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1.
Emerg Med Clin North Am ; 42(2): 209-230, 2024 May.
Article En | MEDLINE | ID: mdl-38641388

Emergency medicine has been called the art of "making complicated clinical decisions with limited information." This description is particularly relevant in the case of diagnosis and treatment of urinary tract infections (UTIs). Although common, UTIs are often challenging to diagnose given the presence of non-specific signs and symptoms and over-reliance on laboratory findings. This review provides an interdisciplinary interpretation of the primary literature and practice guidelines, with a focus on diagnostic and antimicrobial stewardship in the emergency department.


Antimicrobial Stewardship , Urinary Tract Infections , Adult , Humans , Anti-Bacterial Agents/therapeutic use , Urinary Tract Infections/diagnosis , Urinary Tract Infections/drug therapy , Emergency Service, Hospital
2.
Article En | MEDLINE | ID: mdl-38628377

Diagnostic stewardship is increasingly recognized as a powerful tool to improve patient safety. Given the close relationship between diagnostic testing and antimicrobial misuse, antimicrobial stewardship (AMS) pharmacists should be key members of the diagnostic team. Pharmacists practicing in AMS already frequently engage with clinicians to improve the diagnostic process and have many skills needed for the implementation of diagnostic stewardship initiatives. As diagnostic stewardship becomes more broadly used, all infectious disease clinicians, including pharmacists, must collaborate to optimize patient care.

3.
Infect Control Hosp Epidemiol ; 45(4): 405-411, 2024 Apr.
Article En | MEDLINE | ID: mdl-38204365

Diagnostic stewardship seeks to improve ordering, collection, performance, and reporting of tests. Test results play an important role in reportable HAIs. The inclusion of HAIs in public reporting and pay for performance programs has highlighted the value of diagnostic stewardship as part of infection prevention initiatives. Inappropriate testing should be discouraged, and approaches that seek to alter testing solely to impact a reportable metric should be avoided. HAI definitions should be further adapted to new testing technologies, with focus on actionable and clinically relevant test results that will improve patient care.


Cross Infection , Reimbursement, Incentive , Humans , Cross Infection/diagnosis , Cross Infection/prevention & control , Surveys and Questionnaires , Benchmarking , Delivery of Health Care
4.
Microbiol Spectr ; 12(1): e0235123, 2024 Jan 11.
Article En | MEDLINE | ID: mdl-38018984

IMPORTANCE: The rise of multidrug-resistant (MDR) pathogens, especially MDR Gram-negatives, poses a significant challenge to clinicians and public health. These resilient bacteria have rendered many traditional antibiotics ineffective, underscoring the urgency for innovative therapeutic solutions. Eravacycline, a broad-spectrum fluorocycline tetracycline antibiotic approved by the FDA in 2018, emerges as a promising candidate, exhibiting potential against a diverse array of MDR bacteria, including Gram-negative, Gram-positive, anaerobic strains, and Mycobacterium. However, comprehensive data on its real-world application remain scarce. This retrospective cohort study, one of the largest of its kind, delves into the utilization of eravacycline across various infectious conditions in the USA during its initial 4 years post-FDA approval. Through assessing clinical, microbiological, and tolerability outcomes, the research offers pivotal insights into eravacycline's efficacy in addressing the pressing global challenge of MDR bacterial infections.


Anti-Bacterial Agents , Tetracyclines , Humans , Retrospective Studies , Tetracyclines/therapeutic use , Tetracyclines/pharmacology , Anti-Bacterial Agents/adverse effects , Drug Resistance, Multiple, Bacterial , Microbial Sensitivity Tests , Outcome Assessment, Health Care , Gram-Negative Bacteria
5.
Open Forum Infect Dis ; 10(10): ofad512, 2023 Oct.
Article En | MEDLINE | ID: mdl-37901124

