bluuebunny/crossref_metadata_2025 huggingface dataset:
1524. Presentation of Acute Focal Bacterial Nephritis in Children
Authors: Ha Park Geun , Lee Bongjin , Rhim Jung-Woo , Lee Kyung-Yil , Mi Kang Hyun
Published: October 2019

Background

Ascending infections are thought as the main route of infection in acute pyelonephritis (APN). However, among patients diagnosed with APN, a subset has atypical presentation unexplainable by ascending routes of infections. This study aimed to review 8 cases initially diagnosed as APN, however presenting with no or minimal pyuria and presenting as acute focal bacterial nephritis (AFBN).

Methods

This was a retrospective cohort study of children <18 years old without underlying diseases, treated for their first episode of APN during 2006 and 2016. Those that fit the following inclusion criteria were diagnosed as AFBN: (1) characteristic CT findings compatible AFBS, (2) atypical presentation of APN including lack of urinary symptoms, and (3) no antibiotic administration prior to urine culture. Electronic medical records were analyzed, and radiologic images re-evaluated.

Results

During the 11-year period, of the total of 359 patients were diagnosed with the first episode of APN. Of these, 8 were re-diagnosed as AFBN. The mean age was 9.8 years old (1.9–17.4). Abdominal pain with nausea and vomiting were chief complaints (62.5%), and none had urinary symptoms including dysuria, incontinence, or increased frequency. Initial urinalysis in all the patients showed WBC <10–19 hpf, and were negative for nitrite. High initial WBC and CRP levels were observed (median 17.892 × 103/mm3 and 13.1 mg/dL, respectively). Cultures were positive for E. coli in 3 cases. CT findings showed nephromegaly with multifocal wedge-shaped heterogeneous enhancement defects corresponding to blood supply patterns of renal segmental arteries, no hydronephrosis, and no inflammation in the pelviureteric calyceal system. A mean duration of fever was 6.6 days, and time to defervescence after initiation of antibiotics was an average of 3 days.

Conclusion

Lack of urinary symptoms, insignificant pyuria, and CT findings of AFBN support the possibility of an alternative route of infection, other than the ascending route.

Disclosures

All authors: No reported disclosures.
1525. Epidemiology, Management, and Outcomes of Skin and Soft-Tissue Infections in Well-Appearing Infants Less Than 60 Days of Age
Authors: Neese Jeremy , Harik Nada
Published: October 2019

Background

Skin and soft-tissue infections (SSTIs) in children are increasingly common. The IDSA has published guidelines for SSTI treatment in children, adolescents, and adults but data in infants less than 2 months is sparse despite their higher risk of concomitant serious bacterial infection (SBI). Clinical work-up and management of these patients varies widely with little evidence to guide providers.

Methods

We retrospectively identified 536 patients, from 2007 to 2017, seen at our EDs or hospital-associated clinic and diagnosed with SSTI by ICD9/10 code. We excluded those with ill-appearance, prematurity, known immunodeficiency, skin disorder, previous SSTI, or previous procedure at infection site. Remaining patient’s medical records were reviewed to confirm a SSTI. The total included study population was 182 (Figure 1). Data collected included demographics, type/location of infection, laboratory/imaging studies obtained, procedures performed, disposition, treatment, and treatment failure.

Results

Demographics are reported in Table 1. Mean age was 24.2 days (range 2–57 days). Of 182 patients, 13% had fever. 34% had a superficial infection (impetigo or pustulosis), 24% had cellulitis/scalded skin, 35% had an abscess/paronychia, and 7% had periorbital cellulitis. The most common SSTI locations were perineal/genital (30%) and head/scalp/face (23%). 63% of infants had a blood culture obtained and 4/114 grew a pathogenic bacteria. 52% had a wound culture and 72/95 grew a pathogenic bacteria. No infants had bacterial meningitis or a UTI (Table 2). 25% underwent incision/drainage and 93% received any antibiotic. The most commonly prescribed antibiotics were clindamycin and mupirocin. Of 80 non-admitted infants, 21% had an unscheduled return visit within 2 weeks (Table 3): 9% for treatment failure, 6% unrelated to SSTI, and 1% for missed SBI (1 patient with GAS bacteremia).

Conclusion

Most well-appearing infants with SSTI were afebrile. The majority of studied infants had blood cultures obtained but rates of clinically significant bacteremia were low. Management varied considerably and antibiotics were commonly administered. However, overall rates of SBI were low and there was only 1 case of missed SBI. Extensive evaluation of well-appearing infants with SSTI may be unnecessary.

Disclosures

All authors: No reported disclosures.
1527. Clinical Variables Associated with Vancomycin Resistance in Children with Bacteremia Due to Enterococcus spp.
Authors: Jimena Carla , Mussini Soledad , Taicz Moira , Paula Arias Ana , Perez Guadalupe , Reijtman Vanesa , Mastroianni Alejandra , Ines Sormani Maria , Garcia Eva , Teresa Rosanova Maria , Bologna Rosa
Published: October 2019

Background

Enterococcus spp. (E) is an important cause of nosocomial bacteremia. The emergence of vancomycin-resistant E in the nosocomial setting conditions the empirical treatment and limits therapeutic options.

Methods

A retrospective cohort study of children ≥1 month with E bacteremia in a reference pediatric hospital was performed. Study period January 1, 2016–December 31, 2018. Outcome: to describe clinical and epidemiological characteristics of children with bacteremia due to Enterococcus spp. resistant to vancomycin (VRE) vs. sensitive (VSE). Identify variables associated with VRE. STATA 13 was used.

