Angiomyomatous hamartoma of subglottic tracheal wall in a 12-year-old adolescent: a case report

Background Allergic rhinitis is the most common allergic disease encountered in a primary care setting. Diagnosis is often made clinically based on response to empiric therapy. However, with long-term treatment failure and/or atypical disease presentation, a differential diagnosis should be considered. The following is a report of an unusual and rare presentation of a subglottic tracheal angiomyomatous hamartoma in an adolescent, treated for many years as allergic rhinoconjunctivitis and asthma. Case presentation A 12-year-old Caucasian was referred to the allergy clinic with a lifetime history of bronchospasms and rhinoconjunctivitis symptoms, treated for many years for asthma and environmental allergies. Cough, posterior nasal drainage, self-described “choking on phlegm,” and a sensation of “a flap in the throat,”, worsened 5 months prior to the initial evaluation. Puncture skin testing for common environmental allergens was negative. Spirometry, performed due to history of chronic cough, showed blunting of the forced expiratory phase. A chest X-ray, immediately ordered to rule out possible extrapulmonary obstruction, showed bilateral bibasilar infiltrates. A noncontrast computerized tomographic scan of the chest, ordered to further elucidate X-ray findings, revealed a subglottic tracheal mass. Following a subsequent transfer and admission to a tertiary hospital center, microlaryngoscopy, bronchoscopy, and microsuspension laryngoscopy were performed to remove the tracheal mass. Pathology confirmed squamous mucosa with polypoid angiomyomatous changes and chronic inflammatory features consistent with angiomyomatous hamartoma. Surgical intervention was successful, and follow-up 1 year postoperatively revealed a healthy, asymptomatic adolescent child with normal lung function. Conclusions Although posterior nasal drainage and cough are typical presenting symptoms in the general patient population, they may be clinically impactful as they could disguise more serious medical conditions. A detailed history and careful physical examination may provide a high index of suspicion of disease, and can help work the differential diagnosis. This case presentation is the first documentation of subglottic hamartoma reported in the pediatric literature with clinical manifestation of environmental allergy and asthma symptoms.

КЛІНІЧНИЙ ВИПАДОК ГОСПІТАЛЬНОЇ ПНЕВМОНІЇ, ВИКЛИКАНОЇ KLEBSIELLA PNEUMONIA, ВНАСЛІДОК КОНТАКТУ ІЗ ЧЛЕНОМ РОДИНИ

The problem of morbidity and mortality due to infectious lesions of the respiratory tract, in particular nosocomial pneumonia, remain one of the most pressing problems of modern medicine. Nosocomial pneumonia ranks 3rd among all infectious diseases that a patient can contract at a medical institution after urinary and wound inflammation and it is characterized by high mortality. Nosocomial pneumonia is provoked by antibiotic-resistant microorganisms; in the intensive care patients, it is complicated by the re-aspiration of bacteria that accumulate above the cuff of the intubation tube. Identification of nosocomial and community-acquired pneumonia involves a particular flora of pathogens and, accordingly, involves empiric therapy. Routine analysis of sputum according to Gram gives approximate data, which is a clarification for empiric treatment. We present a clinical case, which demonstrates that infection is also possible due to contact of a family member with another one, working at a medical institution. Therefore, in our clinical case, we emphasize that it is very important to collect a thorough history. Careful collection of medical history can provide additional information: working in a team, being a medical professional, relatives working at a medical institution. It should be noted that in this category of patients, the causative agent of infection, including nosocomial pneumonia, may be the strains of nosocomial microorganisms. Regardless of age, we recommend the use of preventive measures (lifestyle modification, acclimatization training, sports, etc.) to increase the non-specific resistance of the body. As a preventive measure, medical personnel should follow the regimes of ventilation and wet cleaning in the premises, wash their hands and rinse their nasal passages as often as possible with saline solutions, use a mask to protect the respiratory organs, disinfect hands with alcohol.

