Skin Structure Infections Research Articles

Necessity of vancomycin trough concentrations to manage uncomplicated acute bacterial skin and skin structure infections: a laboratory stewardship analysis.

Recent recommendations by the American Society of Health System Pharmacists and Infectious Disease Society of America have provided guidance regarding vancomycin dosing and monitoring in serious infections (including methicillin-resistant Staphylococcus aureus); however, trough monitoring for uncomplicated acute bacterial skin and skin structure infections (ABSSSI) were not addressed. Vancomycin use appears to lead to a low incidence of acute kidney injury with short durations and a low trough goal (10-15 mg/L). Nevertheless, clinical studies have found no difference in clinical outcomes for ABSSSI regardless of vancomycin level. Therefore, it can be posed whether trough monitoring is necessary in this patient population. This is a retrospective cohort study comparing vancomycin therapy duration for ABSSSI in adult, general medicine patients who received scheduled vancomycin with an initial creatinine clearance rate of ≥50 mL/minute and had at least one vancomycin trough. The objective of this study was to determine if vancomycin treatment duration differs for patients with ABSSSI with a sub-therapeutic vancomycin trough (ST; <10 mg/L) compared with therapeutic trough (TT; ≥10 mg/L). There were 39 (67.2%) patients with ST compared with 19 (32.8%) with TT. A similar median vancomycin treatment duration for ST (48.25 hours) and TT (59.5 hours; p=0.65) was found. There was no statistical difference for hospital duration, time from last trough to vancomycin discontinuation, or incidence of acute kidney injury (p>0.05 for all). Patients with ST and TT had similar vancomycin durations and clinical outcomes. It may be prudent for institutions to address vancomycin trough laboratory stewardship and associated costs.

Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infection in Patients With Obesity or Diabetes: A Subgroup Analysis of Pooled Phase 3 Clinical Trials.

We assessed the efficacy and safety of dalbavancin, a long-acting lipoglycopeptide with activity against Gram-positive pathogens, for treatment of acute bacterial skin and skin structure infections (ABSSSI) in patients with high body mass index (BMI) and/or diabetes. Data from two phase 3 trials of dalbavancin (1000 mg intravenous [IV], day 1; 500 mg IV, day 8) versus comparator and one phase 3b trial of single-dose (1500 mg IV, day 1) versus 2-dose (1000 mg IV, day 1; 500 mg IV, day 8) dalbavancin in adults with ABSSSI were pooled and summarized separately by baseline BMI and diabetes status. Clinical success at 48 to 72 hours (≥20% reduction in lesion size), end of treatment ([EOT] day 14), and day 28 was evaluated in the intent-to-treat (ITT) and microbiological ITT (microITT) populations. Safety data were reported in patients who received ≥1 dose of study drug. In the dalbavancin ITT population (BMI, n = 2001; diabetes, n = 2010), at 48 to 72 hours (and EOT) clinical success was achieved in 89.3% (EOT, 90.9%) of patients with normal BMI and 78.9% to 87.6% (EOT, 91.0% to 95.2%) of patients with elevated BMI. Clinical success after dalbavancin treatment was achieved in 82.4% (EOT, 90.8%) of patients with diabetes and 86.0% (EOT, 91.6%) of patients without diabetes. Similar trends were observed for infections due to methicillin-resistant Staphylococcus aureus or methicillin-susceptible S aureus (microITT population). Dalbavancin is effective, with sustained clinical success rates in patients with obesity or diabetes, with a similar safety profile across patient groups.

Outpatient care concept and potential inpatient cost savings associated with the administration of dalbavancin – A real-world data and retrospective cost analysis

