bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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&lt; 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

Abstract

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&lt; 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

Abstract

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&lt; 0.001) at 5 hours and a 3.4 log reduction (p&lt; 0.001) at 24 hours compared to antibiotic-free control for MSSA strains (Fig 2). Similarly, levofloxacin resulted in a 1.6-log (p&lt; 0.001) and 1.9-log (p&lt; 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&lt; 0.001) at 5 hours and 4.7-log (p&lt; 0.001) at 24 hours compared to antibiotic-free control (Fig 3). Levofloxacin demonstrated a 1.6-log (p&lt; 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&lt; 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

Abstract

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

Abstract

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

Abstract

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 &lt; =4 mg/L in 96.8% of the tested isolates, excluding NDM producers. For MBLs producers, SUL-AVI MIC values less &lt; =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 &gt;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

Abstract

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 &lt; 30mL/min) compared to low dose (&lt; 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 &lt; 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

Abstract

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)