Background: Early detection of multidrug-resistant Pseudomonas aeruginosa (MDRP) remains challenging. Existing risk prediction tools are difficult to translate to bedside application. The goal of this study was to develop a simple electronic medical record (EMR)-integrated tool for prediction of MDRP infection. Methods: This was a mixed-methods study. We conducted a split-sample cohort study of adult critical care patients with P aeruginosa infections. Two previously published tools were validated using c-statistic. A subset of variables based on strength of association and ease of EMR extraction was selected for further evaluation. A simplified tool was developed using multivariable logistic regression. Both c-statistic and theoretical trade-off of over- versus underprescribing of broad-spectrum MDRP therapy were assessed in the validation cohort. A qualitative survey of frontline clinicians assessed understanding of risks for MDRP and potential usability of an EMR-integrated tool to predict MDRP. Results: The 2 previous risk prediction tools demonstrated similar accuracy in the derivation cohort (c-statistic of 0.76 [95% confidence interval {CI}, .69-.83] and 0.73 [95% CI, .66-.8]). A simplified tool based on 4 variables demonstrated reasonable accuracy (c-statistic of 0.71 [95% CI, .57-.85]) without significant overprescribing in the validation cohort. The risk factors were prior MDRP infection, ≥4 antibiotics prior to culture, infection >3 days after admission, and dialysis. Fourteen clinicians completed the survey. An alert providing context regarding individual patient risk factors for MDRP was preferred. Conclusions: These results can be used to develop a local EMR-integrated tool to improve timeliness of effective therapy in those at risk of MDRP infections.

6.
Article En | MEDLINE | ID: mdl-37592970

Misdiagnosis of bacterial pneumonia increases risk of exposure to inappropriate antibiotics and adverse events. We developed a diagnosis calculator (https://calculator.testingwisely.com) to inform clinical diagnosis of community-acquired bacterial pneumonia using objective indicators, including incidence of disease, risk factors, and sensitivity and specificity of diagnostic tests, that were identified through literature review.

7.
Infect Control Hosp Epidemiol ; 44(12): 1932-1941, 2023 Dec.
Article En | MEDLINE | ID: mdl-37424224

BACKGROUND: Urine-culture diagnostic stewardship aims to decrease misdiagnosis of urinary tract infections (UTIs); however, these interventions are not widely adopted. We examined UTI diagnosis and management practices to identify barriers to and facilitators of diagnostic stewardship implementation. METHODS: Using a qualitative descriptive design, we conducted semistructured interviews at 3 Veterans' Affairs medical centers. Interviews were conducted between November 2021 and May 2022 via Zoom videoconferencing using an interview guide and visual prototypes of proposed interventions. Interviewees were asked about current practices and thoughts on proposed interventions for urine-culture ordering, processing, and reporting. We used a rapid analysis matrix approach to summarize key interview findings and compare practices and perceptions across sites. RESULTS: We interviewed 31 stakeholders and end users. All sites had an antimicrobial stewardship program but limited initiatives targeting appropriate diagnosis and management of UTIs. The majority of those interviewed identified the importance of diagnostic stewardship. Perceptions of specific interventions ranged widely by site. For urine-culture ordering, all 3 sites agreed that documentation of symptomology would improve culturing practices but did not want it to interrupt workflow. Representatives at 2 sites expressed interest in conditional urine-culture processing and 1 was opposed. All sites had similar mechanisms to report culture results but varied in perceptions of the proposed interventions. Feedback from end users was used to develop a general diagnostic stewardship implementation checklist. CONCLUSION: Interviewees thought diagnostic stewardship was important. Qualitative assessment involving key stakeholders in the UTI diagnostic process improved understanding of site-specific beliefs and practices to better implement interventions for urine-culture ordering, processing, and reporting.


Antimicrobial Stewardship , Urinary Tract Infections , Humans , Urinary Tract Infections/diagnosis , Urinary Tract Infections/drug therapy , Antimicrobial Stewardship/methods , Hospitals , Anti-Bacterial Agents/therapeutic use
8.
Curr Opin Infect Dis ; 36(4): 270-275, 2023 08 01.
Article En | MEDLINE | ID: mdl-37431556

