bluuebunny/crossref_metadata_2025_split huggingface dataset:
1471. Evaluation of Antibiotic De-escalation in Post Cardiac Arrest Patients with Culture-Negative versus Culture-Positive Aspiration Pneumonia
Authors: Herzig Natasha R , Harpenau Tara L , Wohlfarth Kevin M , Hochanadel Alicia M 
Published: January 2021

Abstract

Background
Cardiac arrest patients are often empirically treated for aspiration pneumonia with broad-spectrum antibiotics. Previous literature has shown no difference in clinical outcomes when discontinuing antimicrobial therapy for suspected aspiration pneumonia with negative respiratory cultures, but the application is limited in this population. This study aimed to assess antibiotic de-escalation practices for suspected aspiration pneumonia in post cardiac arrest patients with respiratory cultures and explore clinical outcomes.

Methods
This retrospective cohort conducted at a level 1 trauma center included adult out-of-hospital cardiac arrest patients who received antimicrobial therapy for suspected aspiration pneumonia. The primary endpoint was incidence of antibiotic de-escalation before day seven comparing culture-negative and culture-positive patients. De-escalation included discontinuation of methicillin-resistant Staphylococcus aureus (MRSA) coverage, Pseudomonas aeruginosa coverage, atypical coverage or all antibiotics when respective pathogens were not identified from microbiologic or serologic methods. Secondary endpoints included type of de-escalation and clinical outcomes.

Results
Eighty-six patients were included: 45 culture-negative and 41 culture-positive. Figure 1 depicts the breakdown of organisms isolated. Guideline-directed empiric therapy was used in 18.6% of patients, with the remainder receiving excessively broad empiric coverage. Antibiotic de-escalation before day seven occurred in 28 (80%) culture-negative patients and 32 (82%) culture-positive patients (p = 0.82), excluding patients who died before day seven. Providers frequently stopped unnecessary MRSA coverage in both groups. In-hospital mortality was higher in the group of patients without antibacterial de-escalation (62% vs. 33%, p=0.03), but hospital length of stay, ICU length of stay, and number of ventilator-free days were not different between groups.
Figure 1: Epidemiology of Pathogens Isolated From Respiratory Cultures in Cardiac Arrest Patients

Conclusion
Culture results were not associated with antibiotic de-escalation in post cardiac arrest patients with suspected aspiration pneumonia. Opportunities exist for further de-escalation in this population, particularly patients with unnecessary pseudomonal coverage.

Disclosures
All Authors: No reported disclosures
1473. Guideline Adherence in Pediatric Ambulatory Visits for Acute Otitis Media
Authors: Herigon Joshua C , Mousseau Sarah , Kimia Amir , Hatoun Jonathan , Vernacchio Louis 
Published: January 2021

Abstract

Background
Acute otitis media (AOM) is the most common pediatric outpatient condition treated with antibiotics in the United States. Over 30% of children receive inappropriate antibiotics for AOM, contributing to increasing antimicrobial resistance and unnecessary adverse events. Strict adherence to diagnostic and treatment guidelines has been proposed by the American Academy of Pediatrics (AAP) Committee on Infectious Diseases as one strategy to combat inappropriate antibiotic use. Our objective was to describe adherence to the 2013 AAP guidelines on AOM.

Methods
We performed a cross-sectional study on a random sample of visit notes for patients 3 to 59 months old diagnosed with otitis media based on ICD-10-CM codes (H65, H66, H67) and treated with antibiotics between 9/1/2017 and 8/31/2018 in an association of pediatric practices across Massachusetts. Children with tympanostomy tubes or a chronic medical condition increasing their risk for AOM were excluded. Based on the 2013 AAP diagnostic criteria, tympanic membrane exam descriptions were reviewed and classified as describing AOM or not. Antibiotic choices were classified as appropriate or inappropriate. Notes were then labeled as “fully adherent” (exam consistent with AOM and appropriate antibiotic choice), “partially adherent” (exam inconsistent with AOM or inappropriate antibiotic choice), and “non-adherent” (exam inconsistent with AOM and inappropriate antibiotic choice).