The Path of More Resistance: A Comparison of NHSN and CLSI Criteria in Developing Cumulative Antimicrobial Susceptibility Test Reports and Institutional Antibiograms

Background In the absence of antimicrobial susceptibility data, the institutional antibiogram is a valuable tool to guide clinicians in the empiric treatment of infections. However, there is a misunderstanding on how best to prepare cumulative antimicrobial susceptibility testing reports (CASTRs) to guide empiric therapy (e.g., routine antibiogram) versus monitoring antimicrobial resistance, with the former following guidance from the Clinical Laboratory Standards Institute (CLSI), and the latter from Center for Disease Control and Preventions National Healthcare Safety Network (NHSN). These criteria vary markedly in their exclusion or inclusion of isolates cultured repeatedly from the same patient. Methods We compared rates of non-susceptibility (NS)using annual data from a large teaching healthcare system subset to isolates eligible by either NHSN criteria or CLSI criteria. Results For a panel of the three most prevalent gram-negative pathogens in combination with clinically relevant antimicrobial agents (or priority pathogen-agent combinations, PPACs), we found that the inclusion of duplicate isolates by NHSN criteria yielded higher NS rates than when CLSI criteria (for which duplicate isolates are not included) were applied. Conclusions Patients with duplicate isolates may not be representative of antimicrobial resistance within a population. For this reason, users of CASTR data should carefully consider that the criteria used to generate these reports can impact resulting NS rates, and therefore maintain the distinction between CASTRs created for different purposes.

Infected deep vein thrombophlebitis in people who inject drugs: missed opportunities and potential for alternative antimicrobial approaches

Infected deep vein thrombophlebitis (i-DVT) in people who inject drugs (PWID) is a clinically challenging but poorly characterised disease. We undertook a retrospective observational study of 70 PWID presenting acutely with i-DVT to improve the clinical and microbiological characterisation of this disease. i-DVT was frequently associated with bacteraemia (59.1% patients with blood cultures obtained), groin abscesses (in 34.3%; of which 54.2% required surgical drainage), and septic pulmonary emboli (38.6%) requiring anticoagulation. Network analysis identified a cluster of patients presenting with respiratory symptoms but lacking typical DVT symptoms, more likely to have septic pulmonary emboli. A microbiologic diagnosis was frequently achieved (70%). Causative pathogens were predominantly gram-positive (S. aureus and streptococci, especially anginosus group), whereas gram-negative pathogens were identified very infrequently (in 6.1% of microbiological diagnoses). This suggests routine empiric therapy against gram-negative bacteria, though commonly administered, is not required. High rates of clinical cure (88.6%) were observed despite the complex nature of infections and independently of the highly variable intravenous and total antimicrobial durations received. There exists a rationale to devise pragmatic approaches to implement novel individualised treatment plans utilising oral antimicrobial therapy for i-DVT. Despite frequent healthcare interactions, opportunities to address HCV treatment and opioid substitution therapy were frequently missed during these acute admissions.

165. Emergence of Extensively Drug-Resistant Salmonella enterica Serotype Typhi Infections—United States, 2008–2020

Background Typhoid fever, caused by Salmonella Typhi, is fatal in 12%–30% of patients not treated with appropriate antibiotics. In 2016, a large outbreak of extensively drug-resistant (XDR) Typhi infections began in Pakistan with cases reported globally, including the United States. In 2021, the Centers for Disease Control and Prevention (CDC) issued a health advisory on XDR infections among U.S. residents without international travel. We describe resistance of Typhi infections diagnosed in the United States to help guide treatment decisions. Methods Typhoid fever is a nationally notifiable disease. Health departments report cases to CDC through the National Typhoid and Paratyphoid Fever Surveillance system. Isolates are submitted to the National Antimicrobial Resistance Monitoring System for antimicrobial susceptibility testing (AST) using broth microdilution. AST results are categorized by Clinical and Laboratory Standards Institute criteria. We defined XDR as resistant to ceftriaxone, ampicillin, chloramphenicol, and co-trimoxazole, and nonsusceptible to ciprofloxacin. Results During 2008–2019, of 4,637 Typhi isolates, 52 (1%) were ceftriaxone resistant (axo-R); 71% were ciprofloxacin nonsusceptible, 1 azithromycin resistant (azm-R), and none meropenem resistant. XDR was first detected in 2018, in 2% of 474 isolates and increased to 7% of 535 in 2019. Of the 52 axo-R isolates, 46 were XDR, of which 45 were from travelers to Pakistan, and one from a non-traveler; 6 were not XDR, of which 4 were linked to travel to Iraq. In preliminary 2020 reports, 23 isolates were XDR; 14 were from travelers to Pakistan, 8 from non-travelers, and 1 from someone with unknown travel status. Among those with XDR infection, median age was 11 years (range 1–62), 54% were female, and 62% were from 6 states. Conclusion Ceftriaxone-resistant Typhi infections, mostly XDR, are increasing. Clinicians should ask patients with suspected Typhi infections about travel and adjust treatment based on susceptibility results. Carbapenem, azithromycin, or both may be considered for empiric therapy of typhoid fever among travelers to Pakistan or Iraq and in uncommon instances when persons report no international travel. Ceftriaxone is an empiric therapy option for travelers to countries other than Pakistan and Iraq. Disclosures All Authors: No reported disclosures