PURPOSE OF REVIEW: The aim of this study was to review recently published diagnostic stewardship studies of common clinical infectious syndromes and the impact on antibiotic prescribing. RECENT FINDINGS: Diagnostic stewardship can be implemented within healthcare systems and tailored to infectious syndromes, including urinary tract, gastrointestinal, respiratory and bloodstream infections. In urinary syndromes, diagnostic stewardship can decrease unnecessary urine culturing and associated antibiotic prescribing. Diagnostic stewardship of Clostridium difficile testing can decrease antibiotics and test ordering with a reduction in healthcare-associated C. difficile infections. Respiratory syndrome multiplex arrays can decrease time to results and increase detection of clinically relevant pathogens but may not decrease antibiotics use, or worse, could increase over-prescribing if diagnostic stewardship of ordering practices is not exercised. Lastly, blood culturing practices can be improved by clinical decision support to safely decrease collection and broad-spectrum antibiotic use. SUMMARY: Diagnostic stewardship decreases unnecessary antibiotic use in a way that is different from and complementary to antibiotic stewardship. Further studies are needed to quantify the full impact on antibiotic use and resistance. Future considerations should be to institutionalize diagnostic stewardship in patient care activities to leverage integration into systems-based interventions.


Antimicrobial Stewardship , Clostridioides difficile , Cross Infection , Humans , Syndrome , Anti-Bacterial Agents/therapeutic use
10.
Pharmacotherapy ; 43(8): 847-863, 2023 08.
Article En | MEDLINE | ID: mdl-37158053

Antimicrobial stewardship (AMS) programs have been quick to adopt novel molecular rapid diagnostic technologies (mRDTs) for bloodstream infections (BSIs) to improve antimicrobial management. As such, most of the literature demonstrating the clinical and economic benefits of mRDTs for BSI is in the presence of active AMS intervention. Leveraging mRDTs to improve antimicrobial therapy for BSI is increasingly integral to AMS program activities. This narrative review discusses available and future mRDTs, the relationship between the clinical microbiology laboratory and AMS programs, and practical considerations for optimizing the use of these tools within a health system. Antimicrobial stewardship programs must work closely with their clinical microbiology laboratories to ensure that mRDTs are used to their fullest benefit while remaining cognizant of their limitations. As more mRDT instruments and panels become available and AMS programs continue to expand, future efforts must consider the expansion beyond traditional settings of large academic medical centers and how combinations of tools can further improve patient care.


Anti-Infective Agents , Antimicrobial Stewardship , Sepsis , Humans , Rapid Diagnostic Tests , Sepsis/diagnosis , Sepsis/drug therapy , Anti-Infective Agents/therapeutic use , Anti-Bacterial Agents/therapeutic use
11.
Int J Antimicrob Agents ; 61(6): 106811, 2023 Jun.
Article En | MEDLINE | ID: mdl-37037319

INTRODUCTION: Multidrug-resistant (MDR) Gram-negative organisms cause life-threatening infections, and the incidence is rising globally. Timely therapy for these infections has a direct impact on patient survival. This study aimed to determine the impact of a multidisciplinary diagnostic and antimicrobial stewardship (AMS) workflow on time to appropriate therapy (TAP) for these infections using novel beta-lactam/beta-lactamase inhibitors. METHODS: This was a retrospective quasi-experimental study of adult patients with carbapenem-resistant Enterobacterales (CRE) and multidrug-resistant Pseudomonas (MDR PsA) infections at a 1500 bed university hospital. Included patients who received ≥ 72 hours of ceftazidime-avibactam (CZA) or ceftolozane-tazobactam (C/T) from December 2017 to December 2019. During the pre-intervention period (December 2017 to December 2018), additional susceptibilities (including CZA and C/T) were performed only upon providers' request. In 2019, reflex algorithms were implemented for faster identification and testing of all CRE/MDR PsA isolates. Results were communicated in real-time to the AMS team to tailor therapy. RESULTS: A total of 99 patients were included, with no between-group differences at baseline. The median age was 60 years and 56 (56.7%) were in intensive care at the time of culture collection. Identified organisms included 71 (71.7%) MDR PsA and 26 CRE, of which 18 were carbapenemase producers (Klebsiella-producing carbapenemase = 12, New Delhi metallo-ß-lactamase = 4, Verona integron-encoded metallo-ß-lactamase = 2). The most common infections were pneumonia (49.5%) and bacteraemia (30.3%). A decrease was found in median TAP (103 [IQR 76.0-156.0] vs. 75 [IQR 56-100] hours; P < 0.001). Median time from culture collection to final susceptibility results was shorter in the post-intervention group (123 vs. 93 hours; P < 0.001). CONCLUSION: This study identified improvement in TAP in MDR PsA and CRE infections with implementation of a reflex microbiology workflow and multidisciplinary antimicrobial stewardship initiatives.


