Pre-transplant multidrug-resistant infections in liver transplant recipients-epidemiology and impact on transplantation outcome.

BACKGROUND: Cirrhotic patients are highly exposed to healthcare services and antibiotics. Although pre-liver transplantation (LT) infections are directly related to the worsening of liver function, the impact of these infections on LT outcomes is still unclear. This study aimed to identify the effect of multidrug-resistant microorganism (MDRO) infections before LT on survival after LT. METHODS: Retrospective study that included patients who underwent LT between 2010 and 2019. Variables analyzed were related to patients' comorbidities, underlying diseases, time on the waiting list, antibiotic use, LT surgery, and occurrences post-LT. Multivariate analyses were performed using logistic regression, and Cox regression for survival analysis. RESULTS: A total of 865 patients were included; 351 infections were identified in 259 (30%) patients, of whom 75 (29%) had ≥1 pre-LT MDRO infection. The most common infection was spontaneous bacterial peritonitis (34%). The agent was identified in 249(71%), 53(15%) were polymicrobial. The most common microorganism was Klebsiella pneumoniae (18%); the most common MDRO was ESBL-producing Enterobacterales (16%), and carbapenem-resistant (CR) Enterobacterales (10%). Factors associated with MDRO infections before LT were previous use of therapeutic cephalosporin (p = .001) and fluoroquinolone (p = .001), SBP prophylaxis (p = .03), ACLF before LT (p = .03), and days of hospital stay pre-LT (p < .001); HCC diagnosis was protective (p = .01). Factors associated with 90-day mortality after LT were higher MELD on inclusion to the waiting list (p = .02), pre-LT MDRO infection (p = .04), dialysis after LT (p < .001), prolonged duration of LT surgery (p < .001), post-LT CR-Gram-negative bacteria infection (p < .001), and early retransplantation (p = .004). CONCLUSION: MDRO infections before LT have an important impact on survival after LT.

Burden and Management of Multi-Drug Resistant Organism Infections in Solid Organ Transplant Recipients Across the World: A Narrative Review.

Solid organ transplant (SOT) recipients are particularly susceptible to infections caused by multidrug-resistant organisms (MDRO) and are often the first to be affected by an emerging resistant pathogen. Unfortunately, their prevalence and impact on morbidity and mortality according to the type of graft is not systematically reported from high-as well as from low and middle-income countries (HIC and LMIC). Thus, epidemiology on MDRO in SOT recipients could be subjected to reporting bias. In addition, screening practices and diagnostic resources may vary between countries, as well as the availability of new drugs. In this review, we aimed to depict the burden of main Gram-negative MDRO in SOT patients across HIC and LMIC and to provide an overview of current diagnostic and therapeutic resources.

Survey on the approach to antibiotic prophylaxis in liver and kidney transplant recipients colonized with "difficult to treat" Gram-negative bacteria.

BACKGROUND: Performance of active screening for multidrug-resistant Gram-negative bacteria (MDR-GNB) and administration of targeted antibiotic prophylaxis (TAP) in colonized patients undergoing liver (LT) and/or kidney transplantation (KT) are controversial issues. METHODS: Self-administered electronic cross-sectional survey disseminated from January to February 2022. Questionnaire consisted of four parts: hospital/transplant program characteristics, standard screening and antibiotic prophylaxis, clinical vignettes asking for TAP in patients undergoing LT and KT with prior infection/colonization with four different MDR-GNB (extended-spectrum cephalosporin-resistant Enterobacterales [ESCR-E], carbapenem-resistant Enterobacterales [CRE], multidrug-resistant Pseudomonas aeruginosa [MDR-Pa], and carbapenem-resistant Acinetobacter baumannii [CRAb]). RESULTS: Fifty-five respondents participated from 14 countries, mostly infectious disease specialists (69%) with active transplant programs (>100 procedures/year for 34.5% KT and 23.6% LT), and heterogeneous local MDR-GNB prevalence from <15% (30.9%), 15%-30% (43.6%) to >30% (16.4%). The frequency of screening for ESCR-E, CRE, MDR-Pa, and CRAb was 22%, 54%, 17%, and 24% for LT, respectively, and 18%, 36%, 16%, and 11% for KT. Screening time-points were mainly at transplantation 100%, only one-third following transplantation. Screening was always based on rectal swab cultures (100%); multi-site sampling was reported in 40% of KT and 35% of LT. In LT clinical cases, 84%, 58%, 84%, and 40% of respondents reported TAP for prior infection/colonization with ESCR-E, CRE, MDR-Pa, and CRAb, respectively. In KT clinical cases, 55%, 39%, 87%, and 42% of respondents reported TAP use for prior infection/colonization with ESCR-E, CRE, MDR-Pa, and CRAb, respectively. CONCLUSION: There is a large heterogeneity in screening and management of MDR-GNB carriage in LT and KT.