Results
Three hundred and ninety-four visit notes from 39 different practices were analyzed. One hundred and sixty-six notes (42%) were “fully adherent” to the AAP guidelines, 183 (46%) were “partially adherent” and 45 (11%) were “non-adherent” (Figure 1). In the “partially adherent” and “non-adherent” groups combined, exams were inappropriate in 179 notes (45.4%) and antibiotic choice was inappropriate in 94 notes (23.9%). Cefdinir was the most frequent inappropriate antibiotic (44/94, 46.8%) (Table 1). “Watchful waiting” occurred in only 7% (16/229) of eligible cases.
Figure 1. Breakdown of encounters by adherence type

Table 1. Cross-table of indicated and prescribed antibiotics

Conclusion
Our analysis of independent pediatric practices showed moderate adherence to the AAP guidelines for AOM. Substantial room exists for improvement in diagnosing and treating AOM in young children, especially regarding the potential for watchful waiting.

Disclosures
All Authors: No reported disclosures
1479. Incidence of Acute Otitis Media in Children in the United States before and after the introduction of Pneumococcal Conjugate Vaccines (PCV7 and PCV13) during 1998-2018
Authors: Hu Tianyan , Sarpong Eric , Song Yan , Done Nicolae , Orvis Eli , Signorovitch James , Petigara Tanaz 
Published: January 2021

Abstract

Background
Acute otitis media (AOM) leads to considerable healthcare resource utilization in children. Streptococcus pneumoniae is an important cause of AOM. Merck is developing V114, an investigational 15-valent PCV that contains PCV13 serotypes as well as 22F and 33F. To demonstrate the potential value of V114, it is important to estimate the remaining clinical burden associated with AOM. This study estimated AOM incidence rates (IRs) before and after the introduction of 7-valent and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) in the US.

Methods
This was a retrospective observational study using IBM MarketScan® Commercial Claims and Encounters (CCAE) (1998-2018) and Multi-State Medicaid databases (2001-2018). AOM claims in children &lt; 18 years old were identified using ICD9 codes 382.x and ICD10 codes H66.x and H67.x. An episode could comprise one or more AOM-related claims. A gap of at least 14 days between two AOM-related claims was required to define the start of a new episode. IRs were defined as the numbers of episodes per 1,000 person-years (PY). Annual IRs were stratified by age groups (&lt; 2, 2-4, and 5-17), and reported separately for CCAE and Medicaid databases.

Results
AOM IRs declined over time among commercially and Medicaid-insured children in all age groups &lt; 18 years old. In particular, among children &lt; 2 years, AOM IRs declined from 1,111 in 1998 to 727/1,000 PY in 2018 in commercially plans and from 895 in 2001 to 656/1,000 PY in 2018 in Medicaid (Figure 1). In children 2-4 years, AOM IRs declined from 517 in 1998 to 400/1,000 PY in 2018 in commercial plans and from 385 in 2001 to 329/1,000 PY in 2018 in Medicaid (Figure 2). In children 5-17 years, AOM IRs declined from 112 in 1998 to 87/1,000 PY in 2018 in commercial plans and from 98 in 2001 to 87/1,000 in 2018 in Medicaid (Figure 3).
Figure 1. AOM incidence in commercially and Medicaid-insured children ages 0 - 1 years, episodes per 100,000 patient-years (1998 - 2018)

Figure 2. AOM incidence in commercially and Medicaid-insured children ages 2 - 4 years, episodes per 100,000 patient-years (1998 - 2018)

Figure 3. AOM incidence in commercially and Medicaid-insured children ages 5 - 17 years, episodes per 100,000 patient-years (1998 - 2018)

Conclusion
AOM IRs declined following the introduction of PCV7 and PCV13; however, disease burden remains substantial in younger children. The impact of future PCVs on AOM will depend on the proportion of AOM caused by S. pneumoniae and vaccine-type serotypes.

Disclosures
Tianyan Hu, PhD, Merck (Employee, Shareholder) Yan Song, PhD, Merck (Consultant) Nicolae Done, PhD, Merck & Co., Inc. (Consultant) Eli Orvis, BA, Merck (Consultant) James Signorovitch, PhD, Merck & Co., Inc. (Consultant) Tanaz Petigara, PhD, Merck & Co., Inc. (Employee, Shareholder)
1483. Maternal Tdap Vaccination During Pregnancy and Immune Response: A Comparison Between Infants Born to Mothers Primed with Acellular or Whole Cell Pertussis Vaccines
Authors: Havers Fiona , Skoff Tami , Rench Marcia , Epperson Monica , Schiffer Jarad , Hariri Susan , Swaim Laurie S , Baker Carol , Healy C Mary 
Published: January 2021

Abstract

Background
Acellular pertussis (aP) vaccines replaced whole cell pertussis (wP) vaccines for the recommended childhood primary series in the United States in 1997. As women primed with aP vaccines in childhood enter reproductive age, it is unknown how maternal aP-priming will impact pertussis protection conferred to infants through Tdap (tetanus toxoid, reduced diphtheria toxoid and acellular pertussis) vaccination during pregnancy.

