bluuebunny/crossref_metadata_2025 huggingface dataset:
1382. Invasive Infections due to Groupable Streptococci at a Large Veterans Affairs Hospital: Clinical Characteristics and Outcomes
Authors: Seo Jung M , Krause Heidi , Hills Emma , Musher Daniel M , Kulkarni Prathit A
Published: December 2022

Background

Groupable streptococci (A, B, C, etc.) are known to cause a variety of clinical syndromes, including skin and soft tissue infection, primary bacteremia, osteoarticular infection, pneumonia, and endocarditis. However, there is a lack of recent literature on the clinical characteristics and outcomes of these infections. The purpose of this study was to describe the clinical characteristics of patients with invasive infections due to the groupable streptococci, identify risk factors for infection, and evaluate response to antimicrobial therapy.

Methods

We reviewed medical records of patients identified by the Infection Control service database at our Veterans Affairs (VA) hospital as having an invasive infection due to a groupable Streptococcus spp. Study inclusion criteria were: hospitalization between 2016 – 2019, age >18, and growth of a groupable Streptococcus spp in a clinical specimen from a normally sterile site (excluding urine). Patients were excluded from the study if the positive culture was due to colonization rather than true infection and if inpatient admission was not required.

Results

A total of 75 patients were identified. The median age was 63; 97% of patients were male; and 52% were Caucasian. Comorbid conditions included diabetes (73%), peripheral vascular disease (33%), malignancy (20%), and chronic kidney disease (15%). The majority of infections was due to group B Streptococcus (72%), followed by group C (21%) and group A (7%). The most common sites of infection were soft tissue (41%) and bone (41%), and a substantial proportion of patients required intensive care (16%). The overall clinical cure rate was 83%. Reinfection occurred within one year in 11% of patients, and one patient (1%) died from another cause prior to completing the prescribed treatment regimen. The overall mortality rate from initial infection was 5%.

Conclusion

This study demonstrates that the modern clinical cure rate of invasive infections due to the groupable streptococci at a large VA hospital was 83%, even with appropriate source control and correct antimicrobial therapy. A substantial proportion of patients required admission to intensive care. These findings highlight the continued morbidity and mortality of these infections even in the modern era.

Disclosures

Prathit A. Kulkarni, M.D., Vessel Health, Inc.: Grant/Research Support.
1383. Necrotizing Fasciitis and Streptococcus pyogenes (GAS) Infection Seasonality and Risk Factors for Infection— a Multicenter Research Network Study
Authors: Kennis Matthew , Tagawa Alex , Kung Vanessa , Montalbano Gabrielle E , Narvaez Isabella , Franco-Paredes Carlos , Barahona Lilian Vargas , Shapiro Leland , Chastain Daniel B , Henao-Martínez Andrés F
Published: December 2022

Background

Streptococcus pyogenes causes acute pharyngitis and type II necrotizing fasciitis. Seasonal variations in the incidence of S. pyogenes infections are not robustly characterized. We aim to identify seasonal variations and risk factors of S. pyogenes infections and all causes of necrotizing fasciitis.

Methods

From 2010 to 2019, we identified all infectious adult cases of S. pyogenes using ICD-10 diagnoses and lab results (PCR and antigen-based assays) and cases of necrotizing fasciitis using ICD-10 diagnoses within a federated research network. We extracted seasonal (quarterly) incidence rates. We used an autoregressive integrated moving average (ARIMA) model to assess the seasonality of the cases (6-month intervals). Demographic characteristics and 3-month outcomes of S. pyogenes pharyngitis were compared to a cohort of patients with acute upper respiratory illnesses excluding S. pyogenes.

Results

We identified 238,088 cases of S. pyogenes pharyngitis and 26,931 cases of necrotizing fasciitis in adults. S. pyogenes infection average incidence was higher during the winter than the summer: 0.34 vs. 0.20 cases per 1,000 patients. Necrotizing fasciitis diagnoses were highest during the summer months (average 0.026 per 1000 patients). There was a significant ARIMA seasonal variation in the time series analysis for S. pyogenes infections (p=0.006) (figure 1). However, necrotizing fasciitis was not significant (p=0. 0.79) (Figure 2).

Compared to adults with acute respiratory infections other than S. pyogenes, adults with S. pyogenes pharyngitis were more likely to be younger (25.8 ± 14.9 vs. 45.4 ± 19.9 years old, p< 0.0001) and of Hispanic or Latino ethnicity (11% vs. 8%, p < 0.0001). For age-matched outcomes, adults with S. pyogenes pharyngitis had lower rates of hospitalization (0.888% vs. 1.714%, p< 0.0001) and mortality (0.114% vs. 0.174%, p< 0.0001) at three months relative to adults with acute respiratory infections other than S. pyogenes. Figure 1.Seasonal variation of adults with established ICD code or testing for Streptococcus pyogenes (GAS) infectionsFigure 2.Seasonal variation of adults with established ICD code for necrotizing fasciitis

Conclusion

Peaks in S. pyogenes infections are more likely to occur in the winter months, although spring and fall seasons can display variably high rates of S. pyogenes year over year. Necrotizing fasciitis of any microbiological did not show a significant seasonal variation.

Disclosures

All Authors: No reported disclosures.
1387. Prevalence and Risk Factors for Bacterial Resistance in Diabetic Foot Infections at a Hospital in Nicaragua.
Authors: Sandoval-Rojas Kevin A , Maliaños-Miranda Roger , Marenco-Avilés Sunaya , Castillo-Cano Maikelyn A , Porras-Cortés Guillermo D
Published: December 2022

Background

The bacterial resistance could have an deleterious outcome in patients with diabetic foot infections (DFI). The aim of this study was to determine the prevalence, the main risk factors, and clinical outcomes for DFI caused by bacterias that were resistant to different classes of antimicrobials in a hospital in Nicaragua.

