Study Objective
The preferred antibiotic salvage regimen for persistent methicillin‐resistant Staphylococcus aureus bacteremia (MRSAB) is unclear. We sought to evaluate the effectiveness and safety ...of vancomycin plus ceftaroline for persistent MRSAB. The primary outcome was time to MRSAB clearance post‐ceftaroline initiation. Secondary outcomes included microbiological cure, hospital length of stay, 90‐day readmission for MRSAB, 90‐day all‐cause mortality, MRSAB‐related mortality, and incidence of antibiotic‐associated adverse effects.
Design
Single‐center, retrospective cohort study between January 1, 2016, and December 31, 2021.
Setting
State University of New York Upstate University Hospital, a 748‐bed tertiary care, academic medical center in Syracuse, NY.
Patients
Adult patients were included if they had blood cultures positive for MRSA ≥72 h, received vancomycin monotherapy initially, and received vancomycin plus ceftaroline for ≥24 h. Patients were excluded if they received other anti‐MRSA antibiotics, were pregnant, or were incarcerated. Of the 178 patients identified, 30 unique patients were evaluated.
Measurements and Main Results
Patients were medically complex with a median Pitt bacteremia score of 3, 63.3% (19/30) were admitted to the intensive care unit, and 66.7% (20/30) had infective endocarditis. Vancomycin‐associated acute kidney injury was observed in 10% (3/30) of patients, which resulted in dose adjustments. No patients experienced ceftaroline‐associated neutropenia or Clostridioides difficile infection, but 6.7% (2/30) developed a rash attributed to ceftaroline. Median time to MRSAB clearance post‐ceftaroline initiation was 2.6 days. Microbiologic cure occurred in nearly all patients 96.7% (29/30). Median hospital length of stay was 19.5 days, and 6.7% (2/30) of patients had 90‐day readmission for MRSAB. 90‐day all‐cause mortality and MRSAB‐related mortality occurred in 26.7% (8/30) and 13.3% (4/30) of patients, respectively.
Conclusions
Vancomycin plus ceftaroline may represent an effective and well‐tolerated salvage regimen option for persistent MRSAB.
Background:
Free online adaptive vancomycin dosing calculators are available to estimate area under the concentration-time curve (AUC), but the accuracy of predicting vancomycin AUC using these ...calculators compared with using a 2-point pharmacokinetic approach has not been described.
Objective:
To evaluate the accuracy of calculator-predicted AUC (cpAUC) using 4 free online calculators compared with reference AUC (rAUC), and to assess pharmacists’ impressions of the ease of use.
Methods:
Vancomycin AUC was estimated using (1) the reference method via the Sawchuk-Zaske method and linear-logarithmic trapezoidal rule using 2 steady-state postdistributional vancomycin serum concentrations and (2) 4 free online vancomycin dosing calculators including ClinCalc, VancoPK, TDMx, and DMC. Accuracy was calculated by dividing cpAUC by rAUC. Ease of cpAUC estimation was determined by using a 10-point Likert scale.
Results:
All 4 calculators had a median cpAUC accuracy ranging from 89% to 110%. Concordance between cpAUC and rAUC determinations of AUC <400 and > 600 mg·h/L occurred 63.3% to 71.4% and 74.5% to 78.6% of the time, respectively. Pharmacist investigators agreed that ClinCalc and VancoPK calculators were easiest to use.
Conclusion and Relevance:
cpAUC accuracy varied among the 4 calculators, but all consistently identified patients with an rAUC <400 mg·h/L and an rAUC > 600 mg·h/L at comparable frequencies. All 4 calculators demonstrated some imprecision based on their wide 95% CIs and potential inaccuracies in predicting an rAUC <400 mg·h/L or an rAUC > 600 mg·h/L. Clin Calc and VancoPK were most user friendly based on our pharmacists’ impressions.
