The effect of concomitant use of systemic antibiotics in patients with Clostridium difficile infection receiving metronidazole therapy

Abstract

Management of Clostridium difficile infection (CDI) involves discontinuation of the offending antibiotic agent as soon as possible. However, the ongoing infection does not allow discontinuation of the offending antibiotic. We aimed to retrospectively investigate the predictors of treatment failure and impact of the concomitant use of systemic antibiotics in patients receiving metronidazole therapy. This study was conducted among patients hospitalised at a second care academic hospital from January 2013 to December 2014. Eligible patients were identified by reviewing stool toxin enzyme immunoassay results for C. difficile. Diarrhoea was defined as the passage of at least three loose or watery stools within 24 h. Among 314 patients with CDI receiving metronidazole therapy, 62 (19.7%) showed treatment failure and 105 (33.4%) received concomitant antibiotics. Underlying dialysis, fever >38.3 °C, low median serum albumin levels and concomitant use of antibiotics were independent predictors of treatment failure in patients with CDI receiving metronidazole therapy. The concomitant use of antibiotics increased the rates of treatment failure and 30-day mortality in patients receiving metronidazole therapy. These results suggest that metronidazole should be used in mild cases of CDI only after discontinuation of the offending antibiotics.

Metronidazole therapy as initial treatment of Clostridium difficile infection in patients with chronic kidney disease in Korea

“…Nevertheless, when compared with CDI patients without CKD, initial metronidazole therapy in those undergoing dialysis tended to be associated with an increased risk of treatment failure. As reported by others, concomitant antibiotic use alone in CDI patients was a strong predictor for metronidazole treatment failure [18]. Here, even if the association between dialysis and metronidazole failure was more pronounced in CDI patients without the continuous use of antibiotics, a statistically significant interaction effect was not demonstrated in our patient cohort.…”

“…Our primary outcome was metronidazole treatment failure and the secondary outcome was overall treatment failure. Logistic regression analysis was used to examine the association of CKD status with treatment failure upon adjustment for age, sex and factors based on a priori knowledge including serum albumin, fever, risk-stratified concomitant antibiotic use, use of glycopeptide, number of antibiotics prescribed (⩾2 or <2), CRP and leukocytosis (WBC > 15 000/μl) [9, 18, 19]. For sensitivity analysis, we additionally adjusted for a history of previous CDI within 8 weeks before diagnosis of current episode, history of using metronidazole to treat other infectious diseases within 4 weeks before diagnosis of CDI and the length of hospital stay from patient admission to diagnosis of CDI, given that these variables may affect the association of CKD status and outcomes.…”

“…For sensitivity analysis, we additionally adjusted for a history of previous CDI within 8 weeks before diagnosis of current episode, history of using metronidazole to treat other infectious diseases within 4 weeks before diagnosis of CDI and the length of hospital stay from patient admission to diagnosis of CDI, given that these variables may affect the association of CKD status and outcomes. As the continuous use of antibiotics was reported to be a strong predictor of metronidazole treatment failure, we performed subgroup analysis for the primary outcome according to the continuous use of antibiotics and likelihood ratio testing by adding an interaction term between CKD status and the continuous use of antibiotics to the adjusted logistic regression model [18]. All analyses were carried out using STATA version 14.2 (StataCorp LP, College Station, TX, USA).…”

Validation of Clinical Risk Models for Clostridioides difficile-Attributable Outcomes

“…Twenty models for C. difficile infection severity were reviewed from the literature ( Table 1 ) and six (Age Treatment with Systemic Antibiotics Leukocyte Count Albumin and Serum Creatinine [ATLAS] ( 9 ), C. difficile Disease [CDD] [ 8 ], Zar et al [ 42 ], Hensgens et al [ 43 ], Shivashankar et al [ 44 ], C. difficile Severity Score (CDSS) [ 45 ]; Table 4 ) were chosen for validation based on their performance, prominence in the literature, derivation cohort size, prior validation, parameters that could be reliably gathered from the electronic medical record at the time of diagnosis, and ≥4 ordinal scores that could be fitted to an ROC curve. For IDSA Severity, one point was empirically assigned for each criterion for Severe and Fulminant infection from the Updated 2017 IDSA/SHEA Guidelines ( 15 , 16 ).…”

“…Risk model scores were calculated based on parameters gathered electronically for each case at the time of diagnosis. The following features could not be reliably gathered from the electronic record and so were omitted from score calculations: specific computed tomography abdominal imaging findings (thickened colonic wall, dilation, or ascites) from the CDD score ( 8 ), diarrhea as the reason for admission from the Hensgens score ( 43 ), and presence of pseduomembranes on endoscopy from the Zar criteria ( 42 ). Cycle threshold values from the GeneXpert (Cepheid, Sunnyvale CA) PCR platform were available from archived data for 1,484 cases that occurred between November 2013 and June 2018.…”