Preventive isolation criteria for the detection of multidrug-resistant bacteria in patients admitted to the Intensive Care Unit: A multicenter study within the Zero Resistance program.

OBJECTIVE: To verify the validity of a checklist of risk factors (RFs) proposed by the Spanish "Zero Resistance" project (ZR) in the detection of multidrug-resistant bacteria (MRB), and to identify other possible RFs for colonization and infection by MRB on admission to the Intensive Care Unit (ICU). DESIGN: A prospective cohort study, conducted in 2016. SETTING: Multicenter study, patients requiring admission to adult ICUs that applied the ZR protocol and accepted the invitation for participating in the study. PATIENTS OR PARTICIPANTS: Consecutive sample of patients admitted to the ICU and who underwent surveillance (nasal, pharyngeal, axillary and rectal) or clinical cultures. INTERVENTIONS: Analysis of the RFs of the ZR project, in addition to other comorbidities, included in the ENVIN registry. A univariate and multivariate analysis was performed, with binary logistic regression methodology (significance considered for p < 0.05). Sensitivity and specificity analyses were performed for each of the selected factors. MAIN VARIABLES OF INTEREST: Carrier of MRB on admission to the ICU, RFs (previous MRB colonization/infection, hospital admission in the previous 3 months, antibiotic use in the past month, institutionalization, dialysis, and other chronic conditions) and comorbidities. RESULTS: A total of 2270 patients from 9 Spanish ICUs were included. We identified MRB in 288 (12.6% of the total patients admitted). In turn, 193 (68.2%) had some RF (OR 4.6, 95%CI: 3.5-6.0). All 6 RFs from the checklist reached statistical significance in the univariate analysis (sensitivity 66%, specificity 79%). Immunosuppression, antibiotic use on admission to the ICU and the male gender were additional RFs for MRB. MRB were isolated in 87 patients without RF (31.8%). CONCLUSIONS: Patients with at least one RF had an increased risk of being carriers of MRB. However, almost 32% of the MRB were isolated in patients without RFs. Other comorbidities such as immunosuppression, antibiotic use on admission to the ICU and the male gender could be considered as additional RFs.

Augmented renal clearance. An unnoticed relevant event.

Augmented renal clearance (ARC) is a phenomenon that can lead to a therapeutic failure of those drugs of renal clearance. The purpose of the study was to ascertain the prevalence of ARC in the critically ill patient, to study the glomerular filtration rate (GFR) throughout the follow-up and analyze the concordance between the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimation formula and measured GFR. Observational, prospective, multicenter study. ARC was defined as a creatinine clearance greater than 130 ml/min/1.73 m2. Eighteen hospitals were recruited. GFR measurements carried out twice weekly during a 2-month follow-up period. A total of 561 patients were included. ARC was found to have a non-negligible prevalence of 30%. More even, up to 10.7% already had ARC at intensive care unit (ICU) admission. No specific pattern of GFR was found during the follow-up. Patients in the ARC group were younger 56.5 (53.5-58.5) versus 66 (63.5-68.5) years than in the non-ARC group, p < 0.001. ICU mortality was lower in the ARC group, 6.9% versus 14.5%, p = 0.003. There was no concordance between the estimation of GFR by the CKD-EPI formula and GFR calculated from the 4-h urine. ARC is found in up to 30% of ICU patients, so renal removal drugs could be under dosed by up to 30%. And ARC is already detected on admission in 10%. It is a dynamic phenomenon without an established pattern that usually occurs in younger patients that can last for several weeks. And the CKD-EPI formula does not work to estimate the real creatinine clearance of these patients.

Usefulness of therapeutic drug monitoring of piperacillin and meropenem in routine clinical practice: a prospective cohort study in critically ill patients.

Background: Beta-lactam anti-infective levels after standard dosing have been shown to be subtherapeutic when renal clearance is augmented. Objective: To determine if piperacillin and meropenem are found to be in their therapeutic range in infected critically ill patients when administered by continuous intravenous infusion (CII) assisted by a therapeutic drug monitoring (TDM) report issued by the pharmacy service. Methods: This prospective non-controlled intervention study evaluated septic patients in an intensive care unit. Patients received a loading dose of meropenem or piperacillin-tazobactam and the antibiotics were afterwards administered by CII. Blood concentrations were determined by high-performance liquid chromatography assays. The adequacy of ß-lactam therapy in the cohort subjected to intervention was assessed by determining whether plasma levels during CII were >4 times the informed minimum inhibitory concentration during the first 96 hours of treatment. Results: A total of 124 patients were subject to TDM during antibiotic treatment but, for the analysis of the fulfilment of pharmacodynamic requirements, data from 31/124 (25%) were excluded. Of the whole cohort of treatment courses, 57/93 (61.3%) reached the target level. Plasma levels were adequate in 41/70 (58.6%) and 16/23 (69.6%) of the patients treated with piperacillin-tazobactam and meropenem, respectively. Globally, recommendations based on TDM results were followed in 35/93 (37.6%) of the treatment courses. Conclusions: The results of the study show that, in critically ill patients with sepsis, there is a significant proportion of treatment courses where target levels are not reached even if the antibiotics are administered by CII and TDM support is provided by the pharmacy service. This TDM support should be offered on a real-time basis to be really useful.