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Background Antimicrobial stewardship programs (AMS) in Latin America have varying degrees of development. One significant barrier is the lack of clinical pharmacists with specialized training in infectious diseases, as there are no residency programs or certifications available to train pharmacists in AMS in Latin America. To overcome this limitation and based on the roadmap for antimicrobial resistance action from the International Pharmaceutical Federation (FIP), the PFA established a partnership with SIDP to support specialized training and mentoring in AMS for pharmacists working in Latin America. Herein, we describe characteristics of this innovative program and its initial participants. Methods Pharmacist members of associations belonging to the PFA (9 Latin American countries) were invited to apply for the SIDP AMS Certificate Program (SIDP-CP) with additional mentoring. Selection was based on current employment status, support from hospital leadership, and an intermediate level of English. A 14-item survey was disseminated to the participants of this program and responses were collected in March 2022, at the beginning of their SIDP-CP. The survey collected information on demographics, characteristics of the AMS at their hospital, experience with AMS to-date, and support requirements to finish the SIDP-CP. Results The description of the SIDP-CP can be found in Figure 1. Surveys were completed by 11/12 (91.7%) program participants: 6 (54.5%) from Costa Rica, 4 (36.4%) from Colombia, and 1 (9.1%) from Argentina. Seven (63.6%) pharmacists work in hospitals with a formally approved AMS, with 6 providing basic and 1 reporting intermediate AMS services. None of the pharmacists have positions dedicated exclusively to AMS, and the majority of those surveyed work ≤ 25% of their time on AMS-related activities. In addition to completing the SIDP-CP, participants indicated high interest in attending periodic virtual meetings to increase their knowledge of how to implement, strengthen, or begin research in AMS. Conclusion Incorporating antimicrobial stewardship in all healthcare institutions worldwide is vital in the fight to slow antimicrobial resistance. Partnerships like this one between PFA and SIDP can inform future planning for expansion of AMS training. Disclosures José Pablo Díaz-Madriz, PharmD, MSc, Eli Lilly: Stocks/Bonds|Pfizer: Advisor/Consultant Melissa D. Johnson, PharmD, MHS, AAHIVP, Charles River Laboratories: Grant/Research Support|Entasis: Honoraria|Merck: Grant/Research Support|Pfizer: Honoraria|Scynexis: Grant/Research Support|Theratechnologies: Honoraria|UpToDate: Honoraria Scott J. Bergman, PharmD, BCIDP, FCCP, FIDSA, Merck & Co., Inc: Advisor/Consultant|Merck & Co., Inc: Grant/Research Support|Merck & Co., Inc: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Honoraria.

Nontuberculous mycobacteria (NTM) are a group of atypical bacteria that may cause a spectrum of clinical manifestations, including pulmonary, musculoskeletal, skin and soft tissue, and cardiac infections. Antimycobacterial medication regimens for NTM infections require multiple agents with prolonged treatment courses and are often associated with poor tolerance in patients and suboptimal clinical outcomes. This review summarizes NTM pharmacotherapy, including treatment concepts, preferred medication regimens according to NTM species and site of infection, and emerging treatment methods for difficult-to-treat species.

Background Current vancomycin guidelines recommend early and frequent area-under-the-curve monitoring in patients with obesity. Vancomycin's volume of distribution is likely altered in patients with obesity, which may result in lower serum concentrations initially but lead to accumulation with continued use. The objective of this study was to evaluate the incidence of vancomycin accumulation in patients with obesity and identify potential factors associated with accumulation. Methods This was a single-center, retrospective, observational study at a tertiary academic medical center. Adult patients with a body mass index (BMI) ≥ 30 kg/m2 and ≥ 2 vancomycin serum trough concentrations drawn in 2019 were screened for inclusion. The major endpoint was the incidence of vancomycin accumulation defined as ≥ 20% increase in trough concentration within the first 10 days of therapy. Key minor endpoints included incidence of acute kidney injury (AKI) and factors associated with accumulation. Results Of the 443 patients screened, 162 were included. The median age was 56.5 years (interquartile range [IQR], 43–65.3), and 62.3% were male. The median weight was 112.7 kg (IQR, 99.8–122.6) and the median BMI was 36.8 kg/m2 (IQR, 33.1–41). The total daily dose median at initiation was 28.7 mg/kg per day (IQR, 25.4–31.2). Accumulation occurred in 99 of 162 patients (61.1%) and AKI occurred in 20 of 140 patients (14.3%). No specific factors were found to be associated with accumulation. Conclusions Patients with obesity are likely to experience vancomycin accumulation within the first 10 days of therapy. Clinicians should use frequent monitoring of vancomycin and use caution when interpreting early concentrations in patients with obesity.

