1150. Pediatric Osteoarticular Infections Caused by Mycobacteria Tuberculosis Complex: A Twenty-Six Year Review of Cases in San Diego, California

Abstract Background Osteoarticular infections (OAI) account for 10-20% of extrapulmonary Mycobacteria tuberculosis (MTB) complex infections in children. Given the rarity of MTB OAI, the epidemiology, disease manifestations, and treatment are poorly characterized. We describe 21 children treated for MTB complex OAI over a 26-year period at a tertiary pediatric center in southern California. Methods We conducted a retrospective review of children diagnosed with MTB complex OAI and cared for between 31 Dec 1992 to 31 Dec 2018 at a single tertiary care pediatric hospital with close proximity to the United States-Mexico border. Results We identified 21 children with MTB complex OAI during the study period (Table 1). Concurrent pulmonary disease (4.8%), meningitis (9.5%), and intra-abdominal involvement (14.3%) were all observed. MTB complex was identified by culture from operative samples in 15/21 children (71.4%); 8/15 (51.3%) cultures were positive for Mycobacterium bovis. Of the eight cases of vertebral OAI (the most common site), one was culture-positive for M. bovis. Open bone biopsy was the most common procedure for procurement of a tissue sample and had the highest culture yield (Table 2). The median duration of antimicrobial therapy was 52 weeks (IQR 52-58). Successful completion of therapy was documented in 15 children (71.4%). Seven children (33.3%) experienced long term sequelae related to their infection. Table 1. Twenty-one children with Mycobacteria tuberculosis complex osteoarticular infections. Table 2. Surgical sample type and percent positivity. Conclusion Among the 21 children with MTB complex OAI assessed, 8 of 15 (53.3%) children with a positive tissue culture had M. bovis (intrinsically resistant to pyrazinamide), representing a higher percentage than in previous reports and potentially reflecting its presence in unpasteurized dairy products in the California-Baja region. Local epidemiological trends in endemic MTB complex species should be considered when evaluating and managing MTB complex OAI. Bone biopsy produced the highest culture yield in this study. Given the rarity of this disease, multicenter collaborative studies are needed to improve our understanding of the presentation and management of pediatric MTB complex OAI. Disclosures Vanessa Raabe, MD, MSc, Pfizer (Scientific Research Study Investigator, Other Financial or Material Support, Editorial support)Sanofi (Scientific Research Study Investigator)

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1393. Factors Associated with Co-administration of Pentavalent DTaP-IPV/Hib and Monovalent Hepatitis B Vaccine in the United States (US)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1575 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S706-S706

Author(s):

Tanaz Petigara ◽

Ya-Ting Chen ◽

Zhiwen Liu ◽

Michelle Goveia ◽

David Johnson ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

The United States ◽

Vaccination Schedule ◽

Provider Type ◽

Factors Associated ◽

Study Investigator ◽

Region Of Residence ◽

Birth Dose ◽

To Receive

Abstract Background The US vaccination schedule includes DTaP, IPV, Hib and HepB doses in the first 6 months of life. A previous analysis found variability in the timing of HepB doses in infants receiving DTaP-IPV/Hib. We explored factors associated with co-administration of DTaP-IPV/Hib and HepB on the same day. Methods This was a retrospective study using the MarketScan® commercial claims and encounters database. Infants born from 1 July 2010 - 30 June 2016, continuously enrolled in an insurance plan for ≥ 13 months and receiving ≥ 3 DTaP-IPV/Hib doses were included. Infants were assessed for HepB claims relative to the first and third DTaP-IPV/Hib doses. Because a HepB birth dose was assumed, the first HepB claim from 29 - 169 days following birth was counted as Dose 2, and the second claim from 170 days - 12 months as Dose 3. Associations between demographic, provider, and insurance characteristics, receipt of other pediatric vaccines, and co-administration of DTaP-IPV/Hib and HepB were analyzed using multivariate logistic regression. Results Among 165,553 infants who received a first DTaP-IPV/Hib dose, 60.7% received HepB Dose 2 on the same day. Among 162,217 infants who received a third DTaP-IPV/Hib dose, 45.1% received HepB Dose 3 on the same day. Infants in the Northeast were less likely (OR=0.38, 95%CI=0.36-0.39), while those in the West were more likely (OR=1.41, 95%CI=1.36-1.46) than infants in the South to receive the first dose of DTaP-IPV/Hib and HepB Dose 2 on the same day. Infants vaccinated by pediatricians (OR=0.54, 95%CI=0.53-0.55) were less likely to receive the first dose of DTaP-IPV/Hib and HepB Dose 2 on the same day compared to infants vaccinated by family physicians. Infants who received PCV on the same day as the first dose of DTaP-IPV/Hib were more likely to receive HepB Dose 2 (OR=6.96, 95%CI=6.30-7.70) that day. These factors were also associated with co-administration of the third dose of DTaP-IPV/Hib and HepB Dose 3. Conclusion Differences in co-administration of DTaP-IPV/Hib and HepB were associated with region of residence, provider type and co-administration of PCV. The reasons underlying these differences merit exploration. A hexavalent vaccine containing DTaP, IPV, Hib, and HepB could improve timeliness of HepB vaccination, while reducing the number of injections during infancy. Disclosures Tanaz Petigara, PhD, Merck & Co., Inc. (Employee, Shareholder) Ya-Ting Chen, PhD, Merck & Co., Inc. (Employee, Shareholder) Zhiwen Liu, PhD, Merck & Co., Inc., (Employee) Michelle Goveia, MD, Merck & Co., Inc (Employee, Shareholder) David Johnson, MD, MPH, Sanofi Pasteur (Employee, Shareholder) Gary S. Marshall, MD, GlaxoSmithKline (Consultant, Scientific Research Study Investigator)Merck (Consultant, Scientific Research Study Investigator)Pfizer (Consultant, Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Grant/Research Support, Scientific Research Study Investigator, Honorarium for conference lecture)Seqirus (Consultant, Scientific Research Study Investigator)

