , Nathanson Brian , Sulham Kate , Shorr Andrew F
Published: October 2019

Background

Complicated urinary tract infection (cUTI) is common among hospitalized patients. Though carbapenems are an effective treatment in the face of rising resistance, overuse drives carbapenem resistance (CR). We hypothesized that resistance to routinely used antimicrobials is common, and, despite the frequent use of carbapenems, associated with an increased risk of inappropriate empiric treatment (IET), which in turn worsens clinical outcomes.

Methods

We performed a multicenter retrospective cohort study in ~180 hospitals in the Premier database, 2013–2018. Using an ICD-9/10-based algorithm we identified all adult patients hospitalized with cUTI and a positive blood or urine culture (CR excluded). We examined with the impact of triple resistance (TR; resistance to >3 of the following drugs/classes: third-generation cephalosporin [C3R], fluoroquinolones, trimethoprim-sulfamethoxazole, fosfomycin, and nitrofurantoin), on the risk of receiving IET. We derived multivariate models to compute the impact of IET on hospital outcomes.

Results

Among 23,331 patients with cUTI (96.2% community-onset), 3,040 (13.0%) had a TR pathogen. Compared with those with non-TR, patients with TR were more likely male (57.6% vs. 47.7%), black (17.9% vs. 13.6%), and in the South (46.3% vs. 41.5%), P < 0.001 each; had a higher median Charlson score (3 vs. 2), and were more likely to need early ICU (22.3% vs. 18.6%) and mechanical ventilation (7.0% vs. 5.0%), P < 0.001 each. Patients with TR were hospitalized at centers with higher median prevalence of both C3R (16.3% vs. 14.4%) and TR (15.1% vs. 12.2%), P < 0.001 each. IET was more frequent in TR than non-TR group (19.6% vs. 5.4%) despite greater empiric carbapenem use in TP (43.3% vs. 16.2%), P < 0.001 each. Though IET did not have an impact on adjusted hospital mortality or 30-day readmission rate, it was associated with excess adjusted resource utilization ($1,364 in costs and 0.66 day in length of stay).

Conclusion

Among hospitalized patients with cUTI, TR is common, and is associated with a nearly 4-fold increase in exposure to IET, which in turn contributes to excess resource utilization. Given the high prevalence of TR, clinicians should consider a lower threshold for broader empiric treatment in appropriate patients.

Disclosures

All authors: No reported disclosures.
1461. Antimicrobial Susceptibility Patterns of Common Complicated Urinary Tract Infection Pathogens in US Hospitals, 2013–2018
Authors: Zilberberg Marya , Nathanson Brian , Sulham Kate , Shorr Andrew F
Published: October 2019

Background

In response to increasing rates of antimicrobial resistance, carbapenems have become first-line treatments for many infections. This, in turn, fosters the potential for resistance (CR). Efforts to mitigate the emergence of CR through carbapenem-sparing strategies must rest on a fundamental understanding of antibiotic resistance patterns among commonly encountered pathogens. Therefore, we examined the microbiology of complicated urinary tract infections (cUTI) in hospitalized patients in the United States.

Methods

We performed a multicenter retrospective cohort study in the Premier database of approximately 180 hospitals, 2013–2018. Using an ICD-9/10-based algorithm we identified all adult patients hospitalized with cUTI and included those with a positive blood or urine culture. Patients with carbapenem-resistant organisms were excluded. We examined the microbiology and susceptibilities to common cUTI antimicrobials (third-generation cephalosporin [C3], fluoroquinolones [FQ], trimethoprim-sulfamethoxazole [TMP/SMZ], fosfomycin [FFM], nitrofurantoin [NFT], and triple-resistant [TR]) over time.

Results

Among 28,057 organisms from 23,331 patients, the 3 most common pathogens were E. coli (EC, 41.0%), K. pneumoniae (KP, 12.1%), and P. aeruginosa (PA, 11.0%). Among these organisms, resistance to C3 was 10.4% among PA, 12.6% KP and 48.9% EC. EC was most likely to exhibit resistance to all agents of interest, and demonstrated the highest resistance rate to TMP/SMZ (61.5%), and lowest to NFT (10.4%). In contrast, KP had the highest rate of resistance to NFT (27.9%) and lowest to FQ (4.9%). The lowest rate of resistance among PA was to TMP/SMZ (1.9%), and highest to C3 (10.4%). The prevalence of TR in 2013–2014 and 2017–2018, respectively, was 34.2% and 37.4% for EC, 11.8% and 14.2% for KP, and 7.0% and 4.6% for PA.

Conclusion

Among the most common pathogens isolated in hospitalized patients with cUTI, and particularly in EC, high and increasing single resistance and TR rates to common antimicrobials were evident, Current empiric treatment strategies may be insufficient against the growing threat of TR.