Background Sepsis guidelines recommend daily review to de-escalate or stop antibiotics in appropriate patients. This randomized, controlled trial evaluated an opt-out protocol to decrease unnecessary antibiotics in patients with suspected sepsis. Methods We evaluated non–intensive care adults on broad-spectrum antibiotics despite negative blood cultures at 10 US hospitals from September 2018 through May 2020. A 23-item safety check excluded patients with ongoing signs of systemic infection, concerning or inadequate microbiologic data, or high-risk conditions. Eligible patients were randomized to the opt-out protocol vs usual care. Primary outcome was post-enrollment antibacterial days of therapy (DOT). Clinicians caring for intervention patients were contacted to encourage antibiotic discontinuation using opt-out language. If continued, clinicians discussed the rationale for continuing antibiotics and de-escalation plans. To evaluate those with zero post-enrollment DOT, hurdle models provided 2 measures: odds ratio of antibiotic continuation and ratio of mean DOT among those who continued antibiotics. Results Among 9606 patients screened, 767 (8%) were enrolled. Intervention patients had 32% lower odds of antibiotic continuation (79% vs 84%; odds ratio, 0.68; 95% confidence interval [CI], .47–.98). DOT among those who continued antibiotics were similar (ratio of means, 1.06; 95% CI, .88–1.26). Fewer intervention patients were exposed to extended-spectrum antibiotics (36% vs 44%). Common reasons for continuing antibiotics were treatment of localized infection (76%) and belief that stopping antibiotics was unsafe (31%). Thirty-day safety events were similar. Conclusions An antibiotic opt-out protocol that targeted patients with suspected sepsis resulted in more antibiotic discontinuations, similar DOT when antibiotics were continued, and no evidence of harm. Clinical Trials Registration NCT03517007.

Background Current vancomycin guidelines recommend using actual body weight for dosing. However, in patients with obesity, this may result in lower initial vancomycin concentrations that can accumulate with continued doses due to differences in volume of distribution. The objective of this study is to evaluate the incidence of vancomycin accumulation in patients with obesity and identify potential factors associated with accumulation. Methods This is a single-center, retrospective, observational study at a tertiary academic medical center. Adult patients with a BMI ≥ 30 kg/m2 and with ≥ 2 vancomycin serum trough concentrations within the same encounter in 2019 were screened. Patients were excluded if they were pregnant, had unstable renal function or severe renal impairment, received < 3 doses before a concentration was drawn, or had inconsistent dosing prior to a concentration draw. Linear kinetics were used to correct for differences in timing of concentration or dose changes. The major endpoint was the incidence of vancomycin accumulation, defined as a 20% increase in trough concentration between the first and any subsequent trough concentrations within the first 10 days of therapy. Minor endpoints included the percentage of supratherapeutic concentrations and the incidence of acute kidney injury (AKI). Descriptive statistics were used to evaluate endpoints and multivariable logistic regression was used to evaluate factors associated with accumulation. Results We screened 543 patients, and 162 were included in our analysis. The median age was 56.5 years (interquartile range [IQR] 43 - 65.3), and 62.3% were male. The median weight was 112.7 kg (IQR 99.8 - 122.6) and the median BMI was 36.8 kg/m2 (IQR 33.1 - 41). The median total daily vancomycin dose at initiation was 28.7 mg/kg/day (IQR 25.4 - 31.2). Vancomycin accumulation occurred in 99 patients (61.1%) within the first 10 days of therapy and AKI occurred in 21 patients (14.9%). No factors studied, including age, gender, obesity class, initial dose, SCr, or frequency were associated with accumulation. Conclusion Most patients with obesity experienced vancomycin accumulation within the first 10 days of therapy. Providers should be cautious when assessing a vancomycin concentration early in the treatment course. Disclosures All Authors: No reported disclosures