Transmission of Carbapenem-Resistant Enterobacterales in an Overcrowded Emergency Department: Controlling the Spread to the Hospital.

BACKGROUND: Overcrowded emergency departments (EDs) may increase the risk of carbapenem-resistant Enterobacterales (CRE) transmission. METHODS: We conducted a quasi-experimental study divided into 2 phases (baseline and intervention) to investigate the impact of an intervention on the acquisition rate and identify risk factors for CRE colonization in an ED of a tertiary academic hospital in Brazil. In both phases, we did universal screening with rapid molecular test (blaKPC, blaNDM, blaOXA48, blaOXA23, and blaIMP) and culture. At baseline, both screening test results were not reported, and patients were put under contact precautions (CP) based on previous colonization or infection by multidrug-resistant organisms. During the intervention, all patients hospitalized in the ED were placed in empiric CP and the result of CRE screening was reported; if negative, patients were released from CP. Patients were rescreened if they stayed >7 days in the ED or were transferred to an intensive care unit. RESULTS: A total of 845 patients were included: 342 in baseline and 503 in intervention. Colonization at admission was 3.4% by culture and molecular test. Acquisition rates during ED stay dropped from 4.6% (11/241) to 1% (5/416) during intervention (P = .06). The aggregated antimicrobial use in the ED decreased from phase 1 to phase 2 (804 defined daily doses [DDD]/1000 patients to 394 DDD/1000 patients, respectively). Length of stay >2 days in the ED was a risk factor for CRE acquisition (adjusted odds ratio, 4.58 [95% confidence interval, 1.44-14.58]; P = .01). CONCLUSIONS: Early empiric CP and rapid identification of CRE-colonized patients reduce cross-transmission in ED. Nevertheless, staying >2 days in ED compromised efforts.

Crude Mortality Associated With the Empirical Use of Polymyxins in Septic Patients in a Setting of High Prevalence of Carbapenem-Resistant Gram-negative Bacteria: Retrospective Analysis of a Cohort.

BACKGROUND: Our aim in this retrospective cohort study was to assess the impact on mortality of the empirical use of polymyxin as therapy for carbapenem-resistant gram-negative bacteria (CR-GNB) in septic patients. The study was performed at a tertiary academic hospital in Brazil, from January 2018 to January 2020, the pre-coronavirus disease 2019 period. METHODS: We included 203 patients with suspected sepsis. The first doses of antibiotics were prescribed from a "sepsis antibiotic kit", which contained a selection of drugs, including polymyxin, with no preapproval policy. We developed a logistic regression model to assess risk factors associated with 14-day crude mortality. Propensity score for polymyxin was used to control biases. RESULTS: Seventy (34%) of 203 patients had infections with at least 1 multidrug-resistant organism isolated from any clinical culture. Polymyxins in monotherapy or in combination therapy were prescribed to 140 of the 203 (69%) patients. The overall 14-day mortality rate was 30%. The 14-day crude mortality was associated with age (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 1.01-1.05; P = .01), SOFA (sepsis-related organ failure assessment) score value (aOR, 1.2; 95% CI, 1.09-1.32; P < .001), CR-GNB infection (aOR, 3.94; 95% CI, 1.53-10.14; P = .005), and time between suspected sepsis and antibiotic administration (aOR, 0.73; 95% CI, .65-.83; P < .001). The empirical use of polymyxins was not associated with decreased crude mortality (aOR, 0.71; 95% CI, .29-1.71; P = .44). CONCLUSIONS: Empirical use of polymyxin for septic patients in a setting with high CR-GNB prevalence was not associated with decreased crude mortality.

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.

Meet in the middle: Could cell mediated-immunity assays be the answer for ideal Cytomegalovirus prophylaxis after lung transplantation? Observational study from a single center with intermittent antiviral prophylaxis.

BACKGROUND: Cytomegalovirus (CMV) can cause tissue-invasive disease and indirect effects after lung transplantation (LTx) such as acute rejection episodes and chronic lung allograft dysfunction. Monitoring CMV-specific cell immune recovery (CMV-CIR) after LTx can individualize CMV risks and establish better antiviral approach. This study evaluated the dynamics of CMV-CIR, using QuantiFERON-CMV assay (Qiagen Group), in the first year after LTx. METHODS: Prospective observational cohort study included lung transplant recipients from December/2015 to December/2016. Universal antiviral prophylaxis with intravenous ganciclovir 5 mg/kg/day 3 days/week for 3 months was given for CMV-seropositive recipients (R+) and only CMV-seropositive donor and negative recipient (D+/R-) received a 6-month-prophylaxis with ganciclovir and valganciclovir, on alternate days, in the first 3 months and then, 3 more months of valganciclovir. QuantiFERON-CMV was measured at the same time points of surveillance bronchoscopies. CMV infection was defined as any DNAemia detected and CMV disease with proven biopsy or antigenemia pp65 above 10 cells/300.000 neutrophils. RESULTS: Thirty-eight patients were included. On days 45, 90, and 365 days post-LTx, 60%, 72%, and 81% QuantiFERON-CMV were reactive, respectively. Eleven patients (28.9%) presented CMV-disease and 27 DNAemia/CMV infections. Reactive tests were able to predict CMV disease only at 90 days after LTx (p = .027) but failed on DNAemia/CMV infection (p = .148). Daily prophylaxis, for D+/R- patients (13.2%), remained as an independently associated factor for not achieving reactive QuantiFERON-CMV (adjusted OR .27, 95%CI .12-.60, p = .02). CONCLUSION: QuantiFERON-CMV may be another diagnostic tool to help stratify CMV-disease risk and individualized antiviral prophylaxis after LTx.

Validation of the INCREMENT-SOT-CPE score in a large cohort of liver transplant recipients with carbapenem-resistant Enterobacterales infection.

BACKGROUND: Management of infections due to carbapenemase-resistant Enterobacterales (CRE) in solid organ transplant (SOT) recipients remains a difficult challenge. The INCREMENT-SOT-CPE score has been specifically developed from SOT recipients to stratify mortality risk, but an external validation is lacking. METHODS: Multicenter retrospective cohort study of liver transplant (LT) recipients colonized with CRE infection who developed infection after transplant over 7-year period. Primary endpoint was all-cause 30-day mortality from infection onset. A comparison between INCREMENT-SOT-CPE and other selected scores was performed. A two-level mixed effects logistic regression model with random effects for the center was fitted. Performance characteristics at optimal cut-point were calculated. Multivariable Cox regression analysis of risk factors for all-cause 30-day mortality was carried out. RESULTS: Overall, 250 CRE carriers developed infection after LT and were analyzed. The median age was 55 years (interquartile range [IQR]: 46-62) and 157 were males (62.8%). All-cause 30-day mortality was 35.6%. A sequential organ failure assessment (SOFA) score ≥ 11 showed a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 69.7%, 76.4%, 62.0%, 82.0%, and 74.0%, respectively. An INCREMENT-SOT-CPE ≥ 11 reported a sensitivity, specificity, PPV, NPV, and accuracy of 73.0%, 62.1%, 51.6%, 80.6% and 66.0%, respectively. At multivariable analysis acute renal failure, prolonged mechanical ventilation, INCREMENT-SOT-CPE score ≥ 11 and SOFA score ≥ 11 were independently associated with all-cause 30-day mortality, while a tigecycline-based targeted regimen was found to be protective. CONCLUSIONS: Both INCREMENT-SOT-CPE ≥ 11 and SOFA ≥ 11 were identified as strong predictors of all-cause 30-day mortality in a large cohort of CRE carriers developing infection after LT.

