Initial empirical antibiotic therapy in kidney transplant recipients with pyelonephritis: A global survey of current practice and opinions across 19 countries on six continents.

BACKGROUND: Despite the burden of pyelonephritis after kidney transplantation, there is no consensus on initial empirical antibiotic management. METHODS: We surveyed clinicians throughout the world on their practice and opinions about the initial empirical therapy of post-transplant pyelonephritis, using clinical vignettes. A panel of experts from 19 countries on six continents designed this survey, and invited 2145 clinicians to participate. RESULTS: A total of 721 clinicians completed the survey (response rate: 34%). In the hypothetical case of a kidney transplant recipient admitted with pyelonephritis but not requiring intensive care, most respondents reported initiating either a 3rd-generation cephalosporin (37%) or piperacillin-tazobactam (21%) monotherapy. Several patient-level factors dictated the selection of broader-spectrum antibiotics, including having a recent urine culture showing growth of a resistant organism (85% for extended-spectrum ß-lactamase-producing organisms, 90% for carbapenemase-producing organisms, and 94% for Pseudomonas aeruginosa). Respondents attributed high importance to the appropriateness of empirical therapy, which 87% judged important to prevent mortality. Significant practice and opinion variations were observed between and within countries. CONCLUSION: High-quality studies are needed to guide the empirical management of post-transplant pyelonephritis. In particular, whether prior urine culture results should systematically be reviewed and considered remains to be determined. Studies are also needed to clarify the relationship between the appropriateness of initial empirical therapy and outcomes of post-transplant pyelonephritis.

Effect on Antimicrobial Resistance of a Policy Restricting Over-the-Counter Antimicrobial Sales in a Large Metropolitan Area, São Paulo, Brazil.

Although restricting over-the-counter (OTC) antimicrobial drug sales is recommended globally, no data track its effect on antimicrobial resistance (AMR) in bacteria. We evaluated the effect of a national policy restricting OTC antimicrobial sales, put in place in November 2010, on AMR in a metropolitan region of São Paulo, Brazil. We reviewed associations between antimicrobial sales from private pharmacies and AMR in 404,558 Escherichia coli and 5,797 Streptococcus pneumoniae isolates using a dynamic regression model based on a Bayesian approach. After policy implementation, a substantial drop in AMR in both bacterial species followed decreased amoxicillin and trimethoprim/sulfamethoxazole sales. Conversely, increased ciprofloxacin sales were associated with increased ciprofloxacin resistance, and extended spectrum ß-lactamases-positive E. coli isolates and azithromycin sales increases after 2013 were associated with increased erythromycin resistance in S. pneumoniae isolates. These findings suggest that restricting OTC antimicrobial sales may influence patterns of AMR, but multifaceted approaches are needed to avoid unintended consequences.

Immune complexes as a tool for strongyloidiasis immunodiagnosis in kidney and liver transplant candidate.

Strongyloidiasis is a chronic and asymptomatic infection in immunocompetent patients. Immunocompromised patients, such as organ transplant candidates, can develop severe forms of this disease, and the best way to prevent progression to these forms is early diagnosis. Serological techniques using specific IgG and immune complexes (IC) detection can help in the diagnosis of these patients. This study aimed to detect specific anti-Strongyloides IC and IgG antibodies in kidney transplant (KT) and liver transplant (LT) candidates. A total of 100 blood samples was collected from transplant candidates (50 blood samples each from KT and LT candidates). Serum was obtained and analysed using enzyme-linked immunosorbent assay for IC and IgG detections. The IC levels showed frequencies of 18% and 2% in the KT and LT groups, respectively, whereas anti-Strongyloides IgG was detected in 34% and 12% of KT and LT candidates, respectively. The correlation between IC and IgG detection is poor in KT candidates, while in LT candidates, there is a significant positive correlation. The detection of IC can be an additional tool for the diagnosis of strongyloidiasis, especially when associated with the detection of specific IgG anti-Strongyloides antibodies.

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.

SARS-CoV-2 vaccination in solid-organ transplant recipients: What the clinician needs to know.

