Association Between Social Vulnerability and Streptococcus pneumoniae Antimicrobial Resistance in US Adults.

Background: Growing evidence indicates antimicrobial resistance disproportionately affects individuals living in socially vulnerable areas. This study evaluated the association between the CDC/ATSDR Social Vulnerability Index (SVI) and Streptococcus pneumoniae (SP) antimicrobial resistance (AMR) in the United States.

Methods: Adult patients ≥18 years with 30-day nonduplicate SP isolates from ambulatory/hospital settings from January 2011 to December 2022 with zip codes of residence were evaluated across 177 facilities in the BD Insights Research Database.

Association of SARS-CoV-2 status and antibiotic-resistant bacteria with inadequate empiric therapy in hospitalized patients: a US multicenter cohort evaluation (July 2019 - October 2021).

Background: Antibiotic usage and antibiotic resistance (ABR) patterns changed during the COVID-19 pandemic. Inadequate empiric antibiotic therapy (IET) is a significant public health problem and contributes to ABR. We evaluated factors associated with IET before and during the COVID-19 pandemic to determine the impact of the pandemic on antibiotic management.

Use of therapeutic drug monitoring to characterize cefepime-related neurotoxicity.

Study Objectives: Data evaluating cefepime thresholds associated with neurotoxicity remain limited. The objectives of this study were to evaluate the incidence of cefepime-related neurotoxicity (CRN) in patients with plasma cefepime concentrations, assess the relationship between cefepime exposure and CRN, investigate clinical factors associated with CRN, and describe electroencephalogram (EEG) abnormalities in CRN.

Design: This was a retrospective study of adult inpatients admitted between 2016 and 2018 who received cefepime therapeutic drug monitoring (TDM).

A Multicenter Comparison of Prevalence and Predictors of Antimicrobial Resistance in Hospitalized Patients Before and During the Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic.

Background: Antibacterial therapy is frequently used in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) without evidence of bacterial infection, prompting concerns about increased antimicrobial resistance (AMR). We evaluated trends in AMR before and during the SARS-CoV-2 pandemic.

Methods: This multicenter, retrospective cohort analysis included hospitalized adults aged ≥18 years with >1-day inpatient admission and a record of discharge or death from 271 US facilities in the BD Insights Research Database.

Comment on Chandler et al. 23-Valent Pneumococcal Polysaccharide Vaccination Does Not Prevent Community-Acquired Pneumonia Hospitalizations Due to Vaccine-Type . 2022, , 560.

The 23-valent pneumococcal polysaccharide vaccine (PPSV23) targets 23 common serotypes and is recommended for use in adults in various countries to protect against pneumococcal infection. Test-negative design (TND) studies aim to include cases and controls from the same healthcare facilities; however, design choices or limitations associated with conducting real-world research can affect the study results. Here, we highlight how some methodological limitations may have affected results and conclusions of a published study described by Chandler et al.

Use of Novel Antibiograms to Determine the Need for Earlier Susceptibility Testing and Administration for New β-Lactam/β-Lactamase Inhibitors in the United States.

Antimicrobial resistance is a global public health threat, and gram-negative bacteria, such as Enterobacterales and are particularly problematic with difficult-to-treat resistance phenotypes. To reduce morbidity and mortality, a reduction in the time to effective antimicrobial therapy (TTET) is needed, especially among critically ill patients. The antibiogram is an effective clinical tool that can provide accurate antimicrobial susceptibility information and facilitate early antimicrobial optimization, decrease TTET, and improve outcomes such as mortality, hospital length of stay, and costs.

Multicenter Cohort Study of Ceftaroline Versus Daptomycin for Treatment of Methicillin-Resistant Bloodstream Infection.

Background: Observational data suggest ceftaroline may be effective for methicillin-resistant (MRSA) bloodstream infection (BSI), but comparative data with standard of care are limited. This analysis compares the outcomes of MRSA BSI treated with ceftaroline or daptomycin.

Methods: Multicenter, retrospective, observational cohort study of adult patients with MRSA BSI from 2010 to 2017.

Antimicrobial stewardship and antibiograms: importance of moving beyond traditional antibiograms.

The rapid evolution of resistance, particularly among Gram-negative bacteria, requires appropriate identification of patients at risk followed by administration of appropriate empiric antibiotic therapy. A primary tenet of antimicrobial stewardship programs (ASPs) is the establishment of empiric antibiotic recommendations for commonly encountered infections. An important tool in providing empiric antibiotic therapy recommendations is the use of an antibiogram.

Resource Over-Utilization in Hospitalized Patients With Uncomplicated Skin and Soft Tissue Infections.

Background: Inpatient management of SSTIs utilizes considerable healthcare resources. The CREST+SEWS score categorizes patients with SSTIs into 4 severity classes. Hospitalizations can be avoided in Class I as they are treated as outpatients with oral antibiotics, whereas Class IV require hospitalization for intravenous antibiotics.

Early therapeutic monitoring of β-lactams and associated therapy outcomes in critically ill patients.

Background: In the ICU, early and appropriate antimicrobial therapy is important to lower infection-related mortality.

Objectives: Assess whether achieving early β-lactam free concentration above the MIC 100% of the time (fT>MIC) is associated with positive outcomes in the ICU.

Methods: This retrospective study was conducted in ICU patients admitted to UF Health Shands Hospital between 2016 and 2018.

Variable linezolid exposure and response and the role of therapeutic drug monitoring: Case series.

Two patients with normal renal function, yet each showed unexpected, supra- and subtherapeutic linezolid plasma concentrations resulting in toxicity and ineffective therapy, respectively. TDM helps to early identify and correct such excursions.

