Efficacy of ceftazidime-avibactam in solid organ transplant recipients with bloodstream infections caused by carbapenemase-producing Klebsiella pneumoniae.

We aimed to compare the efficacy of ceftazidime-avibactam (CAZ-AVI) versus the best available therapy (BAT) in solid organ transplant (SOT) recipients with bloodstream infection caused by carbapenemase-producing Klebsiella pneumoniae (CPKP-BSI). A retrospective (2016-2021) observational cohort study was performed in 14 INCREMENT-SOT centers (ClinicalTrials.gov identifier: NCT02852902; Impact of Specific Antimicrobials and MIC Values on the Outcome of Bloodstream Infections Due to ESBL- or Carbapenemase-producing Enterobacterales in Solid Organ Transplantation: an Observational Multinational Study). Outcomes were 14-day and 30-day clinical success (complete resolution of attributable manifestations, adequate source control, and negative follow-up blood cultures) and 30-day all-cause mortality. Multivariable logistic and Cox regression analyses adjusted for the propensity score to receive CAZ-AVI were constructed. Among 210 SOT recipients with CPKP-BSI, 149 received active primary therapy with CAZ-AVI (66/149) or BAT (83/149). Patients treated with CAZ-AVI had higher 14-day (80.7% vs 60.6%, P = .011) and 30-day (83.1% vs 60.6%, P = .004) clinical success and lower 30-day mortality (13.25% vs 27.3%, P = .053) than those receiving BAT. In the adjusted analysis, CAZ-AVI increased the probability of 14-day (adjusted odds ratio [aOR], 2.65; 95% confidence interval [CI], 1.03-6.84; P = .044) and 30-day clinical success (aOR, 3.14; 95% CI, 1.17-8.40; P = .023). In contrast, CAZ-AVI therapy was not independently associated with 30-day mortality. In the CAZ-AVI group, combination therapy was not associated with better outcomes. In conclusion, CAZ-AVI may be considered a first-line treatment in SOT recipients with CPKP-BSI.

Predictors of mortality in solid organ transplant recipients with bloodstream infections due to carbapenemase-producing Enterobacterales: The impact of cytomegalovirus disease and lymphopenia.

Treatment of carbapenemase-producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase-producing Enterobacterales bloodstream infections. A multinational, retrospective (2004-2016) cohort study (INCREMENT-SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30-day all-cause mortality. The INCREMENT-SOT-CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT-CPE mortality score ≥8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT-CPE score ≥8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI] 0.76-0.88) and classified patients into 3 strata: 0-7 (low mortality), 8-11 (high mortality), and 12-17 (very-high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very-high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13-7.06, P = .03) and high (HR 9.93, 95% CI 2.08-47.40, P = .004) mortality risk strata. A score-based algorithm is provided for therapy guidance.

Lactated Ringer's Versus 4% Albumin on Lactated Ringer's in Early Sepsis Therapy in Cancer Patients: A Pilot Single-Center Randomized Trial.

OBJECTIVE: To investigate the effects of the administration of 4% albumin on lactated Ringer's, when compared with lactated Ringer's alone, in the early phase of sepsis in cancer patients. DESIGN: Single-center, randomized, double-blind, controlled-parallel trial. SETTING: A tertiary care university cancer hospital. PATIENTS: Cancer patients with severe sepsis or septic shock. INTERVENTIONS: Between October 2014 and December 2016, patients were randomly assigned to receive either bolus of albumin in a lactated Ringer's solution or lactated Ringer's solution alone during the first 6 hours of fluid resuscitation after intensive care medicine (ICU) admission. Primary outcome was defined as death from any cause at 7 days. Secondary outcomes were defined as death from any cause within 28 days, change in Sequence Organ Failure Assessment scores from baseline to day 7, days alive and free of mechanical ventilation, days alive and free of vasopressor, renal replacement therapy during ICU stay, and length of ICU and hospital stay. MEASUREMENTS AND MAIN RESULTS: A total of 360 patients were enrolled in the trial. At 7 days, 46 of 180 patients (26%) died in the albumin group and 40 of 180 (22%) died in the lactated Ringer's group (p = 0.5). At 28 days, 96 of 180 patients (53%) died in the albumin group and 83 of 180 (46%) died in the lactated Ringer's group (p = 0.2). No significant differences in secondary outcomes were observed. CONCLUSIONS: Adding albumin to early standard resuscitation with lactated Ringer's in cancer patients with sepsis did not improve 7-day survival.