In response to the COVID-19 pandemic, SARS-CoV-2 vaccines have been developed at an unparalleled speed, with 14 SARS-CoV-2 vaccines currently authorized. Solid-organ transplant (SOT) recipients are at risk for developing a higher rate of COVID-19-related complications and therefore they are at priority for immunization against SARS-CoV-2. Preliminary data suggest that although SARS-CoV-2 vaccines are safe in SOT recipients (with similar rate of adverse events than in the general population), the antibody responses are decreased in this population. Risk factors for poor vaccine immunogenicity include older age, shorter time from transplantation, use of mycophenolate and belatacept, and worse allograft function. SOT recipients should continue to be advised to maintain hand hygiene, use of facemasks, and social distancing after SARS-CoV-2 vaccine. Vaccination of household contacts should be also prioritized. Although highly encouraged for research purposes, systematic assessment in clinical practice of humoral and cellular immune responses after SARS-CoV-2 vaccination is controversial, since correlation between immunological findings and clinical protection from severe COVID-19, and cutoffs for protection are currently unknown in SOT recipients. Alternative immunization schemes, including a booster dose, higher doses, and modulation of immunosuppression during vaccination, need to be assessed in the context of well-designed clinical trials.

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).

Fatal Yellow Fever in a Kidney Transplant Patient.

A kidney-transplanted patient, unvaccinated against yellow fever (YF), developed high fever, progressed rapidly to hepatic insufficiency and coma, and died 8 days later. Real-time polymarase chain reaction for YF virus collected on the seventh day of symptoms was positive. Autopsy showed disseminated infection and midzonal hepatitis with apoptotic hepatocytes and minimal inflammatory reaction.

Variable sources of Bk virus in renal allograft recipients.

BK virus is the causative agent of polyomavirus-associated nephropathy, a major cause of kidney transplant failure affecting 1%-10% of recipients. Previous studies that investigated the viral source on the kidney recipient pointed that the donor is implicated in the origin of human polyomavirus BK (BKPyV) infection in recipients, but giving the low genetic variability of BKPyV this subject is still controversial. The aim of this study was to determine if BKPyV replicating in kidney recipients after transplantation is always originated from the donor. Urine and blood samples from 68 pairs of living donors and kidney recipients who underwent renal transplantation from August 2010-September 2011 were screened for BKPyV by real time polymerase chain reaction. Only three recipients presented viremia. When both donors and recipients were BKPyV positive, a larger fragment of VP1 region was obtained and sequenced to determine the level of similarity between them. A phylogenetic tree was built for the 12 pairs of sequences obtained from urine and high level of similarity among all sequences was observed, indicating that homology inferences for donor and recipient viruses must be cautiously interpreted. However, a close inspection on the donor-recipient pairs sequences revealed that 3 of 12 pairs presented considerably different viruses and 4 of 12 presented mixed infection, indicating that the source of BKPyV infection is not exclusively derived from the donor. We report that about 60% of the renal recipients shed BKPyV genetically distinct from the donor, confronting the accepted concept that the donor is the main source of recipients' infection.

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.

Cytomegalovirus prophylaxis in seropositive renal transplant recipients receiving thymoglobulin induction therapy: Outcome and risk factors for late CMV disease.

BACKGROUND: Anti-thymocyte globulin (ATG) therapy is a risk factor for cytomegalovirus (CMV) disease in renal transplant (RTx) recipients and therefore antiviral prophylaxis is commonly used. We evaluated the outcome of our current policy of 90 days of CMV prophylaxis in seropositive recipients given ATG and the risk factors for the occurrence of CMV disease after prophylaxis. METHODS: We studied a retrospective cohort of 423 RTx (2010-2014) CMV-seropositive adults given ATG induction therapy. RESULTS: 54 (13%) patients developed CMV disease at a median of 163 days after transplant, of which 29 (54%) had viral syndrome and 25 (46%) had invasive disease. Median prophylaxis time (94 days) and immunosuppressive drugs were similar between groups (CMV vs no-CMV). Those with CMV disease had more deceased donors and higher donor age, lower lymphocyte count, and lower median eGFR at day 90. Multivariable logistic regression analysis at day 90 and 180 found that eGFR ≤40 ml/min/1.73 m2 (but not acute rejection) was associated with late CMV disease. In a separate validation cohort of 124 patients with 8% late CMV disease, eGFR ≤45 and lymphocyte count ≤800 cells/mm3 at the end of prophylaxis remained predictive of late CMV disease occurrence. CONCLUSIONS: These data indicate that antiviral prophylaxis adequately prevented CMV in seropositive recipients given ATG, but late disease still occurred. Low eGFR and low lymphocyte count at the end of prophylaxis may help identify patients at higher risk of CMV disease.

Molecular diagnosis of Strongyloides stercoralis among transplant candidates.