Chronic granulomatous disease (CGD) is a primary immunodeficiency syndrome that results in increased risk for bacterial and fungal infections, as well as inflammatory/autoimmune complications. While CGD historically has been associated with early death in childhood, the life expectancy and morbidity of patients with CGD have greatly improved. Many patients with CGD now survive well into adulthood, and data on adult cohorts of patients with CGD have been published. However, reports of pregnancy management, complications, and outcomes for patients with CGD are sparse. In addition, management of invasive fungal infections, including use of newer triazole antifungals, during pregnancy has not been well described. We report a case of fungal lung infection in a pregnant woman with CGD, diagnosed during her second trimester, which was treated with multiple antifungal agents, including more than 12 weeks of isavuconazole therapy, resulting in resolution of infection and delivery of a healthy newborn at term.

Background Omadacycline is an aminomethylcycline antimicrobial approved by the US Food and Drug Administration in 2018 for community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. It has in vitro activity against nontuberculous mycobacteria, including Mycobacterium abscessus complex, but clinical data for this indication are lacking. Methods Omadacycline use was reviewed at an 804-bed academic medical center. Patients were included if they received omadacycline for culture-proven M abscessus disease in 2019. Results Four patients received omadacycline for the treatment of culture-positive M abscessus disease in 2019. Two patients had cutaneous disease, 1 had pulmonary disease, and 1 had osteomyelitis and bacteremia. The patients received omadacycline for a median duration of 166 days (range, 104–227) along with a combination of other antimicrobial agents. Omadacycline-containing regimens were associated with a clinical cure in 3 of 4 patients, with 1 patient improving on ongoing treatment. Omadacycline’s tolerability was acceptable for patients with M abscessus disease, with 1 patient discontinuing therapy in month 6 due to nausea. Conclusions Omadacycline is a novel oral option for the treatment of M abscessus disease, for which safe and effective options are needed. Although this case series is promising, further data are required to determine omadacycline’s definitive role in the treatment of M abscessus disease.

Background Omadacycline is an aminomethylcycline antimicrobial approved by the US Food and Drug Administration in 2018 for community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. It has in vitro activity against nontuberculous mycobacteria, including Mycobacterium abscessus complex, but clinical data for this indication are lacking. Methods Omadacycline use was reviewed at an 804-bed academic medical center. Patients were included if they received omadacycline for culture-proven M abscessus disease in 2019. Results Four patients received omadacycline for the treatment of culture-positive M abscessus disease in 2019. Two patients had cutaneous disease, 1 had pulmonary disease, and 1 had osteomyelitis and bacteremia. The patients received omadacycline for a median duration of 166 days (range, 104–227) along with a combination of other antimicrobial agents. Omadacycline-containing regimens were associated with a clinical cure in 3 of 4 patients, with 1 patient improving on ongoing treatment. Omadacycline’s tolerability was acceptable for patients with M abscessus disease, with 1 patient discontinuing therapy in month 6 due to nausea. Conclusions Omadacycline is a novel oral option for the treatment of M abscessus disease, for which safe and effective options are needed. Although this case series is promising, further data are required to determine omadacycline’s definitive role in the treatment of M abscessus disease., We describe longer-term use of omadacycline as part of a treatment regimen for 4 patients with Mycobacterium abscessus disease and summarize the evidence to-date for the use of omadacycline in mycobacterial diseases.