121. Evaluation of Multifaceted Antimicrobial Stewardship in Optimizing Antimicrobial Usage in Intraabdominal Infection at a Community Hospital

Background Treatment of intraabdominal infections (IAI) commonly involves broad spectrum antimicrobials based on the severity and etiology of infections as well as the underlying medical conditions. However, the overuse of broad-spectrum agents has driven selection for Gram-negative and -positive resistance, as well as collateral consequences such as Clostridioides difficile colitis. We sought to evaluate the utilization of a pharmacy-driven multifaceted antimicrobial stewardship (AMS) intervention to optimize empiric antimicrobial therapy by risk stratification among IAI patients and reduce the number of antibiotic treatment days. Methods This is a single-center case observation study in hospitalized adult IAI patients on antimicrobial therapy from Dec 2019-Feb 2020 compared to patients from Dec 2020-Feb 2021 after initiation of AMS with daily prospective audit and feedback. The composite primary outcome is reduction of antibiotic treatment days and de-escalation from broad spectrum antibiotics (fluoroquinolones, piperacillin/tazobactam, and carbapenems) to cephalosporins. Results We identified 40 patients each in the baseline (pre-AMS group) and post-AMS group via electronic medical record. Baseline characteristics were well-matched between groups. The majority of patients were diagnosed with community-acquired IAIs such as appendicitis, diverticulitis, and cholecystitis. Fluoroquinolone use as empiric therapy was significantly lower in the post-AMS group vs. pre-AMS group (2.5% vs. 25%, p< 0.001), while non-Pseudomonas cephalosporin use was increased (25% post-AMS vs. 0% pre-AMS, p< 0.001). Oral fluoroquinolone use at discharge was significantly decreased in the post-AMS group (p< 0.001). Antibiotic treatment days remained unchanged. There was no statistical difference between the two groups in 30-day mortality, 30-day readmission, relapse, and C. difficile colitis. Conclusion A multifaceted antimicrobial therapy intervention successfully reduced the use of fluoroquinolones in patients with community-acquired IAI during hospitalization and discharge. No differences in mortality, readmission, or relapse rates were observed. Disclosures All Authors: No reported disclosures

127. Living on the Edge: The Impact of MIC Distributions on Empiric Antibiotic Selection

Background Due to variability in the precision of an MIC, concern may exist in optimizing PK/PD using standard doses when the MIC is at the susceptibility breakpoint (SBP). This is notable when treating infections in critically ill patients. Evaluating MIC distributions among commonly used antibiotics and accounting for isolates at the SBP represents an additional enhancement to inform empiric therapy. The aim of the study was to evaluate antibiotic susceptibility for commonly used β-lactams against Pseudomonas aeruginosa (PA) in a syndromic antibiogram, incorporating MIC distribution. Methods 20 US institutions submitted yearly up to 250 consecutive targeted Gram-negative pathogens from hospitalized patients as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) in 2016-2019. MICs were determined by broth microdilution and interpreted using 2021 CLSI breakpoints. The syndromic antibiogram included PA from a blood or respiratory source based on patient location. Based on CLSI guidance, an empiric antibiotic susceptibility threshold of ≥ 90% was deemed optimal. Results 2,500 PA blood (n=680) and respiratory (n=1,820) isolates were evaluated; piperacillin/tazobactam (P/T), cefepime (FEP), meropenem (MEM), and ceftolozane/tazobactam (C/T) susceptibilities were 69.6%, 74.2%, 75.3%, and 95%, respectively (Figure 1). Isolates with MICs at the SBP were observed in 12.1%, 18.7%, 7.5%, and 6.5% for P/T, FEP, MEM, and C/T, respectively. Susceptibilities were lower when stratified by ICU, 64.8%, 71.2%, 70.7%, and 93.7% for P/T, FEP, MEM, and C/T, respectively with a similar frequency of SBP isolates (Figure 2). Figure 1. Syndromic antibiogram evaluating P. aeruginosa blood and respiratory isolates. Figure 2. Syndromic antibiogram evaluating Pseudomonas aeruginosa blood and respiratory isolates stratified by ICU. *MIC breakpoints used to determine susceptibility included: P/T MIC ≤ 16/4 µg/ml, FEP ≤ 8 µg/ml, MEM ≤ 2 µg/ml, C/T ≤ 4 µg/ml Conclusion Our analysis demonstrated that first line antipseudomonal agents, P/T and FEP, have susceptibility rates lower than the CLSI recommended threshold. A significant portion of the MICs within the susceptible range are at the SBP. Due to the frequency of baseline resistance and challenge in achieving adequate PK/PD in critically ill patients, clinicians may be concerned with relying on certain antibiotics when the MIC is at the SBP. Antimicrobial stewardship programs should consider incorporating MIC distributions into syndromic antibiograms to better inform empiric therapy recommendations. Disclosures Karri A. Bauer, PharmD, Merck & Co., Inc. (Employee, Shareholder) Levita K. Hidayat, PharmD BCIDP, Merck & Co., Inc. (Employee, Shareholder) Kenneth Klinker, PharmD, Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co., Inc. (Employee, Shareholder) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder)

