A joint program of antimicrobial stewardship and hospital-acquired infection control to reduce healthcare-associated infections after kidney transplantation: The Hipomenes study.

Infection is a common complication in kidney transplant recipients (KTRs). The usefulness of antimicrobial stewardship programs (ASP) and hospital-acquired infection control (HAIC) initiatives in the general inpatient population is well established. We performed a quasi-experimental study to evaluate a joint ASP/HAIC initiative focused on KTRs. A dedicated ASP team optimized antimicrobial prescriptions in consecutive KTRs during the intervention period (June 2015-March 2016). A multifaceted, evidence-based HAIC program was concurrently implemented. Results were compared with the preceding period (June 2014-March 2015). We included 96 and 100 KTRs in the intervention and preintervention periods, respectively. There was a reduction in the consumption of meropenem (rate ratio [RR]: 0.63; 95% confidence interval [CI]: 0.53-0.75; P <.0001), ceftazidime (RR: 0.31; 95% CI: 0.21-0.45; P <.0001), vancomycin (RR: 0.65; 95% CI: 0.53-0.8; P <.0001), and ciprofloxacin (RR: 0.66; 95% CI: 0.55-0.81; P <.0001) and an increase of fosfomycin (RR: 1.80; 95% CI: 1.17-2.76; P =.008) during the intervention period. The incidence of cystitis (RR: 0.30; 95% CI: 0.28-0.33; P <.001) and upper urinary tract infection (RR: 0.56; 95% CI: 0.33-0.95; P =.04) decreased. A specific ASP/HAIC initiative was effective in optimizing antimicrobial use and reducing the incidence of common bacterial infections among KTRs.

Risk factors for the development of invasive aspergillosis after kidney transplantation: Systematic review and meta-analysis.

To investigate risk factors for invasive aspergillosis (IA) after kidney transplantation (KT), we conducted a systematic search in PubMed and EMBASE to identify studies published until June 2020. We included case-control or cohort design studies comprising KT recipients with a diagnosis of IA, defined according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group criteria, and assessed risk factors for the development of IA. Random-effect models meta-analysis served to pool data. We identified eleven case-control studies (319 IA cases and 835 controls). There was an increased risk of IA among recipients with underlying chronic lung diseases (odds ratio [OR] = 7.26; 95% confidence interval [CI] = 1.05-50.06) and among those with diabetic nephropathy (OR = 1.65; 95% CI = 1.10-2.48). Requiring posttransplant hemodialysis (OR = 3.69; 95% CI = 2.13-6.37) or surgical reintervention (OR = 6.28; 95% CI = 1.67-23.66) were also associated with an increased risk. Moreover, a positive link was identified between IA and posttransplant bacterial infection (OR = 7.51; 95% CI = 4.37-12.91), respiratory tract viral infection (OR = 7.75; 95% CI = 1.60-37.57), cytomegalovirus infection or disease (OR = 2.67; 95% CI = 1.12-6.32), and acute graft rejection (OR = 3.01; 95% CI = 1.78-5.09). In contrast, receiving a kidney from a living donor was associated with a reduced risk (OR = 0.65; 95% CI = 0.46-0.93). KT recipients that accumulate several of these conditions should be closely monitored and a low threshold of suspicion for IA should be maintained. Future studies should explore the benefit of mold-active prophylaxis to this subgroup of KT recipients at highest risk.

Cryptococcal infection in HIV-infected patients with CD4+ T-cell counts under 100/µL diagnosed in a high-income country: a multicentre cohort study.

OBJECTIVES: The World Health Organization recommends routinely screening HIV-infected patients with CD4+ T-cell counts <100/µL for cryptococcal infection to prevent cryptococcal meningitis (CM), based on studies in Sub-Saharan Africa where the prevalence of positive cryptococcal antigen (CrAg+) is ≥ 3% in this subgroup. Data about such prevalence in Spain are unavailable and rare in other European countries. Thus, the Spanish AIDS Study Group guidelines do not recommend routinely screening. We aim to determine the prevalence and outcomes of cryptococcal infection in this subgroup of patients in Spain. METHODS: We determined CrAg using a lateral flow assay in banked plasma from participants in the cohort of the Spanish AIDS Research Network. Eligible patients had CD4+ T-cell counts ≤100/µL at the time of plasma collection and a follow-up >4 weeks, unless they died. RESULTS: We included 576 patients from June 2004 to December 2017. Of these, 43 were CrAg+ for an overall prevalence of 7.5%. There were no differences depending on birthplace. The CrAg+ was independently associated with a higher mortality at eight weeks (hazard ratio (HR) 5.36, 95% confidence interval (CI) 1.46-19.56) and 6 months (HR 3.12, 95% CI 1.19-8.21). CM was reported in 10 of the 43 CrAg+ patients. There were no cases among negatives. Five patients had CM when the plasma was collected and five developed it during the follow-up. The number of subjects needed to screen to anticipate the diagnosis of one CM case was 114. CONCLUSIONS: The CrAg+ prevalence among HIV-infected patients with CD4+ T-cell counts ≤100/µL diagnosed in Spain, both immigrants and native-born Spanish, is >7%. Consequently, the Spanish AIDS Study Group guidelines have to be updated and recommend routine screening for cryptococcal infection in these patients. Future studies should explore whether this recommendation could be firmly applied to other European populations.

