Missed Antimicrobial Stewardship Opportunities for Hospitalized Patients with Urinary Tract Infections Receiving Ceftriaxone.

Background: Ceftriaxone is a commonly utilized antibiotic for the treatment of urinary tract infections (UTI) despite the limited literature supporting its use. Opportunities for antimicrobial stewardship (ASP), including IV-to-PO conversions and de-escalation of therapy, are often missed in the hospital setting. Objective: The study reported here describes the utilization of ceftriaxone in patients admitted to the hospital and treated for UTIs in a large health system, focusing on opportunities for IV-to-PO conversion of antibiotic therapy. Methods: This was a multi-center, retrospective, descriptive study conducted in a large health system. Patients admitted from January 2019 to July 2019 were included for analysis if they were 18 years or older at admission, diagnosed with acute cystitis, acute pyelonephritis, or unspecified UTI, and received two or more doses of ceftriaxone. The primary outcome was to evaluate the percentage of patients who were eligible for conversion from IV ceftriaxone to oral antibiotics while admitted to the hospital based on the defined criteria for automatic pharmacist conversion in the health system. Percentage of urine cultures with susceptibility to cefazolin, the duration of antibiotic therapy in the hospital, and an evaluation of oral antibiotics prescribed at discharge were also recorded. Results: A total of 300 patients were included; 88% met the pre-specified criteria for IV-to-PO conversion, but only 12% were converted from IV-to-PO antibiotics during hospitalization. Approximately 65% of patients remained on IV ceftriaxone until discharge, at which time they were converted to a PO antibiotic, most commonly fluoroquinolones followed by third-generation cephalosporins. Conclusion: Patients admitted to the hospital and receiving treatment with ceftriaxone for UTI were infrequently converted to oral therapy prior to discharge despite meeting criteria for automatic pharmacist IV-to-PO conversion. Findings highlight opportunities to contribute to antimicrobial stewardship initiatives across the health system and the importance of tracking and reporting results to frontline providers.

Fidaxomicin Compared With Oral Vancomycin for the Treatment of Severe Clostridium difficile-Associated Diarrhea: A Retrospective Review.

Purpose: The most recent published guidelines on Clostridium difficile-associated diarrhea (CDAD) developed by the Infectious Diseases Society of America (IDSA) were released in 2017 and outline its treatment based on severity of the disease and recurrence; however, a clear first-line agent has not been recommended specifically for severe CDAD. Methods: This retrospective chart review was approved by the institutional review board and consisted of three community hospitals and one academic medical center. To be included, patients need to meet criteria for severe CDAD and receive at least 72 hours of therapy. Patients received either oral vancomycin or fidaxomicin, in addition to other therapies for CDAD, and differences in outcomes such as cost obtained from a common charge center, rates of recurrence, time to recurrence as measured at time of positive to negative polymerase chain reaction (PCR) test, and mortality were assessed. Results: Of the 147 patients, 74 patients received fidaxomicin and 73 patients received oral vancomycin. The average hospitalization cost for patients receiving fidaxomicin was $129,338.69 and for patients receiving vancomycin was $153,563.81 (P = .26). Recurrence rates were lower with fidaxomicin compared with vancomycin (6.8% vs 17.6%; P = .047), and time to recurrence was longer with fidaxomicin versus vancomycin, but not statistically significant (96.8 ± 45.9 days vs 63.2 ± 66.9 days; P = .321). Mortality, length of stay in the intensive care unit, and overall length of stay were similar between the two therapies. Conclusions: In the treatment of severe CDAD, recurrence rates were lower and time to recurrence was higher with fidaxomicin compared with oral vancomycin. A clear financial benefit has yet to translate from these known findings.

Real-world daptomycin use across wide geographical regions: results from a pooled analysis of CORE and EU-CORE.

