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.

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.

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.

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.

Procalcitonin-guided protocol is not useful to manage antibiotic therapy in febrile neutropenia: a randomized controlled trial.

Febrile neutropenia (FN) requires immediate use of antibiotics (ATB), and procalcitonin (PCT) is proven to be useful in guiding antibiotic therapy in different settings. This study investigated the use of PCT as a guide for the duration of ATB in FN. A randomized controlled trial was carried out from January-December 2010. A total of 62 hematological adult patients with FN were randomized, in 1:1 ratio, into two groups: (1) PCT group: length of ATB guided by institutional protocol plus PCT dynamics, and (2) control group: duration of ATB in accordance with institutional protocol. There was no difference between groups regarding the use of ATB for the first episode of fever (HR 1.14, 95 % CI 0.66-1.95, p = 0.641), with equivalent median duration of ATB therapy (PCT group 9.0 days and control group 8.0 days, p = 0.67), and median number of days without ATB (0 days, IQR 0-2 days for both groups, p = 0.96). We observed no difference in clinical cure rate (p = 0.68), infection relapse (p = 1.0), superinfection (p = 0.85), length of hospitalization (p = 0.64), and mortality at 28 days (p = 0.39) and at 90 days (p = 0.72). Considering the cut-off of 0.5 ng/ml, PCT was correlated with bacteremia (sensitivity of 51.9 % and specificity of 76.5 %). In this randomized controlled trial, adding a PCT-guided protocol to the standard recommendations did not reduce the use of antibiotics in febrile neutropenia, although no apparent harm was caused. PCT proved to be a marker of bacteremia in this setting.

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.

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.

Phenotypic and genotypic characterization of drug-resistant Mycobacterium tuberculosis strains.

Of 142 pulmonary tuberculosis patients, 76 were considered high risk for the development of resistance, and 24 were confirmed as resistant strain carriers. Resistant isoniazid strains presented a high frequency of katG and ahpC mutations (90%) correlated with an MIC >4 microg/mL (94%). inhA mutations were not seen. rpoB mutations were identified in 78.6% of rifampicin-resistant strains, usually in codon 531 (72.7%), and 75% had an MIC >16 microg/mL. katG and rpoB mutations recognized 88.2% of multidrug-resistant strains and proved more efficient than the katG and rpoB mutations alone. Seventy percent of resistant pyrazinamide strains had pncA mutations between genes 136 and 188, 62.5% of them with an MIC >900 microg/mL. Pyrazinamidase inactivity was not an efficient resistance marker because 60% of pncA-mutated strains maintained enzymatic activity despite displaying good correlation with high resistance levels. Resistant ethambutol strains had embB mutations in codon 306, with MIC >16 microg/mL.

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.

Clinical usefulness of catheter-drawn blood samples and catheter tip cultures for the diagnosis of catheter-related bloodstream infections in neonatology: A systematic review.

OBJECTIVES: Neonatal sepsis is the most frequent health care-associated infection in neonatal units. This study aimed to analyze articles on the clinical usefulness of catheter-drawn blood samples and catheter tip cultures for the diagnosis of intravascular catheter-related bloodstream infection (CRBSI) in neonates. METHODS: A systematic search was performed for studies published from 1987-2017, without language restriction. Observational studies carried out in neonates with CRBSI diagnosed using catheter-drawn blood samples or catheter tip cultures were included. RESULTS: A total of 412 articles were identified in the databases and 10 articles were included. The 7 studies that evaluated central venous catheter tip cultures and cultures of catheter fragments presented sensitivities ranging from 58.5%-100% and specificities ranging from 60%-95.7%. Three studies that evaluated catheter-drawn blood cultures, paired with peripheral blood cultures, reported sensitivity and specificity of 94% and 71% when evaluated for the differential time to positivity. When quantitative evaluation was performed, the sensitivity and specificity were 80% and 99.4%. CONCLUSIONS: Most of the studies analyzed cultures from the central venous catheter tip and catheter fragments for the diagnosis of CRBSI in neonatal populations. The results of this review suggest that the analysis of the catheter-drawn blood samples and catheter tip cultures, paired with peripheral blood cultures, are efficient methods for the diagnosis of CRBSI in neonates.

Recommendations for Management of Endemic Diseases and Travel Medicine in Solid-Organ Transplant Recipients and Donors: Latin America.

The Recommendations for Management of Endemic Diseases and Travel Medicine in Solid-Organ Transplant Recipients and Donors: Latin America clinical practice guideline is intended to guide clinicians caring for solid-organ transplant (SOT) donors, candidates and recipients regarding infectious diseases (ID) issues related to this geographical region, mostly located in the tropics. These recommendations are based on both systematic reviews of relevant literature and expert opinion from both transplant ID and travel medicine specialists. The guidelines provide recommendations for risk evaluation and laboratory investigation, as well as management and prevention of infection of the most relevant endemic diseases of Latin America. This summary includes a brief description of the guideline recommendations but does not include the complete rationale and references for each recommendation, which is available in the online version of the article, published in this journal as a supplement. The supplement contains 10 reviews referring to endemic or travel diseases (eg, tuberculosis, Chagas disease [ChD], leishmaniasis, malaria, strongyloidiasis and schistosomiasis, travelers diarrhea, arboviruses, endemic fungal infections, viral hepatitis, and vaccines) and an illustrative section with maps (http://www.pmourao.com/map/). Contributors included experts from 13 countries (Brazil, Canada, Chile, Denmark, France, Italy, Peru, Spain, Switzerland, Turkey, United Kingdom, United States, and Uruguay) representing four continents (Asia, the Americas and Europe), along with scientific and medical societies.

