Efficacy of β-lactam/β-lactamase inhibitors to treat extended-spectrum beta-lactamase-producing Enterobacterales bacteremia secondary to urinary tract infection in kidney transplant recipients (INCREMENT-SOT Project)

REIPI/INCREMENT-SOT Group.[Background] Whether active therapy with β-lactam/β-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum β-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).This work was supported by: (1) Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III (ISCIII), Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases [RD16/0016/0001, RD16/0016/0002, REIPI RD16/0016/0008; RD16/0016/00010], co-financed by European Development Regional Fund “A way to achieve Europe”, Operative Program Intelligent Growth 2014-2020; (2) European Society of Clinical Microbiology and Infectious diseases Study Group for Infections in Compromised Hosts (ESGICH, grant to J.M.A.); (3) Sociedad Andaluza de Trasplante de Órgano Sólido (SATOT, grant to L.M.M.); (4) Research project PI16/01631 integrated into the Plan Estatal de I+D+I 2013-2016 and co-financed by the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación and the Fondo Europeo de Desarrollo Regional (FEDER); (5) M.F.R. holds a research contract “Miguel Servet” (CP 18/00073) from ISCIII, Ministerio de Ciencia, Innovación y Universidades. The work was also supported by the following European Society of Clinical Microbiology and Infectious diseases (ESCMID) study groups: Infections in Compromised Hosts (ESGICH), Bloodstream Infections and Sepsis (ESGBIS) and Antimicrobial Resistance Surveillance (ESGARS).Peer reviewe

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.Peer reviewe