BackgroundThe treatment of acute bacterial skin and skin structure infections (ABSSSI) usually involves intravenous (i.v.) antibiotics requiring hospitalisation and increasing hospital costs. Since 2014, dalbavancin is approved for ABSSSIs treatment. However, evidence of its health economic impact on the German healthcare system is still limited. MethodsDiagnosis-related groups (DRG) based cost analysis was used to evaluate real-world data (RWD) from a German tertiary care center. All patients treated with i.v. antibiotics in the Department of Dermatology and Venereology at the University Hospital of Cologne were included to detect potential cost savings from a payer perspective. Thus, for the inpatient care German diagnosis-related groups (G-DRG) tariffs, length of stay (LOS), main- and secondary DRG-diagnoses and for the outpatient setting ‘Einheitlicher Bewertungsmaßstab’ (EBM) codes were evaluated. ResultsThis retrospective study identified 480 inpatient cases treated for ABSSSI between January 2016 until December 2020. Complete cost data were available for 433 cases and the detection of long-hospital-stay patients based on surcharges for exceeding the upper limit LOS led to 125 cases (29%) including 67 females (54%) and 58 males (46%) with an overall mean age of 63.6 years; all treated for International Classification of Diseases (ICD −10th revision) code A46 ‘erysipelas’. A sub-analysis focussed on DRG J64B with a total of 92 cases exceeding the upper limit LOS by a median of 3 days resulted in a median surcharge of €636 (mean value €749; SD €589; IQR €459-€785) per case. In comparison, we calculated outpatient treatment costs of approximately €55 per case. Thus, further treatment of these patients in an outpatient setting before exceeding the upper limit LOS might result in a cost-saving potential of approximately €581 per case. ConclusionDalbavancin appears a cost-efficient option to reduce inpatient treatment costs by transitioning to an outpatient setting of patients with ABSSSI potentially exceeding the upper limit LOS.

Role of Oritavancin in the Treatment of Infective Endocarditis, Catheter- or Device-Related Infections, Bloodstream Infections, and Bone and Prosthetic Joint Infections in Humans: Narrative Review and Possible Developments.

Oritavancin is a long-acting lipoglycopeptide with in vitro activity against Gram-positive pathogens, as well as good bactericidal activity and sterilisation ability in biofilm. It has been approved for acute bacterial skin and skin structure infections (ABSSSI), but recent reports have demonstrated possible off-label uses, such as for vancomycin resistant enterococci (VRE), deep-seated infections including those involving prosthetic material and invasive infections. The aim of this work is to review the uses of oritavancin outside of ABSSSI, focusing on its real-life applications on infective endocarditis, catheter- or device-related infections, bloodstream infections, and bone and prosthetic joint infections in humans, as well as possible future applications. We performed a narrative review, collecting the literature published between 1 December 2002 and 1 November 2022 on PubMed and the Cochrane Library using the term 'oritavancin'. Available studies have shown how effective it is in different settings, suggesting an opportunity for step-down strategies or outpatient management of infections requiring a long duration of antibiotic treatment. So far, evidence is still scarce, and limited to a few studies and case reports, mostly focusing on Staphylococcus aureus as the major isolate. Concerns about fluid intake for dilution and interaction with coagulation markers also need to be taken into account. Further studies are required in order to assess the safety and effectiveness of Oritavancin in vascular, prosthetic, or device-related infections, as well as in resistant Gram-positive bacteria or enterococcal infections.

Comparative activity of newer β-lactam/β-lactamase inhibitor combinations against Pseudomonas aeruginosa isolates from US medical centres (2020-2021).

To evaluate the in-vitro activity of ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-relebactam and comparator agents against contemporary Pseudomonas aeruginosa isolates from US hospitals. In total, 3184 isolates were collected consecutively from 71 US medical centres in 2020-2021, and susceptibility tested by reference broth microdilution. Clinical Laboratory Standard Institute breakpoints were applied. Ceftazidime-avibactam [97.0% susceptible (S)], ceftolozane-tazobactam (98.0%S), imipenem-relebactam (97.3%S) and tobramycin (96.4%S) were the most active agents against the aggregate P. aeruginosa isolate collection, and retained good activity against piperacillin-tazobactam-non-susceptible, meropenem-non-susceptible and multi-drug-resistant (MDR) isolates. All other antimicrobials tested showed limited activity against piperacillin-tazobactam-non-susceptible, meropenem-non-susceptible and MDR isolates. The most common infections were pneumonia (45.9%), skin and skin structure infections (19.0%), urinary tract infections (17.0%) and bloodstream infections (11.7%); ceftazidime-avibactam, ceftolozane-tazobactam and imipenem-relebactam showed consistent activity against isolates from these infection types. Susceptibility to piperacillin-tazobactam and meropenem was lower among isolates from pneumonia compared with other infection types. Ceftazidime-avibactam, ceftolozane-tazobactam and imipenem-relebactam were highly active, and exhibited similar coverage against a large contemporary collection of P. aeruginosa isolates from US hospitals. Cross-resistance among the newer β-lactams/β-lactam inhibitors (BL/BLIs) varied markedly; ≥72.1% of isolates resistant to one of the three newer BL/BLIs approved for P. aeruginosa treatment remained susceptible to at least one of the other two BL/BLIs, indicating that all three should be tested in the clinical laboratory. These three BL/BLIs represent valuable therapeutic options for P. aeruginosa infection.