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1386. Current Estimates of the Impact of Routine Childhood Immunizations in Reducing Vaccine-Preventable Diseases in the United States

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1568 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S703-S703

Author(s):

Elizabeth M La ◽

Justin Carrico ◽

Sandra E Talbird ◽

Ya-Ting Chen ◽

Mawuli K Nyaku ◽

...

Keyword(s):

United States ◽

Research Study ◽

Disease Incidence ◽

Age Groups ◽

Scientific Research ◽

The United States ◽

Annual Number ◽

Study Investigator ◽

Routine Childhood ◽

The Impact

Abstract Background Routine immunizations for children aged 10 years and younger in the United States (US) currently cover 14 diseases. Updated estimates of public health impact are needed, given changes in disease epidemiology, evolving recommendations, and the dynamic nature of compliance with the immunization schedule. Methods Pre-vaccine disease incidence was estimated before each routine vaccine was recommended, with average values across multiple years obtained directly from published literature or calculated based on disease surveillance data or annual case estimates from the published literature. Pre-vaccine incidence then was compared to current, post-vaccine incidence, which was generally calculated as average values over the most recent 5 years of available incidence data. Overall incidence estimates and estimates by age group were calculated. Differences in pre- and post-vaccine disease incidence rates were used to calculate the annual number of cases averted, based on 2019 US population estimates. This analysis did not separately estimate the proportion of disease incidence reduction that may be attributed to adult vaccines or booster doses. Results Post-vaccine disease incidence decreased overall and for all age groups across all diseases evaluated (Table 1). Decreases ranged from 17.4% for influenza to 100.0% for polio (Figure 1). Over 90% reduction in incidence was achieved for 10 of the 14 diseases evaluated (including reduction in incidence of rotavirus hospitalizations). Overall post-vaccine disease incidence estimates were highest for influenza, rotavirus, and varicella. Estimated annual cases averted by vaccination in 2019 ranged from 1,269 for tetanus to more than 4.2 million for varicella. Table 1. Pre- and Post-Vaccine Disease Incidence Estimates, Annual Cases, and 2019 Cases Averted, by Disease Figure 1. Percentage Reduction in Disease Incidence Post-Vaccine, by Disease Conclusion Routine childhood immunization in the US continues to result in high, sustained reduction in disease across all vaccines and for all age groups evaluated. Disclosures Elizabeth M. La, PhD, RTI Health Solutions (Employee) Justin Carrico, BS, GlaxoSmithKline (Consultant) Sandra E. Talbird, MSPH, RTI Health Solutions (Employee) Ya-Ting Chen, PhD, Merck & Co., Inc. (Employee, Shareholder) Mawuli K. Nyaku, DrPh, Merck & Co. Inc. (Employee, Shareholder) Cristina Carias, PhD, Merck (Employee, Shareholder) Gary S. Marshall, MD, GlaxoSmithKline (Consultant, Scientific Research Study Investigator)Merck (Consultant, Scientific Research Study Investigator)Pfizer (Consultant, Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Grant/Research Support, Scientific Research Study Investigator, Honorarium for conference lecture)Seqirus (Consultant, Scientific Research Study Investigator) Craig S. Roberts, PharmD, MPA, MBA, Merck & Co., Inc (Employee, Shareholder)

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32. Host Immune-Protein Signature Combining TRAIL, IP-10 and CRP for Early and Accurate Prediction of Severe COVID-19 Outcome

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.032 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S22-S23

Author(s):

Alon Angel ◽

Niv Samuel Mastboim ◽

Oded Shaham ◽

Tahel Ilan Ber ◽

Roy Navon ◽

...

