bluuebunny/crossref_metadata_2025 huggingface dataset:
P-1419. Vaccine failure of the live-attenuated vaccine after liver transplantation depends on the vaccine strain
Authors: Furuichi Munehiro , Ohnishi Takuma , Yaginuma Mizuki , Yamada Yohei , Hoshino Ken , Nakayama Tetsuo , Shinjoh Masayoshi
Published: January 2025

Background

A recent conditional recommendation suggests considering live-attenuated vaccines for solid organ transplant recipients, yet the conditions of their safe and effective administration remain unclear.

Primary vaccine failures after the first dose of live-attenuated vaccines (measles, rubella, and mumps) were significantly different between the vaccine strains.

Methods

This prospective study, conducted at Keio University Hospital from 2002 to August 2023, gave live-attenuated vaccines to liver transplant (LT) recipients fulfilling the criteria for live-attenuated vaccines, including humoral and cell-mediated immunity. Patient background information, immunization date, vaccine strain, immunosuppressive agents at the time of vaccination, and antibody titers were collected. Factors related to primary and secondary vaccine failure were evaluated to enhance the effectiveness of the live-attenuated vaccine program after LT.

Kaplan–Meier curves for the proportion of remaining positive antibody titer after the first dose of indicated live-attenuated vaccine for post-liver transplant recipients.

Results

Among 67 LT recipients, 54, 55, 47, or 55 received at least one dose of live-attenuated vaccine for measles, rubella, varicella, or mumps, respectively. Measles vaccine with the AIK-C strain exhibited significantly lower primary failure rates than the CAM-70 strain (1/38 vs. 4/16, odds ratio: 0.08, 95% confidence interval [CI]: 0.01–0.80, p = 0.02) (Table 1). No primary failures were observed with the TO-336 strain of rubella, whereas 4 of 10 LT recipients with the Matsuura strain of rubella did not seroconvert. For mumps, the Hoshino strain showed lower primary failure rates than the Torii strain (15/52 vs. 3/3, p = 0.03). Among seroconverted LT recipients after the first dose of live-attenuated vaccine, the proportion of remaining positive antibody titer is shown by Kaplan–Meier curves (Figure 1). In the years following the first doses of measles, varicella, and mumps vaccines, the proportion of remaining positive antibody titers decreased gradually. Furthermore, the AIK-C strain exhibited a significantly lower risk of secondary vaccine failure compared to the CAM-70 strain (hazard ratio: 0.29, 95% CI: 0.12–0.72, p = 0.01) (Figure 2).

Kaplan–Meier curves for the proportion of remaining positive antibody titer after the first dose of measles vaccine for post-liver transplant recipients with Log-rank test for the vaccine strains.

Conclusion

Vaccine strains are the most critical factor influencing primary and secondary vaccine failure in post-transplant live-attenuated vaccination.

Disclosures

Masayoshi Shinjoh, MD, PhD, Meiji Seika Pharma Co., Ltd: Honoraria|Mitsubishi Tanabe Pharma Corporation: Honoraria|MSD K.K.: Honoraria|Pfizer Japan Inc: Advisor/Consultant|Shionogi & Co., Ltd: Honoraria
P-1441. Demographic and Clinical Characteristics of New Migrant Patients with HIV in a New York City Open Access HIV Primary Care Clinic
Authors: Parkinson Melissa , Saylor Maureen , Villarreal Jason , Chaudhuri Shaoli , Gunaratne Shauna , Olender Susan
Published: January 2025

Background

Since 2022, New York City has seen an influx of migrants, many seeking asylum due to political strife or discrimination. This study assessed the clinical characteristics of new migrant patients with HIV who sought care at an academic, open access clinic.

Methods

This is a retrospective chart review study of new clinic patients January 2022–March 2023. Patients were included in the study if they were ≥18 years of age, living with HIV, and had migrated to the United States within one year of first clinic visit.

Results

From January 2022 through March 2023, we identified 58 patients who met study criteria. 53 patients (91.4%) identified as male, and the mean age was 33 years (SD 8.8), see Table 1. Most patients were from South America, with just over half from Venezuela alone. 48.3% of patients were walk-ins and 43.1% were connected through an open access line, with a majority referred from community-based organizations. 37 patients (63.8%) were on ART (antiretroviral therapy) at first visit, see Table 2. 67% of patients had an HIV viral load of 200 copies/ml or less. 29.8% of patients had a reactive RPR (rapid plasma reagin) consistent with a current diagnosis of syphilis. 11.8% of patients screened had a positive IGRA (interferon gamma release assay), none with active tuberculosis. 17.9% and 10% of eligible patients were screened for Strongyloides and Schistosoma antibodies, respectively. Only 4 of 56 eligible patients received empiric treatment for helminthic infection. 46.6% of patients reported history of STI (sexually transmitted infection), see Table 3. Nearly all patients (93.1%) were linked to a care coordinator prior to or at first visit. 25 patients were identified as having a possible mental health disorder or history of trauma, and 44% were seen by a licensed social worker same day, see Figure 1.

Conclusion

Most new migrant patients were from South America, identified as male, and had suppressed HIV. There were missed opportunities to screen for and treat helminthic infections. There was a high burden of STIs and mental health disorders. Many patients utilized our open access line or walked into clinic and nearly all were connected to a care coordinator at or prior to first visit. Continued research is needed to better understand the needs of this vulnerable and growing patient population.