•Staphylococcus aureus bacteremia (SAB) is a common infectious disease (ID).•Pharmacists are well-positioned to assist ID consultation (IDC) with SAB management.•We implemented a ...pharmacist-facilitated, SAB evidence-based bundle (EBB) initiative.•We observed improved adherence to the EBB and several clinical outcomes for SAB.•SAB management may be optimized with collaboration between pharmacists and IDC.
To evaluate a pharmacist-facilitated evidence-based bundle (EBB) initiative with infectious disease consultation (IDC) for Staphylococcus aureus bacteremia (SAB).
This was a before-and-after quasi-experimental study of adult patients with SAB before and after the pharmacist-facilitated EBB initiative, which included IDC, timely definitive antibiotics, source control, echocardiography, and repeat blood cultures.
Ninety and 111 patients were included in pre- and post-intervention cohorts, respectively. We observed significant increases in adherence to all 5 (4.4% vs 68.5%, P < 0.001) and 4 (10.0% vs 76.6%, P < 0.001) EBB elements. Time to definitive antibiotics (48 vs 16 hours, P < 0.001), time to IDC (43.5 vs 32 hours, P < 0.001), SAB duration (95 vs 66 hours, P = 0.009), persistent SAB (18.9% vs 9.0%, P = 0.041), and length of stay (14 vs 13 days, P = 0.027) also improved. No statistically significant differences for SAB-related readmission or all-cause mortality were observed.
Our pharmacist-facilitated SAB initiative was associated with improved EBB adherence and clinical outcomes.
Evaluation of adult antibiotic order sets (AOSs) on antibiotic stewardship metrics has been limited. The primary outcome was to evaluate the standardized antimicrobial administration ratio (SAAR). ...Secondary outcomes included antibiotic days of therapy (DOT) per 1,000 patient days (PD); selected antibiotic use; AOS utilization;
infection (CDI) cases; and clinicians' perceptions of the AOS via a survey following the final study phase.
This 5-year, single-center, quasi-experimental study comprised 5 phases from 2017 to 2022 over 10-month periods between August 1 and May 31.
The study was conducted in a 752-bed tertiary care, academic medical center.
Our institution implemented AOSs in the electronic medical record (EMR) for common infections among hospitalized adults.
For the primary outcome, a statistically significant decreases in SAAR were detected from phase 1 to phase 5 (1.0 vs 0.90;
< .001). A statistically significant decreases were detected in DOT per 1,000 PD (4,884 vs 3,939;
= .001), fluoroquinolone orders (407 vs 175;
< .001), carbapenem orders (147 vs 106;
= .024), and clindamycin orders (113 vs 73;
= .01). No statistically significant change in mean vancomycin orders was detected (991 vs 902;
= .221). A statistically significant decrease in CDI cases was also detected (7.8, vs 2.4;
= .002) but may have been attributable to changes in CDI case diagnosis. Clinicians indicated that the AOSs were easy to use overall and that they helped them select the appropriate antibiotics.
Implementing AOS into the EMR was associated with a statistically significant reduction in SAAR, antibiotic DOT per 1,000 PD, selected antibiotic orders, and CDI cases.
Neutralizing monoclonal antibodies (mAbs) were authorized for the treatment of COVID-19 outpatients based on clinical trials completed early in the pandemic, which were underpowered for mortality and ...subgroup analyses. Real-world data studies are promising for further assessing rapidly deployed therapeutics.
Did mAb treatment prevent progression to severe disease and death across pandemic phases and based on risk factors, including prior vaccination status?
This observational cohort study included nonhospitalized adult patients with SARS-CoV-2 infection from November 2020 to October 2021 using electronic health records from a statewide health system plus state-level vaccine and mortality data. Using propensity matching, we selected approximately 2.5 patients not receiving mAbs for each patient who received mAb treatment under emergency use authorization. The primary outcome was 28-day hospitalization; secondary outcomes included mortality and hospitalization severity.
