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.

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.

A surveillance program for long-term central venous access-associated infections in outpatient chemotherapy services.

OBJECTIVE: In this study, we described the first results of a surveillance system for infections associated with long-term central venous catheters (LT-CVC) in patients under outpatient chemotherapy. DESIGN: This was a multicentric, prospective study. SETTING: Outpatient chemotherapy services. PARTICIPANTS: The study included 8 referral cancer centers in the State of São Paulo. INTERVENTION: These services were invited to participate in a newly created surveillance program for patients under chemotherapy. Several meetings were convened to share previous experiences on LT-CVC infection surveillance and to define the surveillance method. Once the program was implemented, all bloodstream infection (LT-CVC BSIs), tunnel infection, and exit-site infections associated with LT-CVC were reported. Data from January to May 2021 were analyzed. The median monthly number of chemotherapy sessions per clinic was 925 (IQR, 270-5,855). We used Poisson regression to analyze the association of rates with the characteristics of the services. RESULTS: In total, 107 LT-CVC infections were reported, of which 95% were BSIs, mostly associated with totally implantable devices (76%). Infections occurred a median of 4 days after the last catheter manipulation and 116 after the LT-CVC insertion. Also, 102 microorganisms were isolated from LT-CVC BSIs; the most common pathogen was Staphylococcus epidermidis, at 22%. Moreover, 44 infections (44%) fulfilled the criteria for CVC-related LT-CVC BSI and 27 infections (27%) met the criteria for mucosal barrier injury. The 1-year cumulative LT-CVC BSI rate was 1.94 per 1,000 CVC days of use. The rates were higher in public hospitals (IRR, 6.00; P < .001) and in hospitals that already had in place surveillance for LT-CVC infections (IRR, 2.01; P < .01). CONCLUSION: Our study describes an applicable surveillance method for infections in cancer outpatients using LT-CVC.

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.

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.

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.

Environmental Clonal Spread of Azole-Resistant Candida parapsilosis with Erg11-Y132F Mutation Causing a Large Candidemia Outbreak in a Brazilian Cancer Referral Center.

Clonal outbreaks due to azole-resistant Candida parapsilosis (ARCP) isolates have been reported in numerous studies, but the environmental niche of such isolates has yet to be defined. Herein, we aimed to identify the environmental niche of ARCP isolates causing unremitting clonal outbreaks in an adult ICU from a Brazilian cancer referral center. C. parapsilosis sensu stricto isolates recovered from blood cultures, pericatheter skins, healthcare workers (HCW), and nosocomial surfaces were genotyped by multilocus microsatellite typing (MLMT). Antifungal susceptibility testing was performed by the EUCAST (European Committee for Antimicrobial Susceptibility Testing) broth microdilution reference method and ERG11 was sequenced to determine the azole resistance mechanism. Approximately 68% of isolates were fluconazole-resistant (76/112), including pericatheter skins (3/3, 100%), blood cultures (63/70, 90%), nosocomial surfaces (6/11, 54.5%), and HCW's hands (4/28, 14.2%). MLMT revealed five clusters: the major cluster contained 88.2% of ARCP isolates (67/76) collected from blood (57/70), bed (2/2), pericatheter skin (2/3), from carts (3/7), and HCW's hands (3/27). ARCP isolates were associated with a higher 30 day crude mortality rate (63.8%) than non-ARCP ones (20%, p = 0.008), and resisted two environmental decontamination attempts using quaternary ammonium. This study for the first time identified ARCP isolates harboring the Erg11-Y132F mutation from nosocomial surfaces and HCW's hands, which were genetically identical to ARCP blood isolates. Therefore, it is likely that persisting clonal outbreak due to ARCP isolates was fueled by environmental sources. The resistance of Y132F ARCP isolates to disinfectants, and their potential association with a high mortality rate, warrant vigilant source control using effective environmental decontamination.

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.

Carbapenem-resistant Enterobacteriaceae among kidney transplant recipients - insights on the risk of acquisition and CRE infection.