14. Effects of an Opt-Out Protocol for Antibiotic De-escalation among Selected Patients with Suspected Sepsis: The DETOURS Trial

Background Sepsis guidelines recommend daily review to de-escalate or stop antibiotics in appropriate patients. We conducted a randomized controlled trial (NCT03517007) of an opt-out protocol to decrease unnecessary antibiotics in selected patients with suspected sepsis. Methods We evaluated non-ICU adults remaining on broad-spectrum antibiotics with negative blood cultures at 48-96 hours at ten U.S. hospitals during September 2018-May 2020. A 23-item safety check excluded patients with ongoing signs of infection, concerning or inadequate microbiologic data, or high-risk conditions (Figure 1). Eligible patients were randomized to the opt-out protocol vs. usual care. The primary outcome was 30-day post-enrollment antibacterial days of therapy (DOT). Clinicians caring for intervention patients were contacted by a pharmacist or physician to encourage antibiotic discontinuation or de-escalation using opt-out language, discuss rationale for continuing antibiotics, working diagnosis, and de-escalation and duration plans. Hurdle models separately compared the odds of antibiotic continuation and DOT distributions among those who continued antibiotics. Components of the De-Escalating Empiric Therapy: Opting-OUt of Rx in Selected patients with Suspected Sepsis (DETOURS) Trial Protocol Results Among 9606 screened, 767 (8%) were enrolled (Figure 2). Common reasons for exclusion were antibiotics given prior to blood culture (35%), positive culture from non-blood sites (26%), and increased oxygen requirement (21%). Intervention patients had 32% lower odds of antibiotic continuation (79% vs. 84%, OR 0.68, 95% confidence interval [0.47, 0.98]). DOT distributions among those who continued antibiotics were similar (ratio of means 1.06 [0.88-1.26], Figure 3). Fewer intervention patients were exposed to extended-spectrum agents (38% vs. 44%). Common reasons for continuing antibiotics were treatment of localized infection (76%) and belief that stopping antibiotics was not safe (31%). Safety outcomes such as mortality, readmission, sepsis relapse, C. difficile, and length of stay did not differ. DETOURS Trial Flow Diagram Flow of participants through the DETOURS Trial. Observed Days of Antibiotic Therapy Among Intervention and Control Subjects in the DETOURS Trial Post-enrollment days of antibiotic therapy among 767 DETOURS Trial participants in 10 US acute care hospitals within 30 days after enrollment. Dark pink color indicates percent overlap between intervention (purple) and control (light pink) groups. Conclusion In this patient-level randomized trial of a stewardship intervention, the opt-out de-escalation protocol targeting selected patients with suspected sepsis resulted in more antibiotic discontinuations but did not affect safety events. Disclosures Rebekah W. Moehring, MD, MPH, UpToDate, Inc. (Other Financial or Material Support, Author Royalties) Michael Z. David, MD PhD, GSK (Board Member) Michael Klompas, MD, MPH, UpToDate (Other Financial or Material Support, Chapter Author)

