Interesting case from Argentina: Kidney transplant recipient with skin lesions-A Latin American perspective.

This is a case of a kidney transplant recipient who presented with skin lesions, low-grade fevers, and pancytopenia 2 months after his transplant.

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.

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.

Lung abscess and empyema in a heart transplant recipient from Thailand.

The case discussed involves a 69-year-old Thai woman who underwent orthotopic heart transplantation 9 months before this event. She presented with fever without localizing signs or symptoms. However, her chest images revealed mass-like consolidation in the left upper lobe. Blood culture and lung tissue identified Rhodococcus equi. She was successfully treated with a combination of antimicrobial therapy, optimization of immunosuppressants, and surgical resection.

Cutaneous lesions in a solid organ transplant recipient: A diagnostic dilemma.

We present the case of a 66-year-old female with a history of renal transplant in 1999 with new onset fevers and diffuse skin ulcerations. In this article, we present the diagnostic studies, differential diagnosis, and treatment decisions for the case.

Propensity Score and Desirability of Outcome Ranking Analysis of Ertapenem for Treatment of Nonsevere Bacteremic Urinary Tract Infections Due to Extended-Spectrum-Beta-Lactamase-Producing Enterobacterales in Kidney Transplant Recipients.

There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.

Donor-Derived Tuberculosis: A Case Report and the Role of Communication Gaps in Transplantation Safety.

Donor-derived tuberculosis (DD-TB) accounts for less than 5% of TB cases and is considered a rare event. In the transplant setting, the frequency of active TB is estimated to be 20 to 74 times higher than that in the general population, and it is associated with high mortality. In this context, the main strategy to minimize the risk of DD transmission is to identify high-risk donors. Despite screening recommendations, failures may result in a breakdown of safety that ends in the transmission of potentially fatal diseases. This report describes a case of DD-TB and emphasizes communication gaps that may occur between organ procurement organizations and transplant centers. Failure in reporting results, lack of exchanging information regarding recipients from the same donor, and inefficient communication between organ procurement organizations and transplant centers are lacks that may be prevented by a more efficient approach towards screening protocols and communication.

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.

Latent tuberculosis: Risk factors, screening and treatment in liver transplantation recipients from an endemic area.

BACKGROUND: Patients undergoing solid organ transplantation, particularly those who live or have lived in tuberculosis (TB) endemic areas, are at a high risk of developing TB. The majority of post-transplantation TB cases are associated with reactivation of latent TB infection (LTBI). Brazil is in a single position with overlapping areas of high TB endemicity and high transplant activity. In liver transplant (LT), one should be aware of the potential hepatotoxicity associated with the treatment regimens for LTBI. AIM: To evaluate the frequency of LTBI in LT patients and treatment-related issues. METHODS: This was a retrospective analysis of a cohort of cirrhotic patients aged ≥ 18 years, who underwent LT at a high-complexity teaching hospital from January 2005 to December 2012. RESULTS: Overall, 429 patients underwent LT during the study period. Of these, 213 (49.7%) underwent the tuberculin skin test (TST) during the pre-transplant period, and 35 (16.4%) of them had a positive result. The treatment for LTBI was initiated after LT in 12 (34.3%) of the TST-positive patients; in 3 (25.0%), treatment was maintained for at least 6 mo. CONCLUSION: The prevalence of LTBI was lower than expected. Initiation and completion of LTBI treatment was limited by difficulties in the management of these special patients.

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).

Antimicrobial use for treatment of healthcare-associated infections and bacterial resistance in a reference neonatal unit.

OBJECTIVE: The use of broad-spectrum antimicrobials, such as third and fourth-generation, are responsible for emergence of multidrug-resistant microorganisms in neonatal units. Furthermore, antimicrobial daily doses are not standardized in neonatology. This study aimed to investigate the association between the use of antimicrobial broad spectrum to bacterial sensitivity profile in a referral unit of neonatal progressive care. METHODS: This is a cohort study conducted in a referral neonatal progressive care unit from January 2008 to December 2016. The data of all hospitalized neonates was collected daily. The infection criteria used were the standardized national criteria, based on definitions of Center for Diseases Control and Prevention. In this study, the use of antimicrobials was evaluated as antimicrobial-day (ATM-day) and the ratio of multidrug-resistant microorganisms per 1000 ATM-day of broad spectrum was also calculated. The study was approved by the Institutional Review Board of the Universidade Federal de Minas Gerais (ETIC 312/08 e CAAE 58973616.2.0000.5149). RESULTS: From 2008 to 2016, 2751 neonates were hospitalized, corresponding to 60,656 patient-days. The ratio of multidrug-resistant microorganisms per 1000 ATM-day of broad spectrum was 1,3 in the first period and 4,3 in the second period (p=0,005). CONCLUSION: It was observed that use of broad-spectrum antimicrobials, especially those with coverage for Gram-negative bacteria, was associated with an increase of multidrug-resistant bacteria.

