Novel quinoline derivatives with broad-spectrum antiprotozoal activities.

Several quinoline derivatives incorporating arylnitro and aminochalcone moieties were synthesized and evaluated in vitro against a broad panel of trypanosomatid protozoan parasites responsible for sleeping sickness (Trypanosoma brucei rhodesiense), nagana (Trypanosoma brucei brucei), Chagas disease (Trypanosoma cruzi), and leishmaniasis (Leishmania infantum). Several of the compounds demonstrated significant antiprotozoal activity. Specifically, compounds 2c, 2d, and 4i displayed submicromolar activity against T. b. rhodesiense with half-maximal effective concentration (EC50) values of 0.68, 0.8, and 0.19 µM, respectively, and with a high selectivity relative to human lung fibroblasts and mouse primary macrophages (∼100-fold). Compounds 2d and 4i also showed considerable activity against T. b. brucei with EC50 values of 1.4 and 0.4 µM, respectively.

Methicillin-Resistant Staphylococcus aureus Bacteremia Treated With Vancomycin Calculated by Area-Under-the-Curve in Patients With Elevated Vancomycin Minimum Inhibitory Concentrations.

Purpose: Vancomycin is recommended as first-line treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, dosed by area-under-the-curve (AUC) with an assumed minimum inhibitory concentration (MIC) of 1 mcg/mL via broth microdilution. The purpose of this study was to compare effectiveness of AUC-based and trough-based dosing in MRSA bacteremia with an MIC > 1 mcg/mL via Etest. Methods: This was a retrospective, observational cohort that compared vancomycin dosed by AUC or trough between January 1, 2017 and September 1, 2022. The primary outcome was a composite of treatment failure defined as peristent bacteremia ≥ 7 days, inpatient mortality within 90 days, or microbiologic relapse or readmission within 30 days. Secondary outcomes compared nephrotoxicity, hospital and ICU length of stay, MIC differences, and difference in exposure measured by AUC. Results: Twenty-four patients in each group met inclusion criteria. For the primary outcome, there was no statistical difference in treatment failure between trough and AUC groups, respectively [10 (41.7%) vs 10 (41.7%), P = 1.000]. There was no statistical difference in secondary outcomes, with incidence of nephrotoxicity [3 (12.5%) trough vs 2 (8.33%) AUC, P = 1.000] and median AUC exposure over treatment course [502.9 mcg.h/mL (454.1-599.9) vs 474 mcg.h/mL (435.3-533), P = .312] similar between groups. Conclusion: There was no statistically significant difference in treatment failure for vancomycin by AUC or trough with an Etest MIC > 1 mcg/mL. Overall exposure to vancomycin and incidence of nephrotoxicty were numerically higher in the trough group, suggesting that dosing by AUC may limit exposure without impact on treatment failure.

Evaluation of an Automated, Pharmacist-Driven, Antimicrobial Patient Acuity Scoring System for Hospitalized Bacteremic Patients.

Purpose: The implementation of an automated, pharmacist-driven, scoring system within the EMR has been shown to improve patient care in patients with Staphylococcus aureus bacteremia by increasing the adherence to disease specific quality-of-care measures. However, there are a lack of studies evaluating the incorporation of blood culture review into standard, non-antimicrobial stewardship pharmacist workflow. Our institution implemented an automated, pharmacist-driven, antimicrobial scoring system in the electronic medical record (EMR) on August 6, 2019. Methods: This was a retrospective, single-center, quasi-experimental study of hospitalized, non-critically ill adult (18-89 years of age) patients with bacteremia between July 6, 2018 and July 5, 2019 (pre-implementation group) and September 6, 2019 and September 5, 2020 (post-implementation group). The primary outcome was time to directed antibiotic therapy in patients with positive blood cultures. Secondary outcomes included hospital length-of-stay, days of therapy (DOT) while inpatient, time to effective therapy, 30-day all-cause mortality, and rates of Clostridioides difficile infections documented within 3 months of positive culture results. Results: Implementation of the antimicrobial scoring system did not result in a significant change in time to directed antibiotic therapy (32.5 hours vs 37.4 hours; P = .757). There was also no difference found for time to effective antibiotic therapy (-12.6 hours vs -14.2 hours; P =.905) and no difference found for all other secondary outcomes. Conclusion: The implementation of the antimicrobial scoring system did not lead to an improvement in clinical outcomes. Further research is needed to better define a patient population that may benefit from this system.