Methods
Infants born at term to women who had been vaccinated with Tdap at 27-36 weeks’ gestation and ≥ 14 days prior to delivery were included. Geometric mean concentrations (GMC) of pertussis-specific antibodies (measured in IU/mL) in umbilical cord blood of infants born to women born after 1997 (aP vaccine primed) were compared with those born to women born before 1992 (wP vaccine primed).

Results
253 and 506 neonates born to aP- and wP-primed women, respectively, were included. Compared with wP-primed women, aP-primed women were younger (19.3 v. 24.5 years), more likely to be Hispanic or non-Hispanic black and to have infants with lower birthweight (3264 v. 3392 grams, p&lt; 0.01 for all). Gestation at Tdap receipt, gestational age at delivery, and interval between Tdap administration and delivery were not statistically different.
Antibodies against pertussis toxin (PT) and filamentous hemagglutinin (FHA) were significantly lower among neonates born to aP-primed versus wP-primed mothers (PT: 17.3 v. 36.4, GMC ratio 0.475 (0.408 – 0.552) (Figure); FHA: 104.6 v. 121.4, GMC ratio 0.861 (0.776 – 0.958)). No significant differences were observed between the aP and wP-primed groups for anti- fimbriae (FIM) or anti-pertactin (PRN) antibodies ((FIM: 469.6 v. 577.2, GMC ratio 0.81 (CI 0.65 – 1.01); PRN 338.8 v. 292.6, GMC ratio 1.16 (CI 0.99 – 1.35)).
Figure. Distribution of anti-PT antibody levels in cord blood in infants born to women who were primed with whole cell pertussis compared with acellular pertussis vaccines in childhood.*

Conclusion
The type of pertussis vaccine a woman received during childhood significantly impacted her response to Tdap vaccination during pregnancy; the largest reduction was in anti-PT antibodies thought to be most important in preventing severe infection in infants. These findings suggest that infants born to aP-primed women who received Tdap during pregnancy may have less passive protection against pertussis during the first months of life than those born to wP-primed women.

Disclosures
All Authors: No reported disclosures
1488. Relationship Between Culture Conversion and Clinical Outcomes in Patients With Mycobacterium abscessus (MAB) Lung Disease: A Systematic Literature Review
Authors: Flume Patrick A , Mange Kevin C , Jumadilova Zhanna , Cline Kristan B , Winthrop Kevin L 
Published: January 2021

Abstract

Background
Treatment of MAB lung disease is difficult, and currently there is no consensus on the best course of treatment. We examined the relationship between culture conversion and clinical outcomes among patients with MAB lung disease.

Methods
English-language MAB lung disease studies with ≥10 patients and reporting culture conversion and/or an outcome of interest (eg, changes in symptoms, lung function, quality of life, and/or radiography) were identified from Embase, PubMed, relevant congress abstracts, and the Cochrane Library (data cutoff, September 24, 2019) using the National Institute for Health and Clinical Excellence guidance for systematic literature reviews. Two independent reviewers screened 1,551 indexed records; relevant data were extracted and are reported as population-weighted means.

Results
No study directly correlated culture conversion with a change in symptoms. In 10 studies (N=869) reporting overall symptoms and culture conversion separately, 72.5% of patients (range 36%–96%) reported symptom improvement and 56.5% (range, 13%-99%) achieved culture conversion; a weak trend between symptomatic improvement and higher culture conversion rates (R2=0.36) was observed. Three additional studies (N=106) reported symptomatic improvement and culture conversion as a single measurement (49.6%, range, 25%-81%). Limited data indirectly correlated improvement in cough, dyspnea, hemoptysis, sputum production, and fatigue with culture conversion (1-2 studies each). Two studies directly correlated improved lung function (N=62) with culture conversion, and one study indirectly reported improved health-related quality of life (N=47) with culture conversion; no study reported radiology outcomes in relation to culture conversion.