BACKGROUND: Pooled data from two large registries, Cubicin(®) Outcomes Registry and Experience (CORE; USA) and European Cubicin(®) Outcomes Registry and Experience (EU-CORE; Europe, Latin America, and Asia), were analyzed to determine the characteristics and clinical outcomes of daptomycin therapy in patients with Gram-positive infections across wide geographical regions. METHODS: Patients receiving at least one dose of daptomycin between 2004 and 2012 for the treatment of Gram-positive infections were included. Clinical success was defined as an outcome of 'cured' or 'improved'. Post-treatment follow-up data were collected for a subset of patients (CORE: osteomyelitis and orthopedic foreign body device infection; EU-CORE: endocarditis, intracardiac/intravascular device infection, osteomyelitis, and orthopedic device infection). Safety was assessed for up to 30 days after daptomycin treatment. RESULTS: In 11,557 patients (CORE, 5482; EU-CORE, 6075) treated with daptomycin (median age, 62 [range, 1-103] years), the most frequent underlying conditions were cardiovascular disease (54.7 %) and diabetes mellitus (28.0 %). The most commonly treated primary infections were complicated skin and soft tissue infection (cSSTI; 31.2 %) and bacteremia (21.8 %). The overall clinical success rate was 77.2 % (uncomplicated SSTI, 88.3 %; cSSTI, 81.0 %; osteomyelitis, 77.7 %; foreign body/prosthetic infection (FBPI), 75.9 %; endocarditis, 75.4 %; and bacteremia, 69.5 %). The clinical success rate was 79.1 % in patients with Staphylococcus aureus infections (MRSA, 78.1 %). An increasing trend of high-dose daptomycin (>6 mg/kg/day) prescribing pattern was observed over time. Clinical success rates were higher with high-dose daptomycin treatment for endocarditis and FBPI. Adverse events (AEs) and serious AEs possibly related to daptomycin therapy were reported in 628 (5.4 %) and 133 (1.2 %) patients, respectively. CONCLUSIONS: The real-world data showed that daptomycin was effective and safe in the treatment of various Gram-positive infections, including those caused by resistant pathogens, across wide geographical regions.

Leveling Up: Evaluation of IV v. PO Linezolid Utilization and Cost after an Antimicrobial Stewardship Program Revision of IV to PO Conversion Criteria within a Healthcare System.

The CDC's Core Elements of an Antimicrobial Stewardship Program (ASP) lists intravenous (IV) to oral (PO) conversion as an important pharmacy-based intervention. However, despite the existence of a pharmacist-driven IV to PO conversion protocol, conversion rates within our healthcare system remained low. We aimed to evaluate the impact of a revision to the current conversion protocol on conversion rates, using linezolid as a marker due to its high PO bioavailability and high IV cost. This retrospective, observational study was conducted within a healthcare system composed of five adult acute care facilities. The conversion eligibility criteria were evaluated and revised on 30 November 2021. The pre-intervention period started February 2021 and ended November 2021. The post-intervention period was December 2021 to March 2022. The primary objective of this study was to establish if there was a difference in PO linezolid utilization reported as days of therapy per 1000 days present (DOT/1000 DP) between the pre- and post-intervention periods. IV linezolid utilization and cost savings were investigated as secondary objectives. The average DOT/1000 DP for IV linezolid decreased from 52.1 to 35.4 in the pre- and post-intervention periods, respectively (p < 0.01). Inversely, the average DOT/1000 DP for PO linezolid increased from 38.9 in the pre-intervention to 58.8 for the post-intervention period, p < 0.01. This mirrored an increase in the average percentage of PO use from 42.9 to 62.4% for the pre- and post-intervention periods, respectively (p < 0.01). A system-wide cost savings analysis showed projected total annual cost savings of USD 85,096.09 for the system, with monthly post-intervention savings of USD 7091.34. The pre-intervention average monthly spend on IV linezolid at the academic flagship hospital was USD 17,008.10, which decreased to USD 11,623.57 post-intervention; a 32% reduction. PO linezolid spend pre-intervention was USD 664.97 and increased to USD 965.20 post-intervention. The average monthly spend on IV linezolid for the four non-academic hospitals was USD 946.36 pre-intervention, which decreased to USD 348.99 post-intervention; a 63.1% reduction (p < 0.01). Simultaneously, the average monthly spend for PO linezolid was USD 45.66 pre-intervention and increased to USD 71.19 post-intervention (p = 0.03) This study shows the significant impact that an ASP intervention had on IV to PO conversion rates and subsequent spend. By revising criteria for IV to PO conversion, tracking and reporting results, and educating pharmacists, this led to significantly more PO linezolid use and reduced the overall cost in a large healthcare system.