Methods

A case-control study was conducted between January 2019 and March 2020 at Hospital Dr. Fernando Vélez Paiz in Managua (Nicaragua). Cases were patients with diabetic foot infections caused by drug-resistant organisms (DRO) and the controls were patients infected by non-drug resistant organisms (NDRO). The resistance to quinolones, beta-lactams, and carbapenems were evaluated in the Gram negative bacterias. In the cases of Staphylococcus aureus the resistant to methicillin was evaluated. Samples of tissue and exudates obtained by aspiration were processed. Conventional methods as blood agar and McConkey agar were used, and the final identification method was Vytek 2 System. Different variables of both groups were compared.

Results

A total of 76 bacterias were identified in 61 patients. Forty-four patients had an infection with at least one resistant bacteria for a prevalence of 72%. Staphylococcus aureus was the most prevalent bacteria and 76.9% of them were resistant to methicillin (MRSA). A 71% of the Gram negative bacterias were resistant to at least one class of antibiotic; 58% of them were resistant to quinolones, 40% were ESBL positive, and 12% were resistant to carbapenems. A total of 12 isolates were multi-drug resistant organisms (MDRO). The main risk factor to have an infection with a resistant bacteria was the use of antibiotics into the previous 3 months (OR:4.28; CI95%: 1.31-13.98). An infection caused by DRO was associated with a increased risk of amputation. Infections caused by NDRO had more probability of clinical resolution (OR:0.14; CI95%:0.04-0.48).

Prevalence of Resistant Bacterias to Different Classes of Antibiotics in Diabetic Foot Infections.

Conclusion

In this setting, the bacterial resistance in diabetic foot infections has to be considered significative. MRSA had a high prevalence and the Gram negative organisms showed an important resistance rate to different classes of antibiotics. The main risk factor was the previous use of antibiotics. The clinical outcome is affected by the bacterial resistance.

Disclosures

All Authors: No reported disclosures.
1388. Seasonality of Microbiology of Combat-related Wound Infections in Afghanistan
Authors: Soderstrom Matthew A , Blyth Dana M , Carson Leigh , Campbell Wesley R , Yabes Joseph , Shaikh Faraz , Stewart Laveta , Tribble David R , Murray Clinton K , Kiley John L
Published: December 2022

Background

We examined the seasonality of wounds and wound infections, including occurrence of multidrug resistance, among combat casualties injured in Afghanistan.

Methods

The Trauma Infectious Disease Outcomes Study is a retrospective observational study of infectious complications among military personnel wounded during deployment (06/09-12/14). Wound cultures obtained ≤7 days following injury in Afghanistan were assessed. Epidemiologic, clinical, and microbiologic data were analyzed by injury season [winter (1 Dec-28/29 Feb), spring (1 Mar-31 May), summer (1 Jun-31 Aug), and fall (1 Sep-30 Nov)]. Multidrug-resistant (MDR) determinations for Gram-negative and Gram-positive organisms were per standardized definitions.

Results

The study population included 316 patients with a median of 3.5 (IQR 3-5) days from injury to initial culture. Gram-negatives (N=188, 59.5%) were more commonly isolated from wound cultures in summer (N=81, 43.1%) and fall (N=57, 30.3%) versus winter (N=18, 9.6%) and spring (N=32, 17%) (p< 0.001). The MDR Gram-negatives (N=69, 21.8%) were more common in summer (N=26, 37.7%), and fall (N=26, 37.7%) versus winter (N=3, 4.3%) and spring (N=14, 20.3%) (p=0.028). Wound infections were diagnosed in 198 (63%) patients. The pattern for infecting Gram-negative isolates (N=143, 72.2%, Table 1) was similar to that of overall Gram-negative isolates: summer (79.5%) and fall (83.6%; p< 0.001); MDR Gram-negatives (summer, 25.6%) and (fall, 41.8%; p=0.015). Escherichia coli and Enterobacter spp. were the most common infecting Gram-negative bacilli with no significant difference across the seasons. There was a higher proportion of infecting Acinetobacter baumannii isolates in the summer and fall compared to winter and spring. Infecting Gram-positive isolates (N=128, 65%) were not significantly different by season. Anaerobes associated with infections were also identified (N=30, 15%) with a higher proportion in the winter compared to summer, fall, and spring (p=0.036).

Conclusion

Gram-negatives, including MDR Gram-negative infecting organisms, were more common in summer/fall months in service members injured in Afghanistan. This may have implications for empiric antibiotic coverage during these months.

Disclosures

David R. Tribble, DrPH, AstraZeneca: The HJF, in support of the USU IDCRP, was funded to conduct or augment unrelated Phase III Mab and vaccine trials as part of US Govt. COVID19 response.
1390. Assessing the Relationship between Community Social Vulnerability and Antibiotic Use in Nursing Homes
Authors: Zipfel Casey M , Paul Prabasaj , Slayton Rachel
Published: December 2022

Background

Health inequities impact healthcare delivery and outcomes, but the impacts of health inequities on antibiotic use and AR infections have been less frequently studied in nursing home residents. Nursing home residents are typically older, often have increased care needs requiring frequent contact with staff, and often have comorbidities or in-dwelling devices that make them vulnerable to infection. The community served by a nursing home may play a role in frequency and variability in antibiotic use, as health inequities may impact healthcare delivery and health status of patients, since both patients and caregivers are likely to be drawn from the surrounding community. We hypothesize that antibiotic use in nursing homes is impacted by the social vulnerability of the surrounding community.

Methods

We collected all reports of the proportion of residents who received antibiotics in the previous 7 days in 2019, which are reported monthly to the CMS Minimum Data Set. We assessed the proportion of facility residents using antibiotics by social vulnerability measures (from CDC Social Vulnerability Index) of the surrounding healthcare-seeking community (Hospital Service Areas from Dartmouth Health Atlas), using a hierarchical model to control for facility factors.

Results

We find considerable variability in antibiotic use across 14,908 US nursing homes (Figure 1A). After controlling for facility characteristics, facilities located in areas of greater community-level social vulnerability were associated with higher antibiotic use (Figure 1B).

Figure 1. Antibiotic use in nursing homes and relationships with community social vulnerability. A) The distribution of the proportion of patients using antibiotics within the previous 7 days by facility.

B) Coefficient estimates of a multilevel regression model. Controlling for facility-level factors (blue), community-level social vulnerability index appears to be related with more antibiotic use.

Conclusion

These findings indicate that community social vulnerability is associated with healthcare delivery within facilities. This association may result from differences in antibiotic prescribing behavior, infection prevention practices, or from disparity-driven differences in the health status of the resident population. This work is important for informing epidemiological models within healthcare facilities: failing to include heterogeneity of the surrounding community could bias transmission models and decrease the accuracy of targeted public health interventions to vulnerable facilities and communities.

Disclosures

All Authors: No reported disclosures.
1404. Factors Associated to Decrease in Quality of Life After Mild-Moderate COVID-19: A Cross-Sectional Study.
Authors: Navarro Alberto Ordinola , Villegas Hector Rivera , Luis Bruno Ali Lopez
Published: December 2022

Background

Post-COVID-19 alterations have been recognized even after mild disease. We aimed to assess which factors are the main contributors to a decrease in quality of life(QOL) of patients with different times elapsed from the COVID-19 diagnosis.

Methods

A cross-sectional study from January 2021 to April 2021 in a Referral Center in Mexico City.

Patients were invited for a follow-up visit in which a structured questionnaire about symptoms, the EQ-5D-5L QOL for QOL, and an objective olfactory evaluation with The Sniffin’ Sticks Screening 12 test.

Results

We included 179 patients, 64% were female with a median age of 33 years. The median time since COVID-19 diagnosis until the evaluation was 219 days (IQR, 94-255). Persistent symptoms were present up to in 158/179 (88%), fatigue, pain/discomfort and cognitive alterations were present in 61%, the median EQ-5D-5L index value preCOVID-19 was 1 (IQR, 0.94-1) and post- COVID-19 was 0.87 (IQR, 0.80-0.94), P< 0.001. There were 101/179 (56%) patients with decreased QOL; In the multivariate analysis, post-COVID-19 pain (aOR, 2.5; P= 0.01), anxiety (aOR, 13; P= 0.03), and the persistence of three or more symptoms (aOR, 2.6; P= 0.05) were factors associated with decreased QOL.

Conclusion

Within the post- COVID-19 alterations, psychological and physical factors such as Pain/discomfort, anxiety, and persistent symptoms explained the decreased QOL in the post-COVID-19 patient. These alterations were present as early as 30 days to more than eight months.

Disclosures

All Authors: No reported disclosures.
1405. High risk or unstable substance use may predict OPAT nonadherence among people who use drugs (PWUD) admitted with invasive infections
Authors: Ching Patrick R , George Nivya , Kottilil Shyam , Narayanan Shivakumar
Published: December 2022

Background

Patients with substance use disorder (SUD) are frequently admitted to hospitals for invasive infections and may have poor infection outcomes including non-adherence and lack of completion of therapy.

Methods

In this retrospective cohort of 263 hospital encounters among 201 patients for invasive infections due to SUD to an urban tertiary care facility, we looked at characteristics of SUD to assess whether there were differences in infections, their management, SUD interventions and parenteral antibiotic outcomes between groups.

Results

Among people with SUD, 79% of antibiotic courses were completed in skilled nursing facilities. Most common infectious syndromes were osteoarticular infections (123, 47%), infective endocarditis (IE) (54, 20%) and non-IE endovascular infection (23, 9%). Among SUD specific interventions, 64% of episodes had documentation of a consultation by substance use services and 68% episodes had documentation of medication for opioid use disorder (MOUD) being prescribed at discharge. Overall, completion of therapy was documented in 163 (62%) of encounters. Overall, treatment non-adherence was seen in 63 encounters (24%). Non-adherence was documented 32% of episodes with documentation of injection drug use (IDU), 28% of encounters where active substance use was documented in the prior year and 33% of encounters where use of more than one substance was documented (P< 0.05 for all 3 groups). Drug or catheter related adverse events seemed to be significantly higher in the IDU group (3.64/1000 OPAT days) and catheter abuse was documented in 7 encounters of which 6 were with IDU or active SUD active documented. Cumulatively an unfavorable outcome (including failure, 30-day readmission, drug or PICC related adverse event, non-adherence or death) seemed to occur in 58% of IDU encounters as compared to non-IDU encounters (42.5%, P=0.011). Medication for opioid use disorder (MOUD) was prescribed at discharge in 68% of overall cohort and was not associated with improved outcomes for any of the above groups.

Demographics, infection details and outcomes by type of SUD

Conclusion

In patients hospitalized with SUD-related infections, interventions need to be focused on those with high risk, unstable SUD through MOUD optimization along transitions of care and linkage to care to improve OPAT outcomes and overall health events

Disclosures

Shyam Kottilil, MD, PhD, Arbutus Pharmaceuticals: Grant/Research Support|Gilead: Grant/Research Support|Merck: Grant/Research Support|Regeneron Pharmaceuticals: Advisor/Consultant|Silverback Therapeutics: Advisor/Consultant|The Liver Company: Advisor/Consultant|Yufan Biotechnologies: Advisor/Consultant.
1658. Using remote Infectious Disease physician expertise to support inpatient antibiotic stewardship activities at three VA medical centers an implementation-effectiveness trial
Authors: Livorsi Daniel J , Sherlock Stacey Hockett , Goedken Cassie Cunningham , Clarke Kim , Goodman David , Pratt Sandra , Cho Hyunkeun , Reisinger Heather , Perencevich Eli N
Published: December 2022

Background

Remote Infectious Disease (ID) physicians can provide stewardship support through telehealth. Using the RE-AIM framework, we assessed the implementation of telehealth-supported prospective-audit-and-feedback (tele-PAF) across 3 rural Veterans Administration medical centers (VAMC).

Methods

All 3 invited sites agreed to participate and lacked ID support for stewardship at baseline. During 2021, an ID physician met virtually 3 times/week with the stewardship pharmacist champion at each participating VAMC to review patients on antibiotics in acute-care (mean daily census 3/site) and nursing-homes (NHs; mean census 71/site); real-time feedback on antibiotic use was given to clinicians. The primary outcome of effectiveness was monthly antibiotic days of therapy (DOT) per 1,000 days-present aggregated across all sites; the secondary outcome was days of antibiotic spectrum coverage (DASC) per 1,000 days-present. An interrupted time-series analysis was performed to asses these outcomes during the 1-year intervention period vs. the 2-year prior baseline. Semi-structured interviews with 20 clinicians and pharmacists were conducted to assess implementation.

Results

RE-AIM elements are summarized in Table 1. Tele-PAF reviewed 502 unique patients and made 681 recommendations to 23 clinicians; 77% of recommendations were accepted. The most common recommendations were to stop antibiotics (28%) and change duration (20%). After the start of tele-PAF, antibiotic DOT and DASC immediately decreased in acute-care (-20%, p=0.01; -22%, p< 0.01) and NHs (-28%, p=0.03; -37%, p< 0.01). Both metrics began to rise again in acute-care (DOT: +2.5%/month, p=0.02; DASC: +2.7%/month, p=0.02) but were stable in NHs (Figure 1). Clinicians generally appreciated feedback, found it compatible with their workflow and responded favorably to collaborative discussions. Barriers included difficulty establishing rapport with some providers.

Conclusion

The implementation of tele-PAF was associated with sustained reductions in antibiotic use across 3 NHs but not in the studied small acute-care units. Overall, clinicians perceived the intervention as acceptable and appropriate. Wider implementation of telehealth-supported stewardship activities may achieve reductions in antibiotic use.

Disclosures

Daniel J. Livorsi, MD, Merck & Co.: Grant/Research Support.
1424. Central Nervous System Tuberculosis in a Large Healthcare System
Authors: Jacobs Annie , Leonard Michael
Published: December 2022

Background

Central nervous system tuberculosis (CNS-TB) accounts for 5-10% of extrapulmonary TB cases. It takes 3 clinical forms: meningitis, tuberculoma, and arachnoiditis. Modern case descriptions of the presentation of CNS-TB are rare. The goal of this study is to examine the presentation, diagnostic studies, and associated comorbidities of CNS-TB.

Methods

In our academic healthcare system, cases of culture confirmed CNS-TB were identified in a database maintained by the infection control group. This is a retrospective case series of the 11 adults with confirmed CNS-TB.

Results

273 patients were identified with TB infection from 2008 to 2022. 104 (38%) had extra pulmonary disease. 11 (4%) had CNS infection. Patient characteristics are described in Table 1. 5 (45%) of the patients with CNS disease also had pulmonary disease. Mean age of diagnosis was 42. 5 (45%) were male and 9 (82%) were African American. 5 (45%) had HIV; mean CD4 count was 100 (8-255). Diagnostics are shown in Table 2. CSF studies revealed a mean WBC of 295/mm3 (4-808), protein of 605 mg/dL (27-4476), and Glucose of 31 (12-64) mg/dL. 4 (36%) patients presented with British Research Medical Council (BMRC) clinical stage I disease and 7 (64%) with stage II disease. 8 (73%) patients had an abnormal CT or MRI scan of the head, with representative images seen in Figure 1. 5 patients (45%) had lesions consistent with tuberculomas. 1 (9%) had arachnoiditis identified on imaging. 1 (9%) patient died.

Conclusion

38% of patients diagnosed with TB at our center had extrapulmonary disease compared to 17.5% reported in the literature. The 4% rate of CNS-TB was similar to previously reported. Our series describes abnormal imaging as well as CSF studies showing leukocytosis, pleocytosis, and hypoglycorrhachia consistent with previously described findings. Though numbers were small, no significant difference was found between HIV positive and negative patients. Although mortality was rare in our series, the patient who died had advanced AIDS and multidrug resistant meningitis. Given the significant global mortality of this disease, this series highlights the need for more current studies describing the presentation and diagnostic characteristics of modern CNS-TB so clinicians can better recognize and treat the condition without delay.

Disclosures

All Authors: No reported disclosures.
1430. Eravacycline associated hypofibrinogenemia during treatment of M.abscessus
Authors: Rausch Ethan , van Duin David , Bartelt Luther A , Daniels Lindsay M
Published: December 2022

Background

Eravacycline, a novel synthetic fluorocycline, is structurally similar to tigecycline. Cases of tigecycline associated hyperfibrinogenemia have been reported in the literature, however the mechanism is not currently well described. At this time it is unknown if this is a class effect.

Methods

Two cases of patients on eravacycline for treatment of Mycobacterium abscessus (M.abscessus) who received regular fibrinogen monitoring are described.

Results

Patient 1 received a kidney transplant (2010) and was admitted for acute hypoxic respiratory failure secondary to COVID-19. Their course was complicated by multiple infections including disseminated M.abscessus with positive cultures from the lung and blood. Eravacycline 1 mg/kg BID (80 mg) was started on D1 and continued through D24. Fibrinogen levels on D1 was 448 mg/dl and on D23 were 120 mg/dl. Eravacycline was stopped and fibrinogen returned to normal range (228 mg/dl) in 5 days. Eravacycline was re-trialed at 80 mg BID and fibrinogen level on D1 was 310 mg/dl and 147 mg/dl on D8. No repeat fibrinogen levels were obtained. Patient 2 was a lung transplant recipient (2019) admitted for treatment of M.abscessus skin and soft tissue infection. The patient was started on eravacycline 1 mg/kg BID (90 mg) due to concerns of hypofibrinogenemia from tigecycline. On D1 of eravacycline fibrinogen was 167 mg/dl , on D19 of therapy fibrinogen was 64 mg/dl and eravacycline was stopped. Fibrinogen level returned to normal 3 days after eravacycline discontinuation (212 mg/dl).

Conclusion

Similar to tigecycline, we observed eravacycline related hypofibrinogenemia. Time to onset was variable in the two cases presented. Hypofibrinogenemia was readily reversible, within 3-5 days, with drug withdrawal and reproducible in one patient with re-challenge of eravacycline. Further analysis into eravacycline related hypofibrinogenemia and its impact on coagulation outcomes are warranted based on these reports.

Disclosures

David van Duin, MD, PhD, Achaogen: Advisor/Consultant|Allergan: Advisor/Consultant|Astellas: Advisor/Consultant|MedImmune: Advisor/Consultant|Melinta: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|NeuMedicine: Advisor/Consultant|Pfizer: Advisor/Consultant|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Sanofi-Pasteur: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|T2 Biosystems: Advisor/Consultant|Tetraphase: Advisor/Consultant.
1443. Nontuberculous Mycobacterial Cervicofacial Lymphadenitis Therapy: Experience from a Tertiary Care Pediatric Center
Authors: Vo Anh N , Singh Prachi , Karandikar Manjiree , Rosbe Kristina
Published: December 2022

Background

Nontuberculous mycobacterial (NTM) infections commonly present as a unilateral, subacute cervical lymphadenitis in immunocompetent children under the age of 5 years. The natural history of NTM lymphadenitis without intervention is slow resolution, and there is a high risk of spontaneous drainage through the skin, often result in a scar. For NTM lymphadenitis, the gold standard is complete surgical excision as it is often curative and limits scar formation. However, surgical intervention, especially complete surgical excision, carries the risk of damage to the facial nerve in the parotid and submandibular region. Antibiotic therapy is thought to interrupt the natural progression of the disease.

Methods

We conducted a retrospective chart review and reviewed >700 patients, who had a diagnosis of cervical lymphadenopathy and/or atypical mycobacterial based on ICD codes. Patients received a diagnosis of NTM if they had clinical adenitis with NTM detected on culture and/or PCR, acid-fast bacilli identified, or histological findings consistent with mycobacterial infection.

Results

A total of 17 cases of NTM were identified. The median age was 27 months; 52% were male and 47% were female. The median time of adenopathy prior to presentation to ENT or ID specialist was 2 months. The average size of the involved lymph node was 2.05 cm. Two patients were treated with only medical management, 6 with surgical management, 8 with both, and 1 had observation alone as patient was near resolution. Of the patients on antibiotics, a total of 4 patients had adverse effects (abdominal discomfort, diarrhea, vomiting, and/or rash). Surgical interventions include FNA, incision and drainage, curettage, and complete excision. Four patients required 2nd intervention. One patient had concerns for sinus formation but resolved in < 1 month. No patients had facial nerve palsy or hypertrophic scarring.

Conclusion

Regardless of management strategy, all children in this study had resolution of NTM. Though there is a consensus that complete surgical resection is the gold standard, we demonstrate that medical management alone (anti-microbial therapy or “wait-and-see” method) can be an alternative first-line treatment. Limitations include retrospective nature of study which is limited by data available in the EMR.

Disclosures

All Authors: No reported disclosures.
1447. Retrospective Study Comparing the Characteristics of NTM Vertebral Osteomyelitis and Tuberculous Vertebral Osteomyelitis
Authors: Park Sunghee , Kim Tark , Ryu Byung-Han , Hong Hyo-Lim , Kwak Yee Gyung , Kim Min Jae
Published: December 2022

Background

Nontuberculous mycobacteria (NTM) species rarely cause vertebral osteomyelitis (VO). The clinical characteristics and radiological findings of NTM VO are not well described since the number of cases are limited. Here we present the clinical characteristics of culture positive NTM VO, compared to those of tuberculous (TB) VO.

Methods

We performed a retrospective, multicenter study at 5 hospitals. Patients with radiologic findings consistent with VO, and positive NTM or TB cultures on biopsy were included. Demographic characteristics and symptoms were collected, along with laboratory, radiologic, and pathologic findings.

Results

Nineteen patients with NTM VO and 105 patients with TB VO were included. M. intracellulare (52.6%) and M. abscessus (26.3%) were the most common NTM pathogens. The mean age of patients was significantly older in the NTM VO group (68.0 vs. 58.5 years, P = .01). Previous steroid or immunosuppressant use was more frequent in the NTM VO group (21.1% vs. 2.9%, P = .01; 15.8% vs. 2.9%, P = .046, respectively), as was a history of vertebral surgery (47.4% vs. 13.3%, P < .001). Symptoms and laboratory findings were similar between the 2 groups, although the proportion of patients with positive interferon-gamma release assays (IGRA) was significantly higher in the TB VO group (14.3% vs. 86.4%, P < .001). Radiologic findings were also similar, with lumbar involvement being the most common (57.9% and 44.8%, respectively). Chronic granulomatous inflammation was more frequently seen in TB VO patients (33.3% vs. 64.0%, P = .04), while inflammation alone was more common in NTM VO. Although there was no significant difference in survival after 1 year, survival at last follow-up (median, 24 months) was significantly lower in the NTM VO group (75.0% vs. 98.8%, P = .02).

