bluuebunny/crossref_metadata_2025 huggingface dataset:
1579. Incidence and Predicting Factors of Opportunistic Infections after Initiation of Antiretroviral Therapy: A Retrospective Cohort Study
Authors: Wongkittipong Prapon , Kiertiburanakul Sasisopin
Published: November 2023

Background

Antiretroviral therapy (ART)-associated opportunistic infections (OIs) is the term proposed to encompass all OIs diagnosed after ART initiation, and it is not uncommon. We aimed to determine the incidence of OIs and the predicting factors for OIs developing after ART initiation among Thai people living with HIV (PLHIV).

Methods

In the university hospital setting, a retrospective cohort study was conducted among naïve PLHIV who initiated ART between January 2016 and December 2019.

Results

A total of 401 PLHIV were included in the analysis. Of these, the mean (SD) age was 37.1 (11.9) years, 74.3% were male, and 57.6% had heterosexual risk. There were 247 (61.6%) diagnosed with AIDS and a median (IQR) CD4 count at ART initiation was 166 (49-314) cells/µL. The most common prior OIs were tuberculosis (26.4%) and Pneumocystis jirovecii pneumonia (11.5%). Of all, 38 (9.5%) PLHIV developed OIs after initiating ART with an incidence rate of 25.6/1000 person-years. The median time (IQR) from ART initiation to the OIs occurrence was 26.5 (14-73) days. PLHIV who develop OI after ART initiation were more likely to have lower mean body mass index (BMI) (20.1 vs 22.3 kg/m2), lower median CD4 counts (36 vs 188 cells/µL), lower mean hemoglobin levels (10.8 vs 12.4 mg/dL), a higher proportion of AIDS diagnosis (86.5% vs 57.9%), having prior OIs (78.9% vs 35.5%), and a higher proportion of initiation with dolutegravir (DTG)-based regimen (10.5% vs 3%) (p < 0.05, all). By multivariate Cox proportional hazard regression, having BMI ≤18.5 kg/m2 (aHR 2.28; 95% CI 1.18-4.42, p=0.015), symptomatic at presentation (aHR 13.59; 95% CI 3.24-56.9, p < 0.001), SGPT >55 U/L (aHR 2.09; 95% CI 1.06-4.15, p=0.035), and initiation with DTG-based regimen (aHR 4.39, 95% CI 1.54-12.48, p=0.006) were statistically significant associated OIs after ART initiation. The OI-associated mortality was 5.3%.

Conclusion

The OIs after ART initiation are not uncommon. Malnutrition, symptomatic at presentation, abnormal liver enzyme, and initiation with DTG-based regimens is predicting factors of OI occurrences. It is crucial for physicians to monitor and appropriate treatment of OIs after ART initiation.

Disclosures

All Authors: No reported disclosures
1595. Accumulating Antiretroviral Therapy Safety Data In Pregnancy: Barriers To Clinician Reporting To The Antiretroviral Pregnancy Registry In North America And Internationally
Authors: Stavroula manta M , O’Bryan Jessica , Giles Michelle , Short William R , logue-Chamberlain Erin , Krishnaswamy sushena
Published: November 2023

Background

Clinical trials evaluating antiretroviral therapy (ARV) often exclude pregnant women, delaying the accumulation of safety data in pregnancy, and use of newer ARVs in women of reproductive age. The Antiretroviral Pregnancy Registry (APR) is the largest international exposure registry of ARV use in pregnancy, but only 0.5% of reports come from Australia and 70% of reports are from the United States (US). A decline in reporting was noted during the COVID-19 pandemic.

Methods

Surveys were developed independently and disseminated to clinicians who provide care to women with HIV or their children through email distribution lists of the peak infectious diseases societies in Australia and the US Reproductive Infectious Diseases and HIV email distribution list. The surveys assessed awareness of the APR and barriers to contributing data.

Results

In total, 146 clinicians (80 Australia, 66 US) completed the surveys. Of US respondents, 59% (39/66) used the APR clinically and 55% (36/65) had contributed data to the APR. The key barriers to reporting included lack of time, funding and staff/administrative support, and complexity of the reporting system. In contrast, in Australia, less than half (47.5%, 38/80) of respondents were aware of the APR, and only 10% (8/80) had ever contributed data. The perceived barriers to contributing data in this context were a lack of knowledge (unaware that clinicians outside the US could report, uncertainty about how to report, belief that only adverse pregnancy outcomes should be reported) and feeling their individual contribution would be insignificant when providing care for small numbers of pregnant women. Clinicians in both countries identified consent and ethics review board requirements as barriers to contributing data.

Conclusion

The barriers to reporting data to the APR are likely context specific. The findings from Australia may apply to other high resource settings. Further efforts are required to address these barriers to increase reporting of ARV use in pregnancy. This would increase the acquisition of ARV pregnancy safety data and address the disparity in treatment options faced by women of reproductive age with HIV.

Disclosures

Stavroula mantaM, B Pharm, Gilead: Received funding for project: BRAVVO Michelle Giles, MBBS PhD, Gilead: Grant/Research Support William R. Short, MD, Gilead Sciences: Advisor/Consultant|ViiV: Advisor/Consultant|ViiV: Honoraria sushena Krishnaswamy, MBBS, Gilead: Grant/Research Support|Pfizer: Advisor/Consultant
1602. Determinants of Early Virologic Failure Among HIV patients on First-line Antiretroviral Therapy
Authors: Ramos Diana G , Roman Arthur Dessi E
Published: November 2023

Background

The initiation of anti-retroviral therapy (ART) effectively restores immune function and reduces HIV-related morbidity and mortality. However, virologic failure while on ART may lead to increased morbidity and compromised quality of life. The aim of this study was to determine the prevalence and determinants of early virologic failure (VF) among HIV patients on first-line ART enrolled at the Research Institute for Tropical Medicine, Philippines.