REDS study: Retrospective effectiveness study of dalbavancin and other standard of care of the same IV antibiotic class in patients with ABSSSI.

Acute bacterial skin and skin-structure infections (ABSSSIs) are a common source of morbidity in both the community and hospital settings. The current standard of care (SoC) requires multiple-dose intravenous (IV) regimens, which are associated with high hospitalisation rates, concomitant event risks and costs. Dalbavancin is a lipoglycopeptide, long-acting antibiotic that is effective against Gram-positive microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA). Dalbavancin allows treatment of ABSSSIs with a single-shot IV administration or once weekly for 2 weeks, enabling clinicians to treat patients in an outpatient setting or to shorten the length of hospital stay. This multicentre, observational, retrospective study compared hospitalised patients who received dalbavancin and patients treated with the three most used IV antibiotics of the same or similar class: vancomycin, teicoplanin and daptomycin. The primary outcome was the time to discharge after starting the study antibiotics. The primary endpoint, time to discharge from the study therapy start, was measured for both groups: the median number of days was 6.5 in the dalbavancin group vs. 11.0 days in the SoC group. Moreover, in subpopulations of patients receiving one or more concomitant antibiotics active for Gram-positives, MRSA and patients with the most prevalent comorbidity (i.e., diabetes), the advantage of dalbavancin in terms of length of stay was confirmed, with a halved time to discharge or more. Safety data on dalbavancin were consistent with data collected in clinical trials. No serious adverse drug reactions related to dalbavancin were reported and most of them were classified as skin and subcutaneous tissue disorders. One serious ADR was reported for daptomycin. Although the analysis was only descriptive, it can be concluded that dalbavancin may enable a remarkable reduction in length of hospital stay, also confirming the clinical effectiveness and good safety profile demonstrated in clinical trials in a real-world setting.

Implementation of indication-based antibiotic order sentences improves antibiotic use in emergency departments

IntroductionPrior data have suggested that suboptimal antibiotic prescribing in the emergency department (ED) is common for uncomplicated lower respiratory tract infections (LRTI), urinary tract infections (UTI), and acute bacterial skin and skin structure infections (ABSSSI). The objective of this study was to measure the effect of indication-based antibiotic order sentences (AOS) on optimal antibiotic prescribing in the ED. MethodsThis was an IRB-approved quasi-experiment of adults prescribed antibiotics in EDs for uncomplicated LRTI, UTI, or ABSSSI from January to June 2019 (pre-implementation) and September to December 2021 (post-implementation). AOS implementation occurred in July 2021. AOS are lean process, electronic discharge prescriptions retrievable by name or indication within the discharge order field. The primary outcome was optimal prescribing, defined as correct antibiotic selection, dose, and duration per local and national guidelines. Descriptive and bivariate statistics were performed; multivariable logistic regression was used to determine variables associated with optimal prescribing. ResultsA total of 294 patients were included: 147 pre-group and 147 post-group. Overall optimal prescribing improved from 12 (8%) to 34 (23%) (P < 0.001). Individual components of optimal prescribing were optimal selection at 90 (61%) vs 117 (80%) (P < 0.001), optimal dose at 99 (67%) vs 115 (78%) (P = 0.036), and optimal duration at 38 (26%) vs 50 (34%) (P = 0.13) for pre- and post-group, respectively. AOS was independently associated with optimal prescribing after multivariable logistic regression analysis (adjOR, 3.6; 95%CI,1.7–7.2). A post-hoc analysis showed low uptake of AOS by ED prescribers. ConclusionsAOS are an efficient and promising strategy to enhance antimicrobial stewardship in the ED.

Evaluation of the Impact of Comorbidities on Omadacycline Pharmacokinetics.