Can't keep it SECRET: system evaluation of carbapenem restriction against empirical therapy.

Objectives: Carbapenems are appealing agents for empirical use given their broad spectrum of activity; however, selective use is vital in minimizing the risk for development of carbapenem-resistant pathogens. We aimed to examine the impact of carbapenem restriction criteria and a pre-authorization process on utilization and cost savings across a health system. Methods: This retrospective study was conducted across five adult hospitals. The pre-implementation period was 8 February 2020 to 30 April 2020 and the post-implementation period was 8 February 2022 to 30 April 2022. The primary outcome was to compare the number of orders for carbapenems between the study periods for both the intervention and non-intervention hospitals. Secondary outcomes included projected annual cost and an estimated cost-savings evaluation using a stratified analysis for the intervention and non-intervention facilities to account for more resource-limited settings. Results: The total number of carbapenem orders decreased between study periods at the intervention hospital (246 versus 61, P < 0.01). At the non-intervention hospitals, orders decreased, although not significantly (333 versus 279, P = 0.58). Meropenem orders decreased by 66% compared with 12% for the intervention and the non-intervention hospitals, respectively (P < 0.001). Annual estimated cost for all facilities was $255 561 in the pre-implementation period compared with $29 593 in the post-implementation period (P < 0.001). Using a stratified analysis to account for available resources, the estimated annual cost saving was $225 968 for the system. Conclusions: Implementation of carbapenem restriction at the intervention hospital decreased utilization and provided significant cost savings. Furthermore, resource-limited facilities can still experience significant cost savings using a stratified antimicrobial stewardship intervention approach.

Residual Infusion Performance Evaluation (RIPE): A Single-Center Evaluation of Residual Volume Post-Intravenous Eravacycline Infusion.

Intravenous (IV) drugs are administered through infusion pumps and IV administration sets for patients who are seen in healthcare settings. There are multiple areas of the medication administration process that can influence the amount of a drug a patient receives. For example, IV administration sets that deliver a drug from an infusion bag to a patient vary in terms of length and bore. In addition, fluid manufacturers report that the total acceptable volume range for a 250 mL bag of normal saline can be anywhere from 265 to 285 mL. At the institution chosen for our study, each 50 mg vial of eravacycline is reconstituted using 5 mL of diluent, and the total dose is administered as a 250 mL admixture. This single-center, retrospective, quasi-experimental study evaluated the residual medication volume after the completion of an IV eravacycline infusion in patients admitted during the pre-intervention study period compared to those in the post-intervention study period. The primary outcome of the study was to compare the residual antibiotic volume remaining in the bags following IV infusions of eravacycline before and after the implementation of interventions. The secondary outcomes included the following: comparing the amount of the drug lost in the pre- and post-intervention periods, determining whether the amount of residual volume was affected by nursing shifts (day versus night), and lastly assessing the cost of facility drug waste. On average, approximately 15% of the total bag volume was not infused during the pre-intervention period, which was reduced to less than 5% in the post-intervention period. Clinically, the average estimated amount of eravacycline discarded decreased from 13.5 mg to 4.7 mg in the pre- and post-intervention periods, respectively. Following the statistically significant results of this study, the interventions were expanded at this facility to include all admixed antimicrobials. Further studies are needed to determine the potential clinical impact when patients do not receive complete antibiotic infusions.