Methods

A retrospective cohort study was conducted involving treatment-naive HIV patients who were started on ART during the period of January 2004 – December 2018. Early virologic failure was defined as HIV-1 viral load of > 1,000 copies / ml of plasma blood taken within 6 months or more of first-line ART. Data regarding patients’ sociodemographic profile, baseline clinical characteristics, and treatment-related information were collected through database review. Data were analyzed using STATA 15.0. Descriptive statistics, cross-tabulations, and univariate and multivariate logistic regressions were utilized. P < 0.05 was used to determine clinical significance.

Results

Among the 1900 subjects included in this study, 1839 were males (96.79 %). The mean age at ART initiation was 30.36 years (SD 6.89) with a baseline CD4 count of 232.30 cells / mm3 (SD 204.19). The average time from ART initiation to the first VL determination was 4 years (SD 28.62). A total of 72 (3.79 %) subjects were found to have virologic failure. Multivariate logistic regression showed that patients with age 15-20 years were 5-6 times more likely to have VF (1 / adjusted OR 0.18 = 5.55, p-value of 0.024) while patients with baseline CD4 count of < 50 cells/mm3 were 3 times (1 / adjusted OR 0.35 = 2.86, p-value < 0.01) more likely to have virologic failure.

Conclusion

The prevalence of early virologic failure among HIV patients on first-line anti-retroviral therapy is 3.79 %, relatively lower compared to other published data. Early virologic failure was most likely to occur among patients 15-20 years old and/or those with baseline CD4 count below 50 cells/mm3. Presence of these factors should be used as a marker for intensified adherence counselling especially in the absence of reliable or readily available viral load monitoring.

Disclosures

All Authors: No reported disclosures
2076. Intestinal colonization with multidrug-resistant organisms, horizontal transmission and risk for bloodstream infection
Authors: Karakosta Polyxeni , Meletis Georgios , Kousouli Elisavet , Protonotariou Efthymia , Vourli Sophia , Christina Georgiou Panagiota , Mamali Vasiliki , Skoura Lemonia , Zarkotou Olympia , Pournaras Spyros
Published: November 2023

Background

The association between rectal colonization and subsequent bloodstream infections (BSI) by multidrug-resistant organisms (MDROs) remains to be clarified. We aimed to investigate the relative risk of BSI in rectal carriers of MDROs and in the case of carbapenem-resistant Enterobacteriaceae (CRE), whether BSI was due to the patient’s own colonizing strain.

Methods

We retrospectively included all adult inpatients hospitalized from Jan 2019 to Dec 2022, in ICUs or medical wards of 3 Greek hospitals (Athens: “Attikon” Hospital, Piraeus: Tzaneio Hospital, Thessaloniki: AHEPA Hospital), who were screened for intestinal MDRO carriage at admission and weekly. Screening was performed by selective media and immunochromatography for the carbapenemase in CRE. Patients were followed up for BSI by the same colonizing organism; relative risk (95% CI) was estimated after adjustment for ICU hospitalization and age. MDROs included CRE, carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA) and vancomycin-resistant enterococci (VRE). The CRE-colonizers and BSI-pathogens were analyzed for carbapenemase type to identify potential similarities.

Results

Of 4,427 patients screened, 1,321 (29.8%) were colonized by CRE, 1,255 (28.3%) with CRAB, 252 (5.7%) with CRPA and 859 (27.9% of 3,082 patients tested) with VRE. Of those, 207 (15.7%), 247 (19.7%), 23 (9.1%) and 30 (3.5%) subsequently developed CRE-BSI, CRAB-BSI, CRPA-BSI and VRE-BSI, respectively. Intestinal CRE colonization was associated with 4-fold higher risk of subsequent CRE-BSI, after adjusted for ICU stay and age [RR (95%CI): 4.1 (3.2, 5.2)]. The respective relative risk (95%CI) for BSI in patients with colonization by CRAB, CRPA and VRE were 2.3 (1.9, 2.8), 8.2 (5.1, 13.4) and 2.1 (1.3, 3.4). To evaluate possible horizontal transmission, 286 paired CRE strains from 143 patients were analyzed; in 111 (77.6%), both colonizers and BSI pathogens belonged to the same bacterial species and carried the same carbapenemase type.Table 1:Rectal colonization with MDROs and the risk for BSI from the same pathogenTable 2:Carbapenemase types in rectal carriers of CRE who developed subsequent BSI with the same pathogen

Conclusion

Intestinal colonization by MDROs was associated with increased risk of BSI by the colonizing bacteria. Clinicians should evaluate this information for empiric treatment, while genome-wide data are needed to substantiate horizontal transmission.

Disclosures

All Authors: No reported disclosures
1673. Time to positivity of blood cultures in a pediatric hospital: more tools to reconsider empirical treatment in suspected infections.
Authors: Andrade-Fernandez Joam C , Gutierrez-Tobar Ivan Felipe , Londono-Ruiz Juan Pablo
Published: November 2023

Background

Blood cultures are essential for diagnosing bacterial infections. Positivity time (TP) measures the time from incubation to bacterial growth detection. Understanding TP for different pathogens and age groups can guide empirical treatment duration. Our aim is to describe microbiological characteristics of blood culture isolates by TP, causative germ, and patient age.

Methods

This retrospective and observational study analyzed all blood culture isolates obtained from a pediatric reference center in Colombia between 2015 and 2021, using the automated BD Phoenix™ detection system. Data was extracted from WHONET and analyzed for average positivity time, patient age, and microorganism type.

