Search

•We developed and validated a qPCR method for quantitative determination of the extent of intestinal colonisation by KPC-producing Klebsiella pneumoniae(KPC-Kp).•This validated qPCR method detects 17% more positives for KPC-Kp and reduces ≥24 h the time required by a reference method based on standard culture.•A rapid and persistent reduction of KPC-Kp intestinal load is observed in about 60% of patients within a month of selective digestive decolonisation with oral gentamicin; however, only 17% of patients reach persitent eradication at this time point.•The death rate was significantly higher among patients with high baseline KPC-Kp intestinal loads.•The validated qPCR method will help to strengthen public health efforts to monitor colonisation by carbapenemase-producing Klebsiella pneumoniaethrough rapid screening of KPC-producing Klebsiella spp.

•The efficacy of ceftazidime/avibactam can be limited by the development of resistance.•Carbapenems are an option to treat infections that are resistant to ceftazidime/avibactam.•Mutations in the Ω-loop can result in a decrease in carbapenem MICs.

Treatment of carbapenemase‐producing Enterobacteralesbloodstream 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 Enterobacteralesbloodstream 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. The authors develop a predictive risk score for a solid organ transplant recipient's for mortality in patients with bloodstream infections due to carbapenemase‐producing Enterobacterales, which is useful to differentiate patients who can be treated with antimicrobial monotherapy from those who should receive combination therapy.

We aimed to compare the efficacy of ceftazidime-avibactam (CAZ-AVI) versusthe 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.govidentifier: NCT02852902). 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% versus 60.6%, P=0.011) and 30-day (83.1% versus 60.6%, P=0.004) clinical success and lower 30-day mortality (13.25% versus 27.3%, P=0.053) 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 [95%CI]: 1.03-6.84, P=0.044) and 30-day clinical success (aOR: 3.14; 95%CI: 1.17-8.40; P=0.023). 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.

•Colonization does not increase crude mortality per se.•Colonization was a necessary although insufficient cause of KPC-Kp infection.•The risk of mortality in colonized patients depends on the development of severe KPC infection.