1366. Deep Neck Infections: Bacteriology and Antimicrobial Susceptibilities, Akron Children’s Experience

Background Deep neck infections (DNI’s) are uncommon (~45,000 US cases annually) but, potentially serious. Published data regarding bacteriology and antibiotic usage for DNI’s in children is limited. In addition, geographic variation in the incidence of pathogens and their antimicrobial susceptibility limits generalization of treatment guidance. Reviewing our practice at Akron childrens we noted considerable variation in the choice of empiric antibiotics (ampicillin-sulbactam vs piperacillin-tazobactam vs Ceftriaxone and Clindamycin/vancomycin/linezolid). Admission unit (floors vs intensive care) and service (hospitalist vs infectious diseases) were some important determinants that influenced choice of empiric antibiotics. This retrospective study aimed to review local data and come up with standard guidance for empiric therapy. Summary of the predominant bacterial isolates. Methods We reviewed records of 125 patients who underwent surgical drainage of DNI’s from 1/2015 – 12/2019. In addition to demographic data we gathered information on bacterial isolates and their susceptibilities. Chart review was performed for patients with staphylococcus aureus, to look for any unique presenting features. Results Up on reviewing the data- peritonsillar abscesses were common in older children (Median age 11 years). As expected, retropharyngeal and parapharyngeal infections were common in younger ones (< 5 years). Group A streptococcus remained the most common aerobic isolate followed by Hemophilus influenzae/parainfluenzae. MRSA was detected in ~7 % of all cultures (see enclosed table). Notably, none of the MRSA isolates were clindamycin resistant. However, MSSA resistance to clindamycin was about 20%. No clinical characters predicted isolation of S. aureus. Anaerobic infections (polymicrobial) were overwhelmingly common across all abscess types. Conclusion Based on our review, Ampicillin-Sulbactam is a good empiric choice antibiotic for deep neck infections in our institution. Ceftriaxone with clindamycin is another option. Clindamycin monotherapy seems to be inadequate. Staph aureus and especially MRSA, were only isolated in a small percentage of cases. Unless a patient is ill appearing, vancomycin use seems unnecessary. Clinical presentation was not helpful to suspect infection with Staph aureus. Disclosures All Authors: No reported disclosures

1160. Predictive Factors to Guide Empiric Antimicrobial Therapy of Acute Hematogenous Osteomyelitis in Children

Background Acute hematogenous osteomyelitis (AHO) is a serious infection in children. ESPID guidelines recommend empiric therapy with antistaphylococcal β-lactams in regions with a low methicillin-resistant S. aureus (MRSA) prevalence. In areas with a moderate-high prevalence of MRSA, selection of empiric therapy can be more challenging. We sought to examine factors present at the time of admission which may predict etiology and guide treatment in pediatric AHO in a region with endemic MRSA. Methods We reviewed admissions with ICD9/10 codes for AHO from 2011-2020 in otherwise healthy children. Patients with chronic infection, open or penetrating trauma, orthopedic hardware in situ, or disease secondary to a contiguous focus were excluded. Medical records were reviewed for clinical and laboratory parameters present on the day of admission. Results 586 cases were included. An etiology was identified in 76.8% of cases and S. aureus was most commonly identified (66.2%, 19% MRSA, Figure 1). Infection due to Kingella kingae (0.7%) occurred in younger children (p=0.01). Significant differences in presenting features were noted across pathogens, although S. aureus dominated in all sub-groups (Figure 2). Among children with respiratory symptoms at presentation, Group A Streptococcus (GAS, 10.7%), and S. pneumoniae (2.6%, p=0.01) were identified twice as frequently. Among children with reptiles exposure, Salmonella was identified in 10.8% (p=0.04). Multifocal infections and those requiring ICU admission were due to S. aureus in 88% and 97% of cases, respectively; these cases were disproportionately MRSA (36.4%, p=0.01 and 54%, p< 0.001). Both ESR and CRP were higher among MRSA compared to any other pathogen (Figure 3, p< 0.01). A CRP at presentation > 7 mg/dl had a 79.6% sensitivity for MRSA infection with a negative predictive value of 91.5%. Among those with either an ESR > 50 mm/hr or a CRP > 7 mg/dl, an organism was identified in 83.2% Depiction of the relative frequency of major pathogens among a cohort of 586 cases of acute hematogenous osteomyelitis in children Depiction of the relative frequency of different organisms in children with AHO with various history, exam and laboratory findings Scatterplot depicting ESR and CRP levels across major hematogenous osteomyelitis pathogens Conclusion Subtle differences in symptoms, history and laboratory parameters can provide clues to etiology in pediatric AHO. A CRP > 7 mg/dl at time of presentation is suggestive of MRSA AHO, and this should be considered when planning empiric therapy. Likewise, the absence of extreme elevation of CRP may serve an antibiotic stewardship role in MRSA endemic regions. Disclosures Sheldon L. Kaplan, MD, Pfizer (Research Grant or Support) Jonathon C. McNeil, MD, Agency for Healthcare Research and Quality (Research Grant or Support)Allergan (Grant/Research Support)Nabriva (Grant/Research Support, Other Financial or Material Support, Site PI for a multicenter trial)