Results

A total of 1258 positive bottles were analyzed: 32.9% [414] were Gram-negative, 65.5% [824] were Gram-positive, and 1.6% [19] were yeast. The overall median positivity time was 14.5 [10.9-20.6] hours, for Gram-positive organisms, the median growth time was 17.2 [13.2-21.6] hours, and for Gram-negative organisms it was 10.8 [8.9-14.1] hours [p=< 0.0001]. 65.7% of Gram-negative organisms were identified within the first 12 hours, compared to 17.7% of Gram-positive organisms. (Figure 1). The pathogen with the fastest median growth time was S. agalactiae with 8.3 [6.7-10.3] hours [n=11], followed by K. pneumoniae with 9.5 [8.3-10.9] hours and S. pyogenes with 9.9 [7.7-12.1] hours [n=9]. Among clinically significant bacterial microorganisms with slower median positivity times were Haemophilus influenzae with 22.7 [14.8-23.9] hours [n=9], followed by coagulase-negative Staphylococcus species with a median of 19.6 [17.1-23.2] hours, then non-fermenting Gram-negative bacteria with a median of 16.4 [13.1-23.2] hours, and Salmonella spp with 16.3 [13.7-28.3] hours [n=22].

Distribution of positivity according to time intervals (Gram positive vs. Gram negative)

Proportion of microorganisms isolated according to age group

Positivity time in hours according to different groups of organisms

Conclusion

Based on the study findings, it can be concluded that in pediatric patients with suspected bloodstream infection, empiric antimicrobial regimens can be shortened to 24-36 hours. The results of the study support this conclusion by demonstrating that the time to blood culture positivity was typically less than 24 hours. However, it would be beneficial to include additional data on the time of positivity associated with severity and clinical outcomes in pediatric patients to further support this conclusion.

Disclosures

All Authors: No reported disclosures
1676. PK, Safety and Tolerability of VABOMERE® (meropenem-vaborbactam) in Infants, Children and Adolescents
Authors: Bokesch Paula M , Arrieta Antonio C , Bradley John S , Hoover Randall K , McCurdy Sandra
Published: November 2023

Background

The worldwide spread of serine carbapenemases threatens carbapenems. VABOMERE (combination of meropenem and vaborbactam (MV), is a new class of beta-lactamase inhibitors including inhibition of Klebsiella pneumoniae. The PK, safety, and efficacy data of MV in adults support study in pediatrics.

Methods

Phase 1, open-label, dose-finding study. Pediatric subjects, 3 mos. to < 18 yrs already on antibiotics received a single-dose weight based infusion of MV over 3 hr. Blood samples were drawn pre-dose, 3,4, and 6 hr. for PK parameters. Population PK model included weight as a covariate. Safety assessments included AEs, vital signs, safety labs, physical exams, infusion tolerance, ECG. A DSMB reviewed safety and PK data before enrolling next cohort.

Results

MV was well-tolerated and safe in all age groups. Clearance per kg body weight of both M and V increased with decreasing body weight over all age groups suggesting an allometric relationship.

Conclusion

Targeted AUC0-8 efficacious in adult trials ranges of 91.7-513 mg•hr/L (meropenem) and 131-494 mg•hr/L (vaborbactam) were achieved in all pediatric cohorts.

Disclosures

Paula M. Bokesch, MD, Melinta Therapeutics: Advisor/Consultant Antonio C. Arrieta, MD, FIDSA, FPIDS, Astellas Pharma Global Development, Inc.: Advisor/Consultant|Astellas Pharma Global Development, Inc.: Grant/Research Support|Astellas Pharma Global Development, Inc.: Honoraria|Cumberland Pharmaceutical: Grant/Research Support|IDbyDNA: Advisor/Consultant|IDbyDNA: Grant/Research Support|Melinta: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Nabriva: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support|Pfizer, Inc: Advisor/Consultant|Pfizer, Inc: Grant/Research Support|Roche/Genentech: Grant/Research Support|The Medicine Company: Grant/Research Support Randall K. Hoover, Ph.D., Melinta Therapeutics: Advisor/Consultant Sandra McCurdy, MS, Melinta Therapeutics: Employee
1679. Successful Control of MSSA Bacteremia Outbreak in Neonatal Intensive Care Unit
Authors: Cho Youngmin , Choi Sujin , Jung Young Hwa , Choi Chang Won , Shin Myoung-jin , Park Jeong Su , Song Kyoung-Ho , Kim Eu Suk , Kim Hong Bin , Lee Hyunju
Published: November 2023

Background

Staphylococcus aureus outbreaks in the neonatal intensive care units (NICU) have been reported with the great majority due to methicillin-resistant Staphylococcus aureus. We describe successful control of an outbreak caused by methicillin-susceptible S. aureus (MSSA) in the NICU.

Methods

We report a MSSA bacteremia outbreak which occurred in the NICU at a tertiary level hospital from November 29, 2020 to January 6, 2021. Molecular typing of MSSA isolates were performed including multi-locus sequence typing (ST) and spa typing.

Results

A total of 5 MSSA bacteremia cases occurred in 39 days. Outbreak investigation was initiated after the 5th case. Infection control measures, including isolation of cases, contact precaution and universal 0.5% chlorhexidine bathing of all NICU patients, were implemented. Surveillance cultures of patients (n=36) and health care workers (HCW) (n=60) were performed. Excluding bacteremia patients, 13% (4/31) of neonates and 32% (19/60) of HCW were identified as MSSA nasal carriers and targeted decolonization with intranasal mupirocin was performed. After implementation of control measures and decolonization, there were no new cases. Molecular analysis identified two strains [ST15 spa type t593 (n=3) and ST101 spa type t4171 (n=2)] as the cause of this bacteremia outbreak. Among MSSA nasal carriers, all 4 neonates colonized the ST15 spa t593 strain. ST15 spa t593 strain was also colonized in one HCW, however antibiotic susceptibility pattern differed. The rest of HCWs colonized many different types of MSSA. All MSSA isolates were negative for Panton-Valentine Leucocidin toxin gene.

