Success and safety of high infliximab trough levels in inflammatory bowel disease.

OBJECTIVE: A prospective trial suggests target infliximab trough levels of 3-7 µg/mL, yet data on additional therapeutic benefits and safety of higher trough levels are scarce. AIM: To explore whether high infliximab trough levels (≥7 µg/mL) are more effective and still safe. MATERIAL AND METHODS: In this cohort study of 183 patients (109 Crohn's disease and 74 ulcerative colitis) on infliximab maintenance treatment at a tertiary referral center we correlated fecal calprotectin and C-reactive protein to trough levels (426 samples) at different time points during treatment. Rates of infections were compared in quadrimesters (four-month periods) with high trough levels to quadrimesters with trough levels <7 µg/mL during 420 patient-years. RESULTS: Fecal calprotectin and C-reactive protein (median [interquartile range]) were lower in patients with high trough levels (fecal calprotectin 66 mg/kg [30-257]; C-reactive protein 3 mg/L [3-3]) compared to trough levels below 7 µg/mL (fecal calprotectin 155 mg/kg [72-474]; C-reactive protein 3 mg/L [3-14.5]) (p < .001). High trough levels were superior also after excluding samples with trough levels <3 µg/mL from analysis. No differences in rates of infections were observed in quadrimesters with high trough levels (16/129 [12.4%]) compared to quadrimesters with trough levels <7 µg/mL (32/344 [9.3%]) (p = .32). Maintaining high trough levels resulted in 32% (interquartile range: 2-54%) increase of infliximab consumption. CONCLUSION: High infliximab trough levels provide better control of inflammation in inflammatory bowel disease without increasing the risk of infection.

Should we consider faecal colonisation with extended-spectrum ß-lactamase-producing Enterobacteriaceae in empirical therapy of community-onset sepsis?

In patients colonised with extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E), the preference for carbapenems (CRBs) over non-CRB antibiotics for empirical therapy of sepsis is questionable from an ecologic perspective. Moreover, how well colonisation predicts an ESBL-E aetiology of infection has been poorly investigated. The purpose of this retrospective observational study was to determine the positive predictive value (PPV) of ESBL-E faecal colonisation for ESBL-E sepsis aetiology and the impact of empirical therapy on treatment outcome. The study included 653 ESBL-E carriers with community-onset sepsis hospitalised at a single medical centre during a 5-year period. The PPV of ESBL-E colonisation for ESBL-E sepsis aetiology was significantly higher (62.6%) when sepsis originated from a urinary tract infection (UTI) than from a respiratory tract infection (24.5%), other known origins (27.1%) or an unidentified origin (21.4%). Among the 653 patients, 177 (27.1%) received CRBs empirically and 476 received non-CRBs, predominantly ß-lactam/ß-lactamase inhibitor combinations. Although univariate analysis suggested a higher 30-day mortality in the non-CRB versus CRB group (26.7% vs. 19.2%; OR = 1.53; P = 0.049), the estimated association was much smaller and was not significant (OR = 1.11, 95% CI 0.66-1.87; P = 0.68) in the multiple regression analysis adjusted for age, sex, Charlson comorbidity index, and severity, origin or aetiology of sepsis. The subgroup of 240 patients with unidentified sepsis aetiology also did not benefit from empirical CRB treatment. In non-critically ill ESBL-E carriers with community-onset sepsis, CRB-sparing empirical therapy seems appropriate, particularly if sepsis originates from a site other than a UTI.

Narrowing of the Diagnostic Gap of Acute Gastroenteritis in Children 0-6 Years of Age Using a Combination of Classical and Molecular Techniques, Delivers Challenges in Syndromic Approach Diagnostics.

BACKGROUND: Twenty-five percent to 50% of acute gastroenteritis (AGE) cases remain etiologically undiagnosed. Our main aim was to determine the most appropriate list of enteric pathogens to be included in the daily diagnostics scheme of AGE, ensuring the lowest possible diagnostic gap. METHODS: Two hundred ninety seven children ≤6 years of age, admitted to hospital in Slovenia, October 2011 to October 2012, with AGE, and 88 ≤6 years old healthy children were included in the study. A broad spectrum of enteric pathogens was targeted with molecular methods, including 8 viruses, 6 bacteria and 2 parasites. RESULTS: At least one enteric pathogen was detected in 91.2% of cases with AGE and 27.3% of controls. Viruses were the most prevalent (82.5% and 15.9%), followed by bacteria (27.3% and 10.2%) and parasites (3.0% and 1.1%) in cases and controls, respectively. A high proportion (41.8%) of mixed infections was observed in the cases. For cases with undetermined etiology (8.8%), stool samples were analyzed with next generation sequencing, and a potential viral pathogen was detected in 17 additional samples (5.8%). CONCLUSIONS: Our study suggests that tests for rotaviruses, noroviruses genogroup II, adenoviruses 40/41, astroviruses, Campylobacter spp. and Salmonella sp. should be included in the initial diagnostic algorithm, which revealed the etiology in 83.5% of children tested. The use of molecular methods in diagnostics of gastroenteritis is preferable because of their high sensitivity, specificity, fast performance and the possibility of establishing the concentration of the target. The latter may be valuable for assessing the clinical significance of the detected enteric, particularly viral pathogens.