Prevalence and molecular characterisation of carbapenemase-producing Enterobacterales in an outbreak-free setting in a single hospital in Uruguay.

OBJECTIVES: This study aimed to characterise all carbapenemase-producing enterobacteria (CPE) isolates obtained from an outbreak-free setting in Uruguay. METHODS: We studied 12 CPE isolated from Hospital de Clínicas between 2012-2016. Bacterial identification and antibiotic susceptibility testing were performed using VITEK®2 and Sensititre or agar dilution, respectively. Antimicrobial resistance genes and mobile genetic elements were identified by PCR and sequencing. Multilocus sequence typing was performed for Klebsiella pneumoniae. Plasmid conjugation was assessed, plasmid size was estimated by S1-PFGE and plasmid incompatibility groups were sought by PCR. RESULTS: Among 8364 enterobacteria, 12 CPE were isolated from urine, blood culture, wound, peritoneal fluid and punch samples. NDM-1 was the most prevalent carbapenemase, followed by VIM-2 and KPC-2. All isolates were resistant to gentamicin, cefotaxime, ceftazidime, trimethoprim/sulfamethoxazole, ciprofloxacin and imipenem and were susceptible to fosfomycin. We characterised six class 1 integrons: dfrA12-orfF-aadA2; aacA4-blaOXA-2-orfD; aadB-aadA2; dfrA1; aadB-blaOXA-10-aadA1; and blaVIM-2-dfrA7. An association between various aminoglycoside, ß-lactam and fluoroquinolone resistance genes were observed, some of them located in transferable plasmids belonging to incompatibility groups IncC, IncHI1 and IncM1. We described a new composite transposon (assigned Tn6935) including blaNDM-1 flanked by two directly-oriented copies of a Tn3-like element ISKox2-like family transposase. The sequence types of K. pneumoniae isolates were ST11, ST14 and ST661. CONCLUSIONS: The presence of CPE is sporadic and could be due to measures taken by the Public Health Committee. Nevertheless, the coexistence of several resistance mechanisms and their presence in conjugative plasmids and high-risk clones is worrisome.

Ustekinumab treatment for moderate to severe psoriasis. Eight-year real-world follow-up of 61 cases in a tertiary level hospital.

Background: Efficacy and safety profiles of ustekinumab have been proved in numerous clinical trials. However, relevant variations with daily practice have been shown and few studies value the long-term response maintenance.Objective: To evaluate the efficacy of long-term ustekinumab therapy in patients with moderate-to-severe plaque-type psoriasis in a real-world setting.Methods: Observational retrospective follow-up study including, patients receiving ustekinumab at least 3 months in our department. Efficacy was expressed as percentage of patients achieving Psoriasis area and severity index (PASI) 50, PASI75, and PASI90 and maintaining PASI ≤5, ≤3, and 0 every 3 months during the first year of treatment, and every 12 months to the end of follow-up or to withdrawal from the study.Results: Sixty-one patients. Fifty patients had previously been treated with other biologic therapies. The percentage of patients maintaining PASI90 was 72.1, 78.3, 70.0, 83.3, 96.2, 91.7, and 100.0%, and PASI value maintained 0 in 68.9, 73.9, 67.50, 80.6, 96.2, 91.7, and 100.0% at 3, 12, 24, 36, 60, 84, and 96 months. Ustekinumab was discontinued in 26.2% of patients. No patients were withdrawn because of adverse events.Conclusions: This real world-setting study shows maintenance of long-term efficacy and safety of ustekinumab treatment in moderate-severe plaque psoriasis in daily practice through 8 years.

Infliximab drug and antibody levels in patients with dermatological conditions.

BACKGROUND: In recent years, studies monitoring infliximab in rheumatoid arthritis and inflammatory bowel disease have confirmed the relationship between the clinical response and the infliximab and anti-infliximab antibodies serum levels. However, there is only limited evidence in the field of dermatology. OBJECTIVE: The aim of this study was to establish the correlation between plasma infliximab levels, the presence of anti-infliximab antibodies and the clinical response in dermatological conditions. SETTING: Retrospective observational study in a tertiary hospital (University Hospital of La Coruña, Spain). METHOD: Patients with dermatological conditions being treated with infliximab (5 mg/kg/8 weeks after the induction dose) were included in the study. The concentrations of infliximab and anti-infliximab antibodies were quantified by two sandwich-type ELISA immunoassays. The patients were classified into three groups based on the efficacy: good, partial or non-efficacy at the time of each blood assessment. The development of adverse reactions was also evaluated. MAIN OUTCOME MEASURES: Plasma levels of infliximab and anti-infliximab antibodies, clinical response and infusion reactions. RESULTS: 17 patients (45 assessments) were included. The good/partial efficacy rate was significantly higher in the case of >0.05 than <0.05 µg/mL infliximab concentration (93.3 vs. 40.0 %, p < 0.001). Anti-infliximab antibodies were only detected in five samples. Their presence was associated with a higher frequency of infusion reactions and a lower efficacy rate in comparison with the group without antiinfliximab antibodies (100.0 vs. 0.0 %, p < 0.001 and 0.0 vs. 85.0 %, p < 0.001 respectively). CONCLUSIONS: The results obtained show that the presence of infliximab concentrations higher than 0.05 µg/mL are correlated with a good clinical response and the absence of toxicity. The incidence of anti-infliximab antibodies is low, although a correlation was observed between the presence of antibodies, absence of infliximab concentration, loss of clinical response and the development of infusion reactions.

Pharmacokinetic monitoring of antiepileptic drugs.

Monitoring plasma levels of antiepileptic drugs for the treatment and prophylaxis of epilepsy is one of the strategies enabling clinical results to improve by reducing adverse affects and increasing effectiveness. The objective of this article is to review the basic aspects in the monitoring of antiepileptic drugs using a consensus document prepared and endorsed by the pharmacokinetics and pharmacogenetics working group (PK.gen) of the Sociedad Española de Farmacia Hospitalaria (Spanish Society of Hospital Pharmacists).

Population pharmacokinetics of digoxin in pediatric patients.

Digoxin pharmacokinetics were studied in a pediatric population with an age range of 6 days to 1 year using the population pharmacokinetic approach. Digoxin data were analyzed by mixed-effects modeling according to a one-compartment steady-state pharmacokinetic model using NONMEM software. The final model selected for the population prediction of digoxin clearance in pediatric patients was as follows: [equation: see text] Individual empirical Bayesian estimates were generated on the basis of the population estimates and were used to correlate the optimum dose of digoxin and patient age according to the following equation: [equation: see text] This equation and its derived nomogram may be used for the initial dosing of digoxin in children aged between 0 and 1 year. The use of this nomogram in routine monitoring requires further pharmacokinetic and clinical validation.