The Hospital Antimicrobial Use Process: From Beginning to End

Hospital antimicrobial stewardship (AMS) programs are responsible for ensuring that all antimicrobials are utilized in the most appropriate and safe manner to improve patient outcomes, prevent adverse drug reactions, and prevent the development of antimicrobial resistance. This Perspectives article outlines the hospital antimicrobial use process (AUP), the foundational system that ensures that all antimicrobials are utilized in the most appropriate and safe manner. The AUP consists of the following steps: antimicrobial ordering, order verification, preparation and delivery, administration, monitoring, and discharge prescribing. AMS programs should determine how each step contributes to how an antimicrobial is used appropriately or inappropriately at their institution. Through this understanding, AMS programs can integrate stewardship activities at each step to ensure that every opportunity is taken to optimize antimicrobial use during a patient’s treatment course. Hence, approaching AMS through the framework of a hospital’s AUP is essential to improving appropriate antimicrobial use

Tigecycline Induction of Phenol-Soluble Modulins by Invasive Methicillin-Resistant \u3cem\u3eStaphylococcus aureus\u3c/em\u3e Strains

We examined the effects of tigecycline on three types of exoproteins, α-type phenol-soluble modulins (PSMα1 to PSMα4), α-hemolysin, and protein A, in 13 methicillin-resistant Staphylococcus aureus isolates compared to those of clindamycin and linezolid. Paradoxical increases in PSMαs occurred in 77% of the isolates with tigecycline at 1/4 and 1/8 MICs and clindamycin at 1/8 MIC compared to only 23% of the isolates with linezolid at 1/8 MIC. Induction was specific to PSMα1 to PSMα4, as protein A and α-hemolysin production was decreased under the same conditions by all of the antibiotics used

Antivirulence Potential of TR-700 and Clindamycin on Clinical Isolates of \u3cem\u3eStaphylococcus aureus\u3c/em\u3e Producing Phenol-Soluble Modulins

Staphylococcus aureus strains (n = 50) causing complicated skin and skin structure infections produced various levels of phenol-soluble modulin alpha-type (PSMα) peptides; some produced more than twice that produced by the control strain (LAC USA300). TR-700 (oxazolidinone) and clindamycin strongly inhibited PSM production at one-half the MIC but exhibited weak to modest induction at one-fourth and one-eighth the MICs, primarily in low producers. Adequate dosing of these agents is emphasized to minimize the potential for paradoxical induction of virulence

A Nonrestrictive Approach to Fluoroquinolone Stewardship at Two Community Hospitals

Background Fluoroquinolones are one of the most prescribed antimicrobials in the United States and have been increasingly used in inpatient and outpatient settings to treat various infectious diseases syndromes. Due to the unwanted collateral effects on antibiotic resistance, poor susceptibility rates among Gram-negative pathogens, and adverse effects, fluoroquinolones are often targeted by hospital antimicrobial stewardship programs to prevent overutilization. This study describes the association of nonrestrictive antimicrobial stewardship interventions at 2 nonacademic community hospitals on levofloxacin utilization, prescribing patterns on alternative antibiotics, and Pseudomonas aeruginosa nonsusceptibility rates to levofloxacin. Methods Nonrestrictive antimicrobial stewardship interventions included monitoring and reporting of fluoroquinolone susceptibility trends to physician groups, performing medication use evaluations of levofloxacin accompanied with prescriber detailing, daily prospective audit and feedback, implementation of beta-lactam-based institutional guidelines for empiric therapy in various infectious disease syndromes, review and adjustment of electronic medical record order sets containing fluoroquinolones, and intensive prescriber education. No preauthorization of levofloxacin was used during this study period. Antibiotic utilization data were collected for the time periods of August 2015 through January 2021. Correlation between levofloxacin and other broad-spectrum antibiotc use was investigated as well as the impact on Pseudomonas aeruginosa levofloxacin nonsusceptibility rates. Results Both hospitals showed an overall downward trend in the prescribing of levofloxacin during the time period of August 2015 to January 2021. There was a significant negative correlation between monthly ceftriaxone and levofloxacin days of therapy for both hospitals (P \u3c .0001). There was a positive correlation between levofloxacin days of therapy and P aeruginosa nonsusceptibility (P \u3c .02 at both hospitals). Conclusions Our results demonstrate that a nonrestrictive approach to fluoroquinolone stewardship interventions had a significant impact on reducing levofloxacin utilization, increasing ceftriaxone utilization, and improving P aeruginosa levofloxacin susceptibility