BACKGROUND: Kidney transplant recipients are a risk group for carbapenem-resistant Enterobacteriaceae infection. OBJECTIVES: This study aimed to identify risk factors for CRE acquisition and infection among kidney transplant recipients. METHODS: We conducted a case-control study; we defined the case as kidney transplant recipient with positive culture for carbapenem-resistant Enterobacteriaceae identified between January 2010 and February 2019. Controls were chosen among kidney transplant recipients hospitalized in the same period of cases (1:2). Surveillance culture for carbapenem-resistant Enterobacteriaceae was performed at admission and weekly during hospital stay. The risk factors analysis for carbapenem-resistant Enterobacteriaceae infection was performed among patients colonized by these bacteria. RESULTS: We identified 331 patients colonized with carbapenem-resistant Enterobacteriaceae; The median time from transplantation to first carbapenem-resistant Enterobacteriaceae positive culture was 42 days (range from 3 to 7399 days); 125(37.8%) patients developed infection; the most common site was urinary tract. Risk factors for carbapenem-resistant Enterobacteriaceae acquisition were recipient age >45-year, diabetes nephropathy, donor age >55-year, ureteral stent at kidney transplantation, delay of graft function, median lymphocytes count <800cells/mm3, and acute cellular rejection. Risk factors for carbapenem-resistant Enterobacteriaceae infection were recipient age at CRE acquisition >50-year; median lymphocytes count ≤700 cells/mm3, carbapenem use, and colonization by polymyxin-resistant strain. Patients colonized by polymyxin and carbapenem resistant Enterobacteriaceae strain who used carbapenem had a 93.8% probability of developing infection by this agent. CONCLUSION: Carbapenem-resistant Enterobacteriaceae acquisition after kidney transplant is related to graft conditions, immunosuppression degree. Among carbapenem-resistant Enterobacteriaceae colonized patients, special attention is needed for those harbouring polymyxin-resistant strains.

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).

Surgical site infection after liver transplantation in the era of multidrug-resistant bacteria: what new risks should be considered?

Surgical site infection (SSI) is a frequent infection site after liver transplantation (LT), and multidrug-resistant bacteria are common agents of those infections. This study aimed to analyze risk factors for SSI, including SSI caused by a multidrug-resistant microorganism (MDRO) after LT. We performed a cohort study of patients who underwent an LT from 2010 to 2018. The outcomes were SSI and SSI caused by MDRO. We analyzed features related to surgical procedure, patients' characteristics, and post-LT intercurrence. Surveillance for carbapenem-resistant Enterobacteriaceae (CRE), vancomycin-resistant Enterococcus (VRE), and carbapenem-resistant Acinetobacter baumannii (CRAB) was performed through rectal swab at the LT admission and weekly until hospital discharge during all study periods. SSI was identified in 30.1% (229/762) of LTs. We observed a decline in the SSI rate from 37.5% in 2014 to 16.7% in 2018 (P 0.02). SSI caused by MDRO occurred in 109 (14.3%) patients. Klebsiella pneumoniae was the most common agent of both SSI and SSI caused by MDRO. The pre-LT colonization was 98 (12.9%) by CRE, 73 (9.6%) by VRE, and 28 (3.7%) by CRAB. Risk factors for SSI caused by MDRO identified were dialysis after LT (P 0.01), CRAB acquisition before LT (0.03), and CRE acquisition before LT (P 0.004); use of adjusted prophylaxis by MDRO risk was the only protective factor identified (P 0.01). MDROs were frequent agents of SSI after LT, and the carbapenem-resistant Gram-negative colonization before LT increased the risk of SSI by these agents.

Institutional protocol adherence in the incidence of recurrent urinary tract infection after kidney transplantation.

OBJECTIVES: Recurrent urinary tract infections (rUTIs) occur frequently after kidney transplantation (KT), however their optimal management remains undefined. This study aimed to identify risk factors for rUTI and to validate a protocol for UTI and rUTI treatment after KT. METHODS: This retrospective cohort study involved patients undergoing KT between January 2013 and July 2016. Patients were followed-up from day of KT until graft loss, death or end of follow-up (31 December 2018). We analysed all episodes of symptomatic UTI. The main outcome measure was rUTI after KT. Analysis was done per episode in a multilevel approach; patient features were considered in the distal level and UTI features in the proximal level. Univariate and multivariate analyses were performed by Cox regression. A propensity score was used to adjust the risk of patients with carbapenem-resistant Enterobacteriaceae. RESULTS: During the study period, 787 patients underwent KT, of whom 152 (19.3%) developed 356 UTI episodes. The most common micro-organisms wereEscherichia coli (165/356; 46.3%) and Klebsiella pneumoniae (101/356; 28.4%). Multidrug-resistant micro-organisms were isolated in 161 UTIs (45.2%). Risk factors for rUTI were diabetic nephropathy as the cause of end-stage renal disease (P = 0.02), UTI in first 180 days after KT (P = 0.04), anatomic alteration of the urinary tract at UTI diagnosis (P = 0.004) and length of time to effective therapy (P = 0.002); UTI treatment duration according to institutional protocol (P = 0.04) was the only protective factor identified. CONCLUSION: Appropriate therapy duration has an impact on rUTI prevention after KT.

The role of therapy with aminoglycoside in the outcomes of kidney transplant recipients infected with polymyxin- and carbapenem-resistant Enterobacteriaceae.

