Clostridium difficile treatment in neutropenic patients: Clinical outcomes of metronidazole, vancomycin, combinations, and switch therapy

Abstract

Background Clostridium difficile infection treatment guidelines exist for immunocompetent patients; however, there is a paucity of data evaluating clinical outcomes and time to C. difficile-associated diarrhea resolution in neutropenic patients. Objective To assess clinical outcomes in neutropenic patients treated with metronidazole, oral vancomycin, the combination of metronidazole plus oral vancomycin, and switch of metronidazole to oral vancomycin. Methods This retrospective, observational cohort study assessed adult neutropenic inpatients with C. difficile-associated diarrhea treated with metronidazole, oral vancomycin, combination (metronidazole and oral vancomycin), or switch therapy (metronidazole to oral vancomycin). The primary outcome was time to diarrhea resolution based on treatment regimen. Secondary outcomes included C. difficile-associated diarrhea resolution of diarrhea by day 14, recurrence, and occurrence of major complications. Results Overall, 44 patients met full inclusion criteria (52.2% metronidazole monotherapy, 22.7% combination, and 25.0% switch therapy). Two patients on oral vancomycin monotherapy were excluded due to insufficient sample size. Overall time to C. difficile-associated diarrhea resolution was 9.1 ± 10.7 days. The Cox regression results suggested both switch and combination therapy were associated with 65.5% (p = 0.002) and 65.9% (p = 0.046) longer time to C. difficile-associated diarrhea resolution compared to metronidazole monotherapy, respectively. An increasing absolute neutrophil count was associated with an increase in C. difficile-associated diarrhea resolution (p = 0.007). Conclusion Switch or combination therapy was associated with a prolonged time to C. difficile-associated diarrhea resolution. The decision to use switch or combination therapy may represent a surrogate marker for more severe disease and need for therapy escalation. It is unknown if initial therapy with oral vancomycin would provide better outcomes as this could not be assessed.

Unveiling the Risk Factors of Clostridioides difficile Infection in Children; A Multicenter Retrospective Case-control Study in the Eastern Region, Saudi Arabia

“…The neutrophil: lymphocyte ratio is a predictor for ICU admission and death within two days of CDI diagnosing 31 . Another retrospective study found a link between neutrophilia and the greater possibility of CDI resolution 32 . Considering the diversity of the WBCs subpopulations in CDI patients, the total WBCs count may not be an accurate indicator of disease severity 33 .…”

Neutrophil Ratio of White Blood Cells as a Prognostic Predictor of Clostridioides difficile Infection

“…However, the clinical significance of neutrophil count in neutropenic patients is different, since in a small cohort of neutropenic patients the increase of absolute neutrophil count was linked to increased likelihood of resolution of CDI. 10 Therefore, the clinical implications of leukocytosis and impaired renal function as outcome indicators of CDI require detailed evaluation of clinical complexity of the care receipts.…”

“…9 In contrast, another retrospective study found that increasing neutrophil count was linked to a higher likelihood of the resolution of CDI in 44 neutropenic patients. 10 An increase in eosinophils and lymphocytes, two other important subpopulations of leukocytes, was associated with milder CDI severity. 9,11 As there were variations in the subpopulations of leukocytes among the CDI patients with at least one comorbidity and polypharmacy, total leukocyte count may not be a perfect indicator of disease severity.…”

“…Increasing neutrophil count in neutropenic patients was associated with an increased chance of CDI resolution. 10 However, an exaggerated inflammatory response during CDI results in host tissue damage, which is associated with worse patient outcomes. 20 Notably, type-2 immune response activation, with a hallmark of an increase in eosinophils and decrease in neutrophils, was proposed as a novel prognostic marker for CDI.…”

Clustering Disease of Clostridioides Difficile Infection: Implication for the Management in Internal Medicine

“…However, it was noted that patients treated with vancomycin had a shorter interval of clinical improvement than those treated with metronidazole [30]. In our center located in central Italy, we prefer the association of the two drugs as a first-line treatment for the first manifestations of CDI as suggested by previous studies which concerned in particular frail and immunosuppressed patients with high care complexity [31][32][33]. Fidaxomycin is an effective bactericidal antibiotic in the treatment of CDI with a specificity restricted to these cases with minimal impact on the intestinal microbiota [34,35].…”