Disclosures

All Authors: No reported disclosures
P-1444. Impacts of LGBT Equality Index and 2016 UN Resolution Vote on AIDS-Related Mortality
Authors: Modi Neil , Ikuta Kevin
Published: January 2025

Background

Stigma surrounding HIV has been well-described as a barrier to HIV care engagement. Much of this arises from a belief that only certain groups of people can get HIV as well as public opinion and government policies toward LGBT people. Recognizing the effects of discriminatory laws against individuals based on sexual orientation and gender identity, the United Nations Human Rights Council adopted resolution A/HRC/RES/32/2 in 2016, deploring acts of violence and discrimination based on these traits. Our study had two aims: first, to assess if a country’s AIDS-related mortality differed based on how the country voted on the 2016 resolution and, second, to describe whether greater legal protection of LGBT rights was associated with reduced AIDS-related mortality.

Methods

We used HIV prevalence and mortality estimates in men aged 15-49 from the Global Burden of Disease 2019 to determine the case fatality rate for men aged 15-49 living with HIV by country. To estimate the legal protection of LGBT rights, we utilized the Equaldex Equality Index, a publicly available rating from 0 to 100 describing LGBT legal protections and public opinion by country, with higher values reflecting greater equality. We then performed multivariate log-linear regression to describe the relationship between a country’s AIDS-related mortality among men 15-49 and that country’s Equality Index and vote on the 2016 resolution, adjusted for WHO region.

Results

AIDS-related fatality rate was available for 204 countries/territories, an Equality Index was available for 196 countries, and 47 countries voted. In the countries that voted in favor, there was a 65% (95% CI 43-79%, p< .001) relative risk reduction in AIDS-related fatality rate. When adjusted for WHO region, the relative risk reduction was 72% (95% CI 35-88%, p< .06). Assessing the impact of the Equality Index, multivariate log-linear analysis adjusting for region showed that for every 1 point increase there was a 1.6% (CI 1.2-2.0%, p< 0.001) relative risk reduction in AIDS-related fatality rate.

Conclusion

The results of this study support the hypothesis that increasing LGBT legal protection can improve HIV care engagement. It also highlights the significant impact public opinion and government policies toward LGBT people has on AIDS-related mortality.

Disclosures

All Authors: No reported disclosures
P-1448. Targeting Smoking Among People with HIV (PWH): Does Intensive Group Therapy Reduce Mortality?
Authors: Goyal Rohan , Kahan Abner A , Shuter Jonathan
Published: January 2025

Background

PWH in the United States smoke cigarettes at rates 2-3 times higher than the general population. Between 2014 and 2017 we conducted a randomized controlled trial (RCT) comparing Positively Smoke Free (PSF), an 8-session intensive group therapy intervention targeting HIV+ smokers, to brief advice to quit. Findings suggested that PSF conditioned participants had higher quit rates at both early and late (approximately 3-year) follow-up. In the present study, we sought to determine whether PSF conditioned participants had a significant difference in mortality compared to controls 7-10 years after study enrollment.Table 1.Baseline Characteristics of Study Participants.

Methods

Participants of the Bronx cohort of the original RCT (n=247) were chart reviewed for vital status. Participants were classified as “alive” if review indicated contact with the patient within six months of review. If no records were available within the prior six months, an attempt was made to contact the patient, pharmacy, or emergency contact as listed either in the medical chart or original study records. Dates of death were recorded for deceased participants. Data were analyzed using R 4.4.0. All identifying patient information was secured in a password-protected spreadsheet only accessible to study authors.Figure 1.Vital Status of Study Participants.

Results

There were no significant differences in baseline characteristics between treatment and control groups (Table 1). 14.2% of all participants were confirmed deceased at the time of data collection; vital status of 25.5% of participants could not be determined (Figure 1). Kaplan-Meier analysis was performed (Figure 2); log-rank test was significant for survival difference favoring the PSF vs control group (p = 0.03). Univariate Cox-proportional analysis showed a hazards ratio of 0.46 (0.23 - 0.94, p = 0.034).Figure 2.Kaplan-Meier Survival Analysis.

Conclusion

Follow-up analysis of Bronx participants in the original RCT suggests that there is a significant mortality benefit over 7-10 years for HIV+ smokers who received PSF intensive group therapy.

Disclosures

All Authors: No reported disclosures
P-1450. Impact of Multi-morbidities on Quality of Life Among People Living with HIV at a tertiary care center in India: A cross-sectional study
Authors: Ramachandran Sai Prasad , Manam Abhigna
Published: January 2025

Background

India is home to an estimated 2.4 million People Living with HIV (PLHIV). The term "multi-morbidity" refers to the simultaneous presence of 2 or more chronic medical conditions in an individual, the prevalence of which is rising. The aim of our study is to assess the impact of multi-morbidities on Quality of Life (QoL) in PLHIV attending the Antiretroviral Therapy (ART) center at a tertiary care hospital in Western Maharashtra, India.

Methods

This was a cross-sectional study, over 2 months with 285 patients recruited. After ethical clearance was obtained, patients were interviewed to gather comprehensive sociodemographic history, with information on treatment and comorbidities obtained from patient charts. The QoL was measured using the WHOQOL-HIV BREF questionnaire which evaluates QoL across six domains: Physical, Psychological, Independence, Social, Environment, and Spiritual.

Results

The cohort exhibited an average of 2.2 comorbidities (SD = 1.4), with a notable prevalence of cardiovascular diseases and diabetes. Participants with 3 or more comorbidities demonstrated significantly lower QoL scores in the Physical (mean = 10.4, SD = 1.8, p < 0.01) and Psychological (mean = 11.9, SD = 1.5, p < 0.05) domains compared to those with fewer comorbidities. A longer duration of ART correlated positively with higher scores in the Independence domain (r = 0.26, p < 0.05). Elevated CD4 counts were linked with improvements in the Environmental and Psychological health domains. (p < 0.05) Participants from higher socioeconomic backgrounds reported significantly better scores in the Environmental and Spiritual domains (p < 0.05). Younger patients (< 40 years) reported better Social and Spiritual QoL scores compared to older individuals Gender-specific analysis indicated that females reported higher scores in the Social and Environmental domains. (p < 0.01).