Iron Effects on \u3cem\u3eClostridioides difficile\u3c/em\u3e Toxin Production and Antimicrobial Susceptibilities

Despite the benefits of red blood cell (RBC) transfusion therapy, it can render patients vulnerable to iron overload. The excess iron deposits in various body tissues cause severe complications and organ damage such as cardiotoxicity and mold infections. Clostridioides difficile infection (CDI) is the most common cause of nosocomial diarrhea among cancer patients and is associated with significant morbidity and mortality. Our study aims to determine the role of iron overload and the effects of iron chelators on CDI. Our results demonstrated that iron (Fe3+) stimulated the growth of C. difficile with increased colony formation units (CFU) in a dose-dependent manner. Exposure to excess iron also increased the gene expression levels of tcdA and tcdB. The production of C. difficile toxin A, necessary for the pathogenesis of C. difficile, was also elevated after iron treatment. In the presence of excess iron, C. difficile becomes less susceptible to metronidazole with significantly elevated minimum inhibitory concentration (MIC) but remains susceptible to vancomycin. Iron-stimulated colony formation and production of C. difficile toxins were effectively diminished by iron chelator deferoxamine co-treatment. Incorporating iron overload status as a potential factor in developing a risk prediction model of CDI and antibiotic treatment response may aid clinical practitioners in optimizing CDI management in oncology patients

The Antibiogram: Key Considerations for Its Development and Utilization

The antibiogram is an essential resource for institutions to track changes in antimicrobial resistance and to guide empirical antimicrobial therapy. In this Viewpoint, data and examples from literature are presented that suggest institutions have not completely adopted the standardized approach in developing antibiograms, as variations in the development methodologies of antibiograms exist despite consensus guidelines (M39) published by CLSI. We emphasize developing antibiograms in line with the M39 recommendations will help ensure that they are accurate, reliable and valid, and highlight that understanding the limitations of antibiogram data is critical to ensuring appropriate interpretation and application to clinical decision-making. We also stress the importance of easy accessibility and education on antibiogram use, to allow for prescribers to select the most optimal empirical treatment regimens and propose the creation of an abbreviated antibiogram for frontline users. Multidisciplinary antimicrobial stewardship programmes are vital to accomplishing these goals

Stability Evaluation of Extemporaneously Compounded Vancomycin Ophthalmic Drops: Effect of Solvents and Storage Conditions

Vancomycin is the drug of choice for methicillin-resistant Staphylococcus aureus keratitis and other ocular infections. Vancomycin ophthalmic drops are not commercially available and require compounding. The present study was designed to investigate the stability of vancomycin ophthalmic drops in normal saline, phosphate-buffered saline (PBS), and balanced salt solution (BSS) while stored at room temperature or under refrigeration. Vancomycin ophthalmic drops (50 mg/mL) were aseptically prepared from commercially available intravenous powder using PBS, BSS, and saline. Solutions were stored at room temperature and in a refrigerator for 28 days. The vancomycin stability was tested by a microbiology assay and high-performance liquid chromatography HPLC analysis immediately after formulation and at days 7, 14, and 28 after storage at room temperature or under refrigeration. The pH, turbidity was also tested. Vancomycin formulations in PBS, BSS and normal saline had initial pH of 5; 5.5; 3 respectively. The formulation in PBS developed turbidity and a slight decrease in pH upon storage. Microbiological assay did not show any change in zone of inhibition with any of the formulation upon storage either at room temperature or under refrigeration. HPLC analysis did not detect any decrease in vancomycin concentration or the accumulation of degraded products in any of the formulations upon storage either at room temperature or under refrigeration. Vancomycin ophthalmic drops prepared using PBS, BSS, and normal saline were stable up to the tested time point of 28 days, irrespective of their storage temperatur

