Infectious Diseases Society of America 2024 Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections.

BACKGROUND: The Infectious Diseases Society of America (IDSA) is committed to providing up-to-date guidance on the treatment of antimicrobial-resistant (AMR) infections. This guidance document focuses on infections caused by extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E), AmpC ß- lactamase-producing Enterobacterales (AmpC-E), carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa with difficult-to-treat resistance (DTR P. aeruginosa), carbapenem-resistant Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia. This updated document replaces previous versions of the guidance document. METHODS: A panel of six infectious diseases specialists with expertise in managing antimicrobial- resistant infections formulated questions about the treatment of infections caused by ESBL-E, AmpC-E, CRE, DTR P. aeruginosa, CRAB, and S. maltophilia. Because of differences in the epidemiology of AMR and availability of specific anti-infectives internationally, this document focuses on the treatment of AMR infections in the United States. RESULTS: Preferred and alternative suggested treatment approaches are provided with accompanying rationales, assuming the causative organism has been identified and antibiotic susceptibility results are known. Approaches to empiric treatment, transitioning to oral therapy, duration of therapy, and other management considerations are discussed briefly. Suggested approaches apply for both adult and pediatric populations, although suggested antibiotic dosages are provided only for adults. CONCLUSIONS: The field of AMR is highly dynamic. Consultation with an infectious diseases specialist is recommended for the treatment of AMR infections. This document is current as of December 31, 2023 and will be updated periodically. The most current version of this document, including date of publication, is available at www.idsociety.org/practice-guideline/amr-guidance/.

Extended-Infusion ß-Lactam Therapy, Mortality, and Subsequent Antibiotic Resistance Among Hospitalized Adults With Gram-Negative Bloodstream Infections.

Importance: Current evidence is conflicting for associations of extended-infusion ß-lactam (EI-BL) therapy with clinical outcomes. Objective: To investigate the association of EI-BL therapy with survival, adverse events, and emergence of antibiotic resistance in adults with gram-negative bloodstream infections (GN-BSI). Design, Setting, and Participants: This cohort study of consecutive adults with GN-BSI admitted to 24 United States hospitals between January 1, 2019, and December 31, 2019, receiving EI-BL were compared with adults with GN-BSI receiving the same agents as intermittent infusion ß-lactam (II-BL; ≤1-hour infusions). Statistical analysis was performed from January to October 2023. Exposures: EI-BL (ie, ≥3-hour infusion). Main Outcomes and Measures: EI-BL and II-BL groups underwent 1:3 nearest-neighbor propensity score matching (PSM) without replacement. Multivariable regression was applied to the PSM cohort to investigate outcomes, all censored at day 90. The primary outcome was mortality; secondary outcomes included antibiotic adverse events and emergence of resistance (≥4-fold increase in the minimum inhibitory concentration of the ß-lactam used to treat the index GN-BSI). Results: Among the 4861 patients included, 2547 (52.4%) were male; and the median (IQR) age was 67 (55-77) years. There were 352 patients in the EI-BL 1:3 PSM group, and 1056 patients in the II-BL 1:3 PSM group. Among 1408 PSM patients, 373 (26.5%) died by day 90. The odds of mortality were lower in the EI-BL group (adjusted odds ratio [aOR], 0.71 [95% CI, 0.52-0.97]). In a stratified analysis, a survival benefit was only identified in patients with severe illness or elevated minimum inhibitory concentrations (ie, in the intermediate range for the antibiotic administered). There were increased odds of catheter complications (aOR, 3.14 [95% CI, 1.66-5.96]) and antibiotic discontinuation because of adverse events (eg, acute kidney injury, cytopenias, seizures) in the EI-BL group (aOR, 3.66 [95% CI, 1.68-7.95]). Emergence of resistance was similar in the EI-BL and II-BL groups at 2.9% vs 7.2%, respectively (P = .35). Conclusions and Relevance: In this cohort study of patients with GN-BSI, EI-BL therapy was associated with reduced mortality for patients with severe illness or those infected with nonsusceptible organisms; potential advantages in other groups remain unclear and need to be balanced with potential adverse events. The subsequent emergence of resistance warrants investigation in a larger cohort.

Impact of the US Food and Drug Administration warning regarding increased risk of aortic aneurysms or aortic dissections on fluoroquinolone prescribing trends.

BACKGROUND: The US Food and Drug Administration (FDA) issued a warning in December 2018 regarding an increased risk of aortic aneurysms and aortic dissections associated with fluoroquinolone (FQ) use. This warning specifically targeted older adults and patients with conditions such as hypertension, Marfan syndrome, Ehlers-Danlos syndrome, atherosclerosis, peripheral vascular disease and history of aneurysms. OBJECTIVE: To evaluate the impact of the safety warning on prescribing trends of FQs in the targeted population. METHODS: This cross-sectional study with an interrupted time series (ITS) analysis (January 2018-December 2019) used a 25% random sample of IQVIA PharMetrics® Plus for Academics health plan claims database. The impact of the warning on FQ utilisation was quantified among the targeted population and a non-targeted population. RESULTS: From 2018 to 2019, both study populations saw a decrease in the year-over-year percent change of FQ prescriptions per 100 000 beneficiaries (-11%, from 14 227 to 12 662, targeted; -15%, from 5227 to 4446, non-targeted) and proportion of FQ use versus other antibiotics (from 15.6% to 13.8%, targeted; from 9.4% to 8%, non-targeted). In the targeted population, the ITS analysis did not show a significant trend change, a change in level or postwarning trend in the monthly rate of FQ prescriptions per 1000 beneficiaries. A positive trend change was observed in the non-targeted population (0.07, <0.01-0.13), but there were no significant changes in level or post-warning trend. CONCLUSION: We did not find a change in FQ prescription rates after the warning. The utility of safety advisories as a primary tool for mitigating FQ use in high-risk populations should be revisited.

Comparison of Adjuvant Clindamycin vs Linezolid for Severe Invasive Group A Streptococcus Skin and Soft Tissue Infections.

Background: Linezolid may be an option for severe group A Streptococcus (GAS) infections based on its potent in vitro activity and antitoxin effects, but clinical data supporting its use over clindamycin are limited. This study evaluated treatment outcomes in patients with severe GAS skin and soft tissue infections who received either linezolid or clindamycin. Methods: This retrospective single-center cohort study examined patients with GAS isolated from blood and/or tissue cultures with invasive soft tissue infection or necrotizing fasciitis who underwent surgical debridement and received linezolid or clindamycin for at least 48 hours. The primary outcome was percentage change in Sequential Organ Failure Assessment (SOFA) score from baseline through 72 hours of hospitalization. Results: After adjustment for time to first surgical intervention among patients with a baseline SOFA score >0 (n = 23 per group), there was no difference in reduction of SOFA score over the first 72 hours in patients receiving clindamycin vs linezolid. In the entire cohort (n = 26, clindamycin; n = 29, linezolid), there was no difference in inpatient mortality (2% vs 1%) or any secondary outcomes, including duration of vasopressor therapy, intensive care unit length of stay, and antibiotic-associated adverse drug events. Conclusions: There was no difference in reduction of critical illness as measured by SOFA score between baseline and 72 hours among patients treated with clindamycin vs linezolid. Given its more favorable side effect profile, linezolid may be a viable option for the treatment of serious GAS infections and should be further studied.