Conclusion

NTM VO should be considered in older patients with a history of immunosuppression or previous vertebral surgery. The pathologic findings and radiologic findings of NTM VO were similar to that of TB VO. Granulomatous inflammation and positive IGRA tests were more common in TB than NTM VO.

Disclosures

All Authors: No reported disclosures.
1453. Clinical Manifestation and Risk Factors Associated with Mortality of Cytomegalovirus Infection in Immunocompetent Patients in King Chulalongkorn Memorial Hospital, Bangkok, Thailand: a 3-year experience
Authors: Kiatsuranon Phimkamon , Vanichanan Jakapat , Jutivorakool Kamonwan
Published: December 2022

Background

Cytomegalovirus (CMV) infection usually occurs in organ transplant or HIV-infected patients. Recently, we found CMV infection was increased in non-transplant and non-HIV infected patients. Our study aimed to determine the epidemiology, clinical manifestation, clinical outcome, and risk factors associated mortality of CMV infection in this population.

Methods

The retrospective study was conducted in King Chulalongkorn Memorial Hospital. Patients aged above 18 years with diagnosis of CMV infection from January 2017 to September 2019 were collected and identified by ICD-10 code. Patients with HIV infection, solid organ transplant and hematopoietic stem cell transplant were excluded.

Results

A total of 51 patients, including 28 males (54.9%) were identified. The median age was 61 years (range 48-73 years). 46 patients (90.2%) had underlying disease which were 19 cases (37.3%) of autoimmune disease, 13 cases (25.5%) of hematologic disease (mostly hematologic malignancy), 4 cases (7.8%) of chronic kidney disease, and 10 cases (21.6%) of others. CMV viremia was found in 31.4%. Regarding CMV end-organ disease, there were 20 cases of gastrointestinal tract CMV infection, 10 cases were CMV retinitis, 5 cases were CMV pneumonitis and 1 case was CMV hepatitis and CMV transverse myelitis. The all-cause mortality was 25.5% and significantly in age over 70-year-old (p=0.037). The end-organ disease and CMV viral load were not different in survived and death group (p=0.445 and p=0.838, respectively).

Factors associated with mortality of CMV infection

Conclusion

CMV infection was an emerging problem in non-transplant and non-HIV infected adult patients, especially in age over 70-year-old in our Institute. The study showed infections predominated in rheumatologic and hematologic malignant patients who were received chemotherapy or immunosuppressive agent. Viremia and gastrointestinal tract were organs that mainly involved. CMV infection will become an important complication in the era of treatment with immuno-chemotherapy. Clinician should be aware of this potentially life-threatening infection.

Disclosures

All Authors: No reported disclosures.
1693. Meropenem-Xeruborbactam: In Vitro Potency against Gram-Negative Bacteria in Comparison with Marketed and Investigational Beta-lactam (BL)/Beta-lactamase Inhibitor (BLI) Combinations
Authors: Lomovskaya Olga , Castanheira Mariana , Lindley Jill
Published: December 2022

Background

Several BLI combinations have entered into clinical testing or been approved for use but there are few comparative studies of their in vitro activity. Xeruborbactam (XER, formerly QPX7728) is a cyclic boronate BLI with potent inhibitory activity against serine and metallo-beta-lactamases (MBL). It is in clinical development in combination with meropenem (MEM). The objective of this study was to compare in vitro potency of MEM-XER to that of other investigational and approved BL/BLI combinations in head-to-head testing against recent isolates of carbapenem-resistant Enterobacterales (CRE) and Acinetobacter baumannii (CRAB) as well as Pseudomonas aeruginosa (PA).

Methods

The test panel of recent worldwide isolates consisted of 507 CRE including 168 MBL producers (157 NDM, 11 VIM, 1 IMP), 506 CRAB, and 506 PA that were representative of current isolates and included 65 MDR (resistant to ≥ 3 antimicrobial classes) strains. MEM-XER was tested with XER at a fixed 8 mg/L conc. and other BL/BLI combinations at their recommended BLI concentrations. MIC testing was conducted blinded to drug identity using CLSI reference methods and controlled using approved quality control bacterial strains and ranges.

Results

The MIC50 and MIC90 for MEM-XER vs CRE ranged from ≤ 0.03 mg/L to 0.06 mg/L and 0.06 mg/L to 1 mg/L, respectively. MEM-XER and cefepime-taniborbactam (FEP-TANI) were the only BL/BLIs with activity against MBL-producers; based on MIC90, MEM-XER (MIC90 of 1 mg/L) was 16-fold more potent than FEP-TANI (MIC90 of 16 mg/L). MEM-XER and sulbactam-durlobactam (SUL-DUR) were the only agents with high potency against CRAB, with MIC50/MIC90 of 0.5/4 mg/L and 1/2 mg/L. For the representative panel of PA, the potency of MEM-XER, FEP-TAN, ceftolozane-tazobactam (TOL-TAZ), imipenem-relebactam (IMP-REL), and CAZ-AVI was similar with MIC90s ranging between 2-8 mg/L; for the MDR panel, MIC90‘s were > 8 mg/L for all combinations, with MER-XER, IMP-REL, TOL-TAZ, and CAZ-AVI having MIC50’s of 2-4 mg/L.

Conclusion

Compared to the marketed or investigational BL/BLIs, MEM-XERU had the broadest coverage of carbapenem-resistant gram-negative bacteria, with the most differentiating property being activity against multiple strains of MBL-producing CRE and CRAB.