Conclusion

There is a pressing need for effective management strategies that encompass comprehensive care approaches to address the complex health needs of this population. Enhancing routine screening for comorbidities and educating patients about the implications of multi-morbidities can empower PLHIV to improve QoL.

Disclosures

All Authors: No reported disclosures
P-1452. Exploration of Associations Between Social Determinants of Health and Treatment Failure in People with HIV
Authors: Gudipati Smitha , Warzocha Victoria , Brar Indira , Baxa Dwayne , Homayouni Ramin , Markowitz Norman
Published: January 2025

Background

Addressing Social Determinants of Health (SDOH) and health disparities is at the core of “Ending the HIV Epidemic.” To address SDOH, there is a funded HIV Care Coordination Program (CCP) at Henry Ford Health (HFH), with support to surmount SDOH in people with HIV (PWH). In this pilot study, we explore associations between SDOH and treatment failure (TF) in this program.

Methods

A retrospective study was conducted on PWH in our CCP at HFH from 2022 to 2023. Variables were extracted from data monitoring. CCP enrollment required referral by HIV providers. PWH were surveyed on SDOH related to ART challenges, and these SDOH were assessed throughout the course of one year. HIV genotypes were obtained upon enrollment, and HIV-1 viral load (VL) was collected every 3 months for one year. Significant differences between PWH with or without TF (defined as VL > 200 copies/mL at 1 year) were determined using Chi-Square test for categorical variables and Kruskal-Wallis for continuous variables. Multivariable logistic regression was used to find associations between independent variables and TF.

Results

A total of 144 PWH were included in this study and divided into with (n=26) and without (n=118) TF (Table 1). There were no statistically significant differences in age, gender, risk factors and mean years living with HIV between the two groups. TF PWH had significantly lower incidence of insurance issues and need for financial assistance. Using linear regression analysis while adjusting for age, race, gender, genotype and other SDOH factors, there was no significant association between insurance issues or financial assistance. Although drug resistant mutations (DRMs) were not linked to specific demographics or SDOH, TF PWH had a significantly higher number of DRMs at baseline (p< 0.0176, OR 3.45, 95% CI 1.24-9.60) and a trend towards increased low frequency (< 10%) DRMs.

Conclusion

TF occurred in 18% of PWH with adverse SDOH at enrollment into CCP. While we were unable to identify an association of specific SDOH with TF, the TF rate was elevated in these PWH. Overcoming SDOH is essential to achieve viral suppression. DRMs at CCP entry were significantly associated with TF, and were present in all those with TF. Our study is ongoing, and with larger numbers, we aim to assess the impact of SDOH in TF PWH in future studies.

Disclosures

Indira Brar, MD, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|Merck: Grant/Research Support|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Honoraria
P-1453. Disparities in PrEP utilization
Authors: Soomro Ayesha
Published: January 2025

Background

In October 2023, the CDC released data regarding PrEP uptake in the United States. The data indicated that in 2022, for the first time, more than one-third of individuals who could benefit from PrEP had been prescribed it. While this advancement is certainly significant, as PrEP coverage is one of the cornerstones in ending the HIV epidemic, the report also highlighted substantial disparities.

According to the report, while 94% of White individuals who could benefit from PrEP had been prescribed it, only 13% of Black and 24% of Hispanic/Latino individuals who could benefit had received prescriptions for PrEP. Another notable disparity was observed regarding sex at birth, with 40% of males who could benefit from PrEP being prescribed it, compared to only 15% of females.

Methods

We aimed to determine if such a magnitude of disparity existed within our patient population receiving care at the infectious disease clinic. We identified 99 patients who had been prescribed PrEP at the ID clinic. These individuals were categorized based on their self-identified race/ethnicity and sex assigned at birth.

Results

Of the 99 individuals prescribed PrEP, 86 were males, while only 13 were females. Regarding race/ethnicity, there were 65 White or Caucasian patients, 24 Black or African American patients, 5 Hispanic or Latino patients, and 5 others.

Conclusion

Compared to national data published by the CDC, our data shows similar disparities. While the PrEP-to-need ratio would be a better indicator of the true disparity, our data still highlights the trend in racial and sex-based differences among users of PrEP prescriptions.

Disclosures

All Authors: No reported disclosures
P-1462. Utilization of a Point-of-Care Hepatitis C Test to Treat in People Experiencing Homelessness with Street Medicine Outreach
Authors: Mann Yasmeen , Ogbenna Ugonna K , Ishak Angela , Kasmikha Lauren , Numi Mariia , Iyer Hari , Rehman Sheema , Kadouh Ali , Mangal Ruchi , Qasawa Austin , Dehghani Ali , Hasso Muneer , Henry Joanna , Santana-Garcés Maria , Rehman Najibah K , Bryce Richard , Zervos Marcus , Joshi Seema
Published: January 2025

Background

Persons experiencing homelessness (PEH) have disproportionately higher rates of untreated chronic hepatitis C virus (HCV) than the public. Improved community funding and resources are needed to expand HCV rapid point-of-care (POC), confirmatory testing, treatment and follow-up. Given that PEH face competing priorities (unstable housing, food access, addiction, other infections), it is our role as clinicians to reduce barriers to HCV treatment, understand hesitancies for deferring treatment, and design programs to improve accessibility. This is the pilot project of a Street Medicine (SM) based initiative to use POC testing for HCV amongst PEH with linkage of care to a federally qualified health clinic (FQHC).