Conclusion

Molecular analysis identified two different MSSA strains in this outbreak. MSSA colonization was prevalent among HCWs, however molecular analysis showed variance in distribution. Although outbreak strains were not found in HCWs, one strain was colonized among other neonates, suggesting horizontal transmission and potential of further cases. The outbreak was successfully controlled with reinforcement of precautions, universal chlorhexidine bathing and surveillance cultures with targeted decolonization. Early recognition and prompt implementation of control measures are important for outbreak control in NICU.

Disclosures

All Authors: No reported disclosures
1688. Naturally-induced Serum Antibody Levels in Children to Pneumococcal Polysaccharide 15B that Correlate with Protection from Nasopharyngeal Colonization but Anti-serotype 15B Antibody has Low Functional Cross-reactivity with Serotype 15C.
Authors: Kaur Ravinder , Gonzalez Eduardo , Pham Minh , Pichichero Michael
Published: November 2023

Background

Pneumococcal infections caused by non-vaccine serotypes, including serotype 15B and 15C, emerged after the introduction of pneumococcal conjugate vaccines (PCVs). Serotypes 15B and 15C have been added to new different pneumococcal-conjugate vaccines (PCV20 and V116, respectively). We sought to derive a serum anti-15B antibody level that would be a correlate of protection (COP) against acute otitis media (AOM) and nasopharyngeal colonization and assess functional cross-reactivity against serotype 15B and 15C in children following natural immunization.

Methods

Method: IgG antibody to serotype15B polysaccharide was measured by ELISA in 402 sera from 6-36 month olds collected before, at the time of, and after pneumococcal culture-confirmed AOM and colonization caused by serotypes 15B and 15C. 153 serum samples from 6-36 month olds where no colonization with either 15B or 15C was observed were included as controls. A two-step method was used for the construction of COP models: a generalized estimating equation followed by logistic-regression. Opsonophagocytic (OPA) assays were used to assess functional cross-reactivity between serotypes 15B and 15C.

Results

The COP for prevention of colonization was 1.41µg/ml for 15B and 0.63µg/ml for 15C with a predictive probability of 80%. Significantly higher anti-15B antibody levels were measured in children who had AOM caused by serotype 15B compared to control children and compared to children who had AOM caused by serotype 15C (p< 0.03). Consequently, a COP for serotypes 15B and 15C could not be calculated for AOM. ELISA-measured antibody levels did not correlate with OPA titers. Thirty percent of child samples, with varying moderate to high amounts of ELISA-measured antibody, showed no OPA titer against either serotype 15B or 15C. For the remaining samples, very low or no functional cross-reactivity between serotypes 15B and 15C was measured.

Conclusion

Conclusions: A COP for prevention of colonization in young children based on naturally-induced antibody levels was derived for serotype 15B and 15C that differed. A COP for AOM could not be derived. ELISA-measured antibody levels correlated poorly with OPA titers and low functional cross-reactivity between serotypes 15B and 15C in child sera was observed.

Disclosures

All Authors: No reported disclosures
1698. Activity of ceftolozane/tazobactam in vitro against Gram-negative isolates from pediatric patients: SMART 2017-2021
Authors: Mu Xinli , Fu Ying , Li Pengcheng , Yu Yunsong
Published: November 2023

Background

The study aims to evaluate the in vitro activity of ceftolozane/tazobactam (C/T) and other common-used antibiotics against clinical Gram-negative bacterial (GNB) isolates obtained from Chinese pediatric patients using data from The Study for Monitoring Antimicrobial Resistance Trends (SMART).

Methods

From 2017-2021, 554 Gram-negative isolates were collected from 16 pediatric departments across China. GNB isolates from pediatric departments were mainly derived from bloodstream (n = 135), intraperitoneal (n = 129), lower respiratory tract (n = 198) and urinary tract (n = 92) infections (Figure 1). The minimum inhibitory concentrations (MICs) were tested using a Trek Diagnostic System (Thermo Fisher Scientific). Susceptibility was determined by CLSI broth microdilution and interpreted with CLSI M100 (2021) breakpoints.

Results

E. coli (34.30%) and K. pneumoniae (27.62%) were the most common pathogens, followed by P. aeruginosa (15.34%). Susceptibility of species with more than 20 isolates were showed in Table 1. The susceptibility of P. aeruginosa to C/T was 89.41%, which was the highest among beta-lactams and was second only to amikacin. The susceptibilities of E. coli and K. pneumoniae isolates to C/T were 92.63% and 58.17%, respectively. When exclude carbapenem-resistant E. coli and K. pneumoniae, the susceptibility to C/T increased to 96.17% and 86.14%. C/T showed similar activities to E. coli and K. pneumoniae isolated from pediatric patients < 1 year (Table 2). Thirteen P. aeruginosa isolates were collected from patients < 1 year and 13/13 were susceptible to C/T (Table 3).

Conclusion

P. aeruginosa and E. coli obtained from pediatric patients in China showed a high susceptibility to C/T. When excluding carbapenem resistant isolates, C/T also showed good activities against K. pneumoniae.

Disclosures

Pengcheng Li, M.D., MSD China: Employee of MSD China
1712. Reduction of Neonatal Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections After Implementation of a S. aureus Screening and Decolonization Protocol
Authors: Weber Rachel , Wharry Jeananne , Malczynski Michael , Lehman Jennifer , Caldarelli Leslie , Bolon Maureen K
Published: November 2023

Background

Staphylococcus aureus (SA) is an endemic, clinically important organism in Neonatal Intensive Care Units (NICUs). An 86-bed level III NICU at an academic medical center saw an increase in patients with methicillin-susceptible SA (MSSA) bloodstream infections (BSIs) from October-December 2020, as well as a cluster of patients with MSSA skin infections associated with intravenous catheters, which led to the intervention described.