Keyword(s):

At Risk ◽

Board Member ◽

Research Study ◽

Scientific Research ◽

The United States ◽

Blood Draw ◽

Predictive Tool ◽

Derivation Cohort ◽

Study Investigator ◽

Patients At Risk

Abstract Background Accurately identifying COVID-19 patients at-risk to deteriorate remains challenging. Dysregulated immune responses impact disease progression and development of life-threatening complications. Tools integrating host immune-protein expression have proven useful in determining infection etiology and hold potential for prognosticating disease severity. Methods Adults with COVID-19 were enrolled at medical centers in Israel, Germany, and the United States (Figure 1). Severe outcome was defined as intensive care unit admission, non-invasive or invasive ventilation, or death. Tumor necrosis factor related apoptosis inducing ligand (TRAIL), interferon gamma inducible protein-10 (IP-10) and C-reactive protein (CRP) were measured using an analyzer providing values within 15 minutes (MeMed Key®). A signature indicating the likelihood of severe outcome was derived generating a score (0-100). Description of derivation cohort RT-PCR, reverse transcription polymerase chain reaction. Results Between March and November 2020, 518 COVID-19 patients were enrolled, of whom 394 were eligible, 29% meeting a severe outcome. Age ranged between 19-98 (median 61.5), with 59.1% male. Patients meeting severe outcomes exhibited higher levels of CRP and IP-10 and lower levels of TRAIL (Figure 2; p < 0.001). Likelihood of severe outcome increased significantly (p < 0.001) with higher scores. The signature’s area under the receiver operating characteristic curve (AUC) was 0.86 (95% confidence interval: 0.81-0.91). Performance was not confounded by age, sex, or comorbidities and was superior to IL-6 (AUC 0.77; p = 0.033) and CRP (AUC 0.78; p < 0.001). Clinical deterioration proximal to blood draw was associated with higher signature score. Scores of patients meeting a first outcome over 3 days after blood draw were significantly (p < 0.001) higher than scores of non-severe patients (Figure 3). Moreover, the signature differentiated patients who further deteriorated after meeting a severe outcome from those who improved (p = 0.004) and projected 14-day survival probabilities (p < 0.001; Figure 4). TRAIL, IP-10, CRP and the severity signature score are differentially expressed in severe and non-severe COVID-19 infection Dots represent patients and boxes denote median and interquartile range (IQR) The signature score of patients meeting a severe outcome on or after the day of blood draw is significantly (p < 0.001) higher than the signature score of non-severe patients. Dots represents patients and boxes denote median and IQR Kaplan-Meier survival estimates for signature score bins Conclusion The derived signature combined with a rapid measurement platform has potential to serve as an accurate predictive tool for early detection of COVID-19 patients at risk for severe outcome, facilitating timely care escalation and de-escalation and appropriate resource allocation. Disclosures Alon Angel, n/a, MeMed (Employee, Shareholder) Niv Samuel Mastboim, BSc, MeMed (Employee, Shareholder) Oded Shaham, PhD, MeMed (Employee, Shareholder) Tahel Ilan Ber, MD, MeMed (Employee, Shareholder) Roy Navon, MSc, MeMed (Employee, Shareholder) Einav Simon, PhD, MeMed (Employee, Shareholder) Michal Rosenberg, PhD, MeMed (Employee) Yael Israeli, PhD, MeMed (Employee) Mary Hainrichson, PhD, MeMed (Employee, Shareholder) Noa Avni, PhD, MeMed (Employee) Eran Reiner, MD, MeMed (Employee) Kfir Oved, MD, PhD, MeMed (Board Member, Employee, Shareholder) Ilya Kagan, MD, MeMed (Scientific Research Study Investigator) Shaul Lev, M.D, MeMed (Scientific Research Study Investigator) Dror Diker, MD, MeMed (Scientific Research Study Investigator) Amir Jarjou’i, MD, MeMed (Scientific Research Study Investigator) Ramzi Kurd, MD, MeMed (Scientific Research Study Investigator) Guy Danziger, MD, MeMed (Scientific Research Study Investigator) Cihan Papan, MD, MeMed (Scientific Research Study Investigator) Sergey Motov, MD, MeMed (Scientific Research Study Investigator) Maanit Shapira, Ph.D, MeMed (Scientific Research Study Investigator) Tanya Gottlieb, PhD, MeMed (Employee, Shareholder) Eran Eden, PhD, MeMed (Board Member, Employee, Shareholder)