Hepatitis C Screening and Treatment Protocol

HCV- Hepatitis C Virus

POC- Point of Care

CHASS- Community Health and Social Services

HbsAg- Hepatitis B Surface Antigen

CBC- Complete Blood Count

CMP- Complete Metabolic Panel

Methods

SM provides medical care to PEH outside of a hospital setting. Medical students and residents were recruited to form a HCV outreach team at Henry Ford Hospital and trained in HCV testing via OraQuick rapid antibody (Ab) test. During SM outreach, PEH were provided education on HCV and offered POC testing with a $10.00 grocery gift card. If a patient was identified as HCV Ab positive they were provided free transportation to a FQHC for confirmatory testing. If diagnosis was confirmed, they were evaluated for eligibility for simplified HCV treatment, check-ins to assess adherence and sustained virologic response (Figure 1).

Results

From February-April 2024, 103 PEH were tested using POC HCV testing on SM runs, with 4 positive results. 3 of 4 patients were confirmed for CHASS clinic appointments. 1 patient presented to clinic follow-up but deferred confirmatory testing bloodwork, demonstrating challenges in arranging for HCV clinic follow-up care.

Conclusion

Previous studies have shown that lack of insurance, prior authorization and referral process, active injection drug use or alcohol use, lack of knowledge of HCV treatment, and limited healthcare workforce and infrastructure have all contributed to the low treatment rate in the homeless. Using trusted community organizations with SM, this initiative aims to reduce testing and transportation barriers in order to eliminate HCV in PEH. Larger numbers of positive patients are needed to best assess the feasibility of the program, and if providing all testing and treatment at the point of care is needed to improve compliance.

Disclosures

Marcus Zervos, MD, Johnson and johnson: Grant/Research Support|Moderna: Grant/Research Support Seema Joshi, MD, AbbVie: Grant/Research Support
P-1463. Ceftaroline Versus Vancomycin for the Treatment of Complicated Skin and Soft Tissue Infections (cSSTIs): A Retrospective Cohort Study
Authors: Althubyani Ali , Holger Dana , Beriashvili Eka
Published: January 2025

Background

Complicated skin and soft tissue infections (cSSTIs) caused by resistant pathogens like methicillin-resistant Staphylococcus aureus (MRSA) require effective treatment. Vancomycin is the standard-of-care for MRSA-associated cSSTIs, but its efficacy is questioned due to poor tissue penetration. Ceftaroline, an anti-MRSA cephalosporin with improved tissue penetration, may offer better outcomes. This real-world study compares the effectiveness of ceftaroline and vancomycin in treating cSSTIs.

Methods

A multicenter retrospective cohort study was conducted in five Memorial Health System hospitals from 2019-2023. Here we present an interim analysis of 90 patients per arm. Included were adults diagnosed with cSSTIs who received ≥48 hours of ceftaroline or vancomycin treatment and were discharged alive. Exclusions were patients with any concurrent infection at initial diagnosis, infections requiring prolonged therapy, combination therapy, pregnancy, or incarceration. The primary outcome was clinical cure rate. Secondary outcomes were hospital length of stay (LOS), 30-day readmission, 30-day recurrence, time to oral antibiotic switch, and nephrotoxicity. Multivariable logistic regression was used to assess the independent association between ceftaroline therapy and clinical cure, adjusting for confounders.

Results

Overall, 180 patients were included. For the ceftaroline and vancomycin groups, median (IQR) APACHE scores were 10.5 (6-13.8) and 8 (6-12) (p=0.09), and SOFA scores were 1 (0-2) and 0 (0-1) (p=0.03), respectively. Clinical cure rates were 93.3% for ceftaroline and 88.9% for vancomycin (p=0.43). Multivariate analysis showed ceftaroline is independently associated with clinical cure (p=0.04). For vancomycin and ceftaroline, median (IQR) LOS was 4 days (2-6) versus 10 days (6-14) (p< 0.01), and 30-day readmission rates were 7.8% and 18.9%, respectively (p=0.04). No significant differences in other outcomes were noted.

Conclusion

Interim analysis shows ceftaroline is associated with numerically higher clinical cure rates than vancomycin, despite higher disease severity in the ceftaroline group. Ceftaroline is an independent predictor of clinical cure. Further investigation is needed to compare the efficacy and safety of both treatments.

Disclosures

All Authors: No reported disclosures
P-1480. Staphylococcus aureus Susceptibilities Among Patients Who Use Illicit Fentanyl in Philadelphia, Pennsylvania
Authors: Dickinson Drew , Saw Steve , Dutcher Lauren , Maguire Christina , Terico Adrienne , Lowenstein Margaret , Patel Sonal
Published: January 2025

Background

Patients who use drugs are at high risk for Staphylococcus aureus infection. Within the Northeastern United States, fentanyl has become the prominent substance in the illicit opioid supply. We developed a S. aureus antibiogram among patients who use fentanyl (PWUF) presenting with acute S. aureus skin or skin structure infections (SSSI) in Philadelphia, Pennsylvania.

Table 1

In vitro susceptibility of S. aureus clinical isolates from the wounds of people who use fentanyl. Susceptibilities presented as a proportion of total isolates tested for each antibiotic.

Methods

In this retrospective, multi-center study, patients presenting to one of four Penn Medicine hospitals with an acute S. aureus SSSI and illicit fentanyl use within the previous year were included. Susceptibilities of S. aureus isolated from skin and skin structure cultures were described among the PWUF cohort and compared to the health system’s outpatient wound antibiogram. Opioid withdrawal parameters were compared between patients who left the hospital prior to and after the availability of S. aureus susceptibilities.