Assessing Vancomycin Dosing Per Pharmacy in Elderly Patients Over the Age of 74 Years

Vancomycin has a complex pharmacokinetic profile and carries potential risks for nephrotoxicity and ototoxicity. The pharmacokinetic profile in elderly patients significantly differs from that of younger patients. It is common practice in many institutions for pharmacists to intentionally round serum creatinine levels to 1 mg/dl in elderly patients with levels \u3c1 mg/ dl to avoid overestimating clearance and toxicities. This can potentially lead to underestimation of creatinine clearance, and subsequently lead to vancomycin under dosing. The aim of this study was to evaluate vancomycin target trough attainment and the time to trough attainment with vancomycin dosing per pharmacy in elderly patients

Assessing Health Conditions and Medication Use Among the Homeless Community in Long Beach, California

Objective: Persons experiencing homelessness are a vulnerable population and are at increased risk for morbidity and all-cause mortality compared to the general population. This study sought to evaluate medication use, regular physician visits, and identify health conditions among the homeless population of Long Beach, California. Methods: Two brown bag medication review events were held at homeless shelters in the Long Beach area. Demographic information, medication use, and comorbid disease states were obtained through surveys. Findings: Three-fourths of the cohort (95 participants) consisted of males, and the average age of participants was 48 years. Psychiatric disorders and cardiovascular disease were the most common disease states reported at 32% and 46%, respectively and so were medications used in treating these chronic diseases. Medication adherence was found to be a significant problem in this population, where more than 30% of patients were nonadherent to medications for chronic diseases. Furthermore, foot problems, hearing and vision difficulties constitute the most commonly overlooked health problems within the homeless population. Conclusion: Based on this and other similar finding, we must accept that the homeless represent a vulnerable population, and that because of this fact, more programs should be focused at improving availability and access to health care among the homeless. Regarding the high number of reported health problems in the study, more studies are needed and more studies should incorporate screening for foot, hearing, and vision issues, both to increase awareness and to provide an opportunity for devising possible solutions to these highly preventable conditions

Design, Synthesis, and Evaluation of Amphiphilic Cyclic and Linear Peptides Composed of Hydrophobic and Positively-Charged Amino Acids as Antibacterial Agents

Antimicrobial peptides (AMPs) contain amphipathic structures and are derived from natural resources. AMPs have been found to be effective in treating the infections caused by antibiotic-resistant bacteria (ARB), and thus, are potential lead compounds against ARB. AMPs’ physicochemical properties, such as cationic nature, amphiphilicity, and their size, will provide the opportunity to interact with membrane bilayers leading to damage and death of microorganisms. Herein, AMP analogs of [R4W4] were designed and synthesized by changing the hydrophobicity and cationic nature of the lead compound with other amino acids to provide insights into a structure-activity relationship against selected model Gram-negative and Gram-positive pathogens. Clinical resistant strains of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) were used in the studies. Our results provided information about the structural requirements for optimal activity of the [R4W4] template. When tryptophan was replaced with other hydrophobic amino acids, such as phenylalanine, tyrosine, alanine, leucine, and isoleucine, the antibacterial activities were significantly reduced with MIC values of \u3e128 μg/mL. Furthermore, a change in stereochemistry caused by D-arginine, and use of N-methyltryptophan, resulted in a two-fold reduction of antibacterial activity. It was found that the presence of tryptophan is critical for antibacterial activity, and could not be substituted with other hydrophobic residues. The study also confirmed that cyclic peptides generally showed higher antibacterial activities when compared with the corresponding linear counterparts. Furthermore, by changing tryptophan numbers in the compound while maintaining a constant number of arginine, we determined the optimal number of tryptophan residues to be four, as shown when the number of tryptophan residues increased, a decrease in activity was observed