Assessing clinical cure of empirical piperacillin/tazobactam for ESBL urinary tract infections (ACCEPT-UTI).

Background: Data are limited regarding use of piperacillin/tazobactam for ESBL urinary tract infections (UTIs). The objective of this study was to compare clinical outcomes of patients treated empirically with piperacillin/tazobactam versus carbapenems for ESBL UTIs. Methods: This retrospective, observational, propensity score-matched study evaluated adults with an ESBL on urine culture. Patients who had UTI symptoms or leukocytosis, and who received a carbapenem or piperacillin/tazobactam empirically for at least 48 h were included. The primary outcome was clinical success within 48 h, defined as resolution of temperature (36-38°C), resolution of symptoms or leukocytosis (WBC <12 × 103/µL) in the absence of documented symptoms, and the absence of readmission for an ESBL UTI within 6 months. Secondary outcomes included time to clinical resolution, hospital length of stay, and in-hospital and 30 day all-cause mortality. Results: Overall, 223 patients were included in the full cohort and 200 patients in the matched cohort (piperacillin/tazobactam = 100, carbapenem = 100). Baseline characteristics were similar between the groups. There was no difference in the primary outcome of clinical success between the carbapenem and piperacillin/tazobactam groups (58% versus 56%, respectively; P = 0.76). Additionally, there was no difference in median (IQR) time to clinical resolution [38.9 h (21.5, 50.9 h) versus 40.3 h (27.4, 57.5 h); P = 0.37], in-hospital all-cause mortality (3% versus 3%; P = 1.00), or 30 day all-cause mortality (4% versus 2%; P = 0.68) between the carbapenem and piperacillin/tazobactam groups, respectively. Conclusions: There was no significant difference in clinical success for patients treated empirically with piperacillin/tazobactam compared with carbapenems for ESBL UTIs.

Evaluation of Dalbavancin in Vancomycin Allergic Patients: A Case Series.

PURPOSE: There is a paucity of data regarding dalbavancin use in patients with a vancomycin allergy because of potential cross-reactivity between the 2 glycopeptide antibiotics. METHODS: A retrospective medical record review was performed between February 2016 and February 2021 in patients with a listed vancomycin allergy who received dalbavancin as an outpatient infusion and had a listed vancomycin allergy in the electronic health record. FINDINGS: There were 559 unique patients during the study period who received dalbavancin as an outpatient infusion, 10 of whom had a documented vancomycin allergy in the electronic health record. Four of the 10 patients had a history of a type I IgE-mediated reaction to vancomycin, 1 patient reported delayed rash, 2 patients reported a vancomycin infusion reaction, 2 patients reported acute kidney injury, and 1 patient reported intolerance with general malaise. All 10 patients received at least 1 dose of dalbavancin with no reported adverse events. IMPLICATIONS: This case series displays that all patients who received dalbavancin tolerated the infusion well with no adverse events reported. Dalbavancin may be a viable option for patients with a listed vancomycin allergy.

A retrospective, multicentre evaluation of eravacycline utilisation in community and academic hospitals.

OBJECTIVES: Eravacycline is a novel, fully-synthetic tetracycline approved by the FDA for treatment of complicated intra-abdominal infections in August 2018. This study sought to characterise early clinical experience with this novel antibiotic. METHODS: Eravacycline utilisation for 66 patients was retrospectively evaluated. RESULTS: Eravacycline was used as monotherapy in 62.1% of cases. Mean duration of therapy was 13.1 ± 9.9 days. The majority (68.2%) of treatment was for off-label indications, including 34.8% for pulmonary and 28.8% for skin/soft tissue infections. A number of difficult-to-treat organisms were encountered: 50% of identified Gram-negative pathogens were resistant to carbapenems in vitro; and 48% of identified Gram-positive pathogens were resistant to vancomycin in vitro. The patient population had a high illness acuity, with 42.4% requiring ICU admission, 59.1% having ≥2 co-morbidities and 33.3% having ≥3 co-morbidities. Nevertheless, 95.5% experienced clinical improvement, with 86.4% achieving full infection resolution following eravacycline. Three patients who did not experience clinical improvement had an intra-abdominal source of infection without adequate source control. The remaining six who did not experience full infection resolution died from unrelated non-infectious causes during hospital admission. Adverse events were uncommon (4.5%), limited to nausea/vomiting, and not leading to eravacycline discontinuation. Although two patients had a history of Clostridioides difficile infection (CDI), no patients developed CDI while receiving eravacycline. CONCLUSION: These results illustrate the potential versatility of eravacycline with a broad activity spectrum, good safety and tolerability profile, flexibility for use in patients with renal injury or antibiotic allergies, and positive clinical outcomes in this real-world cohort.