Kidney transplant recipients are at risk for infections due to carbapenem-resistant Enterobacteriaceae (CRE). Polymyxin-resistant CRE (PR-CRE) infections are especially difficult to treat. The aim of this study was to characterize PR-CRE infections among kidney transplant recipients and identify risk factors for treatment failure. This retrospective cohort study involved all kidney transplant recipients with PR-CRE infection between 2013 and 2017 at our center. Minimal inhibitory concentrations for polymyxin B were determined by broth microdilution. Carbapenem-resistant genes (blaKPC, blaNDM, and blaOXA-48), aminoglycoside-resistance genes, and polymyxin-resistant gene mcr-1 were identified by polymerase chain reaction. All but one of the 47PR-CRE infections identified were due to Klebsiella pneumoniae. The most common type of infection (in 54.3%) was urinary tract infection (UTI). Monotherapy was used in 10 cases. Combined treatment regimens included double-carbapenem therapy in 19 cases, oral fosfomycin in 19, and amikacin in 13. Treatment failure occurred in 21 cases (45.7%). Clinical success was achieved 78.9% of patients who used aminoglycosides versus 37.0% of those who not used this drug (p = 0.007). Multivariate analysis showed diabetes mellitus to be a risk factor for treatment failure; amikacin use and UTI were found to be protective. Nine strains were RmtB producers. Although aminoglycosides constitute an important therapeutic option for PR-CRE infection, the emergence of aminoglycoside resistance could have a major impact on the management of CRE infection.

Role of Lock Therapy for Long-Term Catheter-Related Infections by Multidrug-Resistant Bacteria.

The management of long-term central venous catheter (LTCVC) infections by multidrug-resistant (MDR) bacteria in cancer patient is a challenge. The objectives of this study were to analyze outcomes in cancer patients with LTCVC-associated infection, identify risks for unfavorable outcomes, and determine the impact of MDR bacteria and antibiotic lock therapy (ALT) in managing such infections. We evaluated all LTCVC-associated infections treated between January 2009 and December 2016. Infections were reported in accordance with international guidelines for catheter-related infections. The outcome measures were 30-day mortality and treatment failure. We analyzed risk factors by Cox forward-stepwise regression. We identified 296 LTCVC-associated infections; 212 (71.6%) were classified as bloodstream infections (BSIs). The most common agent was Staphylococcus aureus Forty-six (21.7%) infections were due to MDR Gram-negative bacteria. ALT was used in 62 (29.2%) patients, with a 75.9% success rate. Risk factors identified for failure of the initial treatment were having a high sequential organ failure assessment (SOFA) score at diagnosis of infection and being in palliative care; introduction of ALT at the start of treatment was identified as a protective factor. Risk factors identified for 30-day mortality after LTCVC-associated infection were a high SOFA score at diagnosis, infection with MDR bacteria, and palliative care; introduction of ALT at the start of treatment, hematological malignancies, and adherence to an institutional protocol for the management of LTCVC-associated infection were identified as protective factors. Despite the high incidence of infection with MDR bacteria, ALT improves the outcome of LTCVC-associated infection in cancer patients.

Liberal Versus Restrictive Transfusion Strategy in Critically Ill Oncologic Patients: The Transfusion Requirements in Critically Ill Oncologic Patients Randomized Controlled Trial.

OBJECTIVE: To assess whether a restrictive strategy of RBC transfusion reduces 28-day mortality when compared with a liberal strategy in cancer patients with septic shock. DESIGN: Single center, randomized, double-blind controlled trial. SETTING: Teaching hospital. PATIENTS: Adult cancer patients with septic shock in the first 6 hours of ICU admission. INTERVENTIONS: Patients were randomized to the liberal (hemoglobin threshold, < 9 g/dL) or to the restrictive strategy (hemoglobin threshold, < 7 g/dL) of RBC transfusion during ICU stay. MEASUREMENTS AND MAIN RESULTS: Patients were randomized to the liberal (n = 149) or to the restrictive transfusion strategy (n = 151) group. Patients in the liberal group received more RBC units than patients in the restrictive group (1 [0-3] vs 0 [0-2] unit; p < 0.001). At 28 days after randomization, mortality rate in the liberal group (primary endpoint of the study) was 45% (67 patients) versus 56% (84 patients) in the restrictive group (hazard ratio, 0.74; 95% CI, 0.53-1.04; p = 0.08) with no differences in ICU and hospital length of stay. At 90 days after randomization, mortality rate in the liberal group was lower (59% vs 70%) than in the restrictive group (hazard ratio, 0.72; 95% CI, 0.53-0.97; p = 0.03). CONCLUSIONS: We observed a survival trend favoring a liberal transfusion strategy in patients with septic shock when compared with the restrictive strategy. These results went in the opposite direction of the a priori hypothesis and of other trials in the field and need to be confirmed.