Methods

We created a multidisciplinary team and reviewed infection prevention measures in our NICU, national recommendations and published literature. Previous state, NICU patients were screened for methicillin-resistant SA (MRSA) on day of life 7 or upon admission from an outside hospital or home. On 11/1/2021, we implemented weekly screening cultures for MRSA and MSSA among all NICU patients, performed using a composite swab of the bilateral anterior nares, axilla, peri-umbilical area, and perianal area. Decolonization of SA-colonized patients was performed with mupirocin (MUP) and chlorhexidine gluconate (CHG) bathing. MUP was applied to nares twice per day for 5 days for all colonized patients and 5 days of CHG bathing was administered only to patients greater than 48 weeks postmenstrual age. Patients were decolonized up to 2 times. Incidence rates (IR) and incidence rate ratios (IRR) were calculated.

Results

Between 11/1/2021 – 1/30/23, 1186 unique patients were screened with 177 unique patients colonized with MSSA and 9 unique patients colonized with MRSA. Of those colonized with MSSA, 126 (71.2%) patients were treated, with 123/126 treated with MUP only and 3/126 treated with MUP and CHG. Table 1 describes SA outcomes in the 15 month pre- and post-intervention periods. In the post-intervention period we observed a 73% decrease in MSSA BSIs (IRR, 0.27, 95% CI (0.05, 1.03)).

Conclusion

Implementation of a SA screening and decolonization protocol in our NICU resulted in a statistically non-significant decrease in MSSA BSIs. Future work will seek to identify risk factors for colonization, factors associated with successful decolonization and genomic sequencing of MSSA isolates to characterize the spread of MSSA among neonates.

Disclosures

All Authors: No reported disclosures
1720. Immunogenicity of COVID-19 Vaccines in Youth with Inflammatory Bowel Disease
Authors: Cirks Blake T , Parsons Emily , Samuels Emily , Laing Eric D , Rajnik Michael , Malloy Allison M
Published: November 2023

Background

Youth with special healthcare needs or on immunosuppression are at increased risk for severe COVID-19, yet evaluation of the immunogenicity of SARS-CoV-2 vaccines in this population has been limited. A quarter of individuals with inflammatory bowel disease (IBD) are diagnosed in childhood and require chronic immunosuppressive therapy. Describing the quality and duration of the humoral and cellular responses to novel mRNA vaccines in this population can improve implementation and protection for this vulnerable population.

Methods

This ongoing single-center, prospective, longitudinal cohort study enrolled children aged 6–21 years at-risk for severe COVID-19 beginning in January 2023. On enrollment and at pre-specified times after vaccination peripheral blood samples, epidemiologic and clinical data were obtained. Total SARS-CoV-2 spike (S) and receptor binding domain (RBD)-specific IgG antibodies, as well as endemic coronavirus (eCoV) antibodies, were measured using a multiplex microsphere immunoassay. SARS-CoV-2 specific T cell responses were measured with intracellular cytokine staining (ICS) after peptide stimulation.

Results

11 SARS-CoV-2-immunized children with IBD treated with anti-tumor necrosis factor (TNFα) therapy were enrolled (Table 1). The seroconversion rate was 100% (Figure 1). Anti-S IgG levels increased with more exposures (r =.81 p =.003) and decreased over time with a negative correlation between anti-S IgG and days since last exposure (r = -.691 p =.02), as well as a significant difference in anti-S IgG when grouped by time since last exposure (p =.02) (Figure 2). ECoV antibody levels did not significantly correlate with anti-S IgG. 63% and 81% of participants developed SARS-CoV-2 specific CD4+ and CD8+ T cell responses, respectively, though response magnitude was low (Figure 1). A majority of participants demonstrated measurable antibody (100%) and T cell (90%) responses > 12 months after their last vaccination.

Table 1

Demographics of Enrolled Research Subjects

Figure 1

Cohort Humoral and Cellular Responses. Antibody levels (left) of SARS-CoV-2 wild type plus Delta and Omicron variants in BAU/mL. ECoV antibody levels in U/mL. T cell response (right) evaluated by frequency of CD4+ and CD8+ IFN-γ+ T cells following stimulation with wild type SARS-CoV-2 S, N, M peptides.

Figure 2

Humoral Immune Durability and Response. Significant correlation between SARS-CoV-2 S IgG and days since last exposure (left) and SARS-CoV-2 S IgG and number of exposures (right). Exposure = vaccination or infection. Shaded region 95% CI, n=11.

Conclusion

Our small, ongoing cohort study demonstrates both SARS-CoV-2 antibody and T cell responses can develop following vaccination in children with IBD on anti-TNFα therapy. While the humoral response decreased over time, a durable cellular response persisted at 12 months in most participants.

Disclosures

All Authors: No reported disclosures
1722. Impact of Universal Conjugate Pneumococcal Vaccination in Infants on the Incidence and Mortality of Pneumococcal Meningitis in the General Population in Uruguay, South America (2005 – 2022).
Authors: Delfino Marcos , Ferrer Monica Pujadas , Pírez María Catalina
Published: November 2023

Background

Universal vaccination of children with conjugate vaccines was introduced using the 7 – valent pneumococcal conjugate vaccine (PCV7), which was changed to PCV13 (2 + 1 schedule, years 2008 to 2010), with nationwide coverage of 95 %.

The objective of this study is to analyze the impact of universal children vaccination with PCV7 and PCV13 on the incidence and mortality of pneumococcal meningitis (PM) in the general population in Uruguay.