Conclusion
This systematic literature review underscores the lack of data correlating clinical outcomes and culture conversion in patients with MAB lung disease. Limitations include a small number of studies, inconsistencies/non-reporting of methods, and poorly defined outcomes. Although indirect data indicate a weak correlation between symptom improvement and culture conversion, more evidence is needed to demonstrate a clinical outcome benefit associated with culture conversion.

Disclosures
Patrick A Flume, MD, Insmed Incorporated (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member) Kevin C Mange, MD, MSCE, Insmed Incorporated (Employee) Zhanna Jumadilova, MD, Insmed Incorporated (Employee) Kristan B Cline, PhD, Insmed Incorporated (Employee) Kevin L Winthrop, MD, MPH, Insmed Incorporated (Consultant, Grant/Research Support)
1490. Serious Infections Caused by Carbapenem Susceptible and Carbapenem Resistant Acinetobacter baumannii-calcoaceticus Complex - A Retrospective Review
Authors: Rana Khurram , Wunderink Richard G , Tsuei Betty J , Rahav Galia , Kovalchuk Eugenii , Koksal Iftihar , Maloney Kathleen , Srinivasan Subasree 
Published: January 2021

Abstract

Background
Increasing resistance to available antibiotics, including carbapenems, is limiting effective treatment options for serious Acinetobacter baumannii-calcoaceticus (ABC) complex infections that are associated with high mortality. This multi-center retrospective analysis is to describe the natural history and outcomes of serious ABC infections.

Methods
This was a retrospective review of 125 cases of ABC infections from United States (US), Israel, Turkey and Russia. Baseline, microbiologic, treatment and outcomes data were collected from patients with hospital-acquired (HABP, n=23) or ventilator-associated bacterial pneumonia (VABP, n=26), bacteremia (n=36), urinary tract infections/acute pyelonephritis (n=16), and wound ABC infections (n=24) between 2017-2019.

Results
Fifty percent of cases reviewed were from the US. The median age of patients was 63 years (range 18-93), 46% were &gt; 65 years old, 69% were male, 31% had renal failure, and 22% had septic shock. The most common co-morbidities observed were cardiac disease (41%), diabetes (32%) and moderate or severe renal disease (26%). Rates of resistance were observed as follows: ciprofloxacin 74%, ceftazidime 67%, amikacin 52% and colistin 0%. Carbapenem resistance (CR) was observed in 49% of patients. Most patients (73%) received combination therapy with 37% receiving at least 4 antibiotics. Carbapenems (40%) and penicillin/b-lactamase inhibitors (42%) were mostly used for treatment. Polymyxins were used in 18% of cases. Overall, the 28-day mortality was 34% and was highest in bacteremia (56%) and VABP (50%). CR appears to be a factor in mortality and other outcomes, as well as hospital days (table). In patients who received monotherapy, all 5 patients with CR infection died compared to 29% mortality in patients with carbapenem sensitive (CS) infection. Mortality was 70% in 20 cases when colistin was used for treatment.

Conclusion
Serious ABC infections are associated with substantial comorbidities and a high mortality rate despite treatment with combination therapy. CR appears to be a major factor in mortality. New antibiotics are urgently needed to treat serious ABC infections.

Disclosures
Khurram Rana, PharmD, Entasis Therapeutics (Employee) Galia Rahav, MD, AstraZeneca (Scientific Research Study Investigator) Kathleen Maloney, CCRP, Entasis Therapeutics (Employee) Subasree Srinivasan, MD MPH, Entasis therapeutics (Employee)
1491. Standard- vs. High-dose Trimethoprim-Sulfamethoxazole for Stenotrophomonas maltophilia pneumonia
Authors: Hall Brenton C , Ortwine Jessica , Wei Wenjing , Mang Norman , Prokesch Bonnie C , Pichlinski Elisa 
Published: January 2021

Abstract

Background
Stenotrophomonas maltophilia is a multidrug-resistant pathogen known to cause pneumonia with associated mortality rates up to 44%.1,2 Trimethoprim-sulfamethoxazole (TMP-SMX) is the drug of choice based on available clinical evidence and excellent in-vitro susceptibility rates.3 High-dose TMP-SMX strategies recommend between 15-20mg/kg/day of the TMP component, however this has been associated with increased adverse drug events (ADE).4,5 The optimal dosing strategy remains unclear and it is unknown whether lower doses of TMP-SMX would achieve similar outcomes.