Results

N = 82 patients. Median age was 37.6 months (IQR 2–48), 45 patients (54.9%) were male; 76 patients (92.7%) had underlying disease (intestinal failure (21.9%), heart disease (17.1%), preterm births (12.2%), hematological disease (10.9%), and liver failure (7.3%); 16 patients (19.5%) received immunosuppressive therapy. Sixty bacteremia (73.2%) were by E. faecalis and 22 (26, 8%) by E. faecium. Vancomycin resistance was documented in 13 patients (15.8%), all of which were E. faecium. In the bivariate analysis, patients with VRE bacteremia were significantly older in months than those with VSE bacteremia [75.4 (IQR 6–151) vs. 30.5 (IQR 2–33), P <0.02]; had more frequency of previous colonization with VRE [n: 8 (61.5%) vs. n: 4 (5.8%) P < 0.001], hematological disease [n: 5 (38.5%) vs. n: 5 (5.8%), P = 0.01], liver failure [n: 3 (23.1%) vs. n: 3 (4.4%), P = 0.02] and immunosuppressive therapy [n: 6 (46.2%) vs. n: 10 (14.5%) P = 0.008]. Patients with VRE bacteremia had a lower median white blood cell count [7040 (IQR 2150–10250) vs. 14474 (IQR 6160–17090), P <0.03]. Mortality in P with VRE was 15.4% (n: 2) and 4.3% in P with VSE (n: 3), P = 0.1. No statistically significant differences were found according to history of surgery, previous hospitalization, antibiotic therapy in the last 3 months or clinical presentation. In the multivariate model, predictors of VRE bacteremia adjusted for the rest of the significant variables were hematological disease OR 11.1 (95% CI 2.3–53.8) P = 0.003, and liver failure OR 7.7 (95% CI 1.2–50.4), P = 0.03.

Conclusion

In this cohort of children with enterococcal bacteremia, hematological disease and liver failure were predictive variables of VRE bacteremia.

Disclosures

All authors: No reported disclosures.
1531. A Twenty 3-Year Retrospective Study of Secondary Hemophagocytic Syndrome in a Pediatric Third-Level Referral Center in Mexico City
Authors: Gonzalez Saldaña Napoleon , Mendoza Francisco Javier Otero , Carmona Vargas Ana Jocelyn , Zuyino Mondragon Salinas Izveidy
Published: October 2019

Background

Secondary hemophagocytic syndrome (SHS) may develop as a result of excessive immune activation, with proliferation of T cells and macrophages. It is often fatal and remains ill-recognized in children, leading to false or delayed diagnosis and suboptimal management. This condition has been described more often in association with virus, but it can be secondary to bacteria, fungi, and parasites.

Methods

Retrospective, descriptive, and observational study. We systematically reviewed the clinical files of patients diagnosed with SHS at the Instituto Nacional de Pediatría between January 1995 and December 2018; age, gender, clinical features, laboratory results, management, and final outcome were registered.

Results

49 cases of SHS were diagnosed, 26 (53%) were male, mean age at diagnosis was 67.5 months (newborn–15.5 years), 47 (96%) presented with fever, 46 (94%) hepatomegaly, 37 (76%) splenomegaly, 28 (57%) lymphadenopathy, 18 (37%) jaundice, and 4 (8%) bleeding. The most common laboratory findings were anemia in 29 (59%) patients, thrombocytopenia in 39 (80%), hypertriglyceridemia in 39 (80%), with isolation of Epstein Barr Virus in 18 (35%), followed by Cytomegalovirus in 2 (4%), Escherichia coli in 2 (4%), Salmonella enterica in 2 (4%), and Leptospira, Brucella abortus, Shigella sonnei, Enterococcus faecium, Enterovirus and congenital Rubella in 1 case each (2%). Intravenous Gamma-globulin therapy was administered to 38 (78%) patients, antimicrobials to 26 (53%), systemic steroids to 46 (94%) and VP16 to 32 (65%). 22 (45%) had full recovery, 6 (12%) patients presented with a recurrent episode of SHS, and 21 (43%) died.

Conclusion

Due to the rarity of this syndrome, variable clinical presentation, and lack of specificity of the clinical and laboratory findings, the diagnosis of SHS is often delayed. EBV remains an important etiologic agent of this syndrome, identified in 35% of our cases. The mortality rate around the world is reported approximately around 45%, confirmed in our study in 43% of the cases, remarking the importance of prompt diagnosis and treatment to increase the survival in our population.

Disclosures

All authors: No reported disclosures.
1557. Population Pharmacokinetics of Suvratoxumab (MEDI4893), an Extended Half-life Staphylococcus aureus Alpha Toxin-Neutralizing Human Monoclonal Antibody, in Healthy Adults and Patients on Mechanical Ventilation in Intensive Care Units
Authors: Pierre Vadryn , Francois Bruno , Hernandez-Illas Martha , Sánchez Garcia Miguel , Wu Yuling , Eggimann Philippe , Laterre Pierre-Francois , Huberlant Vincent , Viña Lucia , Boulain Thierry , Ruzin Alexey , Bretonnière Cédric , Pugin Jerome , Trenado Álvarez José , Bellamy Terramika , Shoemaker Kathryn , Ali Omar , Lee Nancy , Dequin Pierre-Francois , Jafri Hasan S , Roskos Lorin , Colbert Susan , Khan Anis
Published: October 2019

Background

Suvratoxumab (suvra), an extended half-life (~80 days), Staphylococcus aureus (SA) alpha toxin-neutralizing IgG monoclonal antibody, is under investigation for prevention of SA pneumonia in patients on mechanical ventilation (MV). We characterized the serum PK of suvra using population pharmacokinetics (popPK) in both healthy volunteers and MV patients and quantified the proportion of patients reaching the serum target of 211 μg/mL at 30 days post-dose.