Population Pharmacokinetics and Target Attainment of Cefepime in Critically Ill Patients and Guidance for Initial Dosing.

Cefepime is commonly used in the intensive care unit (ICU) to treat bacterial infections. The time during which the free cefepime concentration is above the MIC (T) should be optimized to increase the efficacy of the regimen. We aim to optimize the exposure of cefepime in ICU patients by using population pharmacokinetic (PK) modeling and simulations.

Towards precision medicine: Therapeutic drug monitoring-guided dosing of vancomycin and β-lactam antibiotics to maximize effectiveness and minimize toxicity.

Purpose: The goal of this review is to explore the role of antimicrobial therapeutic drug monitoring (TDM), especially in critically ill, obese, and older adults, with a specific focus on β-lactams and vancomycin.

Summary: The continued rise of antimicrobial resistance prompts the need to optimize antimicrobial dosing. The aim of TDM is to individualize antimicrobial dosing to achieve antibiotic exposures associated with improved patient outcomes.

Clinical and Microbiologic Outcomes in Patients with Monomicrobial Stenotrophomonas maltophilia Infections.

is an opportunistic pathogen observed in nosocomial infections. Due to biofilm production and resistance to numerous antimicrobials, eradication is difficult. This study evaluated outcomes for monomicrobial infections.

Training a Drug to Do New Tricks: Insights on Stability of Meropenem Administered as a Continuous Infusion.

Background: The antibiotic armamentarium used to combat multi-drug resistant organisms (MDROs) include carbapenems. Continuous infusion (CI) dosing is frequently employed to maximize beta-lactam efficacy; however, use of meropenem CI has been limited due to concerns with product instability.

Objective: The primary objective of this study was to quantify meropenem serum concentrations to reflect drug stability when administered as CI over 8- or 12-h exchanges.

Preventing the Post-Antibiotic Era by Training Future Pharmacists as Antimicrobial Stewards.

Antimicrobials enable modern medicine, but their efficacy is a limited resource. In the past 20 years, antimicrobial development has slowed dramatically while antimicrobial resistance continues to rise. In response to this, there has been an increased focus on strategically managing antimicrobial use with an approach called "antimicrobial stewardship.

Assessing antimicrobial stewardship initiatives: Clinical evaluation of cefepime or piperacillin/tazobactam in patients with bloodstream infections secondary to AmpC-producing organisms.

Management of micro-organisms harbouring AmpC β-lactamases remains challenging. Carbapenems are often considered first-line agents. Due to growing concern regarding carbapenem-resistant Enterobacteriaceae, integrating non-carbapenem treatment strategies is being explored for these pathogens.

Survival in Patients with Candida glabrata Bloodstream Infection Is Associated with Fluconazole Dose.

Robust pharmacodynamic indices that align fluconazole dose or exposure with outcomes in invasive candidiasis due to remain elusive. The purpose of this retrospective multicenter study was to evaluate a cohort of 127 patients with fungemia treated with fluconazole, using adjusted analyses to identify risk factors for 28-day death. No significant correlations were found between fluconazole area under the curve (AUC), AUC/MIC ratio, or MIC and survival.

Optimization of Voriconazole Therapy for the Treatment of Invasive Fungal Infections in Adults.

Therapeutic concentrations of voriconazole in invasive fungal infections (IFIs) are ensured using a drug monitoring approach, which relies on attainment of steady-state pharmacokinetics. For voriconazole, time to reach steady state can vary from 5-7 days, not optimal for critically ill patients. We developed a population pharmacokinetic/pharmacodynamic model-based approach to predict doses that can maximize the net benefit (probability of efficacy-probability of adverse events) and ensure therapeutic concentrations, early on during treatment.

Ampicillin for the treatment of complicated urinary tract infections caused by vancomycin-resistant Enterococcus spp (VRE): a single-center university hospital experience.

Vancomycin-resistant enterococci (VRE) are a common cause of urinary tract infections (UTIs) and are typically multidrug resistant, including ampicillin. This retrospective study evaluated outcomes of 84 adult patients hospitalized between January 2007 and December 2015 with ampicillin- and vancomycin-resistant enterococcus isolates causing UTI and treated with ampicillin. Treatment response was classified as clinical cure and microbiological eradication.

Acute kidney injury risk associated with piperacillin/tazobactam compared with cefepime during vancomycin therapy in hospitalised patients: a cohort study stratified by baseline kidney function.

Recent studies have found an association between piperacillin/tazobactam when added to vancomycin and acute kidney injury (AKI) risk. However, studies were limited by the small sample size and residual confounding. The aim of this study was to compare the risk of AKI with vancomycin plus piperacillin/tazobactam (VPT) versus vancomycin plus cefepime (VC) and to examine whether pre-existing renal impairment mediates the risk.

Impact of the CYP2C19 genotype on voriconazole exposure in adults with invasive fungal infections.

Objectives: Voriconazole, a first-line agent for the treatment of invasive fungal infections (IFIs), is metabolized by CYP2C19. A significant proportion of patients fail to achieve therapeutic trough concentrations with standard weight-based voriconazole dosing, placing them at increased risk for treatment failure, which can be life threatening. We sought to test the association between the CYP2C19 genotype and subtherapeutic voriconazole concentrations in adults with IFIs.

Multicenter Observational Study of Ceftaroline Fosamil for Methicillin-Resistant Staphylococcus aureus Bloodstream Infections.

Novel therapies for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) are needed in the setting of reduced antibiotic susceptibilities and therapeutic failure. Ceftaroline is a cephalosporin antibiotic with MRSA activity. Although not FDA approved for MRSA BSI, ceftaroline has generated much interest as a potential treatment option.