Benefits of Accepting Infectious Diseases Pharmacist Recommendations: A 5-Year Outcome Study in a Multihospital System.

Background: Infectious diseases (ID) pharmacists are pivotal members of antimicrobial stewardship teams. Prospective audit and feedback is a strong recommendation by The Infectious Diseases Society of America Guidelines for Antimicrobial Stewardship Programs (ASP). Utilizing customized ASP intervention documentation tools known as "ivents" in Epic, we aimed to assess the impact of interventions by measuring outcomes that were accepted compared to those that were rejected in a multihospital health system over 5 years. Methods: A multicenter, retrospective cohort study was conducted to compare clinical outcomes among intensive care unit (ICU) and non-ICU patients with accepted and rejected ASP interventions over 5 years from October 2015 to December 2020. Outcomes measured included antibiotic days of therapy per 1000 patient days (DOT/1000 PD), antibiotic doses per 1000 patient days (doses/1000 PD), hospital length of stay (LOS), in-hospital mortality, hospital-acquired Clostridioides difficile infection (HA-CDI), community-onset C. difficile infection (CO-CDI) within 30 days, and hospital readmission within 30 days. Coarsened exact matching (CEM) was used as a non-parametric matching method to balance covariates between groups and to control for confounding. Results: ASP recommendations by ID pharmacists were well-received by providers in a multihospital system over 5 years as evidenced by an overall acceptance rate of 92%. Acceptance of ASP interventions was associated with substantial reductions in antibiotic utilization without adversely affecting mortality or hospital readmissions. While high-risk C. difficile antibiotic use increased significantly due to frequent de-escalation to ceftriaxone among non-ICU patients with accepted interventions, rates of HA-CDI and CO-CDI within 30 days did not worsen. Furthermore, hospital LOS was notably shorter by an average of 1 day for non-ICU patients with accepted interventions, which resulted in substantial cost avoidance of $7 631 400. Conclusion: Collaboration with ID pharmacists to optimize antimicrobial stewardship was associated with significant reductions in antibiotic utilization, costs, and hospital LOS without worsening patient outcomes.

Asymptomatic Urinary Tract Infection Treatment in Adults Admitted to Inpatient Psychiatry: A Retrospective COHORT study.

Introduction: Treatment of asymptomatic bacteriuria remains prevalent despite recommendations against treatment in most patient populations. Rates of asymptomatic treatment of urinary tract infection (UTI) has not been thoroughly evaluated within the inpatient psychiatry population. The objective of this study is to describe the rate of antibiotic use for the treatment of asymptomatic UTI in psychiatric inpatients and investigate factors contributing to overuse. Methods: This IRB approved retrospective cohort study evaluated adults admitted to inpatient psychiatry from May 1, 2021 to May 1, 2022 that received an antibiotic for UTI. The primary outcome assessed the rate of asymptomatic treatment, defined as treatment without urinary symptoms. Secondary outcomes evaluated most frequently prescribed antibiotics, determined the impact of altered mental status (AMS) on treatment, and correlated the incidence of UTI treatment with primary psychiatric disorder. Results: One hundred nine patients were identified and 61 were included for analysis. The rate of asymptomatic treatment for UTI was 84%. The most prescribed antibiotic was nitrofurantoin (48%). All patients with AMS (23%) were asymptomatic. Altered mental status did not significantly impact the rate of empiric treatment (P = .098). Primary psychiatric disorder did not significantly impact rate of empiric treatment for UTI (P = .696). Common disorders in this population were depression, schizophrenia, and bipolar disorder with rates of asymptomatic treatment of 79% (n = 19), 87% (n = 13), and 78% (n = 7), respectively. Discussion: Frequent asymptomatic treatment of UTI was identified in this inpatient psychiatry population. These results emphasize the need for antibiotic monitoring and stewardship in this setting.

