Vancomycin Pharmacokinetics and Dosing in Critically Ill Patients on CRRT: A Scoping Review

Presenter: Assadoon, Maha

Acute kidney injury is common in critically ill patients, and continuous renal replacement therapy (CRRT) significantly affects drug pharmacokinetics, including vancomycin. This scoping review evaluated existing evidence on vancomycin pharmacokinetics (PK) and dosing in critically ill adults receiving CRRT. Following PRISMA guidelines, studies published up to December 2024 were reviewed, with 22 of 98 identified studies meeting inclusion criteria.

Vancomycin clearance ranged from 1.5 to 4.6 L/hr, with CRRT contributing ≥50% of total clearance. Clearance was strongly influenced by CRRT modality and intensity. The volume of distribution ranged from 0.38 to 1.4 L/kg, and population PK studies showed high interindividual variability. Dose simulation studies supported model-informed precision dosing, recommending 10–15 mg/kg/day or fixed doses of 1500–1750 mg/day.

Vancomycin pharmacokinetics in critically ill patients receiving CRRT are highly variable and significantly influenced by CRRT parameters, supporting the need for individualized, model-informed dosing strategies to optimize therapeutic outcomes.

Inhaled Antibiotics to Treat Ventilator-Associated Pneumonia: A Systematic Review and Meta-analysis

Presenter: Li, Jie

Ventilator-associated pneumonia (VAP) is a serious complication in mechanically ventilated patients. This systematic review and meta-analysis evaluated the efficacy and safety of adjunctive inhaled antibiotics compared with placebo/blank or intravenous antibiotics. A total of 73 studies (32 randomized controlled trials and 41 non-randomized studies) were included following PRISMA guidelines.

Compared with placebo/blank, inhaled antibiotics significantly improved clinical cure (16 RCTs, n=1425; RR 1.24, 95% CI 1.07–1.43) and reduced all-cause mortality (21 RCTs, n=1855; RR 0.84, 95% CI 0.71–0.98). Benefits were greater in VAP-only populations (clinical cure RR 1.29; mortality RR 0.77). Inhaled antibiotics also improved microbiological eradication (RR 1.42, 95% CI 1.27–1.58) and reduced new drug resistance (RR 0.20, 95% CI 0.06–0.64). No significant differences were observed in ICU length of stay, ventilator duration, or adverse events.

Compared with intravenous antibiotics, inhaled antibiotics improved clinical cure (3 RCTs, n=183; RR 1.32, 95% CI 1.11–1.58), reduced ventilator duration (3 RCTs, n=322; mean difference −2.11 days, 95% CI −3.73 to −0.49), and lowered renal impairment risk (RR 0.42, 95% CI 0.26–0.68).

In conclusion, adjunctive inhaled antibiotics improve clinical cure, reduce mortality, and enhance microbiological outcomes in ventilator-associated pneumonia without increasing adverse events, supporting their role as an effective and safe addition to standard therapy.

Empiric Colistimethate May Reduce ICU Survival in MDR Gram-Negative Bacteria: A Retrospective Study

Presenter: Colunga Lozano

This retrospective cohort study evaluated outcomes associated with multidrug-resistant (MDR) Gram-negative bacterial infections in critically ill ICU patients, with a focus on the use of polymyxins. A total of 224 patients (mean age 48.2 years; 55.8% male) with ICU stays >48 hours and confirmed MDR infections between 2022 and 2024 were included. The most common pathogens were Acinetobacter baumannii (56.7%) and Klebsiella pneumoniae (27.2%), with tracheal secretions as the main infection source (66.1%). Carbapenem resistance was present in 78.5% of cases.

ICU mortality was 53.6%, and acute kidney injury (AKI) requiring renal replacement therapy (RRT) occurred in 17.9% of patients. Colistimethate sodium (CMS) was used in 51.8% of patients and was associated with higher ICU mortality (64.5% vs 43.0%; p=0.001; HR 1.52, 95% CI 1.04–2.22) and increased risk of AKI requiring RRT (OR 2.52, 95% CI 1.22–5.20). Additional factors associated with ICU mortality included carbapenem resistance (OR 3.76, 95% CI 1.84–7.34) and AKI requiring RRT (OR 6.45, 95% CI 2.58–16.12).

MDR Gram-negative infections in critically ill ICU patients are associated with high mortality and renal complications, with colistimethate sodium use, linked to increased risk of death and acute kidney injury, underscoring the need for cautious use and alternative therapeutic strategies.

Likelihood of Bacterial Infection in Immunocompromised Patients Treated with IV Antibiotics

Presenter: Gupta, Simran

This retrospective study evaluated the likelihood of bacterial infection in immunocompromised hosts (ICH) compared with non-immunocompromised patients treated for possible sepsis in the emergency department. A total of 350 adults (2022–2024) from nine emergency departments were included, all of whom received early sepsis management (blood cultures, lactate testing, and intravenous antibiotics within 6 hours). Among them, 186 (53.1%) were ICH and 164 (46.9%) non-ICH.

ICH patients were more likely to present with infectious symptoms such as fever, chills, or rigors (66% vs 32%, p<0.001), while non-ICH patients more often had no infectious symptoms (40% vs 21%, p<0.001). Clinicians documented concern for sepsis more frequently in ICH (74% vs 62%, p=0.01). However, the post-hoc likelihood of definite or probable bacterial infection was similar between groups (46.2% vs 48.8%, p=0.48), with over half of cases in both groups classified as possible or highly unlikely bacterial infection.

In ICH patients without confirmed bacterial infection, alternative causes included febrile neutropenia (37%), viral or fungal infections (35%), chronic lung disease exacerbations (17%), malignancy progression (9%), chemotherapy toxicity (7%), aspiration pneumonitis (6%), and chronic heart disease exacerbations (6%).

Although immunocompromised patients presenting with suspected sepsis are more likely to exhibit infectious symptoms and prompt clinician concern, their likelihood of confirmed bacterial infection is comparable to non-immunocompromised patients, highlighting the importance of careful diagnostic evaluation to avoid unnecessary antibiotic use.

Antibiotic De-Escalation and 30-Day Mortality in Culture-Negative Sepsis

Presenter: Ohnuma, Tetsu

This retrospective cohort study evaluated the impact of antibiotic de-escalation on 30-day mortality in patients with culture-negative sepsis. A total of 3,855 adult patients with community-onset sepsis and negative microbial cultures (2016–2023) were included from three hospitals. Antibiotics were categorized by spectrum, and de-escalation was defined as a reduction in antibiotic spectrum within 5 days.

Antibiotic de-escalation was performed in 34% of patients, while 7% underwent escalation. The crude 30-day mortality rates were 16% for de-escalation, 16% for no change, and 19% for escalation. In adjusted analyses, neither de-escalation (aOR 0.98, 95% CI 0.79–1.21) nor escalation (aOR 1.24, 95% CI 0.87–1.78) was associated with 30-day mortality. Subgroup analysis showed no association between de-escalation and mortality regardless of SOFA score changes (improved, unchanged, or deteriorated).

Antibiotic de-escalation in patients with culture-negative sepsis was not associated with increased 30-day mortality, supporting its safety as a stewardship strategy regardless of changes in clinical severity.

Critical Care Congress 2026, March 22-24, Chicago.