Methods

This is a descriptive, retrospective study that includes all cases (children and adults) reported to the Department of Health Surveillance of the Ministry of Public Health with a diagnosis of PM between January 1, 2005, and December 31, 2022. Variables: cases per year, sex, age (≤ 15 years and > 15 years), identified serotype, and deaths by year. The average rates of cases per 100,000 inhabitants are described in two periods: Period 1 or pre – universal vaccination (P1) from 2005 to 2007 and Period 2 or post – universal vaccination (P2) from 2011 to 2022, with their respective confidence intervals. Statistical analysis were established based on frequency distribution and statistical significance tests as appropriate, considering a value of p equal to or less than 0.05 as statistically significant. The research was approved by the institutional Ethics Committee.

Results

The total number of cases (N) is 555, 56.5% are men. 102 cases from the vaccine introduction period (2008 to 2010) were excluded. The N for P1 is 149 (3 years), while for P2 it is 304 (12 years).

The main results of incidence and mortality are shown in Table 1 and in the attached graphs. Lethality remains high (26.5% average for the total period).

The vaccine serotypes (VS) decrease from 28.2% (95% CI: 20 to 35) in P1 to 12.2% (95% CI: 8.4 to 15) in P2, p: 0.00006. The non – VS increase from 18.1% (95% CI: 11 to 24) in P1 to 44.7% (95% CI: 39.1 to 50.3) in P2, p: 0.00000001.

The predominant VS in P1 is 14 (26.2%, 95% CI: 13-39); in P2 there are 8.1%, 95% CI: 0.7-16.9), p: 0.071. The predominant VS in P2 is 3 (46%, 95% CI: 30-62); in P1 9.5% (95% CI: 0.6-18), p: 0.0003.

The non – VS predominant in both periods is 12F.

Evolution of incidence rates of PM in the general population and in people under and over 15 years of age as a function of time (in years).

Mortality rates

Conclusion

The incidence and mortality of PM statistically decreased in children under 15 years old and in the general population, which can be attributed to herd immunity.

Disclosures

Marcos Delfino, Pediatrician, Pediatric Infectious Diseases, Pfizer: Finna María Catalina Pírez, Pediatrician, Pediatric infectologist, microbiologist Professor of pediatric, Degree V, Merck, Pfizer: Expert Testimony|Merck, Pfizer: Honoraria
1759. Maintaining Latin America Polio-Free: A Multidimensional Analysis of Polio Outbreak Risk in Argentina in the Period 2020-2022
Authors: Grisolia Veronica Lucconi , Barrios Rocio Nahir , Olavarría Janisse Requena , Cañete Juan León , Aranda María Jimena , Katz Nathalia , Elbert Raquel Gabriela , Neyro Silvina , Urruti Maria Eugenia , López María Victoria , Selent Carolina , Bertachini Octavia , De Prada Ana Martina , Rapaport Solana , Hernández Adriana Verónica , Pereira Andrés Martín , Bruggesser Florencia
Published: November 2023

Background

Argentina has eliminated the circulation of poliovirus (PV) in 1984, and from 2020 onward only inactivated vaccines (IPV) are included in its national immunization schedule (NIS) which consist of three doses and a booster. The persistence of PV in some countries and the regional use of attenuated vaccines allow for the risk of reintroduction of these viruses. Such risk can be estimated for each population based on the susceptibility to infection, the capabilities to identify an event and prevent its spread. Our main objective was to analyze the PV outbreak risk in Argentina since the exclusive use of IPV.

Methods

Descriptive study. We used the PV outbreak risk analysis model provided by the Regional Certification Commission for the Polio Endgame in the Region of the Americas (RCC). The data of the period 2020-2022 available in the records of the Ministry of Health of the Nation were synthesized. It includes the following dimensions: polio vaccination coverage, epidemiological surveillance, social determinants of health and the occurrence of other vaccine-preventable diseases.

Results

We analyzed the PV outbreak risk in the 512 departments of the country in 2020, 2021 and 2022. For each year, respectively, 83% (n: 425), 86.3% (n: 442) and 94.1% (n: 482) of the departments had high and very high risk. In these departments, the dimension of polio vaccination coverage contributed predominantly to the risk, with an average of 52.6% (SD: 8.9); 57.9% (SD: 7.9); 58.1% (SD: 8.6) in each series. In regards to the coverage in the last 5 years, with the third dose of IPV, 73.4%, 61.3% and 60.8% of the departments reached the average expected. In respect of the coverage with the second dose of IPV, only 26.6%, 16.7% and 29.5% reached as expected for each year. During the vaccination campaign 26.3% of the departments achieved the coverage expected.

Conclusion

Though the exclusive use of IPV in the NIS has represented a big step for Argentina, the multidimensional risk analysis shows a high PV outbreak risk, similar to that described for other Latin American countries. This is an essential tool in the making of national polio elimination programs. We must continue working in order to meet polio vaccination coverage goals and keep the population disease-free.

Disclosures

All Authors: No reported disclosures
1779. Trends in Anaplasmosis Over the Past Decade: A Review of Clinical Features, Laboratory Data and Outcomes
Authors: Katragadda Silpita , Yetmar Zachary A , Chesdachai Supavit , Ranganath Nischal , Wilcock Jonathan , Saleh Omar M Abu , Challener Douglas
Published: November 2023

Background

Human granulocytic anaplasmosis (HGA) is an emerging tick-borne illness endemic to the northeastern and midwestern United States. Risk factors for the severity of infection, predictors for hospitalization, temporal trends, co-infections, and outcomes are poorly studied.

Methods

We conducted a retrospective review of HGA at Mayo Clinic, Rochester, between 2011-2021. Cases were identified by positive Anaplasma PCR at our reference laboratory. Variables included patients’ characteristics, symptoms, risk factors for tick-borne illness, laboratory parameters, co-infections, treatment, and clinical outcomes.

Results

We identified 471 cases with a positive Anaplasma PCR, and 146 cases were included in this interim analysis. Table 1 shows a summary of the baseline characteristics. An increasing annual trend in diagnosis of HGA was noted from 2014 to 2016 with lower rates observed during COVID-19 pandemic (2020 to 2022) (Figure 1). Of the 146 patients, 19 (13%) were immunocompromised secondary to hematologic malignancies, solid organ malignancies, and pharmacological immunosuppression. Frequently reported symptoms included fever (79.5%), malaise (68.5%), chills (51.4%), and myalgia (50%). Tick exposure was documented in 79.2 % of cases. Forty-seven (33%) patients were hospitalized; older patients were more likely to be hospitalized (Table 2). The most common complications among the hospitalized patients included respiratory failure (50%), encephalopathy (44.4%) and renal failure (37.5%). One patient required ICU admission. Twenty-five patients (17.5%) and one patient (0.7%) were co-infected with Lyme and Ehrlichiosis, respectively. Higher rates of leukopenia and thrombocytopenia were associated with mono-infection with Anaplasma (p < 0.001). Follow up data was available for 136 patients; all of them had favorable response to doxycycline.Table 1:Summary of baseline characteristics, labs and treatment.Table 2:Predictors of HospitalizationFigure 1:Annual Trends in Anaplasmosis from 2011-2021.

Conclusion

Our study demonstrated comprehensive clinical characteristics of patients with HGA. Interestingly, tick exposure history was common, yet most patients did not have other tick-borne co-infections. Furthermore, only a minority of patients developed severe diseases and required hospitalization. The recent decline in cases during the early part of the COVID-19 pandemic is worth further investigation.

Disclosures

All Authors: No reported disclosures
2884. Incidence of Invasive Fungal Infections After Pancreas Transplantation
Authors: Nair Vaisak , Yetmar Zachary A , Seville Maria T , Bosch Wendelyn , Beam Elena
Published: November 2023

Background

There is scarce data surrounding the epidemiology of invasive fungal infections (IFI) after pancreas transplantation (PT). Our centers’ PT protocols recommend universal fluconazole prophylaxis for at least 1 month, which is extended to 1 year for recipients who live in Coccidioides endemic areas. The purpose of our study was to evaluate the epidemiology of IFIs after PT while on our antifungal prophylaxis protocol.

Methods

A retrospective cohort study was performed among adult patients who underwent PT at Mayo Clinic sites in Arizona, Florida, or Minnesota between January 1, 2010 and December 31, 2020. IFI was defined based on EORTC/MSGERC criteria. The primary aim was to describe epidemiology and timing of IFI after PT, particularly in the context of the universal antifungal prophylaxis protocol.

Results

Among 482 pancreas transplant recipients, 35 developed IFIs (7.3%). All patients received antifungal prophylaxis per protocol for a median duration of 33 days (Figure 1). Median duration from time of transplant to IFI was 16 (IQR 10.5-28.2) days for Candida IFIs versus 529 (IQR 192.5-1195.0) days for non-Candida IFI. 20 IFIs (57.1%) were secondary to Candida species with 45% of these cases caused by either C. glabrata or C. krusei (Figure 2). 90% were on antifungal prophylaxis (85% fluconazole) at time of diagnosis of invasive candidiasis. All the Candida IFIs were intra-abdominal infections. Amongst the 15 non-Candida IFIs (42.9%), 9 were secondary to endemic mycoses and 4 were secondary to invasive molds.

Conclusion

Our study shows a high incidence of IFIs secondary to Candida, with few patients diagnosed with non-Candida IFIs (Figure 3). Non-Candida IFIs, mostly secondary to endemic mycoses, occurred more than a year after transplant. Patients are at highest risk for Candida IFIs within the first 30 days after PT, likely secondary to organ space surgical site infections, despite receipt of antifungal prophylaxis. Breakthrough invasive candidiasis occurred in 90% of cases. Though our study lacked a comparator group without prophylaxis, these data question the effectiveness of fluconazole prophylaxis after PT.

Disclosures

All Authors: No reported disclosures
1783. Acute Kidney Injury Associations with Antibiotics: A Pharmacovigilance Study of the US FDA Adverse Event Reporting System
Authors: Kochuparambil Jose J , Raju Jomel
Published: November 2023

Background

Antibiotic-associated acute kidney injury is found to be associated with many antibiotics like vancomycin, fluoroquinolones, penicillin combinations, and trimethoprim–sulfamethoxazole. Other antibiotics may also lead to acute kidney injury. Still, no study has systemically compared the cases of acute kidney injury reported to the US FDA Adverse Event Reporting System (FAERS) with the many available antibiotics. Therefore, the study aimed to evaluate the reporting associations between acute kidney injury and different classes of antibiotics through the analysis of the US FDA Adverse Event Reporting System (FAERS).

Methods

FAERS reports from 1 January 2015 to 31 December 2022 were included in the study. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify AKI cases. Reporting odds ratios (RORs) and corresponding 95% confidence intervals (CIs) for the reporting associations between antibiotics and AKI were calculated. A reporting association was considered statistically significant when the lower limit of the 95% CI was > 1.0.

Results

A total of 2,042,801 reports (including 20,138 AKI reports) were considered. Colistin had the greatest proportion of acute kidney injury reports, representing 25% of all colistin reports. acute kidney injury RORs (95% CI) for antibiotics were, in descending order: colistin 33.10 (21.24–51.56), aminoglycosides 17.41 (14.49–20.90), vancomycin 15.28 (13.82–16.90), trimethoprim–sulfamethoxazole 13.72 (11.94–15.76), penicillin combinations 7.95 (7.09–8.91), clindamycin 6.46 (5.18–8.04), cephalosporins 6.07 (5.23–7.05), daptomycin 6.07 (4.61–7.99), macrolides 3.60 (3.04–4.26), linezolid 3.48 (2.54–4.77), carbapenems 3.31 (2.58–4.25), metronidazole 2.55 (1.94–3.36), tetracyclines 1.73 (1.26–2.36), and fluoroquinolones 1.71 (1.49–1.97).