Strongyloidiasis can occur without any symptoms or as a potentially fatal hyperinfection or disseminated infection, principally in immunosuppressed patients. Our study aimed to evaluate the application of conventional polymerase chain reaction (cPCR) and real-time PCR (qPCR). Polymerase chain reaction (PCR) and real-time PCR (qPCR) targeting the 18S rRNA gene for detection of Strongyloides stercoralis infection among transplant candidates were applied in stool samples obtained from 150 transplant candidates, preliminarily analyzed by parasitological methods. S. stercoralis larvae were visualized in 15/150 (10.0%) transplant candidates by parasitological methods. DNA from S. stercoralis was amplified in 26/150 (17.3%) and 49/150 (32.7%) stool samples of transplant candidates, using cPCR and qPCR, respectively. The results suggest that molecular methods, especially qPCR, should be used as an additional tool for diagnostic of S. stercoralis infection among transplant candidates.

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.

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.

Clinical features and outcomes of tuberculosis in kidney transplant recipients in Brazil: a report of the last decade.

BACKGROUND: Among kidney transplant recipients (KTRs), tuberculosis is one of the most common opportunistic infections and is associated with high morbidity and mortality. The aim of this study was to describe the incidence, clinical features, and prognosis of tuberculosis in KTRs. METHODS: Retrospective single-center observational study involving all cases of tuberculosis in KTRs between 2000 and 2010. RESULTS: Of the 1549 KTRs evaluated, 43 (2.8%) developed tuberculosis, translating to an annual incidence of 803 cases/100 000 patients, considerably higher than that reported for the general population of Brazil. The median time to tuberculosis (TB) onset after transplantation was 196 d (range, 19-3626 d). Of the KTRs with tuberculosis, 67% became infected within the first year post-transplant, 74% had pulmonary tuberculosis, and 7% had a previous history of active tuberculosis. No tuberculosis prophylaxis was employed before or after transplantation. The most common symptoms were fever (in 79%), cough (in 35%), and dyspnea (in 16%). The median time from the onset of symptoms to the start of treatment was 28 d. The median duration of antituberculosis therapy was 196 d. In 15 patients (35%), the immunosuppressive therapy was reduced, and the incidence of acute rejection was higher in patients with tuberculosis than in those without (44% vs. 28%). Mortality during tuberculosis treatment was 12% (5 cases), and all five deaths were attributed to tuberculosis. Ten-yr death-censored graft survival and patient survival were similar between patients with tuberculosis and those without. CONCLUSION: Among KTRs, symptoms of tuberculosis are often attenuated, which leads to delayed diagnosis, and tuberculosis-related mortality remains high.

Recipient of kidney from donor with asymptomatic infection by Paracoccidioides brasiliensis.

The increase in solid organ transplantations may soon create a rise in the occurrence of endemic fungal diseases, such as paracoccidioidomycosis, due to the lack of rigorous screening of donors from endemic areas. Here we present the first case of an immunocompetent and asymptomatic kidney donor who had Paracoccidioides brasiliensis infected-adrenal tissue but no glandular dysfunction.

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.

Hydroxychloroquine plus azithromycin early treatment of mild COVID-19 in an outpatient setting: a randomized, double-blinded, placebo-controlled clinical trial evaluating viral clearance.

BACKGROUND: Hydroxychloroquine has shown potential to block viral replication of SARS-CoV-2 in some in vitro studies. This randomised, double-blinded, placebo controlled clinical trial evaluated the efficacy of hydroxychloroquine plus azithromycin (HCQ/AZT) in reducing viral loads in patients with early and mild SARS-CoV-2 infection. METHODS: A single-centre randomised placebo-controlled clinical trial was conducted with outpatients with early and mild SARS-CoV-2 infection. Inclusion criteria were: patients aged 18-65 years with symptoms suggestive of COVID-19 for < 5 days, no significant comorbidities, and positive nasopharyngeal/oropharyngeal swab screening tests (POCT-PCR). Randomised patients received either hydroxychloroquine for 7 days plus azithromycin for 5 days or placebo. The primary endpoint was viral clearance within a 9-day period. Secondary endpoints included viral load reduction, clinical evolution, hospitalization rates, chest computed tomography evolution, and adverse effects. RESULTS: From 107 potential trial participants, 84 were enrolled following predetermined criteria. Statistical analyses were performed on an intention-to-treat (N = 84) and per-protocol (PP) basis (N = 70). On the PP analysis, the treatment (N = 36) and placebo (N = 34) groups displayed similar demographic characteristics. At 95% CI, no statistically significant between-group differences were found in viral clearance rates within 9 days following enrolment (P = 0.26). CONCLUSIONS: This randomised, double-blinded, placebo-controlled clinical trial evaluating outpatients with early and mild COVID-19 showed that viral clearance rates within a 9-day period from enrolment did not change with HCQ/AZT treatment compared with placebo, although no major cardiovascular events were observed in participants without comorbidities. Secondary outcomes were also not significantly improved with HCQ/AZT treatment compared with placebo. These findings do not support use of HCQ/AZT in this setting.

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.