Omadacycline is approved in the United States for the treatment of patients with community-acquired bacterial pneumonia or acute bacterial skin and skin structure infections. Analyses were undertaken to evaluate pharmacokinetic differences among subjects or patients stratified by comorbidities. Differences in clearance by smoking status, history of diabetes mellitus, chronic lung disease, hypertension, heart failure, or coronary artery disease were evaluated using a Welch two-sample t test. Smoking was the only significant comorbidity after correction for sex, with a clinically insignificant difference of 13%. Omadacycline dose adjustments based on these comorbidities do not appear to be warranted.

Insufficient Representation of Patients With Obesity in Randomized Controlled Trials Evaluating the Efficacy and Safety of Antimicrobials for Treatment of Skin and Skin Structure Infections: A Scoping Review.

Persons with obesity (PwO) represent approximately 50% of acute bacterial skin and skin structure infections (ABSSSIs) in the United States (US). There are currently insufficient data in PwO for drugs used for ABSSSIs. We conducted a scoping review of randomized controlled trials (RCTs) published between 2000 and 2022 to describe how frequently body size measures were reported. Weight and/or body mass index (BMI) were recorded in approximately 50% of the 69 RCTs. The average weights or BMIs were lower than US averages for most RCTs reporting data. None evaluated the impact of body size on outcomes in the original publication. Only 30% of newly approved drugs mention PwO representation in the prescribing information. More representative recruitment of PwO into RCTs is needed to help clinicians evaluate efficacy in these patients. We suggest that the Food and Drug Administration require companies to submit plans to ensure adequate PwO inclusion and that authors of RCTs report subgroup results based on body size.

Cost analysis of dalbavancin versus standard of care for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) in two Italian hospitals.

Thanks to its long half-life, dalbavancin qualifies as an optimal drug for saving costs. We aimed to assess the cost and effectiveness of dalbavancin versus the standard of care (SoC). We conducted a multicentre retrospective study, including all hospitalized or outpatients diagnosed with ABSSSIs at Padua University Hospital, Padua and San Paolo Hospital, Milan (1 January 2016 to 31 July 2020). We compared patients according to antibiotic treatment (dalbavancin versus SoC), the number of lines of dalbavancin treatment, and monotherapy or combination (dalbavancin in association with other antibiotics). Primary endpoints were direct medical costs and length of hospital stay (LOS) associated with ABSSSI management; Student's t-test, chi-squared test and one-way ANOVA were used. One hundred and twenty-six of 228 (55.3%) patients received SoC, while 102/228 (44.7%) received dalbavancin. Twenty-seven of the 102 (26.5%) patients received dalbavancin as first-line treatment, 46 (45.1%) as second-line, and 29 (28.4%) as third- or higher-line treatment. Most patients received dalbavancin as monotherapy (62/102; 60.8%). Compared with SoC, dalbavancin was associated with a significant reduction of LOS (5 ± 7.47 days for dalbavancin, 9.2 ± 5.59 days for SoC; P < 0.00001) and with lower mean direct medical costs (3470 ± 2768€ for dalbavancin; 3493 ± 1901€ for SoC; P = 0.9401). LOS was also reduced for first-line dalbavancin, in comparison with second-, third- or higher-line groups, and for dalbavancin monotherapy versus combination therapy. Mean direct medical costs were significantly lower in first-line dalbavancin compared with higher lines, but no cost difference was observed between monotherapy and combination therapy. Monotherapy with first-line dalbavancin was confirmed as a promising strategy for ABSSSIs in real-life settings, thanks to its property in reducing LOS and saving direct medical costs.

Acute bacterial skin and skin structure infections in pediatric patients: potential role of dalbavancin