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1399. Parental Perceptions of the Childhood Vaccination Schedule and Combination Vaccines in the United States (US)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1581 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S708-S708

Author(s):

Tanaz Petigara ◽

Xinyi Ng ◽

Ya-Ting Chen ◽

Jyoti Aggarwal ◽

Jenna Bhaloo ◽

...

Keyword(s):

Online Survey ◽

Research Study ◽

Scientific Research ◽

The United States ◽

Vaccination Schedule ◽

Childhood Vaccination ◽

Multiple Injections ◽

Study Investigator ◽

Vaccine Schedule ◽

Combination Vaccines

Abstract Background Ten different vaccine series are recommended by the US Advisory Committee on Immunization Practices from birth to 18 months. Combination vaccines can reduce the number of injections and visits required to complete the schedule in a timely manner. There is limited current information on parents’ perception of the vaccine schedule and combination vaccines. Methods An online survey was completed by 100 parents who had at least one child under 2 years, were involved in vaccination decisions, and had accompanied their child to a vaccination appointment. Parents who reported not ever vaccinating their children were excluded. Parents’ perception of, and adherence to, the recommended schedule, communication with providers, and knowledge of combination vaccines were collected. Descriptive analyses were performed. Results Ninety-six percent of parents (mean age=30.7 years; range 19.0-50.0; 91% white) reported their provider as a source of vaccination information, followed by internet searches (63%), family and friends (45%). Most (84%) followed all their provider’s recommendations and trusted the information given to them (87%). State day care and pre-school requirements influenced vaccination decisions for nearly 80% of parents. Over 80% of parents thought it is important to protect against diseases covered by the vaccination schedule. One-third had at some time asked to delay or not administer vaccines; depending on the vaccine, up to 50% ultimately had their child vaccinated as recommended. Top reasons for delaying vaccination were to avoid crying and pain from multiple injections (82%), and the concern that too many vaccines would overwhelm the immune system (64%). Top reasons for refusal were religious views (57%) and the belief that the vaccine was not needed (52%). On average, parents would accept their child receiving 3 injections in one visit. Most parents were aware of combination vaccines (84%); however, one-third reported that their child had not received, or they were unaware of their child receiving, a combination vaccine. Conclusion Providers are in a strong position to influence vaccination decisions by parents. Whereas parents are motivated to avoid the pain of multiple injections, many are unaware that their children are receiving combination vaccines. Disclosures Tanaz Petigara, PhD, Merck & Co., Inc. (Employee, Shareholder) Xinyi Ng, PhD, Merck & Co., Inc. (Consultant) Ya-Ting Chen, PhD, Merck & Co., Inc. (Employee, Shareholder) Jyoti Aggarwal, MHS, Merck & Co., Inc. (Consultant) Jenna Bhaloo, MPH, Merck & Co., Inc. (Consultant) Michelle Goveia, MD, Merck & Co., Inc (Employee, Shareholder) David Johnson, MD, MPH, Sanofi Pasteur (Employee, Shareholder) Gary S. Marshall, MD, GlaxoSmithKline (Consultant, Scientific Research Study Investigator)Merck (Consultant, Scientific Research Study Investigator)Pfizer (Consultant, Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Grant/Research Support, Scientific Research Study Investigator, Honorarium for conference lecture)Seqirus (Consultant, Scientific Research Study Investigator)

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1394. Impact of 7-Valent and 13-Valent Pneumococcal Conjugate Vaccines in the United States: A Systematic Literature Review

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1576 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S706-S706

Author(s):

Kristin Kistler ◽

Evelyn F Gomez-Espinosa ◽

Kelly Sutton ◽

Ruth Chapman ◽

Desmond Dillon-Murphy ◽

...

