Systemic absorption of oral vancomycin in patients with Clostridium difficile infection

Rao, Sriharsha; Kupfer, Yizhak; Pagala, Murali; Chapnick, Edward K.; Tessler, Sidney

doi:10.3109/00365548.2010.544671

Cited by 78 publications

(59 citation statements)

References 9 publications

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“…There have also been reports of appreciable circulating levels of vancomycin following oral administration without apparent toxicity in patients with or without CKD [27]. Other investigations found no evidence of absorption in patients with severe CDI and/or CKD [28]. …”

Section: Discussionmentioning

confidence: 99%

Renal Impairment and Clinical Outcomes of Clostridium difficile Infection in Two Randomized Trials

et al. 2013

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Background/Aims: Patients with chronic kidney disease (CKD) have increased risk for Clostridium difficile infection (CDI) and for subsequent mortality. We determined the effect of CKD on response to treatment for CDI. Methods: This is a post hoc analysis of two randomized controlled phase 3 trials that enrolled patients with CDI. Patients received either fidaxomicin 200 mg b.i.d. or vancomycin 125 mg q.i.d. for 10 days. Univariate and multivariate analyses compared end points by treatment received and CKD stage. Results: At baseline, 27, 21, and 9% of the patients had stage 2 (60-89 ml/min/1.73 m²), stage 3 (30-59), and stage 4 or higher (<30) CKD. Cure rates were similar for normal (91%) and stage 2 CKD (92%), but declined to 80% for stage 3 and to 75% for stage 4 CKD (p < 0.001 for trend). Time to resolution of diarrhea (TTROD) increased with stage 3 and stage 4 CKD. CDI recurrence rates 4 weeks after treatment were 16, 20, 27, and 24% for normal, stage 2, stage 3, and stage 4 or higher CKD, respectively. Mortality increased with CKD stage. In multivariate analyses, stage 3 or higher CKD correlated with lower odds of cure, greater chance of recurrence, and lower odds of sustained response 28 days after treatment. Initial cure rates were similar in the vancomycin or fidaxomicin groups; however, the rate of recurrence was higher following vancomycin treatment independent of renal function. The presence of immunosuppression did not alