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Background We assessed the safety and efficacy of oral antibiotic step-down therapy for uncomplicated gram-negative blood stream infections in solid-organ transplant recipients. Methods We identified all solid-organ transplant recipients within the Massachusetts General and Brigham and Women's Hospital systems from 2016 to 2021 with uncomplicated gram-negative bacteremia involving an organism susceptible to an acceptably bioavailable oral antibiotic agent. Using inverse probability of treatment-weighted models based on propensity scores adjusting for potential clinical confounders, we compared outcomes of those transitioned to oral antibiotics with those who continued intravenous (IV) therapy for the duration of treatment. Primary endpoints were mortality, bacteremia recurrence, and reinitiation of IV antibiotics. Secondary endpoints included length of stay, Clostridioides difficile infection, treatment-associated complications, and tunneled central venous catheter placement. Results A total of 120 bacteremia events from 107 patients met inclusion criteria in the oral group and 42 events from 40 patients in the IV group. There were no significant differences in mortality, bacteremia recurrence, or reinitiation of IV antibiotics between groups. Patients transitioned to oral antibiotics had an average length of stay that was 1.97 days shorter (95% confidence interval [CI], −.39 to 3.56 days; P =.005). Odds of developing C. difficile and other treatment-associated complications were 8.4 times higher (95% CI, 1.5–46.6; P =.015) and 6.4 times higher (95% CI, 1.9–20.9; P =.002), respectively, in the IV group. Fifty-five percent of patients in the IV group required tunneled catheter placement. There was no difference in treatment duration between groups. Conclusions Oral step-down therapy was effective and associated with fewer treatment-related adverse events. [ABSTRACT FROM AUTHOR]

Background In the POET (Partial Oral Endocarditis Treatment) trial, oral step-down therapy was noninferior to full-length intravenous antibiotic administration. The aim of the present study was to perform pharmacokinetic/pharmacodynamic analyses for oral treatments of infective endocarditis to assess the probabilities of target attainment (PTAs). Methods Plasma concentrations of oral antibiotics were measured at day 1 and 5. Minimal inhibitory concentrations (MICs) were determined for the bacteria causing infective endocarditis (streptococci, staphylococci, or enterococci). Pharmacokinetic/pharmacodynamic targets were predefined according to literature using time above MIC or the ratio of area under the curve to MIC. Population pharmacokinetic modeling and pharmacokinetic/pharmacodynamic analyses were done for amoxicillin, dicloxacillin, linezolid, moxifloxacin, and rifampicin, and PTAs were calculated. Results A total of 236 patients participated in this POET substudy. For amoxicillin and linezolid, the PTAs were 88%–100%. For moxifloxacin and rifampicin, the PTAs were 71%–100%. Using a clinical breakpoint for staphylococci, the PTAs for dicloxacillin were 9%–17%. Seventy-four patients at day 1 and 65 patients at day 5 had available pharmacokinetic and MIC data for 2 oral antibiotics. Of those, 13 patients at day 1 and 14 patients at day 5 did only reach the target for 1 antibiotic. One patient did not reach target for any of the 2 antibiotics. Conclusions For the individual orally administered antibiotic, the majority reached the target level. Patients with sub-target levels were compensated by the administration of 2 different antibiotics. The findings support the efficacy of oral step-down antibiotic treatment in patients with infective endocarditis. [ABSTRACT FROM AUTHOR]

Background Infections are important complications of end-stage renal disease (ESRD) with few studies having investigated oral antibiotic use. Inappropriate antibiotic prescribing can contribute to multidrug-resistant organisms and Clostridioides difficile infections seen in ESRD. This study investigates antibiotic prescribing practices in ESRD across New York State (NYS). Methods Retrospective case-control study from 2016 to 2017 of NYS ESRD and non-ESRD patients analyzing Medicare part B billing codes, 7 days before and 3 days after part D claims. Frequencies of each infection, each antibiotic, dosages, and the antibiotics associated with infections were assessed using χ 2 analysis. A NYS small dialysis organization comprising approximately 2200 patients was also analyzed. Outcomes measured were the frequencies of infections and of each antibiotic prescribed. Incidence measures included antibiotics per 1000 and individuals receiving antibiotics per 1000. Results A total of 48 100 infections were treated in 35 369 ESRD patients and 2 544 443 infections treated in 3 777 314 non-ESRD patients. ESRD patients were younger, male, and African American. ESRD and non-ESRD patients receiving antibiotics was 520.29/1000 and 296.48/1000, respectively (P  < .05). The prescription incidence was 1359.95/1000 ESRD vs 673.61/1000 non-ESRD patients. In 36%, trimethoprim-sulfamethoxazole dosage was elevated by current ESRD guidelines. Top infectious categories included nonspecific symptoms, skin, and respiratory for ESRD; and respiratory, nonspecific symptoms, and genitourinary in non-ESRD. Conclusions This study identifies issues with appropriate antibiotic usage stressing the importance of antibiotic education to nephrologist and nonnephrologist providers. It provides support for outpatient antibiotic stewardship programs. [ABSTRACT FROM AUTHOR]

