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Empirical antimicrobial therapy for BSIs may decrease in-hospital mortality

Bloodstream infections (BSIs) can result in short-term mortality rates of 10% to 30%, making early antimicrobial treatment critical for patients with BSIs. However, the time needed to identify the cause of the infection as well as increasing antimicrobial resistance can make determining an appropriate antibiotic difficult.

According to the authors of a recent paper in JAMA Network Open, a delicate balance exists between overuse of broad-spectrum antibiotics and undertreatment of infections. The authors of the study, published online on January 4, 2023, investigated whether the use of initial empirical antimicrobial therapy resulted in lower in-hospital mortality in patients with BSIs.

The retrospective cross-sectional study used data from the Premier Healthcare database from 2016 to 2020 and included more than 32,000 adult patients from 183 U.S. hospitals who received at least one new systemic antimicrobial agent within 2 days after blood samples were collected during hospitalization. Patients with polymicrobial infections were excluded from the analysis. Appropriate empirical therapy was defined as initiation of at least one new empirical antimicrobial agent to which the pathogen isolated from blood culture was susceptible either on the day of or the day after the blood sample was collected.

Multilevel logistic regression models were used to estimate the association between receipt of appropriate initial empirical antimicrobial therapy and in-hospital mortality for patients infected with gram-negative rods, gram-positive cocci, and Candida species.

The findings indicated that the crude proportions of appropriate empirical therapy use were 94.4% for gram-negative rods, 97.0% for gram-positive cocci, and 65.1% for Candida species, with lower proportions for resistant pathogens, and resulted in lower in-hospital mortality for patients infected with these three pathogen groups.

The researchers concluded that it is important for clinicians to carefully choose empirical antimicrobial agents to improve outcomes in patients with BSIs. ■

Image of rifampin-resistant tuberculosis

Shorter treatment for rifampin-resistant tuberculosis shows promise

Current guidelines for treatment of rifampin-resistant tuberculosis (TB) involves up to 20 tablets per day for 9 to 20 months; unfavorable outcomes are common, making effective, shorter treatment options critical to controlling TB. A paper in the December 22, 2022, issue of NEJM described the TB-PRACTECAL Study, which evaluated the efficacy and safety of three 24-week, all-oral regimens for the treatment of rifampin-resistant TB.

The researchers conducted an open-label, phase 2–3, multicenter, randomized, controlled, noninferiority trial involving patients in Belarus, South Africa, and Uzbekistan who were 15 years or older and had rifampin-resistant pulmonary TB.

In stage 2 of the trial, a 24-week regimen of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) was compared with a 9- to 20-month standard-care regimen. The primary outcome was an unfavorable status (a composite of death, treatment failure, treatment discontinuation, loss to follow-up, or recurrence of TB) at 72 weeks after randomization.

Among patients who had received at least one dose of trial medication and were diagnosed with microbiologically proven rifampin-resistant TB, 11% had an unfavorable outcome, compared with 48% of patients in the standard treatment group.

In addition, the incidence of serious adverse events was lower in the BPaLM group than in the standard-care group (19% vs. 59%). The authors concluded that the 24-week, all-oral regimen was noninferior to and had a better safety profile than the accepted standard-care treatment. ■

Preventing cardiovascular events in patients with hypertension

Thiazide diuretics are a common first-line treatment for hypertension. Although guidelines have preferentially recommended chlorthalidone, hydrochlorothiazide is also widely used.

A recent study by researchers at several VA hospitals, published in NEJM on December 29, 2022, sought to determine if chlorthalidone is superior to hydrochlorothiazide for preventing major adverse cardiovascular events in patients with hypertension.

The researchers randomly assigned more than 13,500 patients in the Department of Veterans Affairs health system who were 65 years or older and had been receiving hydrochlorothiazide at a daily dose of 25 mg or 50 mg to continue therapy with hydrochlorothiazide or to switch to chlorthalidone at a daily dose of 12.5 mg or 25 mg. The primary outcome was a composite of nonfatal myocardial infarction, stroke, heart failure resulting in hospitalization, urgent coronary revascularization for unstable angina, and noncancer-related death.

At baseline, the mean baseline systolic blood pressure in each group was 139 mm Hg. At a median follow-up of 2.4 years, there was little difference in the occurrence of primary-outcome events between the chlorthalidone group (10.4%) and the hydrochlorothiazide group (10.0%). There were no between-group differences in the occurrence of any of the components of the primary outcome, though the incidence of hypokalemia was higher in the chlorthalidone group than in the hydrochlorothiazide group (6.0% vs. 4.4%).

The authors concluded that at doses commonly used in practice, patients who received chlorthalidone did not have a lower occurrence of major cardiovascular outcome events or noncancer-related deaths than patients who received hydrochlorothiazide. ■

Image of VTE

VTE chemoprophylaxis may not improve outcomes

Current recommendations for prevention of VTE in surgical patients include prophylactic medications based on an evaluation of preoperative risk. But a recent retrospective cohort study, published in the December 2022 issue of Annals of Surgery indicated that while postoperative thromboprophylaxis was broadly applied, it was associated with no decrease in VTE.

Researchers at the University of Michigan hypothesized that a high rate of prescription of VTE chemoprophylaxis would be associated with decreased VTE incidence and mortality. Their study analyzed VTE incidence, morbidity, and mortality among postsurgical patients with and without VTE chemoprophylaxis between April 2013 and September 2017 from 63 hospitals within the Michigan Surgical Quality Collaborative. Most practitioners reported performing formal VTE risk assessment.

Among 32,856 operations, there were 480 (1.46%) cases of postoperative VTE and an overall mortality of 609 (1.85%) patients. Using a propensity matched cohort, the authors found that rates of VTE were similar in those receiving unfractionated heparin or low molecular weight heparin compared to those not receiving chemoprophylaxis.

Surprisingly, even the highest risk patients did not have an associated lower VTE rate. In addition, postoperative transfusion (8.28% vs. 7.50%) and mortality (2.00% vs. 1.62%) rates were similar among those receiving and those not receiving chemoprophylaxis.

The authors concluded that despite wide adoption of VTE risk assessment, VTE remains a significant occurrence and that prophylactic medications don’t appear to improve outcomes. ■

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