Table 2

In vitro susceptibility of S. aureus clinical isolates from the wounds of people who use fentanyl compared to S. aureus isolated from wounds of all outpatients in the health system. Susceptibilities presented as a proportion of total isolates tested for each antibiotic.

Results

Among 131 S. aureus isolates from 131 PWUF presenting with an acute SSSI, 35/131 (26.7%) were susceptible to oxacillin, 73/121 (60.3%) were susceptible to clindamycin, 77/122 (63.1%) were susceptible to tetracycline, and 119/126 (94.4%) were susceptible to trimethoprim-sulfamethoxazole (Table 1). PWUF displayed significantly reduced susceptibility to oxacillin and tetracycline compared to the health system’s outpatient wound S. aureus antibiogram (Table 2). Seventy (53.4%) patients were discharged prior to the availability of S. aureus susceptibilities, 46 (65.7%) of which were patient-directed discharges. Compared to patients discharged prior to the availability of susceptibilities, a greater proportion of patients discharged after the reporting of susceptibilities were administered buprenorphine or methadone in the hospital (82.0% vs 51.4%, p< 0.001).

Conclusion

High rates of non-susceptibility to clindamycin and tetracycline suggest these agents should not be prescribed as empiric therapy for acute S. aureus SSSI in PWUF. PWUF would benefit from joint management by infectious diseases and addiction medicine experts to prevent premature discharge and ensure prescription of active therapy.

Disclosures

Christina Maguire, PharmD, Viiv: Advisor/Consultant
P-1501. Intracellular Activity of Delafloxacin Against Small Colony Variant Staphylococcus aureus
Authors: Tudahl Kristen L , Thompson Hailey , Wimmer Megan , Buss Brian , Smith Jeannina , Rosato Adriana , Volk Cecilia
Published: January 2025

Background

Small colony variants (SCVs) of Staphylococcus aureus (SA) have significant intracellular persistence. Fluoroquinolones demonstrate intracellular activity and are often utilized to treat SCVs. Delafloxacin is a fluroquinolone with increased potency at a low pH, which could lead to enhanced intracellular activity. This study evaluates delafloxacin activity against intracellular MSSA and MSRA SCV isolates.Figure 1.Illustration of SCV co-culture methods

Methods

Six clinical SCV-SA isolates were co-cultured with human macrophages for 1 hour, allowing for phagocytosis (Fig 1). The remaining extracellular bacteria were removed and antibiotic treatments of delafloxacin, levofloxacin, gentamicin, cefazolin, or vancomycin were added. After 5-hour and 24-hour incubation periods, supernatants were collected for extracellular colony forming unit (CFU) enumeration. Macrophages were washed, lysed, collected, and plated for intracellular bacterial CFU enumeration. All conditions were repeated in triplicate and compared using a Mann Whitney U test.Figure 2.Intracellular SCV-MSSA CFUs

Results

Delafloxacin resulted in a 1.9-log reduction in intracellular CFUs (p< 0.001) at 5 hours and a 3.4 log reduction (p< 0.001) at 24 hours compared to antibiotic-free control for MSSA strains (Fig 2). Similarly, levofloxacin resulted in a 1.6-log (p< 0.001) and 1.9-log (p< 0.001) reduction in CFUs after 5 and 24 hours, respectively. Delafloxacin was more effective at clearing intracellular bacteria than levofloxacin at 24 hours (p= 0.004). In MRSA-SCV isolates, delafloxacin demonstrated CFU reduction of 2.4-log (p< 0.001) at 5 hours and 4.7-log (p< 0.001) at 24 hours compared to antibiotic-free control (Fig 3). Levofloxacin demonstrated a 1.6-log (p< 0.001) reduction at 5 hours and 1.5-log (p= 0.034) reduction at 24 hours. In comparison to levofloxacin, delafloxacin led to greater reductions in MRSA CFUs at both 5 hours and 24 hours of incubation, 0.85-log (p= 0.028) and 3.2-log (p< 0.001) respectively.Figure 3.Intracellular SCV-MRSA CFUs

Conclusion

The results demonstrate delafloxacin having greater intracellular activity than levofloxacin and other comparator antibiotics against both MSSA and MRSA SCVs. These results support using delafloxacin to treat recurrent or chronic infections caused by either MSSA or MRSA SCVs and suggest that the observed efficacy may be a result of enhanced intracellular activity.

Disclosures

All Authors: No reported disclosures
P-1502. Clindamycin and Group A Streptococcus: Is It Time To Say Goodbye?
Authors: Mann Keeret , Zijoo Ritika , Lugar Richard G
Published: January 2025

Background

Group A streptococci (GAS) can cause invasive disease leading to Toxic Shock Syndrome (TSS), a condition linked with high mortality. Initial antibiotic therapy for GAS-TSS includes beta-lactams and clindamycin. When clindamycin resistance is noted, linezolid may be used instead until clinical stability is achieved. We reviewed GAS susceptibility at IUH Ball Memorial Hospital to assess appropriateness of initial clindamycin use as adjunctive therapy for GAS-TSS.

Methods

GAS positive cultures recovered from 1/1/23 – 12/31/23 at IU Health Ball Memorial Hospital, Muncie, IN were reviewed.

Results

Out of 162 cultures positive for GAS, 29 (17.9%) had susceptibility results. All 29 GAS specimens were sensitive to penicillin and linezolid, but only 16/29 (55.2%) specimens were sensitive to clindamycin. Table 1. and Chart 1. show susceptibility results for penicillin, clindamycin, erythromycin, and linezolid. Table 2. shows number of specimens with inducible clindamycin resistance. Chart 2. shows various sources of culture specimens.