Methods
Patients with positive respiratory cultures for S. maltophilia who received at least 72 hours of TMP-SMX therapy for hospital-acquired or ventilator-associated pneumonia from January 2010 to March 2020 were included. Doses were categorized as standard-dose (SD) TMP-SMX (&lt; 15 mg/kg/day TMP) or high-dose (HD) TMP-SMX (≥ 15 mg/kg/day TMP) after adjusting for renal function. The primary outcome was clinical success, defined as the composite of resolution of signs/symptoms of pneumonia, in-hospital survival, and no escalation of care. Secondary outcomes included hospital length of stay (LOS), 30-day mortality, 30-day readmission, and ADE.

Results
Of the 44 patients meeting inclusion criteria for the study, 27 received SD and 17 received HD TMP-SMX therapy. Patients received 12 mg/kg/day (IQR 11-14) and 16 mg/kg/day (IQR 16-19) in the SD and HD groups, respectively. There was no difference in clinical success between the SD and HD group (41% vs 59%, p=0.24). Secondary outcomes were similar between both groups except for 30-day hospital readmission; the SD group had significantly lower readmission rates (6% vs 69%, p &lt; 0.01). Rates of adverse events were not statistically different between the two groups.

Conclusion
This study provides evidence that SD TMP-SMX may achieve similar clinical efficacy to HD TMP-SMX. We found no significant difference in clinical success, LOS, 30-day mortality, or adverse events between groups. Although HD TMP-SMX is the current recommendation for S. maltophilia infections, concerns about tolerability and adverse effects suggest that further clinical and pharmacodynamic research is needed.

Disclosures
All Authors: No reported disclosures
1498. Etiology of Community-acquired Pneumonia in Adults: A Systematic Review
Authors: Shoar Saeed , Musher Daniel 
Published: January 2021

Abstract

Background
Background: Recent guidelines recommend immediate empiric antibiotic treatment for patients (pts) with community-acquired pneumonia (CAP). Concerns about treatment recommendations and antibiotic stewardship motivated a systematic literature review of the etiology of CAP.

Methods
We reviewed English-language literature using PRISMA guidelines. Data were stratified into diagnostic categories according to the microbiologic studies that were done (Table1).
Fig.1. Flowchart of systematic literature review and study selection

Table 1. Characteristics of studies reporting the etiology of community-acquired pneumonia

Results
146 articles with 82,674 CAP pts met criteria for inclusion; 63,938 (77.3%) were inpatients, 16,532 (20.0%) were in- or outpatients, and 2,204 (2.7%) were outpatients. Pneumococcus was the most common cause of CAP without regard to which microbiological techniques were used (33-50% of all cases). The proportion due to this organism declined with time, much more strikingly in the US than in Europe. Haemophilus influenzae was the second most common cause (7-16% of cases), followed by Staphylococcus aureus and Enterobacteriaceae each in 4–10%. Pseudomonas (0.8-4.5%) and Moraxella (1.2-3.5%) were less common; all other bacteria were isolated far less frequently. Mycoplasma caused 4-11% of CAP, Legionella 3-8%, Chlamydophila 2-7%, and Coxiella &lt; 2%; some studies showed a much higher frequency of Mycoplasma. With routine use of viral PCR, a virus was identified in 30-40% of pts; bacterial/viral coinfection was found in 25-35% of these cases. In a separate study of CAP pts in whom viral PCR was positive, 40% had bacterial coinfection. Influenza viruses were identified in 6.2-13.7% of cases and rhinoviruses in 4.1-11.5%. RSV and human metapneumovirus were less common (0.4-4.7%), followed more distantly by other viruses. Even with the use of the most sophisticated diagnostic techniques, no etiologic agent for CAP was identified in &gt; 50% of cases.
Trends of identification of S. pneumoniae and H. influenzae as the etiology of CAP (above); and the proportion of S. pneumoniae as the causes of CAP in different geographic regions (below).

Conclusion
Our results justify current guidelines for initial empiric antibiotic treatment of all pts with CAP. With pneumococcus and Haemophilus continuing to predominate, efforts at antibiotic stewardship might be enhanced by greater attention to routine use of sputum Gram stain and culture. Because viral/bacterial coinfection is relatively common, the identification of a virus by PCR does not, by itself, permit the non-use of an antibiotic.

Disclosures
All Authors: No reported disclosures