Hepatic sinusoidal obstruction syndrome secondary to intravesical instillation of mitomycin-C.

Hepatic sinusoidal obstruction syndrome (SOS) is a life-threatening complication with high mortality rate. Even if it is more commonly described after hematopoietic stem-cell transplant, hepatic-SOS may occur following the use of certain chemotherapeutic agents. Mitomycin-C has been previously identified as a causal agent when administered intravenously at high doses. We report herein the first case of hepatic-SOS due to intravesical instillation of mitomycin-C, after a traumatic urinary catheterization with significant hematuria. Although this procedure is usually considered safe, without the systemic side effects related to intravenous administration of the drug, clinicians must be aware of its potential risks to facilitate an early diagnosis, avoid a delay in the withdrawal of the causative drug and set up an appropriate therapy as soon as possible.

Ocular involvement in granulomatosis with polyangiitis: A single-center cohort study on 63 patients.

OBJECTIVE: To analyse the ocular manifestations of patients with GPA, their treatment and outcome. METHODS: Retrospective cohort study performed at the National Referral Center for Vasculitis, Cochin Hospital, Paris (France), from January 2005 to December 2015. Among 308 patients with a new diagnosis of GPA in accordance with the American College of Rheumatology classification criteria and/or revised Chapel Hill nomenclature definitions, we identified those with ocular involvement and a subsequent follow up in our center. RESULTS: The prevalence of ocular involvement in our GPA series was 38.6%; 63 patients were analysed with a median follow-up of 50.5 months (IQR: 17.8-82.8). Scleritis (18 patients, 28.6%) and episcleritis (18 patients, 28.6%) were the most common ophthalmologic manifestations, followed by orbital disease (13 patients, 20.6%). Bilateral involvement and visual acuity loss was seen in 29.1% and 16.7% of patients, respectively. Ocular involvement was the first GPA manifestation in 9 patients (14.3%), concomitant with systemic manifestation in 36 (57.1%), and occurred only during follow-up in 18 (28.6%). The indication for GPA treatment was suggested by ocular involvement in 12 patients (19.0%), by systemic features in 40 (63.5%) and by both ocular and systemic involvement in 11 (17.5%). Remission of ocular involvement was achieved in 51 patients (80.9%). In the remaining 12 (19.1%), symptoms persisted or even worsened, finally leading to rituximab (RTX) therapy in 8 of them (66.7%). Altogether, when used as first line or for refractory disease, ocular remission was achieved in 11 of the 12 cases (91.7%) treated with RTX versus 34 of the 47 cases (72.3%) treated with CYC (P = .260). Eye disease relapsed in 14 patients (22.2%). RTX allowed achievement of remission in 8 of them (57.1%). In the remaining six, other immunosuppressive drugs were used. CONCLUSIONS: Scleritis and episcleritis are the most common ocular manifestations in GPA, most of the time associated with other systemic manifestations. In >40% of cases, ocular manifestations were refractory to initial treatment or recurrent and led to RTX prescription, which appeared to be useful in these situations.

Impact of functional status on 6-month mortality in elderly patients with acute venous thromboembolism: results from a prospective cohort.

Functional status linked to a poor outcome in a broad spectrum of medical disorders. Barthel Activities of Daily Life Index (BADLI) is one of the most extended tools to quantify functional dependence. Whether BADLI can help to predict outcomes in elderly patients with acute venous thromboembolism (VTE) is unknown. The current study aimed to ascertain the influence of BADLI on 6-month all-cause mortality in aged patients with VTE. This is a prospective observational study. We included consecutive patients older than 75-year-old with an acute VTE between April 2015 and April 2017. We analyzed several variables as mortality predictors, including BADLI-measured functional status. Afterward, we performed a multivariate analysis, using logistic regression, to identify all-cause mortality independent predictive factors. Two hundred and two subjects were included. Thirty-five (17%) patients died in the first 6 months. The leading cause of death was cancer (59%). After multivariable logistic regression, we identified BADLI and Charlson index as independent predictors for 6-months mortality [BADLI (every decrease of 10 points) OR 1.21 95% CI (1.03-1.42) and Charlson index OR 1.71 95% CI (1.21-2.43)]. Body mass index (BMI) values were inversely related to mortality [OR 0.85 95% CI (0.75-0.95)]. In conclusion, BADLI, BMI, and Charlson index scores are independent predictive factors for 6-month all-cause mortality in old patients with VTE.