Disclosures

Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Jill Lindley, BS, AbbVie: Grant/Research Support.
1715. In Vitro Antibacterial Activity of Cefiderocol against Difficult-to-treat Resistant (DTR) Gram-negative Pathogens in United States from SENTRY Antimicrobial Surveillance Program in 2020/2021
Authors: Yamano Yoshinori , Takemura Miki , Shortridge Dee , Slover Christine M , Longshaw Christopher M , Echols Roger , Echols Roger , Echols Roger
Published: December 2022

Background

Difficult-to-treat resistant (DTR) isolates are defined as resistance to all first-line high-efficacy, low-toxicity antibiotics (penicillins, cephalosporins, carbapenems and quinolones), leaving physicians with limited treatment options. Cefiderocol (CFDC) is a siderophore cephalosporin with activity against a wide variety of Gram-negative bacteria, including carbapenem-resistant Enterobacterales and non-fermenters. We evaluated the in vitro activity of cefiderocol against DTR isolates collected in United States as part of SENTRY surveillance program in 2020 and 2021.

In vitro susceptibility of cefiderocol and comparator agents to DTR isolates

Methods

Susceptibility testing was performed by broth microdilution according to CLSI guidelines. All antibiotics were tested in cation-adjusted Mueller-Hinton broth (CAMHB) except for CFDC, for which iron-depleted CAMHB was used. Susceptibility rate (%) was determined according to CLSI breakpoints, and DTR pathogens were defined as being resistant to cefepime, ceftazidime ceftriaxone (only for Enterobacterales), imipenem, meropenem, ciprofloxacin and levofloxacin according to CLSI/FDA breakpoints.

Results

Among a total of 8,328 Enterobacterales, 2,241 Pseudomonas aeruginosa, and 586 Acinetobacter calcoaceticus-baumannii complex (ACB) clinical isolates from the United States, 50 Enterobacterales (0.6%), 36 P. aeruginosa (1.6%) and 114 ACB (19.5%) isolates showed a DTR phenotype, respectively. CFDC demonstrated its potent in vitro activity against these DTR isolates with MIC90 of ≤4 μg/mL with a susceptibility rate of ≥92% except for DTR ACB based on FDA breakpoint (75.4%). In contrast, MIC90s of β-lactam/β-lactamase inhibitor combination drugs showed lower activity (Table).

Conclusion

Cefiderocol demonstrated potent in vitro activity against DTR isolates of Enterobacterales, P. aeruginosa and ACB, indicating cefiderocol has high potential for treating infections caused by these difficult-to-treat strains.

Disclosures

Yoshinori Yamano, PhD, Shionogi: Employee Miki Takemura, n/a, Shionogi: Employee Dee Shortridge, PhD, AbbVie: Grant/Research Support|JMI Laboratory: Employee|Melinta: Grant/Research Support|Menarini: Grant/Research Support|Shionogi: Grant/Research Support Christine M. Slover, PharmD, Shionogi: Employee Christopher M. Longshaw, PhD, Shionogi: Employee Roger Echols, MD, Shionogi: Advisor/Consultant Roger Echols, MD, Shionogi: Advisor/Consultant Roger Echols, MD, Shionogi: Advisor/Consultant.
1723. MK-3866, a metallo-β-lactamase inhibitor, is not subject to efflux in Pseudomonas aeruginosa
Authors: Young Katherine , Mirza Asra , Balibar Carl , Dong Shuzhi , Bennett Frank , Jiang Jinlong , Tang Haiqun , Tudge Claire , Scott Jack , Yang Dexi , Pasternak Alexander
Published: December 2022

Background

Metallo-beta (β)-lactamases (MBLs) are in the class B group of β-lactamases due to zinc ions in the active site that are required for enzymatic activity. MK-3866 is a small molecule MBL inhibitor (MBLi) that restores antibacterial activity against resistant MBL-expressing gram-negative bacteria. Efflux is an important mechanism of antibiotic resistance in Pseudomonas aeruginosa (Pa). Imipenem (IMI) is not subject to efflux and neither is relebactam (REL), a β-lactamase inhibitor (BLi) of class A and C β-lactamases that is approved in combination with IMI/cilastatin. An efflux assay was devised to characterize MBLis for potentiation of IMI or cefepime (FEP) in isogenic strain pairs of efflux wild-type and multiply efflux deleted (MED) strains of Pa. Our objective was to determine if MK-3866 and related analogs are subject to efflux in Pa.

Methods

Bacterial isolates were engineered to demonstrate the ability of MBLis to be effluxed by introducing IMI metallo-β-lactamase-1 (IMP-1) (by electroporation) or Verona integron-encoded metallo-β-lactamases (VIM-1, VIM-2) (utilizing the cloning vector pFlp2) into isogenic MED and wild-type (WT) Pa isolates. Susceptibility testing was performed with IMI or FEP at a fixed concentration equal to the Pa Clinical and Laboratory Standards Institute susceptibility breakpoint for each and including a fixed 4 µg/mL of REL to inhibit class A or C enzymes, referred to as the SLICE assay. The concentration of MK-3866 and analogues required to restore susceptibility to either antibiotic in WT and MED strains was assessed.

Results

MICs to the combination of MK-3866/REL/IMI or MK-3866/REL/FEP vary by ≤4-fold between the WT and MED strain of each isogenic strain pair (Table 1). In contrast, large differential MIC values (efflux ratios) can be seen for the MK-3866 analogues A and B, with more moderate efflux ratios observed for other analogues. The exact efflux ratio depended on the MBL studied and the antibiotic partner.

Conclusion

MK-3866 showed a low potential for efflux whether IMP-1, VIM-1, or VIM-2 was expressed, in contrast to analogues of MK-3866 which exhibited differentials from nominal to extreme (≥ 128-fold) between efflux WT versus MED isolates.