Hepatitis Relapse after Yellow Fever Infection: Is There Another Wave?

During the yellow fever (YF) outbreak in Brazil, many cases of fulminant hepatitis were seen, although mild to moderate hepatitis was mostly observed with complete recovery. This report presents a case of late-onset hepatitis due to YF relapse. The patient sought medical attention after jaundice recurrence 40 days after the first YF hepatitis episode. This case highlights the importance of patient follow-up after the complete resolution of YF symptoms and discharge.

Hepatitis Relapse after Yellow Fever Infection: Is There Another Wave?

Abstract During the yellow fever (YF) outbreak in Brazil, many cases of fulminant hepatitis were seen, although mild to moderate hepatitis was mostly observed with complete recovery. This report presents a case of late-onset hepatitis due to YF relapse. The patient sought medical attention after jaundice recurrence 40 days after the first YF hepatitis episode. This case highlights the importance of patient follow-up after the complete resolution of YF symptoms and discharge.

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.

Current approaches to visceral leishmaniasis treatment in solid organ transplant recipients.

INTRODUCTION: The increasing number of transplants performed worldwide and the growing global mobility with migration and travel to and from developing countries and tropical areas are bringing new challenges for the management of transplant infectious diseases, previously less commonly seen, such as Leishmaniasis. However, in this scenario there is a lack of information and the current knowledge is based on a few studies. The selection of the most appropriate treatment depends on various factors, such as patient profile, Leishmania species, disease extent, drug availability, concomitant infections and previous treatments. Therapeutic options may include different formulations of amphotericin B, pentavalent antimonials, miltefosine and paromomycin, among others. These drugs can be used alone or in combination. Areas covered: This review is a practical guide for Visceral Leishmaniasis (VL) specific treatment in solid organ transplant recipients (SOT), including therapeutic options and assessment of therapy response. Expert commentary: The main challenges for treatment of leishmaniasis in SOT recipients are related to the duration of therapy, curative criteria and secondary prophylaxis. Immunosuppression dose reduction is often recommended, but such decisions must be made on an individual basis. At present, Liposomal Amphotericin B is the best choice for treatment and prophylaxis.

Risk factors for central venous catheter-related infections in a neonatal population - systematic review / Fatores de risco para infecção associada a cateteres venosos centrais em população neonatal - revisão sistemática

Abstract Objective: This was a systematic review of the incidence density and risk factors for central venous catheter-related infections in a neonatal population. Data source: The MEDLINE, Embase, Cochrane, BDENF, SciELO, and LILACS databases were used without date or language restriction. Studies that analyzed risk factors for bloodstream infections in newborns were identified. Data synthesis: A total of 134 articles were found that met the eligibility criteria. Of these articles, 14 were selected that addressed risk factors for central venous catheter-related infection in neonates. Catheter-related bloodstream infections remain an important complication, as shown by the incidence rates reported in the studies included in this review. The observed risk factors indicate that low birth weight, prematurity, and longer catheter permanence are related to a higher incidence of bloodstream infections. It has been observed that low rates of catheter-related infections, i.e., close to zero, are already a reality in health institutions in developed countries, since they use infection surveillance and control programs. Conclusion: Catheter-related bloodstream infections still show high incidence density rates in developing countries. The authors emphasize the need for further longitudinal studies and the need for better strategies to prevent risk factors, aiming at the reduction of catheter-related infections.

Resumo Objetivo: Revisão sistemática sobre a densidade de incidência e de fatores de risco para infecção associada a cateter venoso central em população neonatal. Fontes dos dados: Usaram-se os bancos de dados Medline, Embase, Cochrane, Bdenf, Scielo e Lilacs, sem restrição de data ou de idioma. Identificaram-se os estudos que analisaram fatores de risco para infecção da corrente sanguínea em recém-nascidos. Síntese dos dados: Foram encontrados 134 artigos conforme os critérios de elegibilidade. Desses, foram selecionados 14 que abordaram fatores de risco para infecção associada a cateter venoso central em neonatos. A infecção da corrente sanguínea associada a cateter continua a mostrar-se como uma importante complicação, conforme demonstram as taxas de incidência relatadas nos estudos incluídos nesta revisão. Os fatores de risco observados apontam que baixo peso ao nascer, prematuridade e maior tempo de permanência do cateter estão relacionados a maior incidência de infecção da corrente sanguínea. Observou-se que taxas de infecção associada a cateter em valores baixos, próximos a zero, já são uma realidade em instituições de saúde de países desenvolvidos, uma vez que usam programas de vigilância e controle de infecção. Conclusão: A infecção da corrente sanguínea associada a cateter ainda apresenta altas taxas de densidade de incidência em países em desenvolvimento. Destaca-se a necessidade de mais estudos longitudinais e a necessidade de melhores estratégias de prevenção dos fatores de risco para a redução de infecção associada a cateter.