Keyword(s):

United States ◽

Literature Review ◽

Systematic Literature Review ◽

Pneumococcal Disease ◽

Research Study ◽

Scientific Research ◽

The United States ◽

Conjugate Vaccines ◽

Pneumococcal Conjugate Vaccines ◽

Study Investigator

Abstract Background The availability of 7-valent (PCV7) and 13-valent (PCV13) pneumococcal conjugate vaccines (PCVs) in the United States (US) since 2000 and 2010, respectively, has substantially reduced the occurrence, morbidity and mortality of pneumococcal disease. This systematic literature review aimed to assess the impact of the PCVs in reducing the pneumococcal disease burden since their introduction. Methods We searched Embase and Medline and disease-surveillance websites for observational studies of US participants < 19 years, published 1999–2019 and reporting incidence or prevalence of acute otitis media, invasive pneumococcal disease, meningitis, or pneumococcal disease-related morbidity, mortality, healthcare resource utilization (HCRU) or costs. Results Of 499 citations identified from the databases and other sources, 125 met inclusion criteria (Figure), all indicating clear reductions in multiple manifestations of pneumococcal disease with PCV7 and PCV13 use. However, variations across studies in outcomes reported, study years, and age strata, confounded assessment of vaccine impact on specific pneumococcal disease outcomes and key burden indicators, such as tympanostomy tube placement and antibiotic prescriptions. Conclusion PCVs have greatly decreased multiple manifestations of pneumococcal disease in the US. However, granular data on the frequency and morbidity associated with specific pneumococcal diseases and on associated HCRU are needed to quantify the public-health impact of these vaccines. Disclosures Kristin Kistler, PhD, Evidera, Inc. (Employee, Evidera, Inc. received the funding to conduct this study.) Evelyn F. Gomez-Espinosa, BSc, PhD, Evidera Inc (Employee, Scientific Research Study Investigator)Pfizer Inc (Consultant, Scientific Research Study Investigator) Kelly Sutton, PhD, Evidera (Other Financial or Material Support, Evidera, Inc. received the funding to conduct this study.) Ruth Chapman, MSc, PhD, Evidera, Inc, (Evidera, Inc. received the funding to conduct this study.) (Consultant) Desmond Dillon-Murphy, MSc, PhD, Evidera, Inc. (Evidera, Inc. received the funding to conduct this study.) (Consultant) Matthew Wasserman, MSc., Pfizer Inc. (Employee)

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1157. Clinical Safety, Efficacy, and Pharmacokinetics of Fosmanogepix, a Novel First-in-class Antifungal, in Patients with Renal Insufficiency: Subset Analysis from a Phase 2 Candidemia Trial

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1343 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S605-S605

Author(s):

Pierre Bulpa ◽

Galia Rahav ◽

Ilana Oren ◽

Mickaël Aoun ◽

George R Thompson ◽

...

Keyword(s):

Renal Function ◽

Renal Insufficiency ◽

Antifungal Agents ◽

Research Study ◽

Scientific Research ◽

Panel Member ◽

Antifungal Treatment ◽

Successful Outcome ◽

Review Panel ◽

Study Investigator

Abstract Background Fosmanogepix (FMGX) is a first-in-class antifungal agent, with a unique MOA targeting the fungal enzyme Gwt1, and broad-spectrum activity against yeasts and molds, including fungi resistant to other antifungal agents. Patients with candidemia often have underlying renal insufficiency or are receiving medications that affect renal function. This analysis evaluated outcomes in patients with varying degrees of renal insufficiency. Methods This global, multicenter, open-label, non-comparative study evaluated the safety and efficacy of FMGX for first-line treatment of candidemia. Patients with a recent diagnosis of candidemia defined as positive blood culture for Candida spp within 96 hrs prior to study entry with ≤ 2 days of prior antifungal treatment were eligible, including those with renal insufficiency. Patients with neutropenia, C. krusei infection, deep-seated Candida infections or receiving hemodialysis were excluded. Subjects were treated with FMGX for up to 14 days: 1000 mg IV BID for 1 day, then 600 mg IV QD for at least 2 days, followed by either 600 mg IV QD or 700 mg PO QD. Patients requiring antifungal treatment beyond 14 days received fluconazole. The primary efficacy endpoint was outcome at end of study treatment (EOST) as determined by an independent data review committee. Successful outcome was defined as survival with clearance of Candida from blood cultures with no additional antifungal treatment. Results 14/21 (66%) subjects had some degree of renal insufficiency: 7 had mild renal insufficiency (GFR:60-89), 5 had moderate renal insufficiency (GFR:30-59), and 2 had severe renal insufficiency (GFR:15-29). 12/14 (86%) completed study treatment, and treatment was successful at EOST in 12/14 (86%) subjects. Decline in renal function was not observed at EOST. 4 had worsening of renal function during the follow-up period; none required dialysis. Renal impairment did not increase exposure of FMGX. There were no treatment-related adverse events. Conclusion FMGX demonstrated high level treatment success with no evidence of drug-related nephrotoxicity, with no dose adjustments required. These preliminary data support the continued evaluation of FMGX in patients with candidemia and renal dysfunction as an alternative to potentially nephrotoxic antifungal agents. Disclosures Pierre Bulpa, MD, Amplyx Pharmaceuticals (Scientific Research Study Investigator) Galia Rahav, MD, AstraZeneca (Scientific Research Study Investigator) Mickaël Aoun, MD, Amplyx Pharmaceuticals (Scientific Research Study Investigator) Peter Pappas, MD, SCYNEXIS, Inc. (Consultant, Advisor or Review Panel member, Research Grant or Support) Bart Jan Kullberg, MD, FRCP, FIDSA, Amplyx (Advisor or Review Panel member) Sara Barbat, BSN, RN, Amplyx Pharmaceuticals (Employee) Pamela Wedel, BSc, Amplyx Pharmaceuticals (Employee) Haran T. Schlamm, MD, Amplyx (Consultant) Michael Hodges, BSc. MD, Amplyx Pharmaceuticals Inc. (Employee)

