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.

Late cytomegalovirus (CMV) infections after kidney transplantation under the preemptive strategy: Risk factors and clinical aspects.

BACKGROUND: Late cytomegalovirus infections (LCMV) after the cessation of prophylaxis are well described. We aimed to assess clinical and epidemiological data on late-occurring cytomegalovirus (CMV) infections in the absence of CMV prophylaxis in a cohort of kidney transplant patients. METHODS: In a cohort of kidney transplant recipients not employing CMV-specific prophylaxis, patients with CMV infections occurring after 6 months of transplantation were compared to patients with CMV infections diagnosed within the first 6 months (early infections). The main objectives were to compare clinical outcomes and evaluate risk factors for late CMV infection. RESULTS: A total of 556 patients were evaluated. Forty-three patients with LCMV infections were compared to 513 patients with early CMV infections. LCMV infections occurred after a median of 473 days of transplantation and had a more severe course, with a statistically significant higher rate of invasive disease and graft loss (60.5% vs 21.6% and 11.6% vs 3.1% respectively). Thirty-day mortality was twice as high for patients with LCMV, but did not reach statistical significance (9.3% vs 4.3%). By multivariate analysis, employment of antilymphocyte therapy early after transplantation and tacrolimus as initial immunosuppressive therapy were significantly protective for the occurrence of LCMV infections. CONCLUSION: Late CMV infections in the absence of specific prophylaxis after kidney transplantation have a more severe outcome when compared to early infections and occur in patients less immunosuppressed early after transplantation.

Candida glabrata: an emerging pathogen in Brazilian tertiary care hospitals.

Candida glabrata is an infrequent cause of candidemia in Brazilian public hospitals. We investigated putative differences in the epidemiology of candidemia in institutions with different sources of funding. Prospective laboratory-based surveillance of candidemia was conducted in seven private and two public Brazilian tertiary care hospitals. Among 4,363 episodes of bloodstream infection, 300 were caused by Candida spp. (6.9%). Incidence rates were significantly higher in public hospitals, i.e., 2.42 vs. 0.91 episodes per 1,000 admissions (P< 0.01). Patients in private hospitals were older, more likely to be in an intensive care unit and to have been exposed to fluconazole before candidemia. Candida parapsilosis was more frequently recovered as the etiologic agent in public (33% vs. 16%, P< 0.001) hospitals, whereas C. glabrata was more frequently isolated in private hospitals (13% vs. 3%, P < 0.001). Fluconazole resistance among C. glabrata isolates was more frequent in private hospitals (76.5% vs. 20%, P = 0.02). The 30-day mortality was slightly higher among patients in public hospitals (53% vs. 43%, P = 0.10). Candida glabrata is an emerging pathogen in private institutions and in this setting, fluconazole should not be considered as a safe option for primary therapy of candidemia.

Severe Strongyloides stercoralis infection in kidney transplant recipients: A multicenter case-control study.

BACKGROUND: Severe Strongyloides stercoralis infection in kidney transplant recipients is associated with considerable morbidity and mortality, although little is known about the risk factors for such infection. METHODOLOGY/PRINCIPAL FINDINGS: This was a retrospective, multicenter, case-control study in which we assessed the risk factors for and clinical outcomes of severe S. stercoralis infections in kidney transplant recipients in Brazil. We included 138 kidney transplant recipients: 46 cases and 92 controls. Among the cases, the median number of days from transplantation to diagnosis was 117 (interquartile range [IQR], 73.5-965) and the most common clinical findings were gastrointestinal symptoms (in 78.3%) and respiratory symptoms (in 39.1%), whereas fever and eosinophilia were seen in only 32.6% and 43.5%, respectively. The 30-day all-cause mortality among the cases was 28.3% overall and was significantly higher among the cases of infection occurring within the first three months after transplantation (47% vs. 17.2%, P = 0.04). The independent risk factors were receiving a transplant from a deceased donor (odds ratio [OR] = 6.16, 95% confidence interval [CI] = 2.05-18.5), a history of bacterial infection (OR = 3.04, 95% CI = 1.2-7.5), and a cumulative corticosteroid dose (OR = 1.005, 95% CI = 1.001-1.009). The independent predictors of mortality were respiratory failure (OR = 98.33, 95% CI = 4.46-2169.77) and concomitant bacteremia (OR = 413.00, 95% CI = 4.83-35316.61). CONCLUSIONS/SIGNIFICANCE: Severe S. stercoralis infections are associated with considerable morbidity and mortality after kidney transplantation. In endemic areas, such infection may occur late after transplantation, although it seems to be more severe when it occurs earlier after transplantation. Specific risk factors and clinical manifestations can identify patients at risk, who should receive prophylaxis or early treatment.

Treatment of severe infections caused by Staphylococcus aureus: a change in the vancomycin paradigm?

Staphylococcus aureus is a frequent agent of serious intensive care unit infections with high associated mortality rates. Resistance to methicillin is frequent, exceeding 50% in many countries, and for these strains, vancomycin is the agent of choice. Resistance to this drug is now frequent for Enterococcus, but low rates are reported for S. aureus. Nonetheless, treatment failures with vancomycin for infections caused by strains considered susceptible have been reported during recent years. This article aims to review the possible explanations for this phenomenon, which is challenging the old paradigm of S. aureus infections and vancomycin use.