ABSTRACT Introduction Acute bacterial skin and skin structure infections (ABSSSIs) are a subtype of skin and soft tissue infections (SSTI), usually sustained by Gram-positive bacteria, whose incidence is high among children. ABSSSIs are responsible for a considerable number of hospitalizations. Moreover, as multidrug resistant (MDR) pathogens become widespread, the pediatric category seems burdened with an increased risk of resistance and treatment failure. Areas covered To obtain a view on the status of the field, we describe the clinical, epidemiological, and microbiological aspects of ABSSSI in children. Old and new treatment options were critically revised with a focus on the pharmacological characteristics of dalbavancin. Evidence on the use of dalbavancin in children was collected, analyzed, and summarized. Expert opinion Many of the therapeutic options available at the moment are characterized by the need for hospitalization or repeated intravenous infusions, safety issues, possible drug–drug interactions, and reduced efficacy on MDRs. Dalbavancin, the first long-acting molecule with strong activity against methicillin-resistant and also many vancomycin-resistant pathogens represents a game changer for adult ABSSSI. In pediatric settings, the available literature is still limited, but a growing body of evidence supports dalbavancin use in children with ABSSSI, demonstrating this drug to be safe and highly efficacious.

Dalbavancin (Xydalba)

&#x0D; CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.&#x0D; The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec.&#x0D; This review assesses Dalbavancin (Xydalba) for injection, 500 mg (as dalbavancin hydrochloride) per vial, lyophilized powder for solution, IV infusion.&#x0D; Indication: Treatment of adults with acute bacterial skin and skin structure infections caused by susceptible isolates of the following gram-positive micro-organisms: Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant strains), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus anginosus group (including Streptococcus anginosus, Streptococcus intermedius, Streptococcus constellatus), and Enterococcus faecalis (vancomycin-susceptible strains).&#x0D;

Dalbavancin Boosts the Ability of Neutrophils to Fight Methicillin-Resistant Staphylococcus aureus.

Polymorphonuclear leukocytes (PMNs) are the most important cell type involved in the early nonspecific host response to bacterial pathogens. Staphylococcus aureus has evolved mechanisms to evade immune responses that contribute to its persistence in PMNs, and acquired resistance to several antimicrobials. Additionally, methicillin-resistant S. aureus (MRSA) is one of the most common causes of acute bacterial skin and skin-structure infections (ABSSSIs). Dalbavancin (DBV), a lipoglycopeptide, is indicated for the treatment of ABSSSIs, and has a broad spectrum of action against most microorganisms. Here, we sought to determine the effect of DBV on the neutrophil killing of MRSA and its potential immunomodulating activity. Our results revealed that DBV boosts MRSA killing by acting on both bacteria and PMNs. DBV pre-treatment of PMNs did not change the respiratory burst or degranulation, while an increased trend in neutrophil extracellular traps-associated elastase and in the production of TNFα and CXCL8 was revealed. In parallel, DBV caused a delay in the apoptosis of MRSA-infected neutrophils. In conclusion, we demonstrated a cooperative effect between the antimicrobial properties of PMNs and DBV, thus owing to their immunomodulatory activity. In the choice of the treatment management of serious S. aureus infections, DBV should be considered as an outstanding option since it reinforces PMNs pathogen clearance capability by exerting its effect directly, not only on MRSA but also on neutrophils.

Efficacy and safety of tigecycline as monotherapy versus vancomycin plus aztreonam in skin structure infections: A systematic review and meta-analysis

Efficacy and safety of tigecycline as monotherapy versus vancomycin plus aztreonam in skin structure infections: A systematic review and meta-analysis

Cancer is chronic but antimicrobial stewardship is iconic: A retrospective cohort of optimal antibiotic use in ambulatory oncology clinics.

To evaluate antibiotic prescribing in ambulatory oncology clinics and to identify opportunities to improve antibiotic use. Retrospective cohort of adult patients who received care at 4 ambulatory oncology clinics from May 2021 to December 2021. Patients were included if they actively followed with a hematologist-oncologist for a cancer diagnosis and received an antibiotic prescription for uncomplicated upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), urinary tract infection (UTI), or acute bacterial skin-skin structure infection (ABSSSI) at an oncology clinic. The primary outcome was receipt of optimal antibiotic therapy, defined as a composite of drug, dose, and duration according to local and national guidelines. Patient characteristics were described and compared; predictors of optimal antibiotic use were identified using multivariable logistic regression. In total, 200 patients were included in this study: 72 (36%) received optimal antibiotics and 128 (64%) received suboptimal antibiotics. The proportions of patients receiving optimal therapy by indication were ABSSSI (52%), UTI (35%), URTI (27%), and LRTI (15%). The most common suboptimal prescribing components were dose (54%), selection (53%) and duration (23%). After adjusting for female sex and LRTI, ABSSSI (adjusted odds ratio, 2.28; 95% confidence interval, 1.19-4.37) was associated with optimal antibiotic therapy. Antibiotic-associated adverse drug events occurred in 7 patients; 6 occurred patients who received prolonged durations and 1 occurred in a patient who received an optimal duration (P = .057). Suboptimal antibiotic prescribing in ambulatory oncology clinics is common and mostly driven by antibiotic selection and dosing. Duration of therapy may also be an area for improvement as national oncology guidelines have not adopted short-course therapy.