Methods

The popPK analysis included 1,368 serum samples from two early phase studies (NCT02296320; EudraCT 2014-001097-34): (1) Phase 1 study in 26 healthy adults receiving single IV suvra doses ranging from 0.225g to 5g, with PK sampled up to 360 days; and (2) Phase 2 study in MV patients with PCR-confirmed SA colonization of lower respiratory tract receiving one suvra IV dose of 2g (n = 15) or 5g (n = 96), with PK sampled up to 100 days.

Results

A two-compartment linear model with weight-based scaling of the PK parameters adequately described the serum PK data (Figure 1). MV status, number of days on MV, and age impacted the PK of suvra. A moderate between-subject variability (<45% CV) was estimated for key PK parameters. An estimated two-fold increase in MV patients’ volume of distribution parameters compared with healthy volunteers explained the observed Cmax differences between the two groups (1145±369 μg/mL vs. 1783±396 μg/mL) (Figures 2 and 3). Although age, MV status and days on MV post-dose appeared to be associated with higher systemic clearance (CL) in the model, this estimate could be biased due to limited PK data available for only one half-life (~90 days) of the drug in MV patients (Figure 2). More patients achieved suvra levels above the PK target following the 5 g (73.5%; 50/68) vs. 2 g dose (7.6%; 1/13) at 30 days post-dose.

Conclusion

MV status, post-dose duration on MV, body weight, and age were identified as statistically significant covariates influencing the PK of suvra. Serum PK and popPK analyses support the 5g dose for future studies with suvra in MV patients.

Disclosures

All authors: No reported disclosures.
1562. Safety and Efficacy of High-Dose Cefazolin Therapy in Obesity
Authors: Simpson Timothy , Shah Sneha , Pogue Jason M , Wu Janet
Published: October 2019

Background

Obesity leads to altered pharmacokinetics through changes in volume of distribution and clearance, which can impact antimicrobial dosing. Although there is data to support higher cefazolin pre-operative dosing for surgical prophylaxis, data evaluating treatment doses of cefazolin in obese patients is lacking. This study was designed to assess the safety and efficacy of high-dose (HD) cefazolin compared with traditional-dose (TD) cefazolin in obesity.

Methods

This was a multicenter, retrospective, cohort study of patients admitted from September 1, 2013 to August 31, 2018. Obese adults, defined as a BMI > 30 kg/m2, receiving cefazolin for at least 48 hours for bacteremia or skin and soft-tissue infection were eligible for inclusion. Patients with creatinine clearances <30 mL/minute or positive MRSA cultures were excluded. TD cefazolin was defined as 1–2 g IV every 8 hours and HD cefazolin was defined as 2 g every 4–6 hours. Patients were matched 1:1 based on indication, severity of illness, and BMI. Primary objective was to compare rates of treatment-emergent adverse events (TEAE). Secondary outcomes included comparison of treatment failure rates and 30-day readmission.

Results

A total of 332 patients (166 matched pairs) were included in this analysis. Baseline demographics were similar between groups with the exception of higher age in the TD group (61.8 TD vs 55.1 HD; P < 0.001) and more males in the HD group (39.2% TD vs. 65.6% HD; P < 0.001). Median Charlson comorbidity index was also higher in the TD group [4 (2–6) TD vs. 3 (1–4) HD; P < 0.001]. There were no differences in TEAE between groups (24.1% TD vs. 16.9% HD; P = 0.103). Treatment failure occurred more frequently in the TD group (24.7% TD vs. 15.1% HD; P = 0.028), driven primarily by rates of readmission secondary to recurrence or relapse of the index infection (18.7% vs. 11.5%; P = 0.07).

Conclusion

There were no differences in TEAE in patients who received TD cefazolin vs. HD cefazolin therapy. Obese patients receiving TD therapy experienced higher treatment failure than those receiving HD therapy. Dose-optimization strategies with cefazolin in obese patients should be further explored.

Disclosures

All authors: No reported disclosures.
1564. Target Attainment of Empiric Vancomycin Therapy to Achieve Safe and Effective Exposure When it Matters Most: How Much of the Drug Do We Really Need in the First 48 Hours?
Authors: Yassin Arsheena , Chin Titania , Meleshkina Daria , Ghanbar Mohammad , Sassine Joseph , Olivo Freites Christian , Stavropoulos Christine , Farkas Andras
Published: October 2019

Background

Empiric dosing of vancomycin (VAN) to reach targets is a daunting task due to the large variability observed in the pharmacokinetics of this agent. With the change to AUC driven dosing on the horizon, the goal of this study was to establish empiric dosing requirements of vancomycin that effectively achieve the desired AUC of 400 to 600 mg hours/L targets in the first 48 hours of therapy.

Methods

VAN TDM data were used in this analysis. A two-compartment model was fitted with Bayesian routines to establish the AUCs. Then, the AUC achieved was used to identify the desired total daily dose (TDD, capped at 4,500 mg) needed to attain an AUC in the target range for days 1 and 2, per patient. Next, multivariable regression was undertaken to predict this desired dose with frequently calculated weight and renal function indices. Last, model validation in a test data set based on calculated ME, RMSE and their 95% CI took place, and then the best model was used to simulate TDDs at 24 h intervals. To evaluate the agreement between the 2 pharmacists selecting the final TDDs by screening the simulated regimens, a weighted Kappa was calculated.