Monitoring of intracellular adenosine triphosphate in CD4(+) T cells to predict the occurrence of cytomegalovirus disease in kidney transplant recipients.

The measurement of intracellular concentrations of adenosine triphosphate (iATP) in phytohemagglutinin-stimulated CD4(+) T cells constitutes a surrogate marker for post-transplant cell-mediated immunity (CMI). This assay has shown suboptimal accuracy for predicting infection after kidney transplantation (KT). We hypothesize that its predictive capacity depends on the specific contribution of the CMI to host-pathogen interactions. We assessed iATP levels in 100 KT recipients at baseline and months 1, 3, and 6 (363 measurements). No association was found between iATP at month 1 and the risk for overall or bacterial infection, although such association was evident for cytomegalovirus (CMV) disease (multivariate-adjusted hazard ratio [per 50-unit increment]: 0.83; P-value = 0.048). There were no significant differences in mean iATP between stable patients (319.4 ng/ml) and those developing overall (304.1 ng/ml) or bacterial infection (346.9 ng/ml) over the 45 days following monitoring. However, iATP was significantly lower in patients who developed CMV disease (223.5 ng/ml; P-values <0.002). The optimal cutoff (265 ng/ml) for predicting CMV disease in patients not receiving antiviral prophylaxis yielded sensitivity, specificity, positive, and negative predictive values of 85.7%, 68.3%, 15.2%, and 98.6%, respectively. In conclusion, a non-pathogen-specific monitoring of CMI by means of iATP informs the risk of CMV disease in KT recipients.

Bacillus Calmette-Guérin (BCG) infection following intravesical BCG administration as adjunctive therapy for bladder cancer: incidence, risk factors, and outcome in a single-institution series and review of the literature.

Bacillus Calmette-Guérin (BCG) is the most effective intravesical immunotherapy for superficial bladder cancer. Although generally well tolerated, BCG-related infectious complications may occur following instillation. Much of the current knowledge about this complication comes from single case reports, with heterogeneous diagnostic and therapeutic approaches and no investigation on risk factors for its occurrence. We retrospectively analyzed 256 patients treated with intravesical BCG in our institution during a 6-year period, with a minimum follow-up of 6 months after the last instillation. We also conducted a comprehensive review and pooled analysis of additional cases reported in the literature since 1975. Eleven patients (4.3%) developed systemic BCG infection in our institution, with miliary tuberculosis as the most common form (6 cases). A 3-drug antituberculosis regimen was initiated in all but 1 patient, with a favorable outcome in 9/10 cases. There were no significant differences in the mean number of transurethral resections prior to the first instillation, the time interval between both procedures, the overall mean number of instillations, or the presence of underlying immunosuppression between patients with or without BCG infection. We included 282 patients in the pooled analysis (271 from the literature and 11 from our institution). Disseminated (34.4%), genitourinary (23.4%), and osteomuscular (19.9%) infections were the most common presentations of disease. Specimens for microbiologic diagnosis were obtained in 87.2% of cases, and the diagnostic performances for acid-fast staining, conventional culture, and polymerase chain reaction (PCR)-based assays were 25.3%, 40.9%, and 41.8%, respectively. Most patients (82.5%) received antituberculosis therapy for a median of 6.0 (interquartile range: 4.0-9.0) months. Patients with disseminated infection more commonly received antituberculosis therapy and adjuvant corticosteroids, whereas those with reactive arthritis were frequently treated only with nonsteroidal antiinflammatory drugs (p < 0.001 for all comparisons). Attributable mortality was higher for patients aged ≥65 years (7.4% vs 2.1%; p = 0.091) and those with disseminated infection (9.9% vs 3.0%; p = 0.040) and vascular involvement (16.7% vs 4.6%; p = 0.064). The scheduled BCG regimen was resumed in only 2 of 36 patients with available data (5.6%), with an uneventful outcome. In the absence of an apparent predictor of the development of disseminated BCG infection after intravesical therapy, and considering the protean variety of clinical manifestations, it is essential to keep a high index of suspicion to initiate adequate therapy promptly and to evaluate carefully the risk-benefit balance of resuming intravesical BCG immunotherapy.