Rhizopus arrhizus and Fusarium solani Concomitant Infection in an Immunocompromised Host.

Neutropenic patients are at risk of the development of hyalohyphomycosis and mucormycosis. Correct identification is essential for the initiation of the specific treatment, but concomitant mold infections are rarely reported. We report one unprecedented case of concomitant mucormycosis and fusariosis in a neutropenic patient with acute myeloid leukemia. The patient developed rhino-orbital infection by Rhizopus arrhizus and disseminated infection by Fusarium solani. The first culture from a sinus biopsy grew Rhizopus, which was consistent with the histopathology report of mucormycosis. A second sinus biopsy collected later during the patient's clinical deterioration was reported as hyalohyphomycosis, and the culture yielded F. solani. Due to the discordant reports, the second biopsy was reviewed and two hyphae types suggestive of both hyalohyphomycetes and mucormycetes were found. The dual mold infection was confirmed by PCR assays from paraffinized tissue sections. Increased awareness of the existence of dual mold infections in at-risk patients is necessary. PCR methods in tissue sections may increase the diagnosis of dual mold infections. In case of sequential biopsies showing discrepant results, mixed infections have to be suspected.

Staphylococcus aureus isolates colonizing and infecting cirrhotic and liver-transplantation patients: comparison of molecular typing and virulence factors.

BACKGROUND: S. aureus is an important agent of colonization and infection in liver transplant patients. It harbors several virulence factors that can increase its pathogenicity. However, studies of virulence and molecular typing of MRSA in cirrhotic and liver transplantation patients are scarce. RESULTS: Here we use SCCmec, PFGE, spa typing, MLST and virulence factors to characterize MRSA isolates in pre and post liver transplantation patients. Sixteen (13%) of 126 cirrhotic and 15 of the 64 liver-transplanted patients (23%) were colonized by MRSA (p=0.091). SCCmec types I, II and III that are generally associated with nosocomial infections were identified in 91% of the isolates. None of the isolates carried PVL, adhesion factors and fib gene. Only three MRSA colonized isolates carried tst gene and were characterized as SCCmec type I and t149. Ten spa types and five STs were identified; t002 and ST105 were the most frequent profiles. Spa types and ST1510 never described in Brazil and a new spa type t14789 were identified. Nineteen PFGE subtypes were found and grouped into nine types. There was a predominant cluster, which was related to the New York/Japanese epidemic clone and harboured SCCmec type II identified in both cirrhotic and post-transplantation patients. Based on SCCmec and virulence factors the MRSA isolates belonged to NY/Jpn clone seen be more similar to the USA100 MRSA isolates. CONCLUSIONS: Although without significance, liver-transplantation was more frequently colonized by MRSA than cirrhotic patients. The most frequent SCCmec was type II, and the predominant cluster was related to the New York/Japanese clone. A new spa t14789, and ST1510 never reported in Brazil were identified.

Risk factors and outcome of infections with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae in kidney transplant recipients.

INTRODUCTION: Solid organ transplant recipients are especially susceptible to healthcare-associated infections with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp-HAIs). The aim of the study was to evaluate risk factors and outcome of these infections in kidney transplant recipients. METHODS: This was a retrospective cohort of kidney transplant (KTx) recipients between January 2009 and December 2013. Cases were defined as patients who developed KPC-Kp-HAI, confirmed by PCR for bla( KPC) gene after KTx during the study period. We analysed variables related to recipient; induction immunosuppressant therapy; delayed graft function; use of invasive devices; SOFA score on the first day of infection; type of therapy; time from positive culture to appropriate antimicrobial therapy; bacteraemia; and concomitant infection. Outcome measures were the occurrence of KPC-Kp-HAI and 30-day mortality after KPC-Kp-HAI. RESULTS: A total of 1,101 were submitted to KTx in the period, 21 patients were classified as infected with KPC-Kp. Another ten patients had KPC-Kp-HAI in the period and were transplanted before 2009. Of those 31 patients, 48.4 % showed evidence of prior colonization and 38.7 % had bacteraemia. The most common site of infection was the surgical wound. Risk factors for KPC-Kp-HAI were multi-organ transplantation and the use of a ureteral stent. Eight of the infected patients experienced recurrence of the infection. The 30-day mortality rate was 41.9 %. Survival was significantly lower among the patients with KPC-Kp-HAI (72 vs. 89.1 %; P = 0.002). The only risk factor independently associated with 30-day mortality was an elevated SOFA score on the first day of infection. CONCLUSIONS: In KTx recipients, the occurrence of KPC-Kp-HAI was related to invasive devices and type of transplant; these infections had a high rate of recurrence and reduced survival after KTx.