Results

1450 concentrations from 268 patients (60.9% male) with mean (IQR) age of 62.8 (52.7, 75) years, weight of 79.1 (63.2, 90.9) kg and CrCl of 76.7 (36.8, 110.6) mL/minute were analyzed. Fit of the model to data was excellent with R2 = 0.98 (Figure 1). AUC attainment with actual dose vs. the AUCs based on the desired dose was poor (Figure 2). Final regression model [ME (95% CI) 31.58 (−160.38, 217.34) mgs; RMSE (95% CI) 761.98 (628.19, 895.93) mgs] identified adjusted body weight (ABW) (P = 0.02), CrCl (P < 0.001), age (P = 0.05) and sex (P = 0.01) on day 1, vs. CrCl (P < 0.001), age (P = 0.02) and sex (P = 0.002) on day 2 as predictors of TDD. Kappas showed near perfect agreement for day 1 (0.992, P < 0.01) and day 2 (0.883, P < 0.01) between the raters resulting in the selection of the final dosing regimens (Figures 3 and 4).

Conclusion

Our model accurately identified the 4 major variables most likely to explain VAN variability in predicting AUC in the first 48 hours. These detailed dosing recommendations—strengthened by rigorous external validation and near perfect between rater agreements—allow for the design of safe and effective AUC driven empiric dosing regimens.

Disclosures

All authors: No reported disclosures.
1589. Ceftolozane–Tazobactam Activity Against Difficult-to-Treat Resistance in Pseudomonas aeruginosa from Bloodstream Infections in US Hospitals
Authors: Shortridge Dee , Ryan Arends S J , Duncan Leonard R , Streit Jennifer M , Flamm Robert K
Published: October 2019

Background

Infections caused by Pseudomonas aeruginosa (PSA) resistant to first-line agents are difficult to treat and require using more toxic antimicrobials, such as amikacin (AMK) and colistin (COL). Kadri et al. recently described the category of difficult-to-treat resistance (DTR) as intermediate or resistant to all tested first-line agents (fluoroquinolones, carbapenems, and extended-spectrum cephalosporins). Ceftolozane–tazobactam (C-T) is an antibacterial combination of an antipseudomonal cephalosporin and a β-lactamase inhibitor. C-T has been approved in >60 countries to treat complicated urinary tract infections, acute pyelonephritis, and complicated intra-abdominal infections. The filing is in progress for treatment of hospital-acquired pneumonia, including ventilator-associated pneumonia. The Program to Assess Ceftolozane–Tazobactam Susceptibility (PACTS) monitors gram-negative (GN) isolates resistant to C-T worldwide. In this study, the activity of C-T and comparators against PSA bloodstream isolates that are DTR, multidrug-resistant (MDR), or extensively drug-resistant (XDR) were analyzed.

Methods

A total of 922 PSA isolates from BSI were collected between 2011 and 2018 from 35 PACTS hospitals in the United States. Isolates were tested for C-T susceptibility (S) by the CLSI broth microdilution method. Other antibiotics tested included cefepime (FEP), ceftazidime (CAZ), ciprofloxacin, levofloxacin (LEV), doripenem, imipenem, meropenem (MEM), piperacillin–tazobactam (PIP-TAZ), AMK and COL. Antibiotic-resistant phenotypes analyzed using CLSI (2019) breakpoints included MDR (nonsusceptible to ≥ 1 agent in ≥ 3 drug classes), XDR (susceptible to ≤ 1 agent in ≤ 2 drug classes), or DTR.

Results

The percent of DTR isolates was 4.8% when compared with 15.2% MDR and 9.3% XDR. The %S for C-T and other first- and second-line agents are shown in the table for each phenotype.

Conclusion

C-T demonstrated 97.1%S overall for BSI isolates, similar to AMK (97.8%) and COL (99.5%). C-T had better coverage than first-line drugs against MDR (81.4%) and XDR (72.1%), and 50% for the DTR isolates, which represented only 4.8% of isolates. Only AMK and COL had > 75%S for DTR isolates.

Disclosures

All authors: No reported disclosures.
1596. Impact of Vancomycin Area Under Curve on Persistent Methicillin-Resistant Staphylococcus aureus (MRSA) Bloodstream Infections (BSI)
Authors: Alosaimy Sara , Jorgensen Sarah C J , Lagnf Abdulhamid , Zasowski Evan J , Trinh Trang D , Mynatt Ryan , Pogue Jason M , Rybak Michael J
Published: October 2019

Background

Persistent Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) are associated with significant morbidity, mortality, and healthcare expenditures. Vancomycin (VAN) remains the treatment of choice for invasive MRSA BSI. Current guidelines for the treatment of MRSA BSI recommend a VAN AUC24h/MIC ratio ≥400. The Detroit Medical Center (DMC) implemented an AUC guided dosing strategy. However, data on the association between AUC24h and clinical outcomes in MRSA BSI are limited. We aimed to evaluate the association between VAN AUC24h and persistent bacteremia (PB) among patients with BSI.

Methods

Multi-center, retrospective cohort study from January 2015 to November 2018. We included adult patients with MRSA bacteremia treated with VAN for which AUC24h monitoring was performed. AUC was measured using 2-level guided dosing. The primary outcome was PB defined as continued positive cultures >72 hours after VAN initiation. Classification and Regression Tree (CART) analysis was performed to determine the AUC24h breakpoint (BP) most predictive of PB in the cohort. Mann–Whitney and Fischer exact tests were used for univariate analysis. The independent association between AUC24h, dichotomized at the CART-derived cut-point, was then examined through multivariable logistic regression analysis.

Results

Overall, 137 patients were included. The median age was 59 (18–85) years, 69.3% male, and 75.2% African American predominance. Most common sources of BSI were skin/soft tissue (39.4%), pneumonia (25.5%), and osteoarticular (16.8%). The median APACHE II score was 13 (8–20). Median time to microbiological clearance was 2.5 days (0.5–12). Patients with AUC24h ≤ 406.25 were more likely to have PB compared with those with AUC24h > 406.25 (59.4% and 35.2%, respectively; P = 0.002). After controlling for age, intensive care stay, and concomitant β-lactam therapy; AUC of ≤ 406.25 (aOR 2.767, 95% CI 1.212–6.318) and endocarditis (aOR 2.87, 95% CI 1.079–7.638) were independently associated with PB.