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1608. Efficacy of Ceftolozane/Tazobactam for Multidrug-Resistant Gram-Negative Infections in Multiple Urban Hospitals

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1788 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S798-S799

Author(s):

Nicolo Cabrera ◽

Truc T Tran ◽

Travis J Carlson ◽

Faris Alnezary ◽

William R Miller ◽

...

Keyword(s):

Research Study ◽

Clinical Success ◽

Significant Proportion ◽

Scientific Research ◽

Panel Member ◽

Multidrug Resistant ◽

Outcome Data ◽

Research Support ◽

Gram Negative ◽

Study Investigator

Abstract Background Ceftolozane/tazobactam (C/T) is a novel cephalosporin/beta-lactamase inhibitor combination developed for use against multidrug-resistant (MDR) Gram-negative infections, particularly Pseudomonas aeruginosa (PA). C/T is approved for complicated urinary tract and intraabdominal infections as well as hospital-acquired/ventilator-associated bacterial pneumonias. However, comprehensive clinical characterization of patients treated with C/T in non-FDA-approved indications is limited. Methods Patients ≥18 years who received C/T for ≥48 hours while hospitalized in 9 acute care centers in Houston, TX from January 2016 through September 2018 were included. Demographic, microbiologic, treatment and clinical outcome data were retrospectively collected by chart review. In patients who received multiple inpatient courses of C/T, only the first course with C/T was assessed. Results 210 patients met inclusion criteria: 58% were non-white, 35% were female and 13% were immunocompromised. Median age was 61 years (IQR, 48 to 69). Median Charlson comorbidity index was 5 (IQR, 2 to 6). At the onset of the index episode, a significant proportion of patients required intensive care unit admission (44%), mechanical ventilation (37%) and pressor support (22%). Respiratory sources were the most common (50%) followed by urine (15%). Positive cultures were documented in 93% of the cases and PA was found in 86%. Majority (95%) of PA which were MDR. C/T use was guided by susceptibility testing of the index isolate in ca. 52%. In 5.7% of cases, C/T was used to escalate therapy without any documented C/T-susceptible organism. Half (51%) of the cohort received initial dosing appropriate for renal function while 36% receiving a lower than recommended dose. Clinical success (i.e., recovery from infection-related signs and symptoms) occured in 77%. The in-hospital mortality rate in our cohort was 15% with 26 of 31 deaths deemed infection-related. Conclusion We report a large multicenter observational cohort that received C/T. A 77% clinical success with the use of C/T was documented. These data support the use of C/T in critically ill patients infected with MDR PA. Disclosures William R. Miller, MD, Entasis Therapeutics (Scientific Research Study Investigator)Merck (Grant/Research Support)Shionogi (Advisor or Review Panel member) Laura A. Puzniak, PhD, Merck (Employee) Cesar A. Arias, MD, MSc, PhD, FIDSA, Entasis Therapeutics (Scientific Research Study Investigator)MeMed (Scientific Research Study Investigator)Merck (Grant/Research Support)

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673. Updated CLSI Ciprofloxacin Breakpoints from a Multicenter Assessment for Enterobacterales, Salmonella spp. and Pseudomonas aeruginosa Using MicroScan Dried Gram Negative MIC Panels

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.866 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S391-S391

Author(s):

Maria M Traczewski ◽

Denise Beasley ◽

Amanda Harrington ◽

Sharon DesJarlais ◽

Omai Garner ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Reference Panel ◽