Oral minocycline plus rifampicin versus oral linezolid for complicated skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus: the AIDA open label, randomized, controlled Phase 4 trial

The need for oral, cost-effective treatment for complicated skin and skin structure infections (cSSSIs) due to methicillin-resistant Staphylococcus aureus (MRSA) was addressed by the non-inferiority comparisons of oral minocycline plus rifampicin with linezolid. In the AIDA multicenter, open label, randomized, controlled clinical trial, hospitalized adults with cSSSI and documented MRSA were randomly assigned at a 2:1 ratio to either oral 600mg rifampicin qd plus 100mg minocycline bid or oral 600mg linezolid bid for 10 days. The primary endpoint was the clinical cure rate in the clinically evaluable (CE) population at the test-of-cure visit (14 days). Non-inferiority was confirmed if the lower confidence limit (CI) did not fall below the accepted error margin of 15%. The study is registered with EudraCT number 2014-001276-56. 123 patients recruited between November 2014 and January 2017 were randomly assigned to treatment (81 patients to minocycline plus rifampicin and 42 patients to linezolid). Cure rates were 78.% (46/59, 90% CI 67.3-86.5) and 68.6% (24/35, 90% CI 53.4-81.3), respectively (P=0.337). The percent difference in cure rates was 9.4% (90% CI-7.2 to 26.8%). Minocycline plus rifampicin combination was deemed non-inferior to linezolid as the lower CI was-7.2% i.e. smaller than the accepted error margin of-15%. Although statistically not significant, the overall rate of adverse events was higher in the linezolid group (47.6%, 20/42 versus 38.3%, 31/81). Oral minocycline plus rifampicin was non-inferior to oral linezolid treatment providing alternative oral treatment for cSSSI. The EU Seventh Research Framework Programme.

1016. Real-World Use of Omadacycline in Physician Office Infusion Centers (POICs)

Abstract Background Omadacycline (OMC) is approved for the treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. Real-world data on the use of OMC are limited. We present a multicenter observational review of OMC outpatient use in Infectious Disease POICs. Methods Medical records of patients (pts) receiving intravenous OMC from May 2019 to April 2022 from 5 POICs were included in this ongoing study. Data included demographics, diagnosis, medical history, microbiology, OMC regimen, adverse events (AEs), health care utilization and clinical outcomes. Clinical success was defined as complete or partial symptom resolution at completion of OMC with oral antibiotics as needed. Persistent or recurrent infection and premature discontinuation of OMC were deemed non-success. Indeterminate outcomes were excluded in outcome assessment. Chi Square, Fisher’s exact, and t-test were used to identify characteristics associated with clinical outcome. Results Overall, 37 pts (mean age: 61±13 yrs, 65% male) were identified. Infections treated were 62% bone and joint (BJI), 24% complicated skin and skin structure infections (CSSSI), 11% pulmonary nontuberculous mycobacterial (NTM) and 3% diverticulitis. A total of 61 pathogens were identified in 30 pts of which 83% had ≥1 Gram-positive isolate. Polymicrobial pathogens were reported in 13/30 pts (43%). Ten pts (27%) received concomitant IV antibiotics. Median duration of OMC therapy was 38 days (IQR, 21-47). OMC was initiated in the POIC without prior hospitalization in 62% of pts. Overall clinical success was 75% (24/31). Non-success due to persistent infection was reported in 5 pts (3 BJI, 2 CSSSI), of which 4 were hospitalized. Three additional pts were deemed non-successful due to early discontinuations (2 difficulty with administration, 1 AE) (Fig 1). Six pts were non-evaluable for outcome. Ten pts reported 14 AEs, most commonly nausea (4 pts) and elevated liver function tests (3 pts). Figure 1.Clinical outcome of omadacycline by infection type Conclusion These real-world results support the outpatient use of omadacycline in additional, difficult to treat, complicated infections, including bone and joint infections. Disclosures Lucinda J. Van Anglen, PharmD, Merck &amp; Co.: Grant/Research Support|Paratek: Grant/Research Support.

