External validation of clinical prediction rules for complications and mortality following Clostridioides difficile infection

Abstract

BackgroundSeveral clinical prediction rules (CPRs) for complications and mortality of Clostridioides difficile infection (CDI) have been developed but only a few have gone through external validation, and none is widely recommended in clinical practice.MethodsCPRs were identified through a systematic review. We included studies that predicted severe or complicated CDI (cCDI) and mortality, reported at least an internal validation step, and for which data were available with minimal modifications. Data from a multicenter prospective cohort of 1380 adults with confirmed CDI were used for external validation. In this cohort, cCDI occurred in 8% of the patients and 30-day all-cause mortality occurred in 12%. The performance of each tool was assessed using individual outcomes, with the same cut-offs and standard parameters.ResultsSeven CPRs were assessed. Three predictive scores for cCDI showed low sensitivity (25–61%) and positive predictive value (PPV; 9–31%), but moderate specificity (54–90%) and negative predictive value (NPV; 82–95%). One model [using age, white blood cell count (WBC), narcotic use, antacids use, and creatinine ratio > 1.5× the normal level as covariates] showed a probability of 25% of cCDI at the optimal cut-off point with 36% sensitivity and 84% specificity. Two scores for mortality had low sensitivity (4–55%) and PPV (25–31%), and moderate specificity (71–78%) and NPV (87–92%). One predictive model for 30-day all-cause mortality [Charlson comorbidity index, WBC, blood urea nitrogen (BUN), diagnosis in ICU, and delirium] showed an AUC-ROC of 0.74. All other CPRs showed lower AUC values (0.63–0.69). Errors in calibration ranged from 12%- 27%.ConclusionsIncluded CPRs showed moderate performance for clinical use in a large validation cohort with a majority of patients infected with ribotype 027 strains and a low rate of cCDI and mortality. These data show that better CPRs need to be developed and validated.

Prognostic factors for severe and recurrent Clostridioides difficile infection: a systematic review

“…Based on the low quality of the studies and small effects of identified prognostic factors, it is not surprising that external validation of prediction tools show disappointing results [164][165][166].…”

Systemic Inflammatory Mediators Are Effective Biomarkers for Predicting Adverse Outcomes in Clostridioides difficile Infection

“…CDI is associated with an increased risk of mortality, and at present, we are inadequately determining who will experience adverse outcomes. Multiple models have been produced to address this problem, including those utilizing electronic medical records, standard laboratory tests, and medical history (6)(7)(8)(9)(10)(11)(12). However, these models have met with limited success in external validation, and there is room for improvement in predictive ability of CDI adverse outcomes.…”

“…An ideal model would identify cases of CDI at the time of diagnosis that are progressing toward severe systemic disease, so that treatments to halt disease progression can be started. Models built from baseline clinical variables or standard laboratory measurements have met with limited success in accurately predicting adverse outcomes, or they do not validate externally (6)(7)(8)(9)(10)(11)(12). Therefore, we set out to determine if predictive models built from a panel of multiple inflammatory mediators measured at diagnosis of CDI can accurately predict adverse outcomes, specifically, 30-day all-cause mortality and DRCs defined as ICU admission, colectomy, and/or death attributed to CDI.…”

Defining the black box: a narrative review of factors associated with adverse outcomes from severe Clostridioides difficile infection

“… 22 Other systematic reviews also frequently find that leukocytosis associated with severe disease. 92 , 95 With a definition of severe CDI that included at least two of age > 60, albumin < 2.5 mg/dL, leukocytosis and ICU admission, the risk of 90 day mortality increased substantially (OR = 1.8). 22 …”

“…Although the predictive utility of serum albumin is not well defined, in some studies hypoalbuminemia (defined as < 25–35 g/L) alone or as part of various clinical prediction rules has been found to be associated with an increased risk of mortality. 12 , 22 , 92 , 95 …”