Broth Microdilution ◽

Salmonella Spp ◽

Research Personnel ◽

Gram Negative ◽

Material Support ◽

Study Investigator ◽

Support Research

Abstract Background Updated US FDA/CLSI ciprofloxacin breakpoints were evaluated against data from a multicenter clinical study with Enterobacterales, Salmonella spp. and P. aeruginosa on a MicroScan Dried Gram-negative MIC (MSDGN) Panel. MIC results were compared to results obtained with frozen broth microdilution panels prepared according to CLSI methodology. Methods MSDGN panels were evaluated at three clinical sites by comparing MIC values obtained using the MSDGN panels to MICs utilizing a CLSI broth microdilution reference panel. Data from the combined phases of efficacy and challenge included 803 Enterobacterales, Salmonella spp. and P. aeruginosa clinical isolates tested using the turbidity and Prompt® methods of inoculation. To demonstrate reproducibility, a subset of 12 organisms were tested on MSDGN panels at each site during reproducibility. MSDGN panels were incubated at 35 ± 1ºC and read on the WalkAway System, the autoSCAN-4 instrument, and visually. Read times for the MSDGN panels were at 16-20 hours. Frozen reference panels were prepared and read according to CLSI methodology. FDA and CLSI breakpoints (µg/mL) used for interpretation of MIC results were: Enterobacterales ≤ 0.25 S, 0.5 I, ≥ 1 R; Salmonella spp. ≤ 0.06 S, 0.12-0.5 I, ≥ 1 R; P. aeruginosa ≤ 0.5 S, 1 I, ≥ 2 R. Results Essential and categorical agreement was calculated compared to frozen reference panel results. Results for isolates tested during efficacy and challenge with Prompt inoculation and manual read are as follows: Conclusion Ciprofloxacin MIC results for Enterobacterales, Salmonella spp., and P. aeruginosa obtained with the MSDGN panel correlate well with MICs obtained using frozen reference panels using updated FDA/CLSI interpretive criteria in this multicenter study. * PROMPT® is a registered trademark of 3M Company, St. Paul, MN USA. BEC, the stylized logo and the BEC product and service marks mentioned herein are trademarks or registered trademarks of Beckman Coulter, Inc. in the US and other countries. Disclosures Maria M. Traczewski, BS MT (ASCP), Beckman Coulter (Scientific Research Study Investigator) Denise Beasley, BS, Beckman Coulter (Other Financial or Material Support, Research personnel) Amanda Harrington, PhD, Beckman Coulter (Scientific Research Study Investigator) Sharon DesJarlais, BS, Beckman Coulter (Other Financial or Material Support, Research personnel) Omai Garner, PhD, D(ABMM), Beckman Coulter (Scientific Research Study Investigator) Christine Hastey, PhD, Beckman Coulter (Employee) Regina Brookman, BS, Beckman Coulter (Employee) Zabrina Lockett, MS, Beckman Coulter (Employee) Jennifer Chau, PhD, Beckman Coulter (Employee)

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1400. Physician Attitudes towards Combination Vaccine Use in Infants up to 24 months of age in the United States (US)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1582 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S708-S709

Author(s):

Ya-Ting Chen ◽

Xinyi Ng ◽

Tanaz Petigara ◽

Jyoti Aggarwal ◽

Jenna Bhaloo ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Physician Attitudes ◽