Impact of Limiting Vancomycin Loading Doses in Patients With Methicillin-resistant Staphylococcus aureus Infections After Hospital Protocol Revision.

Background: Vancomycin loading doses are commonly used to quickly attain target serum concentrations; however, data supporting their effect on clinical patient outcomes is limited. In April 2020, our institution revised our pharmacist-driven vancomycin dosing protocol to reserve loading doses for hemodynamically unstable patients with suspected serious methicillin-resistant Staphylococcus aureus (MRSA) infections. Prior to the protocol update, all patients treated with vancomycin at our institution received a weight-based loading dose. The purpose of this study is to assess clinical efficacy and safety outcomes related to the use of vancomycin loading doses. Methods: A retrospective, quasi-experimental study was performed to compare clinical outcomes in adult patients treated with vancomycin for laboratory-confirmed MRSA infections. Patients who received vancomycin therapy prior to our institution's vancomycin dosing protocol revisions (pre-intervention) were compared to patients who received vancomycin after the revisions (post-intervention). The primary outcome was all-cause, inpatient mortality. Secondary outcomes included persistent signs and symptoms of infection ≥5 days after vancomycin initiation, switch to alternative anti-MRSA therapy, and nephrotoxicity. Results: A total of 122 patients (63 pre-intervention patients and 59 post-intervention patients) were included. Receipt of a vancomycin loading dose did not impact the rate of inpatient mortality (4.76%vs 6.78%; OR 1.46, 95% CI [0.31, 6.79]). All secondary outcomes were similar between the two groups, including persistent signs and symptoms of infection, switch to alternative anti-MRSA therapy, and nephrotoxicity. Conclusions: Routine use of vancomycin loading doses is not associated with improved outcomes in hemodynamically stable patients with MRSA infections.

Impact of a Pharmacist-Driven Medication Diluent Volume Optimization Protocol on Fluid Balance and Outcomes in Critically Ill Patients.

Background: Volume overload (VO) is common in the intensive care unit (ICU) and associated with negative outcomes. Approaches have been investigated to curtail VO; however, none specifically focused on medication diluent volume optimization. Objective: Investigate the impact of a pharmacist-driven medication diluent volume optimization protocol on fluid balance in critically ill patients. Methods: A prospective, pilot study was conducted in a medical ICU during October 2021 to December 2021 (pre) and February 2022 to April 2022 (post). A pharmacist-driven medication diluent volume optimization protocol focusing on vasopressor and antimicrobial diluent volumes was implemented. Demographics and clinical data were collected during ICU admission up to 7 days. The primary outcome was net fluid balance on day 3. Secondary outcomes were medication volumes administered, net fluid balance, ICU length of stay, and mortality. Results: Supply chain shortages caused the study to stop at the end of February 2022. Overall, 152 patients were included (123 pre group, 29 post group). The most common admission diagnosis was acute respiratory failure (35%). Vasopressors and antimicrobials were utilized in 47% and 66% of patients, respectively. Net fluid balance on day 3 was greater but not significant in the post group (227.1 mL [-1840.3 to 3483.7] vs 2012.3 mL [-2686.0 to 4846.0]; P = .584). Antimicrobial diluent volumes were significantly less in the post group. No differences were seen in other secondary outcomes. Protocol group assignment was not associated with net fluid balance on day 3. Conclusion: Despite decreasing antimicrobial volume contributions, optimizing diluent volumes alone did not significantly impact overall volume status. Future studies should focus on comprehensive approaches to medication diluent optimization and fluid stewardship.

Functionalization of Chlorotonils: Dehalogenil as Promising Lead Compound for In Vivo Application.

