Evaluating the Follow-up of Post-discharge Positive Sterile Site Cultures and the Impact on Infection-Related Complications.

INTRODUCTION: Numerous patients have cultures pending at discharge which, if not addressed, may delay diagnosis and initiation of appropriate antimicrobials. The purpose of the study is to evaluate the appropriateness of discharge antimicrobial therapy and result documentation in patients with positive cultures finalized post-discharge. METHODS: This was a cross-sectional cohort study of patients admitted from July 1 to December 31, 2019 with positive sterile-site microbiologic cultures finalized post-discharge. Pertinent inclusion and exclusion factors were admission ≥ 48 h and non-sterile sites, respectively. The primary objective was to determine the frequency of discharged patients warranting antimicrobial changes based on finalized cultures. Secondary objectives included prevalence and timeliness of result documentation and rates of 30-day readmission, among intervention warranted versus not warranted. Chi-squared or Fisher's exact tests were used as appropriate. Binary multivariable logistic regression was completed for 30-day readmission stratified by infectious disease (ID) involvement due to the potential for effect modification. RESULTS: A total of 208 of 768 patients screened were included. Most patients were discharged from a surgical service (45.7%); deep tissue and blood were the most common culture sites (29.3%). Change in discharge antimicrobial was warranted in 36.5% of patients (n = 76). Result documentation was overall low (35.5%). Time to documentation was significantly shorter in patients warranting antimicrobial intervention (4 days vs. 9 days, P = 0.039), although rates of hospital readmission were higher in this group (32.9% vs. 22.7%, P = 0.109). Finally, in patients not being followed by ID, documentation of finalized results was associated with decreased odds of 30-day readmission (aOR 0.19; 95% CI 0.07-0.53). CONCLUSIONS: A significant number of patients with cultures finalized post-discharge warranted antimicrobial intervention. Acknowledgment of finalized culture results may decrease the risk of 30-day hospital readmission, particularly in patients not followed by ID. Quality improvement efforts should focus on methods to improve documentation and action on pending cultures to positively impact patient outcomes.

Early initiation of three-drug combinations for the treatment of carbapenem-resistant A. baumannii among COVID-19 patients.

OBJECTIVES: We evaluated the clinical characteristics and outcomes of patients with COVID-19 who received three-drug combination regimens for treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections during a single-centre outbreak. Our objective was to describe the clinical outcomes and molecular characteristics and in vitro synergy of antibiotics against CRAB isolates. MATERIALS AND METHODS: Patients with severe COVID-19 admitted between April and July 2020 with CRAB infections were retrospectively evaluated. Clinical success was defined as resolution of signs/symptoms of infection without need for additional antibiotics. Representative isolates underwent whole-genome sequencing (WGS) and in vitro synergy of two- or three-drug combinations was assessed by checkerboard and time-kill assays, respectively. RESULTS: Eighteen patients with CRAB pneumonia or bacteraemia were included. Treatment regimens included high-dose ampicillin-sulbactam, meropenem, plus polymyxin B (SUL/MEM/PMB; 72%), SUL/PMB plus minocycline (MIN; 17%) or other combinations (12%). Clinical resolution was achieved in 50% of patients and 30-day mortality was 22% (4/18). Seven patients had recurrent infections, during which further antimicrobial resistance to SUL or PMB was not evident. PMB/SUL was the most active two-drug combination by checkerboard. Paired isolates collected before and after treatment with SUL/MEM/PMB did not demonstrate new gene mutations or differences in the activity of two- or three-drug combinations. CONCLUSIONS: Use of three-drug regimens for severe CRAB infections among COVID-19 resulted in high rates of clinical response and low mortality relative to previous studies. The emergence of further antibiotic resistance was not detected phenotypically or through WGS analysis. Additional studies are needed to elucidate preferred antibiotic combinations linked to the molecular characteristics of infecting strains.

Evaluating the incidence of bacteriuria in female patients before and after implementation of external urinary collection devices.

External urinary collection devices (ECDs) are increasingly used in female patients, however, their impact on bacteriuria and antimicrobial use is unclear. Comparing the periods before and after the implementation of an ECD use policy, we found an overall decrease in bacteriuria but no significant decrease in trend of monthly rates. Antimicrobial use for genitourinary indications did not change.

Wohlfahrtiimonas chitiniclastica Monomicrobial Bacteremia in a Homeless Man.

We report a case of septic shock attributable to monomicrobial bloodstream infection secondary to Wohlfahrtiimonas chitiniclastica infection. This case suggests that W. chitiniclastica likely possesses the virulence to cause severe disease. Culture-independent techniques were essential in the identification of this organism, which enabled selection of appropriate therapy.

The potential impact of discrepancies between automated susceptibility platforms and other testing metho`dologies for cefazolin in the treatment of Enterobacterales bloodstream infections.

Revised breakpoints for cefazolin (CFZ) against Enterobacterales may be difficult to implement with current automated susceptibility testing platforms and could falsely report organisms as susceptible, leading to inappropriate treatment for bloodstream infections (BSI). This was a retrospective cohort of adult patients with Enterobacterales BSI reported CFZ susceptible per Vitek®2. The primary outcome was the percentage susceptible by minimum inhibitory concentration (MIC) Gradient Test Strips and disk diffusion. Secondary outcomes included clinical outcomes between CFZ and non-CFZ-treated patients. Among 195 isolates reported CFZ-susceptible per Vitek®2, 84 (43.1%) were CFZ susceptible by MIC Gradient Test Strips vs 119 (61%) by disk diffusion. No difference was noted in 30-day all-cause mortality, secondary complications, or 30-day readmissions. Treatment failure was less likely to occur with source control (adjusted OR 0.06) and infectious disease consult (adjusted OR 0.37). There was a large degree of discrepancy between automated testing and manual methods; the clinical impact of this discrepancy warrants further investigation.