Conclusion

VAN AUC24h BP of <406.25 was independently associated with PB in patients with MRSA BSI. Our findings underscore the importance of VAN dose optimization to achieve timely bacterial clearance in MRSA bacteremia.

Disclosures

All authors: No reported disclosures.
1610. Implementation of Clinical Care Pathway Reduces Measles Exposures During Outbreak in New York
Authors: Daniel Jency , Patel Darshan , Sussner Rita M , Mack Lynda , Chen Donald S , Margaret. Nolan Sheila
Published: October 2019

Background

The United States is currently experiencing the largest measles outbreak since 1994. The New York outbreak started in October 2018 in several communities with low immunization rates for measles. Our institution is a referral center for the Hudson Valley and New York City. Failure to immediately recognize the disease early in the outbreak resulted in several exposure investigations and significant expenditure of time and resources. With evidence of ongoing transmission in local communities, we initiated a multi-pronged approach to recognize and limit potential measles exposures.

Methods

We developed a clinical pathway to alert Emergency Department (ED) staff and local Emergency Medical Service (EMS) agencies to the signs and symptoms of measles and provided steps for isolation, care, and testing for patients with possible measles. The ED staff and EMS personnel were educated in meetings and by posters, emails, and huddles. Reports of cases were made to infection control in real time, and local Departments of Health (DOH) were subsequently notified of suspected cases and exposures. We describe data pre and post-intervention. Chi-square was used to compare the number of patients requiring contact investigations for staff and patient exposures pre- and post-pathway implementation.

Results

From October 2018 through April 2019, 31 patients were evaluated for measles. Measles was diagnosed in 15 patients (1 adult, 14 children). Eight patients were admitted to the hospital, 3 required Pediatric ICU care. Pre-pathway implementation, 2 out of 9 (22%) evaluated patients resulted in exposure investigations; post implementation, 1 out of 22 (4.5%) evaluated patients required an exposure investigation (P = 0.18). The investigations conducted by our infection control department included 153 patients, 141 pre-implementation vs. 12 post-implementation. Nine patients required prophylaxis with immunoglobulin, and 10 patients received MMR vaccine as prophylaxis. No exposures resulted in clinical cases of measles.

Conclusion

Implementation of a clinical pathway to recognize and isolate suspected measles patients with ED staff and EMS personnel resulted in reduced exposures and improvement in communication with Infection Control and local DOH.

Disclosures

All authors: No reported disclosures.
1613. Rates of Hospitalization for Community-Acquired Pneumonia Among US Adults: A Systematic Review
Authors: McLaughlin John M , Khan Farid L , Thoburn Elizabeth A , Isturiz Raul E , Swerdlow David L
Published: October 2019

Background

Community-acquired pneumonia (CAP) develops in persons outside of a healthcare facility and is associated with significant morbidity and mortality. Estimating the incidence of CAP is challenging because it lacks a standardized case definition and because study designs and selection criteria vary. Reconciling these differences across studies is critical for understanding the true burden of CAP which, in turn, informs prevention strategies, including vaccination.

Methods

We performed a systemic literature review of studies describing the incidence of hospitalized CAP among adults in the United States. Specifically, we examined the impact of the following study characteristics on estimates of incidence: (i) study population, (ii) study type and data source, and (iii) diagnostic criteria for pneumonia.

Results

After review of 8361 articles as of January 31, 2019, we identified 26 studies which contained 39 unique CAP estimates. Among adults ≥65 years of age, annual rates of hospitalized CAP ranged from 847 to 3,500 per 100,000 persons with median = 1,830. Rates were lower in studies that excluded patients with healthcare-associated (but community-onset) pneumonia (HCAP; median = 2,003 vs. 1,286; P = .02) or immunocompromising conditions (median = 1,895 vs. 1,409; P = .29). Rates of CAP were also lower in studies that used more restrictive criteria for diagnosing pneumonia (e.g., pneumonia coded in any diagnosis position [median = 2,246] vs. pneumonia coded in the first position only [median = 1,375] in studies of administrative claims; P = 0.03). For adults <65 years of age, annual rates of CAP were lower (range = 89 to 1,024 per 100,000; median = 210).

Conclusion

CAP causes a significant disease burden among adults, particularly among those ≥65 years of age where the incidence of hospitalization is approximately 2,000 per 100,000 annually. Commonly-applied exclusion criteria (e.g., persons with HCAP or immunocompromising conditions) or restrictive case definitions (e.g., only including pneumonias coded in the primary diagnosis position) have led to systematic underestimation of CAP incidence in many previous studies. Understanding the true burden of adult CAP is critical for highlighting the ongoing need for expanded prevention programs, including vaccination.

Disclosures

All authors: No reported disclosures.
1617. Mumps in Detention Facilities that House Detained Migrants—United States, September 2018–April 2019
Authors: Leung Jessica , Elson Diana , Cloud Brandy , (Cody) McMurray Dakota , McNall Rebecca J , Hickman Carole J , Marlow Mariel
Published: October 2019

Background

Starting in September 2018, an unusually high number of mumps cases were reported in US adult detention facilities. Detention facilities usually involve close contact among detainees, facilitating transmission of mumps. Detainees in close contact with a mumps patient are at increased risk for acquiring mumps and should be offered a dose of MMR vaccine. We summarize the epidemiologic, clinical, and laboratory data for mumps cases in adult detention facilities during September 2018-April 2019.

Methods

Data were collected by health departments and US Immigration and Customs Enforcement (ICE) Health Services Corps and reported to CDC. Cases were classified according to the CSTE case definition for mumps and confirmed by RT-qPCR; molecular sequencing was performed on mumps-positive specimens.