1385. Pathway with single-dose long-acting intravenous antibiotic dalbavancin is a cost-saving alternative to usual inpatient care of acute bacterial skin and skin structure infections (ABSSSI)

Abstract Background Acute bacterial skin and skin structure infections (ABSSSI) are a common type of bacterial infection, with the cost of hospitalization being the main contributing factor to overall treatment costs. Two pragmatic clinical trials (Table 1) demonstrated that a new treatment pathway in which patients are treated with the intravenous (IV) long-acting antibiotic, dalbavancin, reduced hospital admission rates and length of stay (LOS) in hospitalized patients. The objective of this study is to evaluate the cost-effectiveness of a single dose of dalbavancin administered in the emergency department (ED) compared with IV antibiotics for appropriate patients who would otherwise be admitted to hospital and receive usual care such as vancomycin or daptomycin. Table 1.References of the Two Pragmatic Clinical Trials Methods A decision-analytic cost-effectiveness model was developed from the perspective of the US healthcare system. The population was ABSSSI patients presenting at the ED, who would be eligible to receive IV antibiotic infusion. Patients can receive IV treatment in the ED, and then discharged or followed by hospital admission for continued management (Fig. 1). A 14-day time horizon was used, representing the typical duration of ABSSSI management. Hospital admission rates and LOS were from the two clinical trials. Cost included ED visits, drug cost, inpatient stay, and physician visits. Input parameter uncertainty was examined via one-way and probabilistic sensitivity analyses. Figure 1.Decision Analytic Model Structure Results Providing dalbavancin in the ED resulted in $4,848 savings per patient (2021 USD). The drug cost of dalbavancin treatment was offset by a mean reduction of 4.24 days LOS per patient, which translated as $1,144 savings per hospitalization day avoided. One-way sensitivity analyses demonstrated that the key drivers were the cost of inpatient hospital stay and the LOS with usual care; however, none of the sensitivity analyses resulted in the new pathway being more costly (Fig. 2). Dalbavancin was cost saving in 100% of simulated scenarios. Figure 2.One-way Sensitivity Analysis Conclusion These results could help guide the management of ABSSSI by shifting care for appropriate patients from the inpatient to the outpatient setting where patients can be managed successfully, thereby freeing up hospital resources and reducing the total costs of ABSSSI treatment. Disclosures FRANK LOVECCHIO, DO, MPH, ABBVIE: Speaker|NIH: Grant/Research Support Alasdair D. Henry, PhD, AbbVie: Grant/Research Support Quan V. Doan, PharmD, AbbVie: Advisor/Consultant|AbbVie: Grant/Research Support|Allergan: Advisor/Consultant|Allergan: Grant/Research Support John L. Lock, PharmD, Abbvie: Employee|Abbvie: Stocks/Bonds Rosie D. Lyles, MD, MHA, MSc, AbbVie: AbbVie Employee|AbbVie: Stocks/Bonds Xiaolan Ye, PhD, AbbVie Inc.: AbbVie Employee|AbbVie Inc.: Stocks/Bonds.

2043. In Vitro Activity of Manogepix Against 2,810 Fungal Isolates from the SENTRY Surveillance Program (2020-2021) Stratified by Infection Type