Disclosures

All authors: No reported disclosures.
1473. Structured Patient Interview in Complicated Urinary Tract Infections to Assess Clinical Outcomes vs. Investigator’s Evaluation in the APEKS-cUTI Study
Authors: Portsmouth Simon , Toyoizumi Kiichiro , Den Nagata Tsutae , Tillotson Glenn S , Echols Roger
Published: October 2019

Background

Based on the 2009 US FDA guidance, patient-reported outcome (PRO) measures are recommended in clinical study designs for certain indications to evaluate response to therapy from the patient’s perspective, and a PRO was recommended in the final complicated urinary tract infection (cUTI) guidance in 2014. Several PRO tools have been rigorously validated, but currently, no tool exists for evaluating cUTI. We included a “structured patient interview (SPI)“ while conducting a randomized, double-blind, study (NCT02321800) investigating cefiderocol (CFDC) vs. imipenem–cilastatin (IPM/CS) in cUTI patients to support the physician’s assessment of clinical response.

Methods

Patients, who were fully alert and oriented, were interviewed at randomization, end of treatment, test of cure (TOC), and follow-up (FUP) by the same interviewer. The questionnaire identified the presence or absence of relevant symptoms pertinent to cUTI. Responses were graded as none, or if present, mild, moderate, or severe. Investigator assessment included objective measures of clinical outcome(s) and was performed independently from the patient-reported symptoms collected in the SPI. Changes in the patient’s responses were compared with the investigator’s assessment at randomization and at each study visit. A kappa correlation coefficient comparing the SPI and physician’s clinical assessment was calculated at each evaluation time point.

Results

Based on investigator assessment, 89.7% (226 out of 252 patients) in the CFDC arm and 87.4% (104 out of 119 patients) in the IPM/CS arm achieved clinical cure (adjusted treatment difference: 2.39%; 95% CI: –4.66; 9.44) at TOC. Based on the SPI responses, 89.7% (226 out of 252 patients) in the CFDC arm and 84.9% (101 out of 119 patients) in the IPM/CS arm achieved clinical cure (adjusted treatment difference: 4.96%; 95% CI: –2.48; 12.39) in favor of CFDC. The correlation between SPI evaluation and physician’s assessment of clinical outcomes was very high at TOC and FUP visits (Kappa coefficients: 0.820 and 0.766, respectively).

Conclusion

The strong correlation between patients’ reported symptoms collected in the SPI and investigator assessment showed that SPI responses could be a useful alternative measure of clinical outcomes in cUTI studies.

Disclosures

All authors: No reported disclosures.
1484. Prevalence of Pyuria With and Without Bacteriuria in Healthy Pre-Menopausal Women
Authors: Stapleton Ann E , Roberts Pacita , Hooton Thomas M
Published: October 2019

Background

Pyuria has long been considered key to diagnosis of urinary tract infection in women, but there is a paucity of data on its prevalence and association with asymptomatic bacteriuria (ASB) in healthy women, even though pyuria and ASB often trigger inappropriate antimicrobial treatment.

Methods

We enrolled 104 healthy premenopausal women with a history of recurrent urinary tract infection (UTI) in an observational study and performed daily assessments of bacteriuria, pyuria (leukocyte esterase strips) and UTI symptoms over a 3-month period. These data enabled an evaluation of the prevalence of pyuria and ASB and associations between them.

Results

The mean age of participants was 22 and 74% were white. Pyuria occurred frequently in this cohort of women, with 72 (77%) of 94 evaluable subjects having pyuria on at least one day with no symptomatic UTI diagnosed. The median percent of days with pyuria reported was 7% (range, 0–100%). Asymptomatic bacteriuria (ASB, urine culture with colony count ≥105 CFU/mL of uropathogen on days with no symptomatic UTI diagnosed) occurred in 45 (45%) women on 159 (2.5%) of 6,283 days. ASB was most commonly caused by E. coli, which was present in 1.4% of days with median duration one day (range, 1–10). The positive predictive value of pyuria in detecting ASB was 4%. Five women had 11 transient episodes of pyuria, significant bacteriuria, and UTI symptoms (“preclinical UTI”) but did not seek medical attention.

Conclusion

In this population of healthy women at high risk for UTI and ASB, asymptomatic pyuria was a frequent occurrence and ASB rarely lasted more than 2 days. Pyuria, whether associated with bacteriuria or not, was generally not accompanied by urinary symptoms and did not appear to be clinically meaningful. Young women with recurrent UTI are often advised by their providers to test their urine with dipsticks for pyuria or bacteriuria, and be treated if either are positive, regardless of absence of UTI symptoms. Such practices, which contribute to antimicrobial resistance, are not supported by our data.