Conclusion

This study found 14 classes of antibiotics having significant reporting associations with AKI. Among the antibiotics evaluated in this study, colistin had the highest acute kidney injury ROR and moxifloxacin had the lowest.

Disclosures

All Authors: No reported disclosures
1798. Vaccine Ambassadors: An Educational Model to Spread Awareness About Vaccines in Detroit
Authors: Schmidt Jennifer , Howson Sofia , Maples Catherine , McConnell Jack , Desai Soham , Chopra Teena , Seeger Matthew
Published: November 2023

Background

Since the COVID-19 pandemic, national vaccination rates show a dangerous decline with Detroit being amongst the lowest with only 41.3% of adolescents completing the vaccine series. The Vaccine Ambassador program was created to mitigate the decline in vaccination rates through the education and empowerment of youth via train-the-trainer model of education.

Methods

The program was implemented with eleven high school students who received education on the history and mechanism of vaccines, herd immunity, and how to effectively communicate. The program was created in collaboration with physicians in Infectious Diseases and a professor of communication at Wayne State University.

Ambassadors aimed to spread this knowledge to youth in Detroit communities through outreach events. The impact of the program was measured through a two-pronged approach—through a pre- and post-survey given to the Vaccine Ambassadors and through a pre- and post-test given to the youth at the events. The survey for the Ambassadors included thirty-one items that measured their knowledge about vaccines and immunity and were evaluated through a 5-point Likert scale from 1 (strongly disagree) to 5 (strongly agree). The test for the youth at the outreach events included seven items that tested knowledge about vaccines.

Results

The following prompt is an example from the survey given to the ambassadors: Inactive vaccines create a better immune response than live vaccines. Compared to the pre-survey, six participants (54.5%) indicated a less agreeable response. With regards to the youth outreach events, twenty-five youth participated in the pre- and post-test, and nineteen youth (76.0%) improved their score after the presentation. Post-test scores improved across all seven questions (Figure 1).

Comparison of Pre and Post Test Responses During Outreach Events

Representation of the percent correct questions before and after the Vaccine Ambassador presentation

Conclusion

Based on both pre-test responses, it is apparent that Detroit’s youth lack knowledge regarding vaccines. The Vaccine Ambassador program increased the ambassador’s depth of knowledge and reaffirmed their positive attitudes about vaccines. Not only are youth able to learn, but they are able to apply their knowledge and teach others. By teaching their peers, youth can make informed decisions when older and enact behavioral changes that promote healthier living.

Disclosures

All Authors: No reported disclosures
1837. Evaluation of Disparities in Beta-Lactam Allergies and Subsequent Antibiotic Use in Outpatients with Acute Bacterial Skin and Skin Structure Infections
Authors: Hall Ronald G , Shaw Chip , Cole Travis , Alvarez Carlos
Published: November 2023

Background

Black patients with skin and soft tissue infections are more likely to have a documented penicillin allergy and use of non-beta-lactams than white patients. We sought to compare the prevalence and risk factors for documented beta-lactam allergy (D-BLA) among racial and ethnic minorities (REM) and white patients and beta-lactam (BL) use for outpatient Acute Bacterial Skin and Skin Structure Infections (ABSSSIs).

Methods

We conducted a cohort study of adult outpatients (18-90 years) seen by the Texas Tech University Health Science Center Physicians group (2012-2021). All patients had an ICD-9 or ICD-10 code for an ABSSSI in the primary or secondary position. Descriptive statistics were reported. Logistic regression models were used to determine which factors were statistically associated with D-BLA and which factors were associated with BL use for the ABSSSI. Multivariable (MV) analysis results were reported as odds ratios (OR) and 95% confidence intervals (95%CI). All analyses were conducted in R.

Results

REM represented 38% of the 21,673 patients in the cohort. A D-BLA was present for 18% percent of all patients and was higher in white patients than REM (22 vs 13%). Factors associated with D-BLA on MV analysis of the total cohort were age (OR 1.01 per year, 95%CI 1.01-1.01), Medicaid (OR 1.18, 95%CI 1.04-1.34), or Medicare (OR 1.17, 95%CI 1.05-1.31). Factors associated with a lower likelihood of D-BLA on MV analysis of the entire cohort were REM (OR 0.55, 95%CI 0.51-0.60) and male sex (OR 0.56, 95%CI 0.52-0.60). Regarding BL use, white patients were less likely to receive a BL than REM (26 vs 30%). Factors associated with a reduced likelihood of BL use on MV analysis of the total cohort were D-BLA (OR 0.60, 95%CI, 0.54-0.67), Medicaid (OR 0.83, 95%CI 0.74-0.93), or Medicare (OR 0.64, 95%CI 0.58-0.70). Factors associated with BL use on MV analysis of the entire cohort were REM (OR 1.20, 95%CI 1.12-1.28), male sex (OR 1.45, 95%CI 1.36-1.54), or self-pay (OR 1.52, 95%CI 1.37-1.68). The interaction term between REM and D-BLA was not significant for BL use.

Conclusion

REM were at a reduced risk of a D-BLA in our cohort and were more likely to receive a BL for ABSSSIs. Payor status and sex also significantly impacted rates of D-BLA and BL use.

Disclosures

Ronald G. Hall, II, PharmD, MSCS, Merck: Grant/Research Support Carlos Alvarez, PharmD, MSc, MSCS, Boehringer Ingelheim: Grant/Research Support|Bristol Myer Squibb: Grant/Research Support|Merck: Grant/Research Support