Conclusion

GAS susceptibility testing was performed with invasive infections or when requested. Significant resistance was noted to clindamycin. Although our data is limited by a small sample size, it is in line with trends noted by US CDC’s Active Bacterial Core surveillance reports. This raises concern over initial use of clindamycin for TSS before susceptibilities are available. There are both advantages and disadvantages associated with use of clindamycin or linezolid. There is more data to support clindamycin use, however it is linked with increased risk of C. difficile infections. There is limited data for the use of linezolid for this indication, but it does maintain better susceptibility and negates the use of vancomycin at time of empiric therapy. Even though more data may be needed to definitively recommend linezolid over clindamycin or vice versa, clinical decisions will need to be made prior to susceptibility results. We recommend clinicians utilize their local antibiograms to guide decision making, while also accounting for patient factors. This also provides an opportunity for the development of clinical practice guidelines to better assist clinicians in the community.

Disclosures

All Authors: No reported disclosures
P-1505. Impact of the Introduction of Ceftazidime-Avibactam in the Brazilian Market on Carbapenem and Ceftazidime-Avibactam Resistance in Klebsiella pneumoniae and Pseudomonas aeruginosa: Retrospective Analysis from 2017 to 2023
Authors: Salomão Matias C , Freire Maristela P , dos Santos Nathamy F , Macedo Karin M , De Sá José , Cappellano Paola
Published: January 2025

Background

Bacterial resistance to carbapenems, poses a global health challenge, with Klebsiella pneumoniae and Pseudomonas aeruginosa as significant contributors. Ceftazidime-avibactam (CZA), introduced in Brazil in June 2018, offers a new treatment option for multi-resistant infections. However, increasing resistance to both this drug and carbapenems raises concerns.

Our goal is to evaluate the impact of CZA introduction on resistance patterns, and metallo-betalactamases (MBL) prevalence in Brazil, focusing on K. pneumoniae and P. aeruginosa.

Methods

A retrospective analysis of microbiology data from a Private Laboratory (2017-2023) was conducted. Samples from 9 Brazilian states were assessed. We included all positive blood cultures and all resistant surveillance swab cultures for K. pneumoniae and P. aeruginosa. We excluded repeated positive blood cultures in a week interval with the same agent, and we considered only the first positive resistant surveillance culture.

We considered carbapenem-resistant if the isolate was resistant to any carbapenem. It was evaluated phenotypically or genotypically and carbapenemase production patterns were aggregated into 3 categories: serine-, MBL, or co-production. We used Poisson regression model with a robust error variances variance to compare pre- and post-CZA introduction resistance prevalences. The models were adjusted for COVID-19 national incidence, age, and gender.

Results

We analyzed 9361 positive blood and 16862 carbapenem-resistant surveillance cultures. In blood cultures, CZA resistance rose after its introduction in K. pneumoniae (3% to 9%; 2019 to 2023 (p < 0.001), so did the MBL production (0% to 6%, p 0.02), and serine- and MBL co-production: 0% to 1% (p 0.04). MBL also increased in P. aeruginosa during the study period: 0% to 4% from 2017 to 2023 (p < 0.001).

In surveillance cultures, carbapenemase production increased in P. aeruginosa after CZA introduction: 5% to 22%, p < 0.001.

Conclusion

The observed increases in resistance prevalence and carbapenemase production associated with CZA introduction indicate limitations for its use. Enhanced surveillance and antimicrobial stewardship strategies are urgently needed to address the growing threat of antimicrobial resistance.

Disclosures

All Authors: No reported disclosures
P-1517. Assessing the novel combinations against Carbapenem resistant Acinetobacter baunmannii (CRAB): ceftazidime-avibactam and ampicillin-sulbactam
Authors: Mezcord Vyanka , Pasteran Fernando , Luu Irene , Marucci Miguel Dumas , Corso Alejandra , Tolmasky Marcelo , Bonomo Robert A , Paterson David , Ramirez Maria Soledad
Published: January 2025

Background

Carbapenem-resistant Acinetobacter baumannii (CRAB) poses a serious threat to public health, as treatment options are becoming limited. IDSA Guidance has advocated combination therapies to combat CRAB. Sulbactam (SUL), a β-lactamase inhibitor with inherent antibacterial activity against CRAB, is recognized as an important component of combination therapy. Pairing avibactam (AVI) inhibitor with ceftazidime (CAZ), has also been successful in restoring its antibiotic efficacy against many Gram-negative pathogens but has not proven effective against CRAB when used alone. In vitro assays combining SUL and AVI have shown promise against CRAB with different genetic backgrounds. Our aim is to assess the in vitro efficacy of combining ampicillin-SUL (AMS) and CAZ-AVI (CZA) against CRAB.

Figure 1

Methods

Three different methodological strategies were used. 89 strains underwent MIC evaluation (agar dilution) against SUL plus AVI, AMS (2:1) plus AVI, and AMS plus CZA, with a constant concentration of AVI (4 mg/L) and CAZ (8 mg/L). Additionally, 30 CRAB strains with different genetic backgrounds were used to assess AMS/CZA (14 μg and 50 μg) synergy by the disk stacking method and MTS synergy.

Results

AVI reduced SUL MIC values to < =4 mg/L in 96.8% of the tested isolates, excluding NDM producers. For MBLs producers, SUL-AVI MIC values less < =4 mg/L were tested in 14.3% strains (Fig. 1A). The inclusion of AMP or CAZ in the SUL-AVI combination did not result in any alterations in MIC values (98% of strains with identical values). Using stacking assay, 59% of isolates showed >3 mm increase in halo diameter for AMS with both CZA disks (Fig. 1B). Additionally, we calculated the FICI by using gradient strips (MTS) obtaining a synergistic or additive effect in 69% and 2% of strains, respectively. Antagonism was only seen in two tested NDM-1 positive isolates.

