Reduction of Inappropriate Antibiotic Use and Improved Outcomes by Implementation of an Algorithm-Based Clinical Guideline for Nonpurulent Skin and Soft Tissue Infections.

STUDY OBJECTIVE: Clinicians currently do not reliably adhere to antibiotic treatment guidelines, resulting in unnecessary patient exposure to broad-spectrum antimicrobials. Our objective is to determine whether a treatment intervention for the management of nonpurulent skin and soft tissue infections increases clinician adherence and improves patient outcomes. METHODS: Between January 1 and December 31, 2017, patients presenting to 2 emergency departments (EDs) and who had received a diagnosis of a nonpurulent skin and soft tissue infection were enrolled and assigned to a pre- or postintervention cohort with a treatment intervention implemented on June 1. Primary outcomes were percentage of ED providers following the guidelines and percentage of patients admitted to the hospital. Secondary outcomes were patient self-reported treatment failure and hospital readmission. RESULTS: There were 1,360 patients, 665 in the preintervention and 695 in the postintervention cohorts. After algorithm implementation, guideline adherence increased (43.0% versus 55.1%; P<.001) and number of patients admitted to the hospital declined (36.5% versus 12.0%; P<.001). In addition, patients reported fewer treatment failures (26.8% versus 16.5%; P=.02) and fewer readmissions (22.3% versus 12.7%; P=.013). After multivariate adjustment, guideline adherence increased by 22% (adjusted relative risk [RR] 1.22; 95% confidence interval [CI] 1.10 to 1.37), whereas hospital admissions were reduced by 26% (adjusted RR 0.74; 95% CI 0.64 to 0.87). In addition, the risks of treatment failure and readmission were reduced by 46% (adjusted RR 0.64; 95% CI 0.43 to 0.97) and 45% (adjusted RR 0.55; 95% CI 0.34 to 0.87), respectively. CONCLUSION: Among patients with a nonpurulent skin and soft tissue infection, implementing an easy-to-follow treatment algorithm can reduce unnecessary antibiotic exposure by increasing clinician guideline adherence while reducing patient treatment failure rates.

Antibiotic Use in the Intensive Care Unit: Optimization and De-Escalation.

Appropriate antimicrobial therapy is essential to ensuring positive patient outcomes. Inappropriate or suboptimal utilization of antibiotics can lead to increased length of stay, multidrug-resistant infections, and mortality. Critically ill intensive care patients, particularly those with severe sepsis and septic shock, are at risk of antibiotic failure and secondary infections associated with incorrect antibiotic use. Through the initiation of active empiric antibiotic therapy based upon local susceptibilities, daily evaluation of signs and symptoms of infection and narrowing of antibiotic therapy when feasible, providers can streamline the treatment of common intensive care unit (ICU) infections. Optimizing antibiotic dosing through prolonged infusions can be beneficial in intensive care populations with altered pharmacokinetics. Antimicrobial stewardship teams can assist ICU providers in managing and implementing these tactics. This review will discuss the current literature on antibiotic use in the ICU applying antimicrobial stewardship strategies. Based upon the most recent evidence, ICUs would benefit from employing empiric guidelines for antibiotic use, collecting appropriate specimens and implementing molecular diagnostics, optimizing the dosing of antibiotics, and reducing the duration of total therapy. These strategies for antibiotic use have the potential to enhance patient care while preventing adverse outcomes.

Cefepime extended infusion versus intermittent infusion: Clinical and cost evaluation.

Background: Extended infusion cefepime (1 gram every 6 hours administered over 3 hours) achieves pharmacodynamic efficacy against bacteria with a MIC of ≤8 mg/L in Monte Carlo simulations. This regimen has not been evaluated in clinical practice. Objective: Compare clinical and economic outcomes for cefepime by intermittent infusion and by extended infusion in the acute-care setting. Design: Single-center, retrospective cohort study. Setting: Tertiary-care academic medical center. Patients: Hospitalized adults who received cefepime between August 2016 and July 2018 with a diagnosis of sepsis or pneumonia. Methods: Clinical and economic outcomes were compared for patients who received empiric cefepime via intermittent infusion (30-minute infusion of 2 g every 8 hours) or extended infusion (3-hour infusion of 1 g every 6 hours). Clinical outcomes analyses were carried out using appropriate statistical methods. Results: Overall, 111 patients received intermittent infusion and 93 patients received extended infusion. Approximately half of the included patients had a positive culture for a bacterial pathogen (intermittent infusion 45.9% vs extended infusion 47.3%). Median hospital length of stay (intermittent infusion 6 days vs extended infusion 6 days; P = .67) and 90-day readmission rates (intermittent infusion 61.3% vs extended infusion 67.7%; P = .34) did not differ between the groups. Mortality was infrequent in both groups (intermittent infusion 2.9% vs extended infusion 1.5%; P = .45). Cefepime cost per patient was lower with cefepime by extended infusion: average total daily cost $86.06 for intermittent infusion versus $43.39 for extended infusion. Conclusions: Cefepime via extended infusion (4 grams/day) did not differ in clinical outcomes compared to intermittent infusion (6 grams/day) but reduced drug expenditure. Prospective, multicenter, high-quality studies should be conducted to evaluate a mortality difference between these regimens.

Establishing a baseline of antibiotic use in Massachusetts jails reveals heterogeneity in quantity of prescriptions and duration of therapy.