The natural product chlorotonil displays high potency against multidrug-resistant Gram-positive bacteria and Plasmodium falciparum. Yet, its scaffold is characterized by low solubility and oral bioavailability, but progress was recently made to enhance these properties. Applying late-stage functionalization, we aimed to further optimize the molecule. Previously unknown reactions including a sulfur-mediated dehalogenation were revealed. Dehalogenil, the product of this reaction, was identified as the most promising compound so far, as this new derivative displayed improved solubility and in vivo efficacy while retaining excellent antimicrobial activity. We confirmed superb activity against multidrug-resistant clinical isolates of Staphylococcus aureus and Enterococcus spp. and mature transmission stages of Plasmodium falciparum. We also demonstrated favorable in vivo toxicity, pharmacokinetics and efficacy in infection models with S. aureus. Taken together, these results identify dehalogenil as an advanced lead molecule.

Establishment of an In Bacterio Assay for the Assessment of Carbon Storage Regulator A (CsrA) Inhibitors.

Polymicrobial infections involving various combinations of microorganisms, such as Escherichia, Pseudomonas, or Yersinia, can lead to acute and chronic diseases in for example the gastrointestinal and respiratory tracts. Our aim is to modulate microbial communities by targeting the posttranscriptional regulator system called carbon storage regulator A (CsrA) (or also repressor of secondary metabolites (RsmA)). In previous studies, we identified easily accessible CsrA binding scaffolds and macrocyclic CsrA binding peptides through biophysical screening and phage display technology. However, due to the lack of an appropriate in bacterio assay to evaluate the cellular effects of these inhibitor hits, the focus of the present study is to establish an in bacterio assay capable of probing and quantifying the impact on CsrA-regulated cellular mechanisms. We have successfully developed an assay based on a luciferase reporter gene assay, which in combination with a qPCR expression gene assay, allows for the monitoring of expression levels of different downstream targets of CsrA. The chaperone protein CesT was used as a suitable positive control for the assay, and in time-dependent experiments, we observed a CesT-mediated increase in bioluminescence over time. By this means, the cellular on-target effects of non-bactericidal/non-bacteriostatic virulence modulating compounds targeting CsrA/RsmA can be evaluated.

Small-molecule metabolites in SARS-CoV-2 treatment: a comprehensive review.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has quickly spread all over the world. In this respect, traditional medicinal chemistry, repurposing, and computational approaches have been exploited to develop novel medicines for treating this condition. The effectiveness of chemicals and testing methods in the identification of new promising therapies, and the extent of preparedness for future pandemics, have been further highly advantaged by recent breakthroughs in introducing noble small compounds for clinical testing purposes. Currently, numerous studies are developing small-molecule (SM) therapeutic products for inhibiting SARS-CoV-2 infection and replication, as well as managing the disease-related outcomes. Transmembrane serine protease (TMPRSS2)-inhibiting medicinal products can thus prevent the entry of the SARS-CoV-2 into the cells, and constrain its spreading along with the morbidity and mortality due to the coronavirus disease 2019 (COVID-19), particularly when co-administered with inhibitors such as chloroquine (CQ) and dihydroorotate dehydrogenase (DHODH). The present review demonstrates that the clinical-stage therapeutic agents, targeting additional viral proteins, might improve the effectiveness of COVID-19 treatment if applied as an adjuvant therapy side-by-side with RNA-dependent RNA polymerase (RdRp) inhibitors.

Evaluating the druggability of TrmD, a potential antibacterial target, through design and microbiological profiling of a series of potent TrmD inhibitors.

The post-transcriptional modifier tRNA-(N1G37) methyltransferase (TrmD) has been proposed to be essential for growth in many Gram-negative and Gram-positive pathogens, however previously reported inhibitors show only weak antibacterial activity. In this work, optimisation of fragment hits resulted in compounds with low nanomolar TrmD inhibition incorporating features designed to enhance bacterial permeability and covering a range of physicochemical space. The resulting lack of significant antibacterial activity suggests that whilst TrmD is highly ligandable, its essentiality and druggability are called into question.

Diarylpentanoids, the privileged scaffolds in antimalarial and anti-infectives drug discovery: A review.