Background Trimethoprim-sulfamethoxazole (TMP-SMX) use for PJP prophylaxis has been associated with a variety of adverse reactions including myelosuppression, hypersensitivity reactions, acute kidney injury, and hyperkalemia. Atovaquone is used as an alternative drug, but it has several disadvantages, such as breakthrough PJP risk, dysgeusia, and higher cost compared with TMP-SMX. Indications for atovaquone prophylaxis at our institutions include severe cytopenias, hypersensitivity, renal impairment, or hyperkalemia. We evaluated atovaquone use and compliance with institutional PJP prophylaxis guidelines. Methods This was a retrospective study of inpatient atovaquone prescribing for PJP prophylaxis at Brigham and Women’s Hospital and Dana-Farber Cancer Institute from 7/1/18 to 9/30/18. We included adult patients who received ≥1 dose of atovaquone and ≥3 months of PJP prophylaxis with any agent. The primary endpoint of this study was the proportion of patients who could have been safely switched to TMP-SMX 3 months after atovaquone initiation. Other endpoints included the incidence of breakthrough PJP, reasons for TMP-SMX avoidance, and estimated cost savings. Results Two-hundred and eighteen patients were evaluated and 164 were included. Most common indications for atovaquone prophylaxis were bone marrow transplant (44.5%), solid-organ transplant (30.5%) and use of immunosuppressive agents (21.9%). Atovaquone was started in 145 patients (88.4%) according to institutional guidance. Three months after initiation, 89 patients (45.7%) could have been safely switched to TMP-SMX. Failure to timely change to TMP-SMX was associated with 1,615 additional patient-days of atovaquone therapy and $103,683 in excess costs within 3 months of initiation. Major reasons for TMP-SMX avoidance were thrombocytopenia (51.3%), neutropenia (35.4%), renal impairment (31.7%), allergy history (26.8%), and hyperkalemia (19.5%). No breakthrough PJP infections were observed while patients were on atovaquone. Conclusion Institutional-guideline compliance was high during atovaquone initiation. However, after 3 months, many patients who could have been safely transitioned to TMP-SMX continued to receive atovaquone. This resulted in excess costs and potentially sub-optimal therapy. Disclosures All authors: No reported disclosures.

Background Dalbavancin (DAL) received Food and Drug Administration (FDA) approval for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by Gram-positive organisms including Methicillin-resistant Staphylococcus aureus (MRSA). Due to its unique activity and dosing schedule, use in non-FDA approved indications has been increasing. We evaluated the clinical and safety outcomes of patients treated with DAL for various infections. Methods A multicenter, retrospective observational study was conducted from April 2017 to February 2019. We included adult patients who received 1 dose of DAL for any indication. The primary outcome was clinical success defined as 30-day survival from DAL initiation, resolution of signs and symptoms of infection, and absence of therapy escalation/change. Reasons for DAL therapy selection were also investigated. Results A total of 30 patients were included. The median age was 49 (35–58) years, 50% were female and 93.3% were Caucasian. Median APACHE II score was 9 (5–12). Persons who inject drugs (PWID) comprised 50%. Common DAL indications were bacteremia (53.3%), bone and joint infections (33.3%) and ABSSSI (26.7%). Pathogens were MRSA (43.3%), coagulase-negative Staphylococci (23.3%) and methicillin-susceptible S. aureus (MSSA) (13.3%). Previous antibiotics were administered in 93.3% of patients for a median of 9 (7–15) days and (13.3%) received combination antibiotic therapy with DAL. In a subgroup of patients with confirmed microbiological eradication (73.3%), DAL was initiated at a median of 8 days (4–14) after clearance. Clinical success was achieved in 80% of patients and 10% were de-escalated to oral therapy. Rash/pruritus and hypotension occurred in two and one patient, respectively. DAL was selected because of ease of administration (60%), inability to be discharged with a line (43.3%), poor candidacy for outpatient therapy (36.7%), and/or inadequate adherence (30%). Conclusion DAL appears to be well tolerated and results in high clinical success. Larger studies with longer follow would be valuable to more precisely define the role of DAL in complicated Gram-positive infections, particularly in comparison to other long-acting lipoglycopeptides. Disclosures All authors: No reported disclosures.