Antimicrobial Stewardship , Arthritis, Psoriatic , Humans , Middle Aged , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Retrospective Studies , Workflow , Arthritis, Psoriatic/drug therapy , Ceftazidime/pharmacology , Gram-Negative Bacteria , beta-Lactamase Inhibitors/therapeutic use , beta-Lactamase Inhibitors/pharmacology , beta-Lactamases , Carbapenems/pharmacology , Drug Combinations , Azabicyclo Compounds/pharmacology , Microbial Sensitivity Tests , Pseudomonas aeruginosa
12.
J Antimicrob Chemother ; 78(4): 1034-1040, 2023 04 03.
Article En | MEDLINE | ID: mdl-36869724

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.


Acinetobacter Infections , Acinetobacter baumannii , COVID-19 , Humans , Carbapenems/pharmacology , Carbapenems/therapeutic use , Retrospective Studies , Acinetobacter Infections/drug therapy , Drug Synergism , Anti-Bacterial Agents/therapeutic use , Drug Combinations , Acinetobacter baumannii/genetics , Microbial Sensitivity Tests
13.
Infect Dis Ther ; 12(3): 989-996, 2023 Mar.
Article En | MEDLINE | ID: mdl-36884212

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.

14.
Drugs Context ; 122023.
Article En | MEDLINE | ID: mdl-36843619

Novel diagnostic stewardship in infectious disease consists of interventions that modify ordering, processing, and reporting of diagnostic tests to provide the right test for the right patient, prompting the right action. The interventions work upstream and synergistically with traditional antimicrobial stewardship efforts. As diagnostic stewardship continues to gain public attention, it is critical that antimicrobial stewardship programmes not only learn how to effectively leverage diagnostic testing to improve antimicrobial use but also ensure that they are stakeholders and leaders in developing new diagnostic stewardship interventions within their institutions. This review will discuss the need for diagnostic and antimicrobial stewardship, the interplay of diagnostic and antimicrobial stewardship, evidence of benefit to antimicrobial stewardship programmes, and considerations for successfully engaging in diagnostic stewardship interventions. This article is part of the Antibiotic stewardship Special Issue: https://www.drugsincontext.com/special_issues/antimicrobial-stewardship-a-focus-on-the-need-for-moderation.

15.
Article En | MEDLINE | ID: mdl-36483413

Objective: Ventilator-associated pneumonia (VAP) can be overdiagnosed on the basis of positive respiratory cultures in the absence of clinical findings of pneumonia. We determined the perceived diagnostic importance of 6 clinical attributes in ordering a respiratory culture to identify opportunities for diagnostic stewardship. Design: A discrete choice experiment presented participants with a vignette consisting of the same "stem" plus variations in 6 clinical attributes associated with VAP: chest imaging, oxygenation, sputum, temperature, white blood cell count, and blood pressure. Each attribute had 3-4 levels, resulting in 32 total scenarios. Participants indicated whether they would order a respiratory culture, and if yes, whether they preferred the bronchoalveolar lavage or endotracheal aspirate sample-collection method. We calculated diagnostic utility of attribute levels and relative importance of each attribute. Setting and participants: The survey was administered electronically to critical-care clinicians via a Qualtrics survey at a tertiary-care academic center in the United States. Results: In total, 59 respondents completed the survey. New radiograph opacity (utility, 1.15; 95% confidence interval [CI], 0.99-1.3), hypotension (utility, 0.88; 95% CI, 0.74-1.03), fever (utility, 0.76; 95% CI, 0.62-0.91) and copious sputum (utility, 0.75; 95% CI, 0.60-0.90) had the greatest perceived diagnostic value that favored ordering a respiratory culture. Radiograph changes (23%) and temperature (20%) had the highest relative importance. New opacity (utility, 0.35; 95% CI, 0.17-0.52) and persistent opacity on radiograph (utility, 0.32; 95% CI, 0.05-0.59) had the greatest value favoring bronchoalveolar lavage over endotracheal aspirate. Conclusion: Perceived high diagnostic value of fever and hypotension suggest that sepsis vigilance may drive respiratory culturing and play a role in VAP overdiagnosis.