Does the Simultaneous Use of a Neuroendoscope Influence the Incidence of Ventriculoperitoneal Shunt Infection?

BACKGROUND: The relationship between the use of an endoscope during ventriculoperitoneal shunt (VPS) procedures and infection remains poorly defined. In this study, we sought to analyze whether the simultaneous use of an endoscope could in fact increase the infection rate associated with VPS procedures. METHODS: This study included 438 VPS procedures, 49 in which an endoscope was used (11.2%) and 389 in which an endoscope was not used (88.8%). The infection rates in these 2 main groups were calculated and compared. Subsequently, 4 new groups were created, composed of patients with a shunt inserted for the first time (groups 1A and 1B) and patients with a shunt reviewed or inserted for a second time (groups 2A and 2B). Groups 1A and 2A comprised patients in whom an endoscope was used simultaneously with VPS surgery, and groups 1B and 2B comprised patients in whom an endoscope was not used. These groups were compared to determine the infection rate. RESULTS: The overall infection rate was 18.5%, including 22.4% in the groups in which an endoscope was used and 18% in those in which an endoscope was not used (P = 0.449). Groups 1A and 1B and groups 2A and 2B were matched for possible intervening risk factors. The infection rate was 28.6% in group 1A and 16.2% in group 1B (P = 0.27), and 20% in group 2A and 19.8% in group 2B (P = 0.977). CONCLUSIONS: In the present study, the use of an endoscope during VPS procedures did not increase the risk of surgical infection.

Empirical antimicrobial therapy for late-onset sepsis in a neonatal unit with high prevalence of coagulase-negative Staphylococcus.

OBJECTIVE: The aim of this study was to compare two different empiric treatments for late-onset neonatal sepsis, vancomycin and oxacillin, in a neonatal intensive care unit with a high prevalence of coagulase-negative Staphylococcus. METHODS: A cross-sectional study was conducted in an neonatal intensive care unit from 2011 to 2014. Data from the medical records of at-risk newborns were collected daily. Infections were defined according to the National Health Surveillance Agency criteria. Data analysis was performed using an internal program. RESULTS: There was a significant reduction in the number of Staphylococcus aureus infections (p=0.008), without endocarditis, meningitis, or lower respiratory tract infection, as well as a reduction in the frequency of deaths related to S. aureus infection. There were no significant changes in the incidence of Gram-negative bacterial or fungal infections. An increase in coagulase-negative Staphylococcus infections was observed (p=0.022). However, there was no measured increase in related morbidity and mortality. There was a reduction in the median number of days of treatment with oxacillin from 11.5 to 6 days (p<0.001) and an increase of one day in the median number of days of treatment with vancomycin (p=0.046). CONCLUSIONS: Modification of the empiric treatment regimen for neonatal late-onset sepsis with use of oxacillin showed a significant reduction in S. aureus infections, as well as a reduction in the frequency of infections with major organ system involvement and mortality due to infection with this microorganism. As a result, oxacillin can be considered as an effective treatment for late-onset sepsis, making it possible to avoid broad-spectrum antibiotics.

Serum levels of vancomycin: is there a prediction using doses in mg/kg/day or m(2)/day for neonates?

Coagulase-negative Staphylococcus has been identified as the main nosocomial agent of neonatal late-onset sepsis. However, based on the pharmacokinetics and erratic distribution of vancomycin, recommended empirical dose is not ideal, due to the inappropriate serum levels that have been measured in neonates. The aim of this study was to evaluate serum levels of vancomycin used in newborns and compare the prediction of adequate serum levels based on doses calculated according to mg/kg/day and m(2)/day. This is an observational reprospective cohort at a referral neonatal unit, from 2011 to 2013. Newborns treated with vancomycin for the first episode of late-onset sepsis were included. Total dose in mg/kg/day, dose/m(2)/day, age, weight, body surface and gestational age were identified as independent variables. For predictive analysis of adequate serum levels, multiple linear regressions were performed. The Receiver Operating Characteristic curve for proper serum vancomycin levels was also obtained. A total of 98 patients received 169 serum dosages of the drug, 41 (24.3%) of the doses had serum levels that were defined as appropriate. Doses prescribed in mg/kg/day and dose/m(2)/day predicted serum levels in only 9% and 4% of cases, respectively. Statistical significance was observed with higher doses when the serum levels were considered as appropriate (p<0.001). A dose of 27mg/kg/day had a sensitivity of 82.9% to achieve correct serum levels of vancomycin. Although vancomycin has erratic serum levels and empirical doses cannot properly predict the target levels, highest doses in mg/kg/day were associated with adequate serum levels.