Asia is a hotspot for infectious diseases, including malaria, dengue fever, tuberculosis, and the pandemic COVID-19. Emerging infectious diseases have taken a heavy toll on public health and the economy and have been recognized as a major cause of morbidity and mortality, particularly in Southeast Asia. Infectious disease control is a major challenge, but many surveillance systems and control strategies have been developed and implemented. These include vector control, combination therapies, vaccine development, and the development of new anti-infectives. Numerous newly discovered agents with pharmacological anti-infective potential are being actively and extensively studied for their bioactivity, toxicity, selectivity, and mode of action, but many molecules lose their efficacy over time due to resistance developments. These facts justify the great importance of the search for new, effective, and safe anti-infectives. Diarylpentanoids, a curcumin derivative, have been developed as an alternative with better bioavailability and metabolism as a therapeutic agent. In this review, the mechanisms of action and potential targets of antimalarial drugs as well as the classes of antimalarial drugs are presented. The bioactivity of diarylpentanoids as a potential scaffold for a new class of anti-infectives and their structure-activity relationships are also discussed in detail.

Appropriateness of Empirical Antibiotic Therapy for Cervicitis and Urethritis Prescribed in the Emergency Department.

Objectives: Sexually transmitted infections are a prevalent global health care problem. Treatment guidelines have recently been updated as a result of antimicrobial resistance and public health trends. The aim of the study was to assess the appropriateness of empirical antibiotic therapy prescribed for cervicitis and urethritis in the emergency department. Methods: We designed a retrospective observational cohort study. We included adult patients with suspected cervicitis or urethritis who attended the emergency department of a tertiary hospital in 2020. We excluded patients with suspected pelvic inflammatory disease, pregnancy or prostatitis and those requiring admission to hospital. Appropriateness of empirical antibiotic therapy was evaluated taking into account 4 aspects: indication, dosing, duration of therapy, and route of administration. Data were obtained from the electronic medical record, the electronic prescription program, and the discharge summary. Results: The study population comprised 176 patients; mean age was 28.9 years (SD = 7.7), and 90.9% were men. The most prescribed treatment was the combination of ceftriaxone and azithromycin (83.0%). Treatment was inappropriate in 71.6% of patients. A total of 159 drug errors were recorded. The most frequent cause was undertreatment (36.4%) related to underdosing (46.5%), particularly with regard to ceftriaxone. The percentage of errors was 11.9% for indication, 84.9% for dosing, 3.1% for duration, and 0% for route of administration. Conclusions: A high percentage of patients who attended the emergency department for suspected cervicitis or urethritis received an inappropriate empirical antibiotic regimen. The main reason was undertreatment due to underdosing.

Impact of Antimicrobial Stewardship Program Intervention Acceptance on Hospital Length of Stay.

Background: Inappropriate antibiotic use is a major public health concern. Excessive exposure to antibiotics results in the proliferation of multidrug-resistant bacteria, increase in potentially avoidable adverse drug reactions, healthcare utilization, and cost. Currently, systematic reviews and controlled trials assessing the effects of antimicrobial stewardship programs (ASP) on hospital length of stay (LOS), mortality, and cost-savings are conflicting. Some studies reported a significant cost-savings driven by shorter hospital LOS while the others found no effect and, in some cases, prolonged LOS. Shortening the time to appropriate therapy and reducing unnecessary days of therapy have been shown to reduce hospital LOS. Objective: The purpose of this study was to evaluate the effects of prescriber acceptance to ASP interventions on hospital LOS. Methods: Between January 2018 and December 2019, 764 charts were retrospectively reviewed for patients who received antimicrobial treatment and in whom an ASP intervention was performed. Patients were allocated into 2 groups: those whose ASP interventions were accepted and those whose were rejected. Provider responses were then documented within 24 hours of being communicated. The primary outcome was hospital LOS. Secondary outcomes included 30-day readmission rates and inpatient antimicrobial duration of therapy (DOT). Results: There were 384 patients with an accepted ASP intervention and 380 with a denied intervention. Baseline characteristics were similar between both groups, except for a difference in the types of intervention performed (P < 0.001). The median hospital LOS for patients in the accepted intervention group was 6.5 days compared to 7 days in the rejected intervention group (P = 0.009). Antimicrobial DOT was also shorter in the accepted intervention group (5 vs 7 days; P < 0.001). There was no difference in 30-day readmission rates (P = 0.98). Conclusion: Prescriber acceptance to ASP interventions decreases hospital LOS and antimicrobial DOT without affecting 30-day readmission rates.