Background Intramedullary abscess of the spinal cord (IASC) symptoms are often nonspecific with the diagnosis rarely considered on the initial differential. This can delay surgical management and may lead to permanent neurological deficits or mortality. Additionally, many organisms are implicated in IASC, leading to uncertainty in empiric antimicrobial therapy. Methods This case report follows a patient with IASC due to Streptococcus anginosus group (SAG). We also review a 25-case meta-analysis of IASC and 5 cases of SAG IASC. Results A 65-year-old woman with an unremarkable past medical history presented with 2 weeks of neck pain and paresthesias. She was afebrile with no systemic signs of infection or abnormal laboratory markers. MRI revealed an 8mm lesion at C4-C5 with edema C1-T1 and she received high-dose steroids for suspected malignancy. Follow-up MRI 4 days later revealed rapid progression of the lesion to 14mm, consistent with an infectious process (Figure 1). The patient received empiric therapy with ceftriaxone, vancomycin, and metronidazole. She underwent a C2-C7 laminectomy with midline myelotomy for evacuation of the abscess. Due to clinical and radiographic progression she required a second surgical wash-out 4 days later. Her intraoperative cultures grew SAG and her regimen was changed to penicillin and vancomycin. Her course was complicated by eosinophilia requiring meropenem and later linezolid to complete a 6-week course, during which she improved clinically and neurologically. Our review demonstrated that 40% of cases presented with fever. The majority of cases were idiopathic with the organisms known in 70% of cases. Surgery and IV antibiotics were used in 83% of cases and one case required a second surgery. A wide range of antibiotic regimens were reported with no consensus on how to best preserve neurological function. Conclusion This case highlights the complexities in diagnosing and managing IASC. We suspect that due to the protected nature of the intramedullary space, the infection may not trigger constitutional symptoms or a systemic inflammatory response. In patients who present with significant neurological deficits, MRI may reveal IASC and this should prompt immediate initiation of antibiotics that penetrate the blood–brain barrier and surgical intervention. Disclosures All authors: No reported disclosures.

Background Antimicrobial stewardship programs (ASPs) may improve patient outcomes by reducing antimicrobial adverse effects and resistance. Pneumonia is the most common infectious reason for hospitalization and is a key target for improvement in antimicrobial use. The purpose of this study was to measure the impact of a prospective audit and feedback program for patients with pneumonia in addition to an already robust pre-authorization program at an academic teaching hospital. Methods We analyzed the impact of a prospective audit and feedback initiative among inpatients with pneumonia treated with antimicrobials for at least 72 hours. The primary outcome was the percent of optimal antimicrobial days of therapy received based on hospital-approved pneumonia guidelines, compared pre- and postintervention. This outcome was defined as the number of optimal days of therapy compared with the total days of therapy over the entire study period from the hospital’s perspective. Secondary outcomes included the incidence rate of optimal antimicrobial days of therapy on a patient-specific level, overall antimicrobial days of therapy, length of hospital stay, rates of Clostridium difficile infection (CDI), and in-hospital mortality. Results The study included 248 patients, 125 pre- and 123 postintervention. Forty interventions were made post-implementation, with duration (47.5%) and de-escalation (35%) recommendations most commonly suggested. 50.8% of patients were male, the median [interquartile range (IQR)] age was 71 (60–83) years old, 45.6% of patients had community-acquired pneumonia, and patients had a median (IQR) Elixhauser comorbidity score of 5 (3–6). The overall rate of guideline concordance was 65.8% pre- and 77.5% postintervention (P = 0.041). On an individual level, patients were 17% more likely to have optimal antimicrobials postintervention [Incidence rate ratio 1.17 (95% confidence interval 1.03–1.32, P = 0.013)]. Length of stay, days of therapy, CDI, and in-hospital mortality rates did not differ significantly between groups. Conclusion Initiating a prospective audit and feedback program in addition to pre-authorization led to a significant increase in concordance with hospital pneumonia guidelines, but no difference in secondary outcomes in our patient population. Disclosures M. V. Mahoney, Melinta Therapeutics: Consultant, Consulting fee. Cutis Pharma: Consultant, Consulting fee. Tetraphase Pharmaceuticals, Inc.: Consultant, Consulting fee. Roche Diagnostics USA: Consultant, Consulting fee. C. McCoy, Merck Inc: Scientific Advisor, Consulting fee. Allergan: Scientific Advisor, Consulting fee.