Criteria Restricting Inappropriate Meropenem Empiricism (CRIME): a quasi-experimental carbapenem restriction pilot at a large academic medical centre.

The broad-spectrum activity of carbapenems makes them appealing for empirical use; however, they are associated with development of Clostridioides difficile infection (CDI) and multidrug resistance. Selective carbapenem use is vital in maintaining their effectiveness. We examined the impact of meropenem restriction criteria on utilisation and patient outcomes. This quasi-experimental study was conducted at a single academic medical centre after medication use evaluation found frequent inappropriate meropenem utilisation. Antimicrobial stewardship-led restriction criteria were developed and implemented in February 2022. Investigators aimed to determine how restriction criteria affected meropenem utilisation across 8 weeks in the pre- (February-April 2020) versus post-implementation period (February-April 2022). The primary outcome was inappropriateness of meropenem utilisation. Secondary outcomes included days of therapy per 1000 patient-days (DOT/1000 PD), hospital length of stay (LOS), CDI Standardized Infection Ratio (SIR), and acquisition cost. Across the 8-week timeframes, reductions in inappropriate meropenem use (64.5% vs. 12.8%; P < 0.001), duration of therapy [5.8 (3.2-7.3) vs. 2.4 (1.0-5.5) days; P < 0.001] and utilisation (30.5 vs. 8.3 DOT/1000 PD; P < 0.001) pre- versus post-implementation were observed. Total meropenem orders decreased by 65% (P < 0.001). Median hospital LOS also decreased between periods [11.9 (7.8-20.4) vs. 9.2 (5.4-15.2) days], although not statistically significant (P = 0.051). There was no difference in CDI SIR (0.1 vs. 0.1; P = 0.99). Projected annual cost savings were ∼US$57 300. Implementation of antimicrobial stewardship-initiated restriction criteria can reduce inappropriate meropenem utilisation, overall number of orders, and total duration of therapy.

Asymptomatic colonic histoplasmosis in a patient receiving methotrexate.

Disease due to infection with Histoplasma capsulatum usually manifests as a disseminated infection in patients with the Acquired Immunodeficiency Syndrome (AIDS). However, it may also present with focal disease in patients with or without AIDS. Unusual presentations or less well-recognized risk factors may make diagnosis of histoplasmosis more difficult. We describe the case of a patient who presented for screening colonoscopy and was found to have isolated asymptomatic colonic histoplasmosis.

Scedosporium apiospermum infection presenting as a pneumothorax and cavitary lung lesions in a patient with acquired immune deficiency syndrome.

The Scedosporium genus consists of filamentous fungi that inhabit soil, sewage, manure, and polluted waters, and contains two medically important species: Scedosporium apiospermum and Scedosporium prolificans. Scedosporiosis is caused by inhalation or traumatic subcutaneous implantation of the organism, and may have varied clinical presentations. A variety of pulmonary manifestations can occur, but to our knowledge, pneumothorax as initial presentation has not been reported. Treatment may be difficult, as the disease occurs more commonly in immunocompromised patients, and the organism may demonstrate resistance to various antifungal agents. We describe successful treatment of extensive pulmonary disease due to S apiospermum in a patient with acquired immune deficiency syndrome (AIDS).