Results

From September 2018-April 2019, 389 confirmed and probable mumps cases in adult migrants detained by ICE in 44 detention facilities were reported in 16 states (figure). The median age of patients was 24 years (range: 18–66); 94% were male. Vaccination status was unknown for all patients. Most (80%) patients were exposed while in custody of ICE or other US legal agency, 7% were exposed before apprehension, and custody status at exposure was unknown for 13%. Among 265 patients with data on complications, 15% had orchitis; at least 3 were hospitalized. Mumps genotype G, the most common genotype in US, was identified in specimens from 70 patients. This mumps response included >7,000 MMR vaccine doses distributed to affected facilities, and hundreds of exposed detainees placed under restricted movement in their facility each week. The response is ongoing as new cases continue to be reported.

Conclusion

This is the first report of mumps outbreaks occurring in multiple states and detention facilities during the same period. These outbreaks are costly and challenging to control. Identifying target groups for vaccination is challenging since detainees are frequently transferred and MMR vaccine does not prevent mumps in persons already exposed and infected. Effective public health interventions require an understanding of detention settings. Development of national guidance and resources for public health response to mumps and other infectious diseases in detention facilities would be beneficial.

Disclosures

All authors: No reported disclosures.
1619. Carbapenemase Producing Enterobacteriaceae in River Estuaries and Coastal Water of Netanya, Israel
Authors: Cohen Regev , Paikin Svetlana , Astrahan Peleg
Published: October 2019

Background

The role of the environment in the human epidemiology of carbapenem-resistant Enterobacteriaceae (CREs) is poorly understood. Several reports described carbapenemase-producing Enterobacteriaceae (CPE), cultivated from freshwaters of rivers and seawater, but there are no data from Israel. We encountered a young patient diagnosed as a rectal-carrier of 2 CPEs, both harboring the blaKPC sequence, after near-drowning in seawater near Netanya. In this study, we aimed to study river estuaries and the nearby Netanya beaches for the presence of CPEs.

Methods

On 2 occasions (June, July 2018) we filtered coastal water (Beit-Yanai and Sironit beaches) and freshwater (Alexander and Poleg estuaries) through 0.2µm sterile cellulose acetate membranes. Filtered bacteria were cultured in thioglycolyte broth media and transferred to different solid media. Enterobacteriaceae growing on Chromagar MSupercarba (Hylabs®) plates were isolated, identified, and subjected to modified Hodge test or CARBA-NP hydrolysis. Carbapenemase genes (blaKPC, blaVIM, blaNDM, blaIMP, blaOXA-48) were identified using Cepheid® GeneXpert Carba-R and blaIMI using homemade-PCR in the reference laboratory.

Results

Four CREs were identified from the environment: 2 CP E. cloacae blaIMI, found in both Alexander estuary and seawater of Beit-Yanai; 1 CP E. coli blaOXA-48 found in Poleg estuary, and 1 E. cloacae non-CP CRE found in Alexander estuary (Table 1, Figure 1). The 3 Enterobacter spp had similar antibiogram phenotype.

Conclusion

On two occasions CREs were easily cultivated from seawater of a popular recreational beach as well as from 2 river estuaries in Netanya. The bacterial species as well as the carbapenemase types found in the environment are quite rare compared with the clinical human epidemiology in the hospital serving the population of this district. More research is required in order to reproduce these findings, to investigate sources and persistence of rivers and coastal water pollution and to define the role “environmental” strains have in human epidemiology and disease.

Disclosures

All authors: No reported disclosures.
1624. Primary Care Physician Knowledge, Attitudes, and Diagnostic Testing Practices for Norovirus and Acute Gastroenteritis
Authors: Cardemil Cristina , O’Leary Sean , Beaty Brenda , Ivey Kathryn , Lindley Megan , Kempe Allison , Crane Lori , Hurley Laura , Brtnikova Michaela , Hall Aron
Published: October 2019

Background

Norovirus is a leading cause of acute gastroenteritis (AGE) across the age spectrum; candidate vaccines are in clinical trials. While norovirus diagnostic testing is increasingly available, stool testing may not be performed routinely, which can hamper surveillance and burden of disease estimates. Our objectives were to understand physicians’ stool testing practices in outpatients with AGE, and physician knowledge of norovirus, in order to improve surveillance and prepare for vaccine introduction.

Methods

Internet and mail survey on AGE and norovirus conducted January to March 2018 among national networks of primary care pediatricians (Peds), family practice (FP) and general internal medicine (GIM) physicians.

Results

The response rate was 59% (820/1,383). During peak AGE season, physicians estimated they ordered stool tests for a median of 15% (interquartile range: 5–33%) of their outpatients with AGE. Stool tests were more often available for ova and parasites, Clostridioides difficile, and bacterial culture (>95% for all specialties) than for norovirus (6–33% across specialties); even when available, norovirus-specific tests were infrequently ordered. Most providers were unaware that norovirus is a leading cause of AGE across all age groups (Peds 80%, FP 86%, GIM 89%) or that alcohol-based hand sanitizers are ineffective against norovirus (Peds 51%, FP 66%, GIM 62%).

Conclusion

Physicians infrequently order stool tests for outpatients with AGE, and have knowledge gaps on norovirus prevalence and hand hygiene for prevention. Understanding the limitations of surveillance that relies on physician-ordered stool diagnostics, and closing physician knowledge gaps, can help support norovirus vaccine introduction.