Abstract Background Manogepix is a new antifungal with a novel mechanism of action and potent in vitro activity against Candida (except C. krusei), Aspergillus, and rare mold isolates. The manogepix prodrug fosmanogepix is in Phase 2 development for the treatment of invasive mold infections caused by Aspergillus and rare molds (NCT04240886) and has completed Phase 2 studies for candidemia (NCT03604705) and C. auris (NCT04148287) infections. We evaluated the in vitro activity of manogepix and comparators against 2,810 geographically diverse fungal isolates collected in the SENTRY Surveillance Program during 2020-2021 and stratified them by infection type. Methods Antifungal susceptibility testing of manogepix and comparator agents was conducted according to CLSI M27 (2017) and M38 (2017) guidelines. Fungal surveillance isolates were collected from medical centers located in North America (30 sites; 37.9%), Europe (30 sites; 38.4%), Asia-Pacific (11 sites; 14.7%), and Latin America (6 sites; 9.0%). Infection sites included bloodstream infections (BSI; 48.3%), pneumonia in hospitalized patients (PIHP; 19.9%), skin and skin structure infections (SSSI; 7.8%), urinary tract infections (UTI; 3.1%), intra-abdominal infections (IAI; 1.6%), and other infection types (19.3%). Results Manogepix demonstrated potent in vitro activity against Candida spp. isolates (MIC50/90, 0.004-0.03/0.008-0.06 mg/L) regardless of infection type (Table). Similarly, manogepix was highly active against 534 Aspergillus spp. isolates (MEC50/90, 0.015/0.03 mg/L). Manogepix was active against 53 Cryptococcus neoformans var. grubii (MIC50/90, 0.25/1 mg/L), 19 Fusarium spp. (MEC50/90, 0.015/0.06 mg/L), 12 Lomentospora prolificans (MEC50/90, 0.03/0.06 mg/L), and 17 Scedosporium spp. isolates (MEC50/90, 0.06/0.12 mg/L). Conclusion Manogepix showed potent in vitro activity against Candida spp., Aspergillus spp., C. neoformans var. grubii, and rare molds, including Fusarium spp., L. prolificans, and Scedosporium spp. isolates. Notable activity was also demonstrated by manogepix against C. auris isolates. Further clinical development of fosmanogepix in difficult-to-treat, resistant fungal infections is warranted. Disclosures Michael D. Huband, BS, AbbVie: Grant/Research Support|Melinta: Grant/Research Support Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.

1702. Platelet Counts in Contezolid Complicated Skin and Soft Tissue Infection Phase 2 and Phase 3 Clinical Trials

Abstract Background Contezolid (CZD; MRX-I) is a novel oral (PO) oxazolidinone with potent activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococccus (VRE). Nonclinical and Phase 1 (Ph1) clinical data indicate CZD may cause less myelosuppression, particularly with longer duration therapy, and with reduced risk of monoamine oxidase inhibition compared with linezolid (LZD). In Phase 2 (Ph2) and Phase 3 (Ph3) complicated skin and soft tissue infections (cSSTI) clinical trials, CZD was compared with LZD with dosing for 7-14 days, and noninferiority was demonstrated in the Ph3 study. Overall safety was comparable to LZD, and the most common treatment emergent adverse events (TEAEs) in both the CZD and LZD groups were gastrointestinal; however, hematologic laboratory abnormalities and TEAEs were less common with CZD. In June 2021, CZD was approved in China for cSSTI. Sequential therapy with intravenous contezolid acefosamil (CZA; double prodrug of CZD) followed by CZD PO is being evaluated in global Ph3 diabetic foot infection (DFI) and acute bacterial skin and skin structure infection (ABSSSI) clinical trials. Because DFI requires longer treatment (14-28 days), changes in platelet counts with therapy ≥11 days were evaluated in completed Ph2 and Ph3 CZD cSSTI studies. Methods In Ph2 and Ph3 cSSTI studies, mean percent changes in platelet counts from baseline (BSL) to the end of therapy (EOT) visit were compared for all subjects in the safety analysis sets (SS) who received CZD 800 mg and LZD, and also the subjects who received ≥11 days of therapy. Results In the Ph2 and Ph3 cSSTI studies, the mean platelet count values for LZD subjects decreased compared with CZD subjects, and the difference was greater in subjects who received ≥11 days of therapy. Conclusion In Ph2 and Ph3 cSSTI clinical trials with treatment durations of 7-14 days, mean platelet counts did not decrease for CZD subjects while mean values for LZD subjects did decline, consistent with nonclinical and Ph1 clinical data. Differences were more significant in subjects who received ≥11 days of therapy. In the current Ph3 global DFI study which compares 14-28 days of CZA/CZD to LZD, evaluation of hematological safety is an important outcome measure. Disclosures Edward Fang, MD, MicuRx Pharmaceuticals Inc: Employee Huahui Yang, MS, MicuRx Pharmaceuticals Inc: Employee.