Performance of two methods of carbapenem-resistant Enterobacterales surveillance on a kidney transplant ward: selective culture of and real-time PCR directly from rectal swabs.

BACKGROUND: Infection with carbapenem-resistant Enterobacterales (CRE) is associated with a high mortality rate in kidney transplant recipients, and colonization with CRE is one of the major risk factors for CRE infection. There is, therefore, a need to improve the capacity to detect colonization with CRE among inpatients. METHODS: In this prospective study, we compared the performance of real-time PCR for carbapenemase directly from rectal swabs with that of conventional CRE surveillance culture in all patients admitted to a kidney transplant ward between February 2019 and March 2020. Surveillance culture and real-time PCR were performed at admission and weekly until hospital discharge. Two perineum-rectal swabs were collected: one for culture and one for PCR. RESULTS: We collected 905 paired samples for CRE surveillance from 399 patients, of whom 347 (87.0%) were kidney transplant recipients and 52 were waiting list patients. CRE was detected by culture and/or PCR in 75 patients (18.8%). Positivity for CRE was identified by PCR in 62 (15.5%) of the 399 patients and by culture in 55 (13.8%); 20 (5.0%) of the patients tested positive only on PCR, and 13 (3.3%) tested positive only on culture. The most common carbapenemase and species were, respectively, blaKPC (in 85.5%) and Klebsiella pneumoniae (in 80.0%). Infection with CRE occurred in 21.6% of the colonized patients, those cases occurred only among kidney transplant recipients. None of the patients who tested negative on culture developed CRE infection. CONCLUSION: In conclusion, the two methods are complementary and could be useful in a scenario of high CRE prevalence.

Brazilian perspective: antimicrobial stewardship in solid organ transplant.

BACKGROUND: The incidence of multidrug resistant organisms (MDROs) infections among solid organ transplant (SOT) patients is very high in Brazil. METHODS: This review will discuss antimicrobial use and resistance in SOT in Brazil, highlighting the main barriers and facilitators for implementation of an antimicrobial stewardship programme (ASP). RESULTS: The most common group of MDROs is carbapenem-resistant Gram-negative bacteria and vancomycin-resistant Enterococcus. Carbapenem-resistant Enterobacterales (CREs) are the most frequent MDROs and have been reported as donor-derived as well. Although ASPs are mandatory in the country, there is a lack of information regarding ASPs in SOT recipients. The main barriers for the implementation of ASPs in Brazilian hospitals are lack of electronic medical records, absence of national guidelines specific to SOT recipients, lack of recommendations on surveillance culture to evaluate colonization and transmission of donor-derived MDROs, limited availability of rapid diagnostic tests, and insufficient pharmacist and clinician time allocated to ASP activities in some SOT centers. CONCLUSIONS: The incidence of MDRO infections caused mainly by VREs and CREs is very high in the country. There is limited data regarding antimicrobial use among SOT recipients in Brazil. The absence of antimicrobial stewardship national guidelines specific to SOT recipients is one of the main barriers for the implementation of ASPs in Brazilian hospitals.

Prediction models for carbapenem-resistant Enterobacterales carriage at liver transplantation: A multicenter retrospective study.

BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) colonisation at liver transplantation (LT) increases the risk of CRE infection after LT, which impacts on recipients' survival. Colonization status usually becomes evident only near LT. Thus, predictive models can be useful to guide antibiotic prophylaxis in endemic centres. AIMS: This study aimed to identify risk factors for CRE colonisation at LT in order to build a predictive model. METHODS: Retrospective multicentre study including consecutive adult patients who underwent LT, from 2010 to 2019, at two large teaching hospitals. We excluded patients who had CRE infections within 90 days before LT. CRE screening was performed in all patients on the day of LT. Exposure variables were considered within 90 days before LT and included cirrhosis complications, underlying disease, time on the waiting list, MELD and CLIF-SOFA scores, antibiotic use, intensive care unit and hospital stay, and infections. A machine learning model was trained to detect the probability of a patient being colonized with CRE at LT. RESULTS: A total of 1544 patients were analyzed, 116 (7.5%) patients were colonized by CRE at LT. The median time from CRE isolation to LT was 5 days. Use of antibiotics, hepato-renal syndrome, worst CLIF sofa score, and use of beta-lactam/beta-lactamase inhibitor increased the probability of a patient having pre-LT CRE. The proposed algorithm had a sensitivity of 66% and a specificity of 83% with a negative predictive value of 97%. CONCLUSIONS: We created a model able to predict CRE colonization at LT based on easy-to-obtain features that could guide antibiotic prophylaxis.

