Dynamic prediction of mortality in COVID-19 patients in the intensive care unit: A retrospective multi-center cohort study.

Background: The COVID-19 pandemic continues to overwhelm intensive care units (ICUs) worldwide, and improved prediction of mortality among COVID-19 patients could assist decision making in the ICU setting. In this work, we report on the development and validation of a dynamic mortality model specifically for critically ill COVID-19 patients and discuss its potential utility in the ICU. Methods: We collected electronic medical record (EMR) data from 3222 ICU admissions with a COVID-19 infection from 25 different ICUs in the Netherlands. We extracted daily observations of each patient and fitted both a linear (logistic regression) and non-linear (random forest) model to predict mortality within 24 h from the moment of prediction. Isotonic regression was used to re-calibrate the predictions of the fitted models. We evaluated the models in a leave-one-ICU-out (LOIO) cross-validation procedure. Results: The logistic regression and random forest model yielded an area under the receiver operating characteristic curve of 0.87 [0.85; 0.88] and 0.86 [0.84; 0.88], respectively. The recalibrated model predictions showed a calibration intercept of -0.04 [-0.12; 0.04] and slope of 0.90 [0.85; 0.95] for logistic regression model and a calibration intercept of -0.19 [-0.27; -0.10] and slope of 0.89 [0.84; 0.94] for the random forest model. Discussion: We presented a model for dynamic mortality prediction, specifically for critically ill COVID-19 patients, which predicts near-term mortality rather than in-ICU mortality. The potential clinical utility of dynamic mortality models such as benchmarking, improving resource allocation and informing family members, as well as the development of models with more causal structure, should be topics for future research.

Carriage of antibiotic-resistant Gram-negative bacteria after discontinuation of selective decontamination of the digestive tract (SDD) or selective oropharyngeal decontamination (SOD).

BACKGROUND: Selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) reduce colonization with antibiotic-resistant Gram-negative bacteria (ARGNB), incidence of nosocomial infections and improve survival in ICU patients. The effect on bacterial gut colonization might be caused by growth suppression by antibiotics during SDD/SOD. We investigated intestinal colonization with ARGNB after discharge from ICU and discontinuation of SDD or SOD. METHODS: We performed a prospective, observational follow-up study in regular hospital wards of three teaching hospitals in the Netherlands in patients discharged from the ICU, who were participating in a cluster randomized trial comparing SDD with SOD. We determined rectal carriage with ARGNB at ICU discharge (time (T) = 0) and 3, 6 and 10 days after discharge. The primary endpoint was time to first colonization with ARGNB that was not present at T = 0. Bacteria that are intrinsically resistant to antibiotics were not included in the primary analysis, but were included in post-hoc analysis. RESULTS: Of 1370 patients screened for inclusion, 996 patients had samples at T = 0 (507 after SDD and 489 after SOD). At ICU discharge, the prevalence of intestinal carriage with any ARGNB was 22/507 (4.3%) after SDD and 87/489 (17.8%) after SOD (p < 0.0001): 426 (SDD) and 409 (SOD) patients had at least one follow-up sample for analysis. The hazard rate for acquiring carriage of ARGNB after discontinuation of SDD, compared to SOD, in the ICU was 0.61 (95% CI 0.40-0.91, p = 0.02), and cumulative risks of acquisition of at least one ARGNB until day 10 were 13% (SDD) and 18% (SOD). At day 10 after ICU discharge, the prevalence of intestinal carriage with ARGNB was 11.3% (26/230 patients) after SDD and 12.5% (28/224 patients) after SOD (p = 0.7). In post-hoc analysis of all ARGNB, including intrinsically resistant bacteria, colonization at ICU discharge was lower after SDD (4.9 vs. 22.3%, p < 0.0001), but acquisition rates after ICU discharge were similar in both groups. CONCLUSIONS: Intestinal carriage at ICU discharge and the acquisition rate of ARGNB after ICU discharge are lower after SDD than after SOD. The prevalence of intestinal carriage with ARGNB at 10 days after ICU discharge was comparable in both groups, suggesting rapid clearance of ARGNB from the gut after ICU discharge. TRIAL REGISTRATION: Netherlands Trial Registry, NTR3311 . Registered on 28 february 2012.