Evaluation of Fosphenytoin Therapeutic Drug Monitoring in the Neurocritical Care Unit.

OBJECTIVE: The aim of this study was to determine whether the current method of calculating a fosphenytoin reloading dose results in a therapeutic free phenytoin level on subsequent days. METHODS: Medical records of patients receiving fosphenytoin in the neurocritical care unit between July 2017 and June 2018 were screened. Included patients were those who had received at least three doses of fosphenytoin and required reloading doses according to concentrations obtained through therapeutic drug monitoring. Free phenytoin levels were categorized based on the prespecified patient-specific target range, generally between 1.5 and 2.5 mcg/mL. RESULTS: Of the fosphenytoin reloading doses administered, 48% (73/152) resulted in a therapeutic free phenytoin concentration on the subsequent day, with the remaining 52% resulting in nontherapeutic levels (39% subtherapeutic, 13% supratherapeutic). Our evaluation of reloading dose calculation strategies indicated that patients were two times as likely to obtain a therapeutic level when a modified pharmacokinetic equation omitting the use of volume of distribution or salt formulation was used (58%, n = 39) than they were with doses calculated using the current pharmacokinetic model (41%, n = 20) or doses based on provider preference (39%, n = 14). CONCLUSION: The current method of calculating a fosphenytoin reloading dose in the critically ill population does not consistently result in therapeutic concentrations. With multiple factors affecting the pharmacokinetics of critically ill patients, the creation of a new pharmacokinetic model with less emphasis on volume of distribution may more consistently result in therapeutic concentrations.

The Battle Is on: New Beta-Lactams for the Treatment of Multidrug-Resistant Gram-Negative Organisms.

PURPOSE OF REVIEW: Resistant gram-negative infections are becoming increasingly difficult to treat, prompting increased focus on drug development. This review will focus primarily on the new beta-lactam agents developed in the past 5 years that target multidrug-resistant (MDR) gram-negative organisms, including those producing carbapenemases. RECENT FINDINGS: Four new agents including ceftazidime-avibactam (CAZ-AVI), meropenem-vaborbactam (MER-VAB), imipenem-relebactam (IMI-REL), and cefiderocol have recently been approved for the treatment of resistant gram-negative infections. CAZ-AVI remains an option for blaOXA-48-producing isolates and potentially MDR Pseudomonas aeruginosa, but the concern for resistance arises when using the agent for KPC-producing Enterobacteriales. MER-VAB appears to be more stable than CAZ-AVI in the treatment of KPC-producing Enterobacteriales but less is known about its propensity for the development of resistance and the drug does not reliably expand the coverage of meropenem-resistant P. aeruginosa isolates. IMI-REL expands the spectrum of imipenem-cilastatin to include KPC-producing Enterobacteriales as well as MDR P. aeruginosa but much less is known about its real-world clinical utility. Cefiderocol is the only of the four new agents with efficacy against metallo-beta-lactamases and resistant Acinetobacter species, but comparator studies using best available therapy for carbapenem-resistant gram-negative bacterial infections show higher mortality rates with the new drug, making its role in clinical therapy still to be determined. The new beta-lactams differ in their mechanisms of combatting resistance and thus have unique roles in therapy. Additional evidence is needed regarding the potential for development of resistance in the newer combination agents, as well as for the role of cefiderocol in carbapenem-resistant gram-negative infections.

Influential Factors of Successful Hepatitis C Treatment in Elderly Patients.

BACKGROUND: Chronic Hepatitis C virus (HCV) is an infection associated with an increased risk of cirrhosis, hepatocellular carcinoma (HCC), and morbidity and mortality. Treating HCV poses challenges in the elderly population due to the lack of evidence and complexity of patients. OBJECTIVE: This study aims to evaluate factors that influence HCV treatment success in elderly patients, especially those over age of 70, such as pill burden and comorbidities, in addition to drug interactions and adverse effects. METHODS: This was a retrospective chart review of patients treated at our urban academic institution from 2014-2016. RESULTS: Sixty-two patients over the age of 70 were included in this study. The sustained virologic response rate 12 weeks after the completion of treatment (SVR12) was 79%. In a multi-variate analysis, cirrhosis, age closer to 70, and longer duration of treatment were statistically significantly more likely to lead to treatment failure. Though not statistically significant, other factors that may negatively influence achievement of SVR12 were cognitive impairment, cardiovascular disease, multi-tablet HCV regimen, time to initiation of HCV treatment > 90 days, and prior treatment experience. Pill burden of other prescribed medications did not impact SVR12. Adverse events and drug interactions were common in the population. CONCLUSIONS: Overall SVR12 rate in the elderly population was lower than that reported in the literature. Factors associated with lower treatment success, especially cirrhosis, should be considered when treating an elderly population. Further data is needed on the impact of other factors on SVR12 attainment in an elderly patient population.