Bordetella bronchiseptica bacteremia in a patient with AIDS.

Bordetella bronchiseptica bacteremia is often associated with various infection in animals. The majority of B bronchiseptica infections reported in humans are cases of pneumonia. Very few cases have been reported in patients with a history of acquired immune deficiency syndrome (AIDS). The patient described herein, who had a history of AIDS, was likely infected with B bronchiseptica as a result of his hemodialysis catheter. The patient was successfully treated with antibiotics without the removal of the catheter.

Clinical Experience with Telavancin for the Treatment of Patients with Bacteremia and Endocarditis: Real-World Results from the Telavancin Observational Use Registry (TOUR™).

BACKGROUND: Bacteremia and endocarditis caused by Staphylococcus aureus (S. aureus), particularly methicillin-resistant S. aureus (MRSA), are challenging to treat and are associated with high morbidity and mortality. Telavancin is a lipoglycopeptide antibacterial active against susceptible Gram-positive pathogens, including MRSA. OBJECTIVE: This registry study assessed the real-world use and clinical outcomes of telavancin in patients with bacteremia or endocarditis enrolled in the Telavancin Observation Use Registry (TOUR™). METHODS: The subset of patients enrolled in TOUR who were diagnosed with endocarditis and/or bacteremia with a known or unknown primary source (N = 151) were analyzed. Data including demographics, infection type, baseline pathogens, prior or concomitant antimicrobial therapy, dosing regimen, clinical response, treatment-emergent adverse events (TEAEs) of interest, and mortality were collected by retrospective medical chart review. RESULTS: Telavancin was primarily used as a second-line or greater therapy (n = 132, 87.4%). MRSA was present in 87 (57.6%) patients. Median telavancin dose was 740.6 mg (interquartile range (IQR) 206.0 mg) and median duration of therapy was 9.0 days (IQR 24.0 days). Of the 132/151 (87.4%) patients with an available assessment at the end of telavancin therapy, a positive clinical response was achieved in 98/132 (74.2%), while 14/132 (10.6%) failed therapy and 20/132 (15.2%) had an indeterminant outcome. TEAEs occurred in 24 (15.9%) patients. The most frequent TEAE was renal failure (n = 12, 7.9%); seven of these patients were receiving concomitant nephrotoxic medications. There was no change in creatinine clearance for 67/89 (75.3%) patients with values recorded at the beginning and the end of telavancin therapy. CONCLUSIONS: In real-world clinical practice, overall positive clinical outcomes are observed in patients with bacteremia or endocarditis treated with telavancin, including in those patients infected with MRSA or another S. aureus pathogen. Telavancin may be an alternative treatment option for these patients. TRIAL REGISTRATION: This trial was registered with clinicaltrials.gov (NCT02288234) on 11 November 2014.

Real-world use of telavancin in the treatment of osteomyelitis.

This is a retrospective analysis of patients with osteomyelitis who received telavancin at some time during their treatment course. The primary outcome was the percent of patients cured or improved at the end of telavancin therapy (EOTT). The secondary outcome was the percent of patients cured or improved three months after discontinuation of telavancin therapy. There were 32 cases of osteomyelitis with methicillin-resistant Staphylococcus aureus identified in 17 (56.7%), methicillin-sensitive Staphylococcus aureus 2(6.6%), coagulase negative staphylococci 6 (20.0%) and other pathogens, 5 (16.7%). At EOTT, 87.5% of patients had their osteomyelitis cured and 94.6% had the infection cured at three months after telavancin was completed. The most common adverse events associated with telavancin were gastrointestinal in nature (nausea (25.8%), vomiting (9.7%) and diarrhea (3.2%)) followed by metallic taste (6.5%). A favorable outcome was achieved for many patients receiving the antimicrobial regimen that included telavancin for the treatment of osteomyelitis.