Cefepime Versus Piperacillin-Tazobactam for the Treatment of Intra-Abdominal Infections Secondary to Potential AmpC Beta-Lactamase-Producing Organisms.

Background: Recent studies have established cefepime as an effective treatment option for AmpC beta-lactamase (AmpC) Enterobacterales; however, the efficacy of beta-lactam/beta-lactamase inhibitors is unclear. Objective: The objective of this study was to determine if piperacillintazobactamis an appropriate alternative to cefepime for the treatment of intra-abdominal infections (IAIs) secondary to AmpC-producing organisms. Methods: This multicenter, retrospective cohort study was conducted in hospitalized adults with an IAI caused by an AmpC-producing organism and received either cefepime or piperacillin-tazobactam for definitive treatment after a source control procedure. The primary outcome was a composite of surgical site infections, recurrent IAIs, or in-hospital mortality. Secondary outcomes included the individual components of the composite outcome, hospital length of stay (LOS), microbiologic failure, study antibiotic duration, time to clinical resolution, and incidence of Clostridioides difficile infection (CDI). Results: This study included 119 patients. There was no difference in the primary outcome between the cefepime and piperacillin-tazobactam groups (35% vs 27%, P = 0.14). Microbiological failure was the only secondary outcome with an observed difference between groups (17% vs 0%, P = 0.01): hospital LOS (15 vs 13 days, P = 0.09), days of therapy (7 vs 7 days, P = 0.87), time to clinical resolution (7 vs 4 days, P = 0.30), and CDI (1% vs 2%, P = 0.58) were all similar.

Association Between Vancomycin AUC and Clinical Failure in Patients with Streptococcal Bacteremia.

Background: Monitoring of vancomycin using the area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio is now preferred for serious methicillin-resistant Staphylococcus aureus infections. Vancomycin AUC/MIC monitoring is being investigated but is not yet well elucidated with other bacterial pathogens. Methods: A retrospective cross-sectional study was conducted assessing patients with streptococcal bacteremia treated with vancomycin definitive therapy. AUC was calculated using a Bayesian approach, and classification and regression tree analysis was used to identify a vancomycin AUC threshold predictive of clinical failure. Results: Eleven patients had a vancomycin AUC < 329 of which 8 (73%) experienced clinical failure, while 35 patients had a vancomycin AUC ≥ 329 of which 12 (34%) experienced clinical failure (P = .04). Hospital length of stay was longer in the AUC ≥ 329 group (15 vs 8 days, P = .05), whereas time to bacteremia clearance (29 [22-45] vs 25 [20-29] hours, P = .15) and toxicity incidence (13% vs 4%, P = 1) were similar between groups. Conclusions: This study identified a VAN AUC threshold of <329 to be predictive of clinical failure in patients with streptococcal bacteremia which should be interpreted as hypothesis-generating. Studies evaluating VAN AUC-based monitoring for streptococcal bloodstream infections along with other infection types are needed before implementation into clinical practice can be recommended.

The Effect of Vancomycin and Piperacillin-Tazobactam on Incidence of Acute Kidney Injury in Patients With Obesity.