The article provides information on the influence of medical education and the need for clinician educators to stay updated on evidence-based practices. It discusses a study that examines the optimal duration of antibiotic treatment for complicated urinary tract infections with concomitant bacteremia, emphasizing the inclusion of immunocompromised and critically ill patients.

Background. In recent years, the price of many older generic drugs, including numerous antibiotics, has increased substantially. We sought to analyze recent price changes and extent of generic competition within a cohort of commonly prescribed off-patent oral antibiotics. Methods. We extracted oral antibiotics recommended for common outpatient conditions in the Infectious Diseases Society of America Practice Guidelines. We determined all US Food and Drug Administration-approved manufacturers for each formulation and strength in 2013 and 2016 and the yearly national average drug acquisition cost (NADAC) price between 2013 and 2016. Wilcoxon signed rank test was used to compare changes in drug prices and number of manufacturers from 2013 to 2016. Spearman correlation coefficient was used to assess the association between drug prices and number of manufacturers. Results. Twenty-two antibiotics (81 formulations and strengths) were analyzed. There was no change in the median NADAC price or the number of manufacturers between 2013 and 2016. However, 11 (14%) formulations increased in price by 90% or more, and 13 (16%) had 2 or fewer manufacturers during all 4 years. Antibiotic prices were negatively associated with the number of available manufacturers. Conclusions. While prices and the number of manufacturers for common oral antibiotics were overall stable between 2013 and 2016, reduced manufacturer competition was associated with increased prices. A subset of antibiotics exhibited substantial price increases, and most, but not all, had limited manufacturer competition. Policy solutions are needed to ensure availability of low-cost, essential generic antibiotics. [ABSTRACT FROM AUTHOR]

Background. Fluoroquinolones have equivalent oral and intravenous bioavailability, but hospitalized patients with communityacquired pneumonia (CAP) generally are treated intravenously. Our objectives were to compare outcomes of hospitalized CAP patients initially receiving intravenous vs oral respiratory fluoroquinolones. Methods. This was a retrospective cohort study utilizing data from 340 hospitals involving CAP patients admitted to a non- intensive care unit (ICU) setting from 2007 to 2010, who received intravenous or oral levofloxacin or moxifloxacin. The primary outcome was in-hospital mortality. Secondary outcomes included clinical deterioration (transfer to ICU, initiation of vasopressors, or invasive mechanical ventilation [IMV] initiated after the second hospital day), antibiotic escalation, length of stay (LOS), and cost. Results. Of 36 405 patients who met inclusion criteria, 34 200 (94%) initially received intravenous treatment and 2205 (6%) received oral treatment. Patients who received oral fluoroquinolones had lower unadjusted mortality (1.4% vs 2.5%; P = .002), and shorter mean LOS (5.0 vs 5.3; P < .001). Multivariable models using stabilized inverse propensity treatment weighting revealed lower rates of antibiotic escalation for oral vs intravenous therapy (odds ratio [OR], 0.84; 95% confidence interval [CI], .74-.96) but no differences in hospital mortality (OR, 0.82; 95% CI, .58-1.15), LOS (difference in days 0.03; 95% CI, -.09-.15), cost (difference in $-7.7; 95% CI, -197.4-182.0), late ICU admission (OR, 1.04; 95% CI, .80-1.36), late IMV (OR, 1.17; 95% CI, .87-1.56), or late vasopressor use (OR, 0.94; 95% CI, .68-1.30). Conclusions. Among hospitalized patients who received fluoroquinolones for CAP, there was no association between initial route of administration and outcomes. More patients may be treated orally without worsening outcomes. [ABSTRACT FROM AUTHOR]