Disclosures

All authors: No reported disclosures.
1626. A Primary Amebic Meningoencephalitis Case Associated with Surfing in an Inland Surf Park
Authors: Cope Jennifer R , Mattioli Mia , Shah Vaidehi , Greeley Rebecca , Hlavsa Michele , Hill Vincent
Published: October 2019

Background

Naegleria fowleri is a thermophilic ameba that is found in freshwater and causes primary amebic meningoencephalitis (PAM; 0–8 infections per year in the United States) when it enters the nose and migrates to the brain. Patient exposure to water containing the ameba typically occurs in warm freshwater lakes and ponds during recreational water activities. In September 2018, a 29-year-old man died of PAM after visiting a Texas inland surf park.

Methods

To determine water exposures, we reviewed medical records and conducted interviews with family and individuals who had traveled with the patient. To further investigate the inland surf park as a possible exposure source, we visited the facility and collected water, biofilm, and sediment samples from the surf park and other venues (water slides, lazy river, and cable park) within the facility. We assessed water sources and treatment practices, performed water quality tests, and tested for the presence of N. fowleri by culture and real-time PCR.

Results

Interviews revealed that the case-patient’s most probable water exposure in the 10 days before becoming ill occurred while surfing in an inland freshwater surf park where he fell off the surfboard into the water multiple times. The on-site investigation of the facility revealed a practice of manual chlorine treatment with monitoring, but no water filtering or record keeping to document water quality. Surf park water temperature was warm (25°C) and chlorine residual was negligible. N. fowleri was detected in 1 water and 1 sediment sample collected at the cable park venue, and viable thermophilic amebae were detected in all samples collected from the surf park, water slide, and cable park venues, as well from the sediment in the open-air groundwater reservoir feeding the venues.

Conclusion

This investigation documents a novel exposure in an inland surf park as the likely exposure causing PAM. Conditions in the surf park were conducive to amebic growth. Novel types of recreational water venues that do not meet traditional definitions of swimming pools, such as this surf park, might not meet the water quality standards for pools or similar treated venues. Clinicians and public health officials should remain vigilant for nontraditional exposures to water.

Disclosures

All authors: No reported disclosures.
1632. Different Healthcare Utilization Pattern in Vaccine Hesitant Children
Authors: Sohn Sangho , Hong Kwan , Hwang Hari , Chul Chun Byung
Published: October 2019

Background

National Immunization Program (NIP) in Korea provides 17 types of mandatory vaccines for all children free of charge. However, vaccine-hesitant group refusing the NIP are being a major threat to public health. We analyzed the healthcare utilization pattern observed in NIP eligible children and sought to identify those who remain unvaccinated using national population data.

Methods

History of receiving protein conjugate pneumococcal vaccine (PCV) was reviewed to determine the vaccination status of children born between 2013 and 2015. Children who had 3-doses or more out of 3 + 1 schedule were defined vaccinated, while those with no record of vaccination were defined unvaccinated. Their healthcare utilization records, including a number of visits, total duration, type of institution (hospitals, complementary and alternative medicine [CAM]), and purpose of visits (outpatient care, hospitalization), were retrieved from the National Health Insurance (NHI) Review and Assessment Service. Annual healthcare utilization rate and incidence of pneumococcal infections were estimated with Poisson regression and compared between study arm. The proportion of CAM out of total healthcare utilization was also compared.

Results

Among 1,272,685 children, 51% were boys and median age was 29.4-months. Two-percent of the cohort remained unvaccinated until study end. Annual hospital visiting rates were 26.9 times (95% confidence interval [CI] 26.9–27.0) for vaccinated and 3.4 (95% CI 3.4–3.5) for unvaccinated. Average NHI benefit period per year was 28.8 days (95% CI 28.8–29.0) for vaccinated and 3.9 (95% CI 3.8–3.9) for unvaccinated. The discrepancy resulted in under-detection of pneumococcal incidence in unvaccinated with 10.1 cases (95% CI 9.9–10.4) per 1,000 child-months whereas that of vaccinated was 42.5 (95% CI 42.4–42.6). Vaccine hesitant children preferred CAM at least 3-times more than vaccinated children (CAM proportion 3.5% in hesitant group vs. 1.07% in vaccinated group, P < 0.001).

Conclusion

Vaccine hesitant group not only refuses vaccination but also tends to opt-out from the entire medical attention and prefer CAM. Active detection considering this different pattern should be implemented in order to ensure the public benefits from the vaccination program.

Disclosures

All authors: No reported disclosures.
1657. Notes From the Field: A Survey of Mobile Device Usage Among Individuals in KwaZulu-Natal, South Africa
Authors: Campbell Breanna R , Choi Koeun , Gray Megan , Canan Chelsea , Moll Anthony , Dillingham Rebecca , Shenoi Sheela
Published: October 2019

Background

mHealth (mobile health) is a promising tool to deliver healthcare interventions to underserved populations. Across low- and middle-income countries (LMIC), the prevalence of smartphones has risen to 42%. Effective mHealth deployment in LMIC requires an understanding of how LMIC populations use mobile technology. We characterized the use of mobile devices in rural KwaZulu-Natal, South Africa to tailor mHealth interventions for people living with HIV and at risk for acquiring HIV.

Methods

We surveyed participants in community settings and offered free HIV counseling and testing. Participants self-reported their gender, age, relationship status, living distance from preferred clinic, receipt of monthly grant, condomless sex frequency, and circumcision status (if male). Outcomes included cell phone and smartphone ownership, private data access, health information seeking, and willingness to receive healthcare messages. We performed multivariable logistic regression to assess the relationship between demographic factors and outcomes.

Results

Among 788 individuals surveyed, the median age was 28 (IQR 22–40) years, 75% were male, and 86% owned personal cell phones, of which 43% were smartphones. The majority (59%) reported having condomless sex and most (59%) males reported being circumcised. Although only 10% used the phone to seek health information, 93% of cell phone owners were willing to receive healthcare messages. Being young, female, and in a relationship were associated with cell phone ownership. Smartphone owners were more likely to be young and female, less likely to live 10–30 minutes from preferred clinic, and less likely to receive a monthly grant. Those reporting condomless sex or lack of circumcision were significantly less likely to have private data access.