Conclusion

Our results demonstrated synergy between AMS and CZA in geographically diverse CRAB, including extensively drug-resistant isolates, such as those producing widespread oxacillinases.

Some methods, mainly disk-based, may underestimate the true extent of AMS-CZA synergy. These findings could facilitate the implementation AMS/CZA in clinical settings and provide a potential alternative in regions where the latest approved drugs are not accessible.

Disclosures

David Paterson, Infectious Diseases Physician, AMR Action Fund: Board Member|Aurobac: Advisor/Consultant|bioMerieux: Grant/Research Support|bioMerieux: Honoraria|CARB-X: Advisor/Consultant|Entasis: Expert Testimony|Menarini: Honoraria|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support|Shionogi: Honoraria
P-1522. Optimal Dosing and Outcomes In Patients Treated for Acinetobacter Baumannii Pneumonia and Bacteremia
Authors: Kale-Pradhan Pramodini , Channey Sarah , Adragna Sabrina , Giuliano Christopher , Coyle Merideth , Johnson Leonard B
Published: January 2025

Background

Acinetobacter baumannii 

(ABM) is a gram-negative coccobacillus associated with infections in healthcare facilities and has a high mortality rate. Guidelines recommend nine grams ampicillin/sulbactam (amp/sulb) every eight hours for moderate to severe ABM infections. We assessed the dosing and effectiveness of amp/sulb in the treatment of ABM pneumonia and bacteremia.

Methods

We conducted a retrospective cohort study of patients receiving high dose (≥ 3.1 gms q4h or CrCl < 30mL/min) compared to low dose (< 3.1gms q6h or if CrCl ≥ 30 mL/min) amp/sulb for ABM bacteremia and pneumonia infections from 2017-2022. Patients were also included in the high dose group if CrCl < 30 ml/min and were receiving 3.1 gms q4h. The primary outcome was all cause mortality during hospitalization. The secondary outcome was ventilator free days.

Results

Of the 277 patients screened; 173 did not receive amp/sulb, 38 did not have ABM infection, 10 had penicillin allergy and 4 were duplicate patients. Of the 52 included patients, 18 (34.6%) received low dose and 34 (65.3%) received high dose. The mean age of the patients was 64.8 and 71.1% were males. The most common infection was pneumonia 27(51.9%) followed by 25 (48.1%) treated for bacteremia. Of the low dose group three patients (16.6%) died compared to four patients (11.7%) in the high dose group during their admission. Four patients (22.2%) and five patients (14.7%) in low dose and high dose groups were discharged to hospice respectively. Eleven of the 18 patients (61.1%) and 25 of 34 (73.6%) patients were discharged to home following resolution of ABM infection in the low and high dose groups respectively.

Conclusion

No difference was found between the low and high dose amp/sulb for the treatment of ABM pneumonia and bacteremia in patient outcomes. Further studies are needed to confirm these findings.

Disclosures

All Authors: No reported disclosures
P-1527. Update on the Activity of Ceftobiprole against Gram-positive Clinical Bacterial Isolates Causing Skin and Skin-structure Infections in the United States (2016–2020)
Authors: Mendes Rodrigo E , Maher Joshua , Kimbrough Hank , Smart Jennifer , Jones Mark E , Castanheira Mariana , Sader Helio S
Published: January 2025

Background

Ceftobiprole (BPR) is a fifth-generation cephalosporin with broad spectrum activity against both Gram-negative and -positive (GP) bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). BPR was approved for treatment of community- and hospital-acquired pneumonia in Europe and other regions. This agent was recently approved by the US-FDA for treatment of adult S. aureus bacteremia, including right-sided infective endocarditis, acute bacterial skin and skin structure infections (ABSSSIs) in adults, and adult and pediatric community-acquired bacterial pneumonia. This study assessed the in vitro activity of BPR and comparator agents against contemporary clinical isolates causing SSSIs in the US.

Methods

Between 2016–2020, the SENTRY Antimicrobial Surveillance Program collected over 12,200 isolates causing SSSI in patients at 33 US medical centers. Isolates were tested for susceptibility (S) by broth microdilution according to CLSI reference methodology with CLSI, FDA, and EUCAST interpretive criteria applied, where applicable.

Results

Evaluated SSSI causing GP bacteria (n=8,120) comprised primarily of the following species: S. aureus (6,406, 78.9%), beta-hemolytic streptococci (BHS; 741, 9.1%), and Enterococcus faecalis (401, 4.94%). BPR was active against S. aureus (MIC50/90, 0.5/1 mg/L; 99.8% S by EUCAST and FDA criteria). Against MRSA (n=2,729) and MSSA (n=3,677) isolates, BPR maintained activity with 99.5% MRSA and 100% MSSA inhibited at the FDA/EUCAST S breakpoint of ≤2 mg/L. BPR displayed activity against other GP species groups, including BHS (MIC50/90, 0.015/0.03 mg/L), Viridans group streptococci (MIC50/90, 0.06/0.12 mg/L) and E. faecalis (MIC50/90 0.5/2 mg/L). BPR also displayed activity against resistant subsets, such as clindamycin-R MRSA, tetracycline-R MRSA, and vancomycin-R E. faecalis (MIC50/90, 1-2/2 mg/L).

Conclusion

BPR showed potent in vitro activity against clinical GP bacterial isolates from major SSSI pathogen groups causing SSSI in US hospitals. In addition, BPR sustained activity when tested against antibiotic-resistant subsets. With the recent FDA approvals for various serious bacterial infections, BPR becomes an additional option to treat SSSI in the US.