Of 36,077 patients with SARS-CoV-2 infection, 2,675 receiving mAbs were matched to 6,677 patients not receiving mAbs. Compared with mAb-untreated patients, mAb-treated patients had lower all-cause hospitalization (4.0% vs 7.7%; adjusted OR, 0.48; 95% CI, 0.38-0.60) and all-cause mortality (0.1% vs 0.9%; adjusted OR, 0.11; 95% CI, 0.03-0.29) to day 28; differences persisted to day 90. Among hospitalized patients, mAb-treated patients had shorter hospital length of stay (5.8 vs 8.5 days) and lower risk of mechanical ventilation (4.6% vs 16.6%). Results were similar for preventing hospitalizations during the Delta variant phase (adjusted OR, 0.35; 95% CI, 0.25-0.50) and across subgroups. Number-needed-to-treat (NNT) to prevent hospitalization was lower for subgroups with higher baseline risk of hospitalization; for example, multiple comorbidities (NNT = 17) and not fully vaccinated (NNT = 24) vs no comorbidities (NNT = 88) and fully vaccinated (NNT = 81).
Real-world data revealed a strong association between receipt of mAbs and reduced hospitalization and deaths among COVID-19 outpatients across pandemic phases. Real-world data studies should be used to guide practice and policy decisions, including allocation of scarce resources.
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Languages differ in the extent to which phonologicalcontrasts observed in onsets are neutralized syllable finally. We examined theacquisition of English syllable-final /m n ŋ/ by L2 learners whose L1 ...nasalcodas lack independent place (Japanese) or neutralize to a single place(Spanish). Three learning outcomes were hypothesized, based on whetherlearners’ production is shaped mainly by coda complexity, perception of thecontrast or L1 dialectal realizations. Data from three reading tasks collectedfrom six learners (three of each L1) and two English-speaking controls wereexamined using electropalatography (EPG). Linguopalatal contact patterns wereanalyzed quantitatively and qualitatively (presence, absence, and degree ofalveolar and velar closures). While difficulty in realizing place contrasts wasobserved with all L2 speakers, contrary to our hypothesis, the L1 Spanishspeakers were less accurate than their Japanese-speaking peers, particularly inthe production of word-final prevocalic /ŋ/ for which a high rate ofneutralization to /n/ was witnessed. However, the Japanese learners’ greaterapparent accuracy was due to the presence of non-target final devoicedepenthetic vowels and/or stop-like releases. Overall, the results provideinsights into developmental stages in the acquisition of new positionalcontrasts, including evidence for first language and even idiolectal influence,and highlight the difficulty of blocking L1 neutralization processes.
In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been ...peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.
While some guidelines recognize the need for β-lactam therapeutic drug monitoring (TDM), there is still a paucity of data regarding the prevalence of and barriers to performing β-lactam TDM in the United States. We sought to estimate the prevalence of β-lactam TDM, describe monitoring practices, and identify actual and perceived barriers to implementation among health systems in the US.
A multicenter, cross-sectional, 40-item electronic survey was distributed to all postgraduate year 2 (PGY2) infectious diseases (ID) pharmacy residency program directors (RPDs) listed in the American Society of Health-System Pharmacists pharmacy residency directory. The primary outcome was the percentage of institutions with established β-lactam TDM. Secondary outcomes included assessing β-lactam TDM methods and identifying potential barriers to implementation.
The survey was distributed to 126 PGY2 ID RPDs, with a response rate of 31.7% (40 of 126). Only 7.7% of respondents (3 of 39) performed β-lactam TDM. Patient populations, therapeutic targets, and frequency and timing of obtaining repeat β-lactam concentration measurements varied among institutions. The greatest barrier to implementation was lack of access to testing with a rapid turnaround time. Institutions were unlikely to implement β-lactam TDM within the next year but were significantly more inclined to do so within 5 years (P < 0.001).