Background: Increasing evidence suggests that administration of combination vancomycin and piperacillin-tazobactam (VPT) increases the incidence of acute kidney injury (AKI) beyond that of vancomycin alone. But these investigations have not evaluated AKI risk specifically in an increasingly prevalent obese population in whom VPT pharmacokinetics are altered. Objective: To evaluate AKI risk with VPT administration to patients with obesity. Methods: We conducted a multicenter retrospective study of obese patients admitted to 2 separate academic teaching hospitals from January 2010 to December 2021, who received VPT, or vancomycin plus either cefepime, meropenem, or ceftazidime. The primary outcome evaluated AKI when patients were treated with or without VPT. Results: A total of 227 patients were evaluated (114 in VPT, vs 113 in control group). Overall, body mass index (35.6 kg/m2 ± 4.8vs 36.1 kg/m2 ± 5.2; P = .44) was similar between the VPT and control groups respectively. Total vancomycin dose on day 1 of antibiotic therapy (3,432 mg ± 935 vs 2,732 mg ± 912; P < .01) and nephrotoxin administration (75.4% vs 62.8%; P = .04) were higher in the VPT group. Incidence of AKI was higher in the VPT group (37.7%vs 14.2%; P = .01) and on regression analysis VPT was predictive of developing AKI (OR = 3.9; 95% CI = 2.0-7.7; P < .01). Conclusion and Relevance: In this retrospective study, the incidence of AKI was increased in obese patients receiving therapy with VPT. Vancomycin combination therapy with ceftazidime, cefepime, and meropenem appeared to be safe and was associated with less nephrotoxicity. Cautious use of VPT and further investigation with larger studies are warranted in this area.

Impact of a Medication Reconciliation Pharmacist Program on Appropriateness of Community-Acquired Pneumonia Treatment Durations at Hospital Discharge.

Background: Antimicrobial stewardship programs have made large efforts to minimize the inappropriate use of antibiotics. Implementation of these programs can be challenging, since many institutions have limited resources. Utilizing resources that already exist may be beneficial, including medication reconciliation pharmacist (MRP) programs. This study aims to evaluate the impact of a MRP program on appropriateness of community-acquired pneumonia (CAP) treatment durations at hospital discharge. Methods: This study was a retrospective, observational, single-center study comparing the total days of antibiotic therapy for CAP in the preintervention period (9/2020-11/2020) versus the post-intervention period (9/2021-11/2021). Implementation of a new clinical intervention occurred between the 2 periods and included education to MRPs on appropriate CAP treatment durations and on documentation of recommendations. Data was collected utilizing a chart review of the electronic medical record of patients diagnosed with CAP using ICD-10 codes. The primary objective of this study was to compare the total days of antibiotic therapy in the pre-intervention period versus the postintervention period. Results: One-hundred fifty-five patients were included in the primary analysis. When observing total days of antibiotic therapy, there was no change from the pre-intervention period at 8 days compared to the postintervention period (P = .109). When analyzing antibiotic days of therapy at discharge, there was a decrease from 4.55 days in the preintervention period compared to 3.8 days in the post-intervention period (P = .109). The incidence of those with appropriate treatment durations, defined as 5 to 7 days of antibiotic therapy, was higher in the post-intervention period (26.5% in the pre-intervention group vs 37.9% in the post-intervention group, P = .460). Conclusions: There was a non-statistically significant decrease in median days of antimicrobial therapy for CAP at hospital discharge after implementation of a new clinical intervention targeting antibiotic days of therapy. Though median total antibiotic days of therapy were similar between both time periods, patients had an overall increase in incidence of appropriate duration of therapy, defined as 5 to 7 days, after intervention. Further studies are necessary to show how MRPs have a positive impact on improving outpatient antibiotic prescribing at hospital discharge.

Maribavir.

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are available online to subscribers. Monographs can be customized to meet the needs of a facility. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, contact Wolters Kluwer customer service at 866-397-3433.

Delayed Hemolysis With Parenteral Artesunate.

Artesunate is an effective and first-line therapy option in patients with severe malaria caused by Plasmodium species. Among adverse effects of the drug is a phenomenon of delayed hemolysis. This usually occurs at least 7 days after initiation of therapy, and is characterized by reductions in hemoglobin and haptoglobin and an increase in lactate dehydrogenase. Here, we report an instance of delayed hemolysis in a patient probably attributed to parenteral artesunate therapy.