Elderly people confined to chronic care facilities face an increased risk of acquiring infections by multidrug-resistant organisms (MDROs). This review presents the current knowledge of the prevalence and risk factors for colonization by MDROs in long-term care facilities (LTCF), thereby providing a useful reference to establish objectives for implementing successful antimicrobial stewardship programs (ASPs). We searched in PubMed and Scopus for studies examining the prevalence of MDROs and/or risk factors for the acquisition of MDROs in LTCF. One hundred and thirty-four studies published from 1987 to 2020 were included. The prevalence of MDROs in LTCF varies between the different continents, where Asia reported the highest prevalence of extended-spectrum ß-lactamase (ESBL) Enterobacterales (71.6%), carbapenem resistant (CR) Enterobacterales (6.9%) and methicillin-resistant Staphylococcus aureus (MRSA) (25.6%) and North America the highest prevalence to MDR Pseudomonas aeruginosa (5.4%), MDR Acinetobacter baumannii (15.0%), vancomycin-resistant Enterococcus spp. (VRE) (4.0%), and Clostridioides difficile (26.1%). Furthermore, MDRO prevalence has experienced changes over time, with increases in MDR P. aeruginosa and extended spectrum ß-lactamase producing Enterobacterales observed starting in 2015 and decreases of CR Enterobacterales, MDR A. baumannii, VRE, MRSA and C. difficile. Several risk factors have been found, such as male sex, chronic wounds, the use of medical devices, and previous antibiotic use. The last of these aspects represents one of the most important modifiable factors for reducing colonization with MDROs through implementing ASPs in LTCF.

Experience with high-dose ganciclovir for the management of resistant cytomegalovirus (CMV) replication in transplant patients is limited despite its adoption as an effective therapy by some consensus documents. We studied six cases of CMV replication in solid organ transplant patients whose genotypic testing showed mutations associated with different levels of resistance to ganciclovir. All were treated with high-dose intravenous ganciclovir (7.5-10 mg/kg/12 hr) or oral valganciclovir (1350-1800 mg/12 hr) corrected according to creatinine clearance. The virologic response was considered positive if the CMV plasma viral load was undetectable. Safety was evaluated by clinical assessment, including the review of vital signs and laboratory tests. All patients had asymptomatic replication, except one who had digestive disease. Four patients received universal prophylaxis with valganciclovir. Two patients received preemptive therapy with valganciclovir for individual episodes of replication. Two of the six patients received steroid boluses before the episode of replication by resistant CMV. All patients responded to treatment, including those with mutations associated with a high level of ganciclovir resistance. Four patients had neutropenia (<1.5 × 10/L), but only one received treatment. High-dose ganciclovir/valganciclovir can be an option in the treatment of resistant CMV replication and could be considered an alternative treatment in nonsevere patients for whom the use of foscarnet should be avoided. The toxicity of this regimen does not appear to limit its use.

Background. It has been suggested that preemptive therapy against cytomegalovirus (CMV) infection after transplantation promotes a CMV-specific immune response. Our objective was to determine whether solid-organ transplant patients at high risk for CMV infection treated preemptively acquire a CMV-specific immune response and whether the acquired immune response confers immunity by controlling subsequent CMV replication episodes and by protecting from late-onset CMV disease. Methods. Patients were followed up for 18 months after transplantation. CMV viral load was determined using real-time polymerase chain reaction assays, and the T-cell immune response was characterized by intracellular cytokine staining. Results. The 21 patients studied developed CMV replication episodes at a median of 4 weeks (range 2–8 weeks) after transplantation and a CMV-specific T-cell response within a median of 12 weeks (range 10–20 weeks). The decline in the incidence of CMV replication episodes is inversely correlated with the acquisition of the CMV-specific T-cell response (linear regression r²=0.781, Pearson correlation=−0.883; P=0.001). There were no CMV replication episodes after week 47 of transplantation. In addition, after acquisition of the immune response, 42 replication episodes were cleared without treatment. The time taken for immune clearance of replication correlated with the peak viral load (P=0.01). No incidence of CMV early or late-onset disease was detected. Conclusions. Our results demonstrate that preemptive therapy is a safe and an effective strategy for the control of CMV infection in solid-organ transplant recipients at high risk for CMV infection. This is the first study that reports a therapeutic effect of the acquisition of CMV-specific immune response during preemptive treatment.

Despite advances in prevention, cytomegalovirus (CMV) recurrence is an important challenge in high‐risk organ recipients. The present study prospectively evaluates the impact of CMV‐specific T‐cell immune response and secondary prophylaxis on the risk of recurrence in a cohort of CMV high‐risk organ recipients and whether it is possible to determine a safe standardized viral load value below which CMV disease is unlikely. Thirty‐nine recipients were included. Thirty‐six had primary infections, and 88.9% recurred. Rate and duration of recurrent CMV infection was similar in patients with and without secondary prophylaxis: 57.9% vs. 53.6%, P = 0.770 and 16 vs. 15 days, P = 0.786, respectively. The only factor independently associated with no episodes of CMV recurrence was the acquisition of CMV‐specific T‐cell immune response (OR: 0.151, 95% CI: 0.028–0.815; P = 0.028). Cytomegalovirus diseases (N = 5) occurred in patients with CMV viral load above 1500 IU/ml who did not follow the planned monitorization schedule. Our observations suggest that episodes of recurrent CMV infection are common after preemptive therapy despite secondary prophylaxis and that CMV‐specific T‐cell immune response is associated with a decreased risk of recurrent infections. Preemptive therapy may be safe in patients at high risk for CMV infection with strict close monitoring of the CMV viral load.