Disclosures

Katherine Young, M.S., Merck & Co., Inc.: Stocks/Bonds Asra Mirza, MS, Merck & Co., Inc.: Stocks/Bonds Carl Balibar, PhD, Merck & Co., Inc.: Stocks/Bonds Shuzhi Dong, PhD, Merck & Co., Inc.: Stocks/Bonds Frank Bennett, PhD, Merck & Co., Inc.: Stocks/Bonds Jinlong Jiang, PhD, Merck & Co., Inc.: Stocks/Bonds Haiqun Tang, PhD, Merck & Co., Inc.: Stocks/Bonds Claire Tudge, PhD, Merck & Co., Inc.: Stocks/Bonds Jack Scott, PhD, Merck & Co., Inc.: Stocks/Bonds Dexi Yang, PhD, Merck & Co., Inc.: Stocks/Bonds Alexander Pasternak, PhD, Merck & Co., Inc.: Stocks/Bonds.
2298. Clinical and Demographic Characteristics of COVID-19 in Pediatric Patients in the United States
Authors: Ho Milan , Most Zachary M , Diaz Marlon , Casazza Julia A , Thakur Bhaskar , Saleh Sameh , Pickering Madison , Perl Trish M , Lehmann Christoph U , Medford Richard J , Turer Robert W
Published: December 2022

Background

The percentage of children infected with COVID-19 has outpaced that of adults. As children >5 years are now eligible to receive vaccines, it is necessary to understand the effect of vaccination in the context of demographic characteristics, clinical factors, and variants on pediatric COVID-19 illness severity.

Methods

We conducted a descriptive study of patients ≤18 years from the Optum® COVID-19 electronic health record dataset. Patients were included if positive for COVID-19 by polymerase chain reaction or antigen testing for the first time from 3/12/2020 to 1/20/2022. We compare race and ethnicity, age, gender, US region of residence, vaccination status, body mass index (BMI), pediatric comorbidity index (PCI) (Sun, Am. J. Epidemiol. 2021), and predominant variant (by time and region) with 2-tailed t-test, multi-category chi-square test, and odds ratios (R version 4.1.2; α = 0.05). PCI is a validated comorbidity index predicting hospitalization in pediatric patients.

Results

Of all pediatric patients in our dataset, 165,468 (13.2%) tested positive for COVID-19. 3,087 (1.9%) were hospitalized, 1,417 (0.9%) were admitted to the ICU, 1545 (0.9%) received respiratory support, and 31 (0.02%) died, comparable to AAP-reported hospitalization and mortality rates in US children. Patients with severe outcomes were more likely to be younger, non-Caucasian, from the US South, unvaccinated, and have a higher PCI (Figure 1). Excluding non-severe outcomes, rates of death and ICU admission were higher in 0–4-year-olds compared to 5–11 or 12–18-year-olds (Figure 2). All patients receiving at least one dose of the vaccine survived. The odds ratio of a severe outcome is 0.11 (95% CI 0.07–0.16) in fully vaccinated patients compared to unvaccinated patients. The odds ratio of a severe outcome is 0.55 (95% CI 0.49–0.63) in partially vaccinated patients compared to unvaccinated patients.

Demographic and clinical characteristics of pediatric patients with COVID-19

Relative proportion of clinically severe outcomes within age groups, excluding non-severe outcomes

Conclusion

In this large population, incidence rate of severe outcomes from COVID-19 in pediatric patients was higher among non-Caucasian patients, living in the South, with underlying comorbid illness, and those not yet eligible for vaccination. These findings reinforce the need for a vaccine for younger patients and targeted vaccine outreach to racial and ethnic minorities and children with chronic conditions.

Disclosures

Christoph U. Lehmann, MD, Celanese: Stocks/Bonds|Markel: Stocks/Bonds|Springer: Honoraria|UTSW: Employee.
1735. The Pig Skin Commensal D. incerta Exhibits Antimicrobial Activity Against Methicillin-Resistant Staphylococcus aureus
Authors: Wei Monica , Knight Simon , Flowers Laurice , Walsh Jasmine , Grice Elizabeth A
Published: December 2022

Background

Methicillin-resistant Staphylococcus aureus (MRSA) infections occur commonly on skin and cause significant healthcare burden. MRSA can also stably colonize the skin and nasal passages, contributing to community spread. This colonization results in long-term interaction with the skin microbiome, which harbors a diverse community of bacteria that often use antimicrobial molecules to compete for ecologic niches. We hypothesize that the skin microbiome contains bacteria that secrete novel antimicrobial agents against MRSA.

Methods

Pigs are an established model organism for skin whose microbiome is not well explored. We mined the pig skin microbiome for bacterial species that inhibited MRSA via a modified disc diffusion assay.

Results

We find that the novel pig skin commensal D. incerta inhibits USA300 strain MRSA via a secreted antimicrobial protein that can be isolated from cell-free supernatant. Analysis of the D. incerta genome shows little homology to known antimicrobial genes clusters. The identity of the antimicrobial molecule and whether its antimicrobial activity persists in the context of MRSA skin infection remain unclear. We characterize the identity of this antimicrobial molecule via parallel genomic and biochemical approaches. Finally, we propose to test the ability of D. incerta to impede MRSA colonization and improve healing of MRSA-mediated skin infection, two clinically important skin conditions.

Conclusion

We screened the pig skin microbiome and successfully identified bacterial inhibitors of MRSA. Preliminary data suggest that the pig skin commensal D. incerta secretes a novel antimicrobial protein. Our current efforts focus on identifying this antimicrobial molecule and investigating its therapeutic potential in animal models of skin.

Disclosures

All Authors: No reported disclosures.