Combination Vaccine ◽

Hexavalent Vaccine ◽

Family Practitioners ◽

Study Investigator ◽

Vaccine Schedule ◽

Combination Vaccines ◽

Number Of Injections

Abstract Background Combination vaccines reduce the number of injections and improve the timeliness of vaccination coverage. US Advisory Committee on Immunization Practices (ACIP) recommendations state that combination vaccines are generally preferred over equivalent individual component vaccines. Healthcare providers strongly influence parental decisions about vaccination. We sought a contemporary understanding of physician’s attitudes towards combination vaccine use in infants. Methods We conducted an online survey of US physicians (70 pediatricians and 30 family practitioners) who administer vaccines to infants aged 0-24 months and spend at least 2 days a week providing patient care. Information was collected on attitudes towards combination vaccines and factors that influence the choice of combination vaccine used in clinical practice. Descriptive analyses were performed. Results Physicians (mean age=50.2 years, range 30.0-70.0; 66% white; 37% women) reported a median of 4 injections (range 2-9) as the maximum that parents would accept at a single visit, and 71% routinely explained what combination vaccines are to parents. When deciding which pentavalent vaccine to use, physicians considered how the brand fits into the current vaccine schedule (71%); upfront purchase costs (64%); and availability as a prefilled syringe (61%). The main reasons for using combination vaccines were to reduce the number of injections (96%); ensure the infant is up-to-date with vaccinations (86%); and reduce the pain that the infant experiences with multiple injections (68%). More than half reported that their institution or practice has a program to incentivize infant vaccination according to schedule. If a hexavalent vaccine-based schedule was available, 76% of physicians said they would choose it over their current schedule comprising pentavalent or equivalent component vaccines. Conclusion Choice of pentavalent combination vaccine among pediatricians and family practitioners was largely dependent on convenience and cost-related factors. Over three-quarters would be inclined to use a hexavalent vaccine schedule if available. Disclosures Ya-Ting Chen, PhD, Merck & Co., Inc. (Employee, Shareholder) Xinyi Ng, PhD, Merck & Co., Inc. (Consultant) Tanaz Petigara, PhD, Merck & Co., Inc. (Employee, Shareholder) Jyoti Aggarwal, MHS, Merck & Co., Inc. (Consultant) Jenna Bhaloo, MPH, Merck & Co., Inc. (Consultant) Michelle Goveia, MD, Merck & Co., Inc (Employee, Shareholder) David Johnson, MD, MPH, Sanofi Pasteur (Employee, Shareholder) Gary S. Marshall, MD, GlaxoSmithKline (Consultant, Scientific Research Study Investigator)Merck (Consultant, Scientific Research Study Investigator)Pfizer (Consultant, Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Grant/Research Support, Scientific Research Study Investigator, Honorarium for conference lecture)Seqirus (Consultant, Scientific Research Study Investigator)

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1510. Infant Pneumonia and Subsequent Risk of Chronic Respiratory Disorders

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1691 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S758-S759

Author(s):

Stephen I Pelton ◽

Rotem Lapidot ◽

Matthew Wasserman ◽

Melody Shaff ◽

Ahuva Hanau ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Airway Disease ◽

Research Support ◽

Recurrent Wheezing ◽

Recurrent Pneumonia ◽

Respiratory Disorders ◽

Study Investigator ◽

Study Population ◽

Research Grant

Abstract Background Community-acquired pneumonia (CAP) in infancy (i.e., among children aged < 2 years) may have long-term consequences for the rapidly developing lung. We examined the impact of pneumonia in infancy on subsequent respiratory health. Methods A retrospective matched-cohort design and data from Optum’s de-identified Integrated Claims-Clinical dataset (2009-2018) were employed. Study population comprised children who were hospitalized for CAP before age 2 years (“CAP patients”) as well as matched comparators without evidence of pneumonia before age 2 years (“comparison patients”). CAP patients and comparison patients were matched (fixed 1:5 ratio, without replacement) using estimated propensity scores and a nearest-neighbor approach; those with evidence of selected medical conditions (e.g., extreme prematurity, congenital diseases, respiratory diseases) before age 2 years were excluded. Study outcomes included recurrent pneumonia and a composite of asthma, recurrent wheezing, and hyperactive airway disease. Rates of study outcomes from age 2 to 5 years were estimated for all CAP and comparison patients as well as subgroups of CAP patients (and corresponding comparison patients) stratified by etiology (bacterial, viral, unspecified). Results Study population totaled 1,343 CAP patients and 6,715 comparison patients. CAP patients and comparison patients were well-balanced on their baseline characteristics and mean duration of follow-up was 757 and 729 days, respectively. Rates of chronic respiratory disorders from age 2 to 5 years were significantly higher among CAP patients versus comparison patients. Analyses of subgroups stratified by etiology demonstrated higher rates of study outcomes among CAP patients across all strata. Rates of recurrent pneumonia and a composite of asthma, recurrent wheezing, and hyperactive airway disease from age 2 to 5 years among CAP patients and matched comparison patients Conclusion Infant CAP foreshadows an increase in subsequent risk of chronic respiratory disorders. Further studies are needed to determine whether this elevated risk is due to infant pneumonia or whether infant pneumonia is a marker of at-risk children. Disclosures Stephen I. Pelton, MD, Merck vaccine (Consultant, Grant/Research Support)Pfizer (Consultant, Grant/Research Support)Sanofi Pasteur (Consultant, Other Financial or Material Support, DSMB)Seqirus Vaccine Ltd. (Consultant) Rotem Lapidot, MD, MSCI, Pfizer (Consultant) Matthew Wasserman, MSc., Pfizer Inc. (Employee) Melody Shaff, BA, Pfizer, Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Ahuva Hanau, BS, Pfizer, Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Alexander Lonshteyn, PhD, Pfizer, Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Derek Weycker, PhD, Pfizer Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)

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