Conclusion

Most participants were willing to receive healthcare messages via phone, indicating that mHealth interventions may be feasible in rural KwaZulu-Natal. Smartphone-based mHealth interventions specifically geared to prevent or support the care of HIV in young women in KwaZulu-Natal may be feasible. mHealth interventions encouraging condom use and medical male circumcision should consider the use of non-smartphone SMS and be attuned to mobile data limitations.

Disclosures

All authors: No reported disclosures.
1658. Lipase and Factor V (but not Viral Load) Are Prognostic Factors for the Evolution of Severe Yellow Fever Cases
Authors: Casadio Luciana Vilas Boas , Salles Ana Paula , Malta Fernanda , Fialkovitz Gabriel , Ho Yeh-Li , Gomes-Gouvêa Michele , Malbouisson Luiz Marcelo , Levin Anna S , Azevedo Raymundo , Carrilho Flair , Nastri Ana Catharina , Renato Rebello Pinho João
Published: October 2019

Background

Yellow Fever (YF) is still a major threat in developing countries and a cause of outbreaks in Africa and Latin America, despite a highly efficacious vaccine. In 2018, the Brazilian state of São Paulo witnessed a new YF outbreak in areas where the virus has not been detected before. In our study, we included all patients who were admitted to Intensive Care Units of Hospital das Clínicas, University of São Paulo Medical School during the 2018 YF outbreak. The aim is to describe the clinical and laboratorial characteristics of severe cases of YF, evaluate viral parameters such as viral load and genotype among these cases, and determine markers associated with fatal outcome.

Methods

Acute severe YF cases (n = 62) were admitted to the Intensive Care Unit of a reference hospital and submitted to routine laboratorial evaluation on admission. YFV-RNA was detected in serum and urine by RT–qPCR and then sequenced. Patients were classified in two groups: survival or death.

Results

In the univariate analysis the following variables were associated with outcome: ALT, AST, AST/ALT ratio, total bilirubin, CKD-EPI, ammonia, lipase, factor V, INR, lactate, and bicarbonate. Logistic regression model showed two independent variables associated with death: lipase (OR 1.018, 95% CI 1.007 to 1.030, P = 0.002), and factor V (OR −0.955, 95% CI 0.929 to 0.982, P = 0.001). The estimated lipase and factor V cut-off values that maximized sensitivity and specificity for death prediction were 147.5 U/L (AUC = 0.879), and 56.5% (AUC = 0.913). Patients who were discharged from the hospital continued to be followed-up in the outpatient clinic. Seven patients had their urine and blood screened weekly for YFV until the test was negative. After the onset of symptoms, viremia and viruria were present for a maximum period of 28 days and 47 days, respectively.

Conclusion

YF acute severe cases show a generalized involvement of different organs (liver, spleen, heart, kidneys, intestines, and pancreas), and different parameters were related to outcome. Factor V and lipase are independent variables associated with death, reinforcing the importance of hemorrhagic events due to fulminant liver failure and pointing to pancreatitis as a relevant event in the outcome of the disease.

Disclosures

All authors: No reported disclosures.
1677. Prevalence and Patterns of Outpatient Antibiotic Prescription at a Public Tertiary Medical Center in Southern Province, Sri Lanka
Authors: Zhang Helen L , Wijayaratne Gaya B , Jayatissa Pasangi , Piyasiri Bhagya , Sheng Tianchen , Bodinayake Champica K , Nagahawatte Ajith , Woods Chris W , Tillekeratne L Gayani
Published: October 2019

Background

The global emergence of antimicrobial resistance poses a major public health threat. However, there are little data regarding antimicrobial use from many low- or middle-income countries. In this study, we determined the prevalence and patterns of antibiotic prescription among outpatients at a tertiary healthcare facility in Sri Lanka.

Methods

The study was conducted at the Outpatient Department (OPD) of the largest public tertiary care center in Southern Province, Sri Lanka. This is a free walk-in clinic serving upwards of 1,000 patients per day. Adult and pediatric OPD patients were recruited for a cross-sectional survey in February–April 2019. Pre-visit and post-visit questionnaires were verbally administered to obtain information regarding participants’ demographics and presenting illness. The OPD pharmacy’s electronic prescribing system was queried to calculate the prevalence of antibiotic prescriptions among enrolled patients. Logistic regression was performed to identify features associated with antibiotic prescription.

Results

Of 408 patients surveyed, 246 (62.9%) were female and 88 (21.7%) were children <18 years. Median age was 38 (IQR 19–54) years, and median duration of illness at enrollment was 7 (IQR 3–30) days. Medications were prescribed for 291 (72.4%) patients during the OPD visit, with 146 (35.8% of all patients) receiving an antibiotic. The most frequently prescribed antibiotics were amoxicillin (41, 28.1%), first-generation cephalosporins (38, 26.0%), and amoxicillin/clavulanate (30, 20.5%). The most frequent chief complaints among antibiotic recipients were cough (35, 24.0%), rhinorrhea/congestion (26, 17.8%), and fever (18, 12.3%). Diagnostic investigations were ordered for 38 (26.0%) antibiotic recipients. On bivariable analysis, younger age (P = 0.01), shorter duration of illness (P < 0.001), and lack of prior evaluation (P = 0.001) were positively associated with antibiotic prescription.

Conclusion

We show a high prevalence of outpatient antibiotic prescription despite limited diagnostic evaluation at a tertiary medical facility in Southern Province, Sri Lanka. Antibiotic stewardship efforts, especially targeting respiratory illness, may help improve antibiotic use in this setting.

Disclosures

All authors: No reported disclosures.