IMPORTANCE Oral β-lactam antibiotics are traditionally not recommended to treat Enterobacterales bacteremia because of concerns over subtherapeutic serum concentrations, but there is a lack of outcomes data, specifically after initial treatment with parenteral antibiotics. Given the limited data and increasing limitations of fluoroquinolones or trimethoprim-sulfamethoxazole (TMP-SMX), oral β-lactam antibiotics may be a valuable additional treatment option. OBJECTIVE To compare definitive therapy with oral β-lactam antibiotics vs fluoroquinolones or TMP-SMX for Enterobacterales bacteremia from a suspected urine source. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study was conducted from January 1, 2007, to September 30, 2015, at 114 Veterans Affairs hospitals among 4089 adults with Escherichia coli, Klebsiella spp, or Proteus spp bacteremia and matching urine culture results. Additional inclusion criteria were receipt of active parenteral antibiotic(s) followed by conversion to an oral antibiotic. Exclusion criteria were previous Enterobacterales bacteremia, urologic abscess, or chronic prostatitis. Data were analyzed from April 15, 2019, to July 26, 2020. EXPOSURES Conversion of therapy to an oral β-lactam antibiotic vs fluoroquinolones or TMP-SMX after 1 to 5 days of parenteral antibiotics. MAIN OUTCOMES AND MEASURES The main outcome was a composite of either 30-day all-cause mortality or 30-day recurrent bacteremia. Propensity-based overlap weights were used to adjust for differences between groups. Log binomial regression models were used to estimate adjusted relative risks (aRRs) and adjusted risk differences (aRDs). RESULTS Of the 4089 eligible patients (3731 men [91.2%]; median age, 71 years [interquartile range, 63-81 years]), 955 received an oral β-lactam antibiotic, and 3134 received fluoroquinolones or TMP-SMX. The primary outcome occurred for 42 patients (4.4%) who received β-lactam antibiotics and 94 patients (3.0%) who received fluoroquinolones or TMP-SMX (aRD, 0.99% [95% CI, −0.42% to 2.40%]; aRR, 1.31 [95% CI, 0.87-1.95]). Mortality rates were 3.0% (n = 29) for patients receiving β-lactam antibiotics vs 2.6% (n = 82) for those receiving fluoroquinolones or TMP-SMX (aRD, 0.06% [95% CI, −1.13% to 1.26%]; aRR, 1.02 [95% CI, 0.67-1.56]). Recurrent bacteremia rates were 1.5% (n = 14) among those receiving β-lactam antibiotics vs 0.4% (n = 12) among those receiving fluoroquinolones or TMP-SMX (aRD, 1.03% [95% CI, 0.24%-1.82%]; aRR, 3.43 [95% CI, 0.42-27.90]). CONCLUSIONS AND RELEVANCE In this cohort study of adults with E coli, Klebsiella spp, or Proteus spp bacteremia from a suspected urine source, the relative risk of recurrent bacteremia was not significantly higher with β-lactam antibiotics compared with fluoroquinolones or TMP-SMX, and the absolute risk and risk difference were small (ie, <3%). No significant difference in mortality was observed. Oral β-lactam antibiotics may be a reasonable step-down treatment option, primarily (continued) Key Points Question Are mortality and recurren...
e To date, no comparative clinical studies have investigated the effects of different vancomycin products on nephrotoxicity. The objective of this single-center, retrospective, matched-cohort study was to investigate the impact of two different vancomycin products on the development of nephrotoxicity. The study population included adults receiving a single vancomycin product, from either Pfizer or Hospira, for their entire course of therapy. Patients were matched based on underlying nephrotoxicity risk factors. Secondary outcomes included the need for renal replacement therapy, length of hospital stay, and in-hospital mortality. One-hundred forty-six matched pairs (n ؍ 292) were included, and they had no significant differences in demographics, comorbid conditions, severity of illness, or vancomycin-associated nephrotoxicity risk factors. The frequency of nephrotoxicity was 8.9% in the Pfizer group and 11.0% in the Hospira group as defined by the 2009 consensus vancomycin guidelines (P ؍ 0.56), 17.1% in the Pfizer group and 13.0% in the Hospira group as defined by the Acute Kidney Injury Network (AKIN) (P ؍ 0.33), and 10.3% in the Pfizer group and 11.6% in the Hospira group as defined by RIFLE (risk, injury, failure, loss, and end-stage renal disease) criteria (P ؍ 0.71). There were no differences between groups in regard to nephrotoxicity by any definition or in secondary outcomes. In multivariate analysis of overall nephrotoxicity risk factors, the type of vancomycin product was not independently associated with increased odds of developing nephrotoxicity according to the RIFLE criteria. Based on our results, there are no discernible differences between Pfizer and Hospira vancomycin products in the frequency of nephrotoxicity. Confirmation of these results with other types of vancomycin and different patient populations is warranted.
The Infectious Diseases Society of America infection-specific guidelines provide limited guidance on the management of focal infections complicated by secondary bacteremias. We address the following 3 commonly encountered questions and management considerations regarding uncomplicated bacteremia not due to Staphylococcus aureus: the role and choice of oral antibiotics focusing on oral beta-lactams, the shortest effective duration of therapy, and the role of repeat blood cultures.
Background Skin and soft tissue infections (SSTIs) are a key antimicrobial stewardship target because they are a common infection in hospitalized patients, and non-guideline-concordant antibiotic use is frequent. To inform antimicrobial stewardship interventions, we evaluated the proportion of veterans hospitalized with SSTIs who received guideline-concordant empiric antibiotics or an appropriate total duration of antibiotics. Methods A retrospective medication use evaluation was performed in 34 Veterans Affairs Medical Centers between 2016 and 2017. Hospitalized patients who received antibiotics for uncomplicated SSTI were included. Exclusion criteria were complicated SSTI, severe immunosuppression, and antibiotics for any non-SSTI indication. Data were collected by manual chart review. The primary outcome was the proportion of patients receiving both guideline-concordant empiric antibiotics and appropriate treatment duration, defined as 5–10 days of antibiotics. Data were analyzed and reported using descriptive statistics. Results Of the 3890 patients manually evaluated for inclusion, 1828 patients met inclusion criteria. There were 1299 nonpurulent (71%) and 529 purulent SSTIs (29%). Overall, 250 patients (14%) received guideline-concordant empiric therapy and an appropriate duration. The most common reason for non-guideline-concordance was receipt of antibiotics targeting methicillin-resistant Staphylococcus aureus (MRSA) in 906 patients (70%) with a nonpurulent SSTI. Additionally, 819 patients (45%) received broad-spectrum Gram-negative coverage, and 860 patients (48%) received an antibiotic duration >10 days. Conclusions We identified 3 common opportunities to improve antibiotic use for patients hospitalized with uncomplicated SSTIs: use of anti-MRSA antibiotics in patients with nonpurulent SSTIs, use of broad-spectrum Gram-negative antibiotics, and prolonged durations of therapy.
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