Disclosures

All authors: No reported disclosures.
1489. Clinical Utility and Patterns of the use of the Gastrointestinal PCR Panel Over a 2-Year Period at a University Hospital
Authors: Cushman Teresa , Barron Michelle , Arbet Jaron , Weber Rachel , Zhuang Yaxu , Jeffers Alexiss , Huang Misha
Published: October 2019

Background

Up to 80% of cases of acute infectious gastroenteritis do not have an identifiable etiologic agent. Molecular syndromic diagnostic panels, such as the Biofire® Filmarray® gastrointestinal (GI) panel, can improve pathogen detection, including frequent causes of community-onset diarrhea. There are little data about the real-world use and test characteristics of the GI panel in the clinical setting. The objective of this study was to evaluate the patterns of use and clinical utility of the GI panel.

Methods

We conducted a retrospective cohort study of adults (age >18 years) admitted to the University of Colorado Hospital for whom a GI Panel was ordered from October 1, 2015 to August 31, 2017. Primary outcomes included patient demographics and co-morbidities, time since admission to test order, and cumulative test results. Descriptive statistics were utilized to summarize the frequencies of the primary outcome measures.

Results

1684 panels were ordered and completed during the study period compared with 1379 stand-alone C. difficile PCRs. Seventeen of the 22 components of the panel had been validated by our lab prior to the study period; therefore, results were only available for these pathogens. Most GI panels (78%) were ordered in the first 48 hours of admission, with 6% ordered between 48 and 72 hours after admission, and 16% >72 hours after admission. The GI panel yielded an organism 34% of the time. The most frequently identified organism was C. difficile (18.5%) followed by Norovirus (5.2%) and Enteropathogenic E. coli (5.1%).

Conclusion

Over a 2-year period at a University hospital, the GI panel only had a positive result in 20% of patients tested. Although most of the tests were ordered in the first 48 hours after admission, 22% were ordered after 48 hours, after which etiologies of hospital-onset diarrhea are expected to be more common. Among all GI Panel tests ordered, C. difficile was the most common organism identified, followed by Norovirus. Each of these organisms has an accurate and less costly alternative test. Stand-alone testing for C. difficile and Norovirus should be considered prior to the GI Panel for patients admitted to the hospital, particularly when admitted >48 hours.

Disclosures

All authors: No reported disclosures.
1529. Kawasaki Disease Shock Syndrome: Identifying Risks
Authors: Downey Quick Rachel , Sehgal Ila , Feldman Alexandra , Murphey Donald , Fernandez Mariosl , Bhaduri. Hauger Sarmistha
Published: October 2019

Background

Kawasaki disease shock syndrome (KDSS) is a severe and less common complication of Kawasaki disease (KD). KDSS may progress rapidly and mimic other types of shock. Limited data are available in the literature describing recognition, evaluation, and treatment of KDSS. This report compares children with KDSS with those with KD without shock syndrome in 149 consecutive patients over 4.5 years in Central Texas.

Methods

Inpatient medical records of children with ICD diagnosis code for KD who were hospitalized between January 2014 and July 2018 at one children’s hospital in Texas were identified and charts were manually reviewed for inclusion. Cases were categorized as having KDSS if they had a diagnosis of KD with sustained systolic hypotension for age or signs or symptoms of shock with poor perfusion including tachycardia with delayed capillary refill, change in mental status, or weak peripheral pulses. Information about each case was collected from the chart including demographics, presentation, medical treatments, laboratory data, and initial echocardiograms.

Results

KD was identified in 149 patients; 22 were categorized as KDSS (14.8%). Among cases of KDSS, sustained systolic hypotension for age was observed in 19 patients; 3 patients had other signs of hemodynamic instability. Select details for each cohort are in Figure 1. Patients with KDSS were overall older on admission (6.2 vs. 2.3 years; P <0.001), and more likely to have anemia, neutrophilia, bandemia, thrombocytopenia, hypoalbuminemia, or hyponatremia. On acute echocardiogram, 5 of the 22 patients had coronary artery changes including ectasia, and dilation, and highest Z-score between 2.2–4.24. Patients with KDSS were more likely to receive steroids or adjunctive medications and had a longer length of stay (6 vs. 3.7 days; P < 0.001).

Conclusion

The current literature has relatively few cases of KDSS and suggests risk of misdiagnosis of KDSS initially as other types of shock. We demonstrate a higher incidence of KDSS; 14.8% compared with between 1.5 and 7% at KD diagnosis reported in the literature. The cause of this is unclear but may indicate regional or genetic differences in disease course. Patients with KD should be monitored for KDSS to avoid unexpected decompensation or delay in treatment. Lab abnormalities may indicate risk for KDSS.

Disclosures

All authors: No reported disclosures.