Optimizing antibiotic prescribing is a crucial element of the fight against antibiotic resistance. Antibiotic prescribing patterns in jails have not been studied. We established a baseline of antibiotic prescribing between Massachusetts jails. We detected heterogeneity in quantity and duration of antibiotic prescriptions, revealing an opportunity for improved practice.

Low frequency of allergy referral for penicillin allergy evaluation in an urban Boston primary care setting.

Background: A key strategy to combat the public health crisis of antimicrobial resistance is to use appropriate antibiotics, which is difficult in patients with a penicillin allergy label. Objective: Our aim was to investigate racial and ethnic differences related to penicillin allergy labeling and referral to allergy/immunology in primary care. Methods: This was a retrospective study of Tufts Medical Center's Boston-based primary care patients in 2019. Univariable and multivariable logistic regression models were used to examine demographic associations with (1) penicillin allergy label and (2) allergist referral. Results: Of 21,918 primary care patients, 2,391 (11%) had a penicillin allergy label; of these, 249 (10%) had an allergist referral. In multivariable logistic regression models, older age (adjusted odds ratio [aOR] = 1.06 [95% CI = 1.04-1.09]) and female sex (aOR = 1.58 [95% CI = 1.44-1.74]) were associated with higher odds of penicillin allergy label carriage. Black race (aOR = 0.77 [95% CI = 0.69-0.87]) and Asian race (aOR = 0.47 [95% CI = 0.41-0.53]) were associated with lower odds of penicillin allergy label carriage. In multivariable regression, allergist referral was associated with female sex (aOR = 1.52 [95% CI = 1.10-2.10]) and Black race (aOR = 1.74 [95% CI = 1.25-2.45]). Of 93 patients (37%) who completed their allergy visit, 26 (28%) had received penicillin allergy evaluation or were scheduled to receive a penicillin allergy evaluation at a future visit. Conclusions: There were racial differences in penicillin allergy labeling and referral. Allergy referral for penicillin allergy assessment was rare. Larger studies are needed to assess penicillin allergy labeling and delabeling with an equity focus on optimizing patient health outcomes.

Population pharmacokinetics and pharmacodynamics of cefazolin using total and unbound serum concentrations in patients with high body weight.

The objective of this study was to evaluate the steady state pharmacokinetics and pharmacodynamics of cefazolin in patients with a high body weight. Cefazolin was administered by 0.5-h infusions to 11 patients with total body weight (TBW) ≥120 kg receiving 3 g q8h, and 12 patients with TBW <120 kg receiving 2 g q8h. Total and unbound serum concentration-time data obtained from serial blood samples were analysed simultaneously by population pharmacokinetic modelling using NONMEM. Probability of target attainment (PTA) was calculated for various dosing regimens through Monte Carlo simulations based on the cumulative percentage of the dosing interval that the unbound concentration exceeds the minimum inhibitory concentration (MIC) value for the pathogen at steady state (fTMIC) ≥40%, ≥60% and 100%. A two-compartment model with non-linear protein binding and allometric scaling of the central volume of distribution using TBW best characterized both total and unbound concentration-time data. Unbound clearance was significantly associated with creatinine clearance, and maximum protein binding constant was significantly associated with serum albumin concentration and body mass index (P <0.05). Based on unbound concentration-time profiles, all simulated regimens achieved PTA >90% at MIC values ≤2 mg/L using fTMIC ≥40%, at MIC values ≤1 mg/L using fTMIC ≥60%, and at MIC values ≤0.5 mg/L using fTMIC of 100%. At fTMIC ≥60%, 0.5-h infusion of cefazolin 1 g q8h achieved PTA <90% at MIC values ≥2 mg/L in patients with TBW≥120 kg; however, prolonged-infusion and higher-dose regimens improved PTA to >90%. Overall, cefazolin pharmacokinetics are altered considerably in obese patients. Higher-dose and/or prolonged-infusion cefazolin regimens should be considered in patients with TBW ≥120 kg, particularly those with less-susceptible Gram-negative infections.

Inadequate Cerebrospinal Fluid Concentrations of Available Salvage Agents Further Impedes the Optimal Treatment of Multidrug-Resistant Enterococcus faecium Meningitis and Bacteremia.

BACKGROUND: Vancomycin-resistant Enterococcus faecium (VRE) in particular has evolved as an important cause of hospital acquired infection, especially in immunocompromised hosts. METHODS: We present a complex case of a patient with relapsed acute myeloid leukemia who underwent allogenic hematopoietic stem cell transplantation complicated by persistent VRE bacteremia and meningitis. To optimize therapy, various blood and cerebrospinal fluid (CSF) samples were sent to a research laboratory for extensive susceptibility testing, pharmacokinetic analyses, and time-kill experiments. RESULTS: In vitro testing revealed resistance to all first-line treatment options and CSF sampling demonstrated sub-optimal central nervous system concentrations achieved by each antimicrobial agent administered in relation to their respective MIC value. Time-kill analyses at observed CSF concentrations confirmed the lack of bactericidal activity despite use of a four-drug combination regimen. CONCLUSIONS: This work is the first to report CSF concentrations of oritavancin and tedizolid in humans and adds to the limited data regarding in vitro susceptibility of new antimicrobial agents such as eravacycline, omadacycline, and lefamulin against VRE. Our study provides new insights into various aspects of treatment of extensively drug-resistant Enterococcus faecium meningitis and bacteremia and supports the continued pursuit of precision medicine for these challenging cases.