Predicting the outcome for COVID-19 patients by applying time series classification to electronic health records.

BACKGROUND: COVID-19 caused more than 622 thousand deaths in Brazil. The infection can be asymptomatic and cause mild symptoms, but it also can evolve into a severe disease and lead to death. It is difficult to predict which patients will develop severe disease. There are, in the literature, machine learning models capable of assisting diagnose and predicting outcomes for several diseases, but usually these models require laboratory tests and/or imaging. METHODS: We conducted a observational cohort study that evaluated vital signs and measurements from patients who were admitted to Hospital das Clínicas (São Paulo, Brazil) between March 2020 and October 2021 due to COVID-19. The data was then represented as univariate and multivariate time series, that were used to train and test machine learning models capable of predicting a patient's outcome. RESULTS: Time series-based machine learning models are capable of predicting a COVID-19 patient's outcome with up to 96% general accuracy and 81% accuracy considering only the first hospitalization day. The models can reach up to 99% sensitivity (discharge prediction) and up to 91% specificity (death prediction). CONCLUSIONS: Results indicate that time series-based machine learning models combined with easily obtainable data can predict COVID-19 outcomes and support clinical decisions. With further research, these models can potentially help doctors diagnose other diseases.

Correlating drug prescriptions with prognosis in severe COVID-19: first step towards resource management.

BACKGROUND: Optimal COVID-19 management is still undefined. In this complicated scenario, the construction of a computational model capable of extracting information from electronic medical records, correlating signs, symptoms and medical prescriptions, could improve patient management/prognosis. METHODS: The aim of this study is to investigate the correlation between drug prescriptions and outcome in patients with COVID-19. We extracted data from 3674 medical records of hospitalized patients: drug prescriptions, outcome, and demographics. The outcome evaluated was hospital outcome. We applied correlation analysis using a Logistic Regression algorithm for machine learning with Lasso and Matthews correlation coefficient. RESULTS: We found correlations between drugs and patient outcomes (death/discharged alive). Anticoagulants, used very frequently during all phases of the disease, were associated with good prognosis only after the first week of symptoms. Antibiotics very frequently prescribed, especially early, were not correlated with outcome, suggesting that bacterial infections may not be important in determining prognosis. There were no differences between age groups. CONCLUSIONS: In conclusion, we achieved an important result in the area of Artificial Intelligence, as we were able to establish a correlation between concrete variables in a real and extremely complex environment of clinical data from COVID-19. Our results are an initial and promising contribution in decision-making and real-time environments to support resource management and forecasting prognosis of patients with COVID-19.

Development of a Risk Prediction Model for Carbapenem-resistant Enterobacteriaceae Infection After Liver Transplantation: A Multinational Cohort Study.

BACKGROUND: Patients colonized with carbapenem-resistant Enterobacteriaceae (CRE) are at higher risk of developing CRE infection after liver transplantation (LT), with associated high morbidity and mortality. Prediction model for CRE infection after LT among carriers could be useful to target preventive strategies. METHODS: Multinational multicenter cohort study of consecutive adult patients underwent LT and colonized with CRE before or after LT, from January 2010 to December 2017. Risk factors for CRE infection were analyzed by univariate analysis and by Fine-Gray subdistribution hazard model, with death as competing event. A nomogram to predict 30- and 60-day CRE infection risk was created. RESULTS: A total of 840 LT recipients found to be colonized with CRE before (n = 203) or after (n = 637) LT were enrolled. CRE infection was diagnosed in 250 (29.7%) patients within 19 (interquartile range [IQR], 9-42) days after LT. Pre- and post-LT colonization, multisite post-LT colonization, prolonged mechanical ventilation, acute renal injury, and surgical reintervention were retained in the prediction model. Median 30- and 60-day predicted risk was 15% (IQR, 11-24) and 21% (IQR, 15-33), respectively. Discrimination and prediction accuracy for CRE infection was acceptable on derivation (area under the curve [AUC], 74.6; Brier index, 16.3) and bootstrapped validation dataset (AUC, 73.9; Brier index, 16.6). Decision-curve analysis suggested net benefit of model-directed intervention over default strategies (treat all, treat none) when CRE infection probability exceeded 10%. The risk prediction model is freely available as mobile application at https://idbologna.shinyapps.io/CREPostOLTPredictionModel/. CONCLUSIONS: Our clinical prediction tool could enable better targeting interventions for CRE infection after transplant.