Selective digestive and oropharyngeal decontamination in medical and surgical ICU patients: individual patient data meta-analysis.

OBJECTIVES: Selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD) improved intensive care unit (ICU), hospital and 28-day survival in ICUs with low levels of antibiotic resistance. Yet it is unclear whether the effect differs between medical and surgical ICU patients. METHODS: In an individual patient data meta-analysis, we systematically searched PubMed and included all randomized controlled studies published since 2000. We performed a two-stage meta-analysis with separate logistic regression models per study and per outcome (hospital survival and ICU survival) and subsequent pooling of main and interaction effects. RESULTS: Six studies, all performed in countries with low levels of antibiotic resistance, yielded 16 528 hospital admissions and 17 884 ICU admissions for complete case analysis. Compared to standard care or placebo, the pooled adjusted odds ratios for hospital mortality was 0.82 (95% confidence interval (CI) 0.72-0.93) for SDD and 0.84 (95% CI 0.73-0.97) for SOD. Compared to SOD, the adjusted odds ratio for hospital mortality was 0.90 (95% CI 0.82-0.97) for SDD. The effects on hospital mortality were not modified by type of ICU admission (p values for interaction terms were 0.66 for SDD and control, 0.87 for SOD and control and 0.47 for SDD and SOD). Similar results were found for ICU mortality. CONCLUSIONS: In ICUs with low levels of antibiotic resistance, the effectiveness of SDD and SOD was not modified by type of ICU admission. SDD and SOD improved hospital and ICU survival compared to standard care in both patient populations, with SDD being more effective than SOD.

Selective decontamination of the oropharynx and the digestive tract, and antimicrobial resistance: a 4 year ecological study in 38 intensive care units in the Netherlands.

OBJECTIVES: Selective oropharyngeal decontamination (SOD) and selective decontamination of the digestive tract (SDD) are associated with improved outcomes among patients in intensive care units (ICUs), but uncertainty remains about their long-term effects on resistance levels. We determined trends in antibiotic resistance among Gram-negative bacteria in 38 Dutch ICUs using and not using SOD/SDD. METHODS: The Infectious Disease Surveillance Information System-Antibiotic Resistance (ISIS-AR) was used to identify all Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. isolates from blood and respiratory tract specimens from ICUs between January 2008 and April 2012. Per patient, the last isolate per species per specimen per month was selected to determine cumulative resistance rates (per 100 beds/month) for colistin, tobramycin, ciprofloxacin, ceftazidime and cefotaxime/ceftriaxone in ICUs that continuously used or did not use SOD/SDD, and ICUs that introduced SOD/SDD. Time trends were analysed by multilevel Poisson regression. RESULTS: Seventeen ICUs continuously used SOD/SDD (859 months), 13 did not use SOD/SDD (663 months) and 8 introduced SOD/SDD (223 and 117 months before and after introduction). There were no discernible trends in antibiotic resistance among 637 blood isolates. For the 8353 respiratory isolates, resistance to cefotaxime/ceftriaxone increased in ICUs that did not use SOD/SDD (P < 0.001) and decreased in those that continuously used SOD/SDD (P = 0.04), as did resistance to ciprofloxacin (P < 0.001). The introduction of SOD/SDD was followed by statistically significant reductions in resistance rates for all antimicrobial agents. CONCLUSIONS: Continuous use of SOD/SDD was associated with decreasing trends for resistance to cefotaxime/ceftriaxone and ciprofloxacin. The introduction of SOD/SDD was associated with reductions in resistance rates for all antimicrobial agents included.