Disclosures

Rodrigo E. Mendes, PhD, GSK: Grant/Research Support Jennifer Smart, PhD, Basilea Pharmaceutica International Ltd: Employee|Basilea Pharmaceutica International Ltd: Stocks/Bonds (Public Company) Mark E. Jones, PhD, Basilea Pharmaceutica International Ltd: Employee|Basilea Pharmaceutica International Ltd: Stocks/Bonds (Public Company)
P-1528. In Vitro Activity of Omadacycline and Comparator Agents against a Collection of Neisseria Gonorrhoeae Urine Isolates Collected from the United States During 2018-2020
Authors: Ryan Arends S J , Pierce J V , Becker Holly , Lindley Jill , Serio Alisa W , Castanheira Mariana
Published: January 2025

Background

Omadacycline (OMC) is a third-generation tetracycline (TET) class antibacterial approved for treatment of adults with acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia caused by indicated organisms. OMC is active against bacterial isolates expressing common TET resistance mechanisms and strains resistant (R) to other drug classes. In this study, the in vitro activity of OMC and comparator agents was evaluated against a contemporary collection of N. gonorrhoeae clinical isolates. In addition, analysis of publicly available genomic sequences for these isolates was performed to determine the molecular mechanisms of TET resistance.

Antimicrobial activity of omadacycline and comparators tested against 100 Neisseria gonorrhoeae isolates

Methods

The modal minimal inhibitory concentration (MIC) of OMC and comparator agents was determined by testing in triplicate by agar dilution for 100 N. gonorrhoeae clinical isolates (BEI Resources) collected from the urethra of patients with urethritis within the US (2018-2020). R or non-susceptible (NS) phenotypes were interpreted using breakpoints published by Clinical and Laboratory Standards Institute. Resistance genes were identified from genome sequences using ResFinder 4.0.

Cumulative distribution of omadacycline MIC values tested against comparator-resistant or non-susceptible N. gonorrhoeae subsets

Results

OMC displayed activity against N. gonorrhoeae isolates (MIC50/90, 2/4 µg/mL) that had limited susceptibility (S) to TET (13%), ciprofloxacin (CIP) (60%) and penicillin (PEN) (4%) but high S to azithromycin (AZM), cefixime (CFX), and ceftriaxone (CFN) (Table 1). Among isolates with NS or R phenotypes for comparators, the OMC MIC50/90 (when calculated) were generally not impacted, although some of these subsets had very low numbers (Table 2). The rpsJ mutation was widespread among TET-R isolates, including those with additional mutations in porB, the mtrR promoter and tet(M) (Table 3). The highest OMC MIC (8 µg/mL) correlated with combined mutations in porB and rpsJ. OMC had MICs < 1 µg/mL among isolates (n=3) with high level TET-R (MIC> 16 µg/mL), including those with tet(M).

Tetracycline resistance mechanisms among tetracycline resistant Neisseria gonorrhoeae isolates

Conclusion

OMC MICs were 0.12-8 µg/mL against this set of N. gonorrhoeae clinical isolates and the MIC distribution was minimally impacted by isolates NS/R to AZM, CFX, CFN, CIP, PEN, or TET. These results support the further research of OMC for N. gonorrhoeae infections, especially for those with high level TET-R.

Disclosures

J.V. Pierce, PhD, Paratek Pharmaceuticals: Employee Alisa W. Serio, PhD, Paratek Pharmaceuticals: Employee
P-1531. Two against One: Ceftazidime-Avibactam plus Aztreonam vs Cefiderocol in the Treatment of Metallo-Beta-Lactamase-Producing Bacterial Infections
Authors: Harris Spencer A , Huang Vanthida
Published: January 2025

Background

Metallo-beta-lactamase-producing Gram-negative bacteria (MBL-GNB) has become a global healthcare threat. MBL-GNB are resistant to all first-line antimicrobials, leading to high mortality rates. Ceftazidime-avibactam plus aztreonam (CAZ-AVI+AZT) and cefiderocol (CFDC) are treatment options due to their in vitro activity against MBL-GNB. However, the optimal treatment for MBL-GNB infections remains unclear. Therefore, we sought to evaluate the outcomes of CAZ-AVI+AZT vs CFDC in patients with MBL-GNB infections.

Methods

Adult patients admitted to HonorHealth Network (Phoenix, AZ) from January 2018 to December 2024 who received ≥1 dose of either CAZ-AVI+AZT or CFDC with culture-confirmed MBL-GNB were included. Patients who were treated for < 48 h were excluded. The primary outcome was all-cause in-hospital mortality. Secondary outcomes were 14-day microbiological cure, post-diagnosis intensive care unit (ICU) and hospital length of stay (LOS), and duration of therapy.

Results

A total of 24 patients were included, of whom 8 received CAZ-AVI+AZT and 16 received CFDC. Baseline characteristics were similar in both arms; however, CAZ-AVI+AZT patients experienced an increase in ICU admission and sepsis at baseline. Sources of infections included urine (50%), blood (42%), and respiratory tract (42%). For CAZ-AVI+AZT vs CFDC patients, all-cause in-hospital mortality occurred in 2 vs 3 patients (25% vs 19%; p = 0.72); microbiological cure occurred in 7 vs 7 patients (88% vs 44%, p = 0.11), respectively. Hospital length of stay was 9.5 ± 4 days for CAZ-AVI+AZT vs 6.5 ± 3 days for CFDC (p = 0.09). Duration of therapy and post-diagnosis ICU length of stay were similar in both groups.

Conclusion

CAZ-AVI+AZT compared to CFDC demonstrated no mortality benefit; however, it may achieve greater microbiological cure. Further studies are warranted to corroborate these findings.

Disclosures

All Authors: No reported disclosures