16.
Open Forum Infect Dis ; 9(7): ofac289, 2022 Jul.
Article En | MEDLINE | ID: mdl-35873287

Background: Prospective audit with feedback (PAF) is an impactful strategy for antimicrobial stewardship program (ASP) activities. However, because PAF requires reviewing large numbers of antimicrobial orders on a case-by-case basis, PAF programs are highly resource intensive. The current study aimed to identify predictors of ASP intervention (ie, feedback) and to build models to identify orders that can be safely bypassed from review, to make PAF programs more efficient. Methods: We performed a retrospective cross-sectional study of inpatient antimicrobial orders reviewed by the University of Maryland Medical Center's PAF program between 2017 and 2019. We evaluated the relationship between antimicrobial and patient characteristics with ASP intervention using multivariable logistic regression models. Separately, we built prediction models for ASP intervention using statistical and machine learning approaches and evaluated performance on held-out data. Results: Across 17 503 PAF reviews, 4219 (24%) resulted in intervention. In adjusted analyses, a clinical pharmacist on the ordering unit or receipt of an infectious disease consult were associated with 17% and 56% lower intervention odds, respectively (adjusted odds ratios [aORs], 0.83 and 0.44; P ≤ .001 for both). Fluoroquinolones had the highest adjusted intervention odds (aOR, 3.22 [95% confidence interval, 2.63-3.96]). A machine learning classifier (C-statistic 0.76) reduced reviews by 49% while achieving 78% sensitivity. A "workflow simplified" regression model that restricted to antimicrobial class and clinical indication variables, 2 strong machine learning-identified predictors, reduced reviews by one-third while achieving 81% sensitivity. Conclusions: Prediction models substantially reduced PAF review caseloads while maintaining high sensitivities. Our results and approach may offer a blueprint for other ASPs.

17.
Open Forum Infect Dis ; 9(5): ofac173, 2022 May.
Article En | MEDLINE | ID: mdl-35531383

The role of follow-up blood cultures (FUBCs) in gram-negative bloodstream infections to improve clinical outcomes remains controversial, especially among immunocompromised patients. Among 139 patients, FUBCs were common (117, 84.2%); however, positive FUBCs were rare (3, 2.6%). Only presence of fever was associated with a positive FUBC.

18.
J Antimicrob Chemother ; 77(8): 2245-2250, 2022 07 28.
Article En | MEDLINE | ID: mdl-35640658

OBJECTIVES: To assess differences in vancomycin AUC estimates from two common, clinically applied first-order pharmacokinetic equation methods compared with Bayesian estimates. METHODS: A cohort of patients who received vancomycin and therapeutic drug monitoring was studied. First-order population pharmacokinetic equations were used to guide initial empirical dosing. After receipt of the first dose, patients had peak and trough serum levels drawn and steady-state AUC was estimated using first-order pharmacokinetic equations as standard care. We subsequently created a Bayesian model and used individual Empirical Bayes Estimates to precisely calculate vancomycin AUC24-48, AUC48-72 and AUC72-96 in this cohort. AUC at steady state (AUCSS) differences from the first-order methods were compared numerically and categorically (i.e. below, within or above 400-600 mg·h/L) to Bayesian AUCs, which served as the gold standard. RESULTS: A total of 65 adult inpatients with 409 plasma samples were included in this analysis. A two-compartment intravenous infusion model with first-order elimination fit the data well. The mean of Bayesian AUC24-48 was not significantly different from AUC estimates from the two first-order pharmacokinetic equation methods (P = 0.68); however, Bayesian AUC48-72 and Bayesian AUC72-96 were both significantly different when compared with both first-order pharmacokinetic equation methods (P < 0.01 for each). At the patient level, categorical classifications of AUC estimates from the two first-order pharmacokinetic equation methods differed from categorizations derived from the Bayesian calculations. Categorical agreement was ∼50% between first-order and Bayesian calculations, with declining categorical agreement observed with longer treatment courses. Differences in categorical agreement between calculation methods could potentially result in different dose recommendations for the patient. CONCLUSIONS: Bayesian-calculated AUCs between 48-72 and 72-96 h intervals were significantly different from first-order pharmacokinetic method-estimated AUCs at steady state. The various calculation methods resulted in different categorical classification, which could potentially lead to erroneous dosing adjustments in approximately half of the patients.