Impact of pre-transplant carbapenem-resistant Enterobacterales colonization and/or infection on solid organ transplant outcomes.

The impact of pre-transplant (SOT) carbapenem-resistant Enterobacterales (CRE) colonization or infection on post-SOT outcomes is unclear. We conducted a multi-center, international, cohort study of SOT recipients, with microbiologically diagnosed CRE colonization and/or infection pre-SOT. Sixty adult SOT recipients were included (liver n = 30, hearts n = 17). Klebsiella pneumoniae (n = 47, 78%) was the most common pre-SOT CRE species. Median time from CRE detection to SOT was 2.32 months (IQR 0.33-10.13). Post-SOT CRE infection occurred in 40% (n = 24/60), at a median of 9 days (IQR 7-17), and most commonly due to K pneumoniae (n = 20/24, 83%). Of those infected, 62% had a surgical site infection, and 46% had bloodstream infection. Patients with post-SOT CRE infection more commonly had a liver transplant (16, 67% vs. 14, 39%; p =.0350) or pre-SOT CRE BSI (11, 46% vs. 7, 19%; p =.03). One-year post-SOT survival was 77%, and those with post-SOT CRE infection had a 50% less chance of survival vs. uninfected (0.86, 95% CI, 0.76-0.97 vs. 0.34, 95% CI 0.08-1.0, p =.0204). Pre-SOT CRE infection or colonization is not an absolute contraindication to SOT and is more common among abdominal SOT recipients, those with pre-SOT CRE BSI, and those with early post-SOT medical and surgical complications.

Carbapenem-resistant Serratia marcescens bloodstream infection in hematopoietic stem cell transplantation patients: Will it be the next challenge?

Surveillance programs have been reporting decreasing rates of carbapenem-sensitivity in Serratia marcescens, leading to a concern regarding the few remaining therapeutic options to treat these multidrug-resistant (MDR) organisms. Here, we describe a case series of 11 stem cell hematopoietic transplantation patients infected (N = 6) or colonized (N = 5) by carbapenem-resistant S marcescens (CrSm) from 2010 to 2013. The comorbidities found were acute renal insufficiency (3/11), neutropenia (7/11), and mucositis (8/11), and the mortality rate was 64%. KPC was the most prevalent carbapenemase detected (8/11) and tigecycline and gentamicin were the antimicrobials used as treatment.

Efficacy of ß-lactam/ß-lactamase inhibitors to treat extended-spectrum beta-lactamase-producing Enterobacterales bacteremia secondary to urinary tract infection in kidney transplant recipients (INCREMENT-SOT Project).

BACKGROUND: Whether active therapy with ß-lactam/ß-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear. METHODS: We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively. RESULTS: Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count ≤500 cells/µL at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes. CONCLUSIONS: Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902).

Increased Risk for Carbapenem-Resistant Enterobacteriaceae Colonization in Intensive Care Units after Hospitalization in Emergency Department.

Carbapenem-resistant Enterobacteriaceae (CRE) colonization is common in hospital patients admitted to intensive care units (ICU) from the emergency department. We evaluated the effect of previous hospitalization in the emergency department on CRE colonization at ICU admission. Our case-control study included 103 cases and 201 controls; cases were patients colonized by CRE at admission to ICU and controls were patients admitted to ICU and not colonized. Risk factors were emergency department stay, use of carbapenem, Simplified Acute Physiology Score, upper digestive endoscopy, and transfer from another hospital. We found that ED stay before ICU admission was associated with CRE colonization at admission to the ICU. Our findings indicate that addressing infection control problems in EDs will help to control carbapenem resistance in ICUs.

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.