Β-lactam TDM was infrequently performed at the surveyed US health systems. Lack of access to serum concentration testing with rapid turnaround and lack of US-specific guidelines appear to be considerable barriers to implementing β-lactam TDM. Among institutions that have implemented β-lactam TDM, there is considerable variation in monitoring approaches.
To determine the impact of a pharmacist-driven beta-lactam allergy interview on antimicrobial therapy.
Tertiary care academic medical center.
Clarification of beta-lactam allergy may expand treatment ...options for patients and potentially improve outcomes, reduce toxicity, and reduce costs.
At our institution, a pilot service using a pharmacy resident and infectious diseases clinical pharmacist was implemented to clarify beta-lactam allergy information and, where appropriate, recommend a change to the patient's antibiotic therapy.
Adult patients with a documented beta-lactam allergy who had received non-penicillin antibiotics and who had undergone a beta-lactam allergy interview were identified via pharmacy intervention data. A pharmacist interviewed these patients with the use of an internally developed allergy questionnaire. Recommendations for beta-lactam therapy were made to the patient's primary medical team based on the results of the allergy interview and factors including infection type and culture results. The primary objectives were to determine the percentage of patients successfully switched to beta-lactam therapy as a result of the drug allergy interview, to identify allergy discrepancies between the electronic medical record (EMR) and pharmacist's interview, and to quantify the acceptance rate of the pharmacist's antimicrobial recommendations after drug allergy clarification.
Thirty-two patients were interviewed, and 24 were candidates for a beta-lactam recommendation. As a result of the interview, 21 patients (65.6%) were successfully switched from a non-penicillin antibiotic to a cephalosporin, carbapenem, or penicillin. A discrepancy between the EMR-reported allergy and history obtained on interview was identified in 11 patients (34.4%). Medical providers accepted 87.5% of pharmacists' antimicrobial recommendations.
A pharmacist-driven beta-lactam allergy interview was effective in switching eligible patients to beta-lactam therapy and identifying discrepancies between EMR-documented allergies and confirmed allergies. Antimicrobial recommendations were well received by medical providers with a high acceptance rate.
Study Objective
To compare rates of nephrotoxicity, time to nephrotoxicity onset, and clinical failure among patients who received continuous infusion (C‐I) or intermittent infusion (I‐I) vancomycin ...in an outpatient parenteral antimicrobial therapy (OPAT) program. Nephrotoxicity was defined as an increase in serum creatinine greater than 0.5 mg/dl or a 50% increase from baseline for two consecutive measurements while receiving vancomycin during OPAT. Clinical failure was defined as unplanned readmission, extension of therapy, or change in antibiotics.
Design
Single‐center propensity score‐matched retrospective cohort study.
Setting
OPAT clinic affiliated with two nearby hospitals.
Patients
We identified 300 patients who received C‐I or I‐I vancomycin for at least 1 week in the OPAT program between October 1, 2017, and March 31, 2019. Propensity score matching based on age, sex, and infection was performed to minimize differences in patient characteristics between groups.
Measurements and Main Results
After propensity score matching and exclusion criteria, 74 patients were included in each cohort. Continuous infusion vancomycin was associated with a 3.22‐fold decrease in nephrotoxicity risk (C‐I 6.8% 5/74 patients vs I‐I 18.9% 14/74 patients; odds ratio 3.22, 95% confidence interval 1.10–9.46, p=0.027) and a significantly slower onset to nephrotoxicity compared with I‐I (p=0.035). No statistically significant difference in clinical failure rates was observed between the C‐I and I‐I groups (13.5% 10/74 patients vs 23.0% 17/74 patients, p=0.147).
Conclusion
In an OPAT setting, C‐I vancomycin was associated with a lower risk of and slower onset to nephrotoxicity than I‐I vancomycin; however, no statistically significant difference in clinical failure rates was observed with C‐I versus I‐I vancomycin.
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