Anti-Bacterial Agents , Vancomycin , Adult , Anti-Bacterial Agents/therapeutic use , Area Under Curve , Bayes Theorem , Drug Monitoring/methods , Humans
19.
Bone Jt Open ; 3(4): 284-290, 2022 Apr.
Article En | MEDLINE | ID: mdl-35363046

AIMS: There is increasing evidence to support the use of topical antibiotics to prevent surgical site infections. Although previous research suggests a minimal nephrotoxic risk with a single dose of vancomycin powder, fracture patients often require multiple procedures and receive additional doses of topical antibiotics. We aimed to determine if cumulative doses of intrawound vancomycin or tobramycin powder for infection prophylaxis increased the risk of drug-induced acute kidney injury (AKI) among fracture patients. METHODS: This cohort study was a secondary analysis of single-centre Program of Randomized Trials to Evaluate Pre-operative Antiseptic Skin Solutions in Orthopaedic Trauma (PREP-IT) trial data. We included patients with a surgically treated appendicular fracture. The primary outcome was drug-induced AKI. The odds of AKI per gram of vancomycin or tobramycin powder were calculated using Bayesian regression models, which adjusted for measured confounders and accounted for the interactive effects of vancomycin and tobramycin. RESULTS: Of the 782 included patients (mean age 48 years (SD 20); 59% male), 83% (n = 648) received at least one vancomycin dose (cumulative range 1 to 12 g). Overall, 45% of the sample received at least one tobramycin dose (cumulative range 1.2 to 9.6 g). Drug-induced AKI occurred in ten patients (1.2%). No association was found between the cumulative dose of vancomycin and drug-induced AKI (odds ratio (OR) 1.08 (95% credible interval (CrI) 0.52 to 2.14)). Additional doses of tobramycin were associated with a three-fold increase in the adjusted odds of drug-induced AKI (OR 3.66 (95% CrI 1.71 to 8.49)). Specifically, the risk of drug-induced AKI rose substantially after 4.8 g of tobramycin powder (7.5% (95% CrI 1.0 to 35.3)). CONCLUSION: Cumulative doses of vancomycin were not associated with an increased risk of drug-induced AKI among fracture patients. While the risk of drug-induced AKI remains less than 4% with three or fewer 1.2 g tobramycin doses, the estimated risk increases substantially to 8% after four cumulative doses. Level of evidence: Therapeutic Level III Cite this article: Bone Jt Open 2022;3(4):284-290.

20.
Open Forum Infect Dis ; 9(3): ofab606, 2022 Mar.
Article En | MEDLINE | ID: mdl-35146040

BACKGROUND: Observational data suggest ceftaroline may be effective for methicillin-resistant Staphylococcus aureus (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. Patients treated with ≥72 hours of ceftaroline or daptomycin were included. Those clearing BSI before study drug and those with a pneumonia source were excluded. The primary outcome was composite treatment failure, defined as 30-day mortality, BSI duration ≥7 days on study drug, and 60-day MRSA BSI recurrence. Inverse probability of treatment weighted risk difference in composite failure between daptomycin and ceftaroline groups was computed and 15% noninferiority margin applied. RESULTS: Two hundred seventy patients were included; 83 ceftaroline and 187 daptomycin. Ceftaroline was noninferior to daptomycin with respect to composite failure (39% daptomycin, 32.5% ceftaroline; weighted risk difference, 7.0% [95% confidence interval, -5.0% to 19.0%]). No differences between treatment groups was observed for 30-day mortality or other secondary efficacy outcomes. Creatine phosphokinase elevation was significantly more common among daptomycin patients (5.3% vs 0%, P = .034). Rash was significantly more common among ceftaroline patients (10.8 vs 1.1%, P = .001). CONCLUSIONS: No difference in treatment failure or mortality was observed between MRSA BSI treated with ceftaroline or daptomycin. These data support future study of ceftaroline as a primary MRSA BSI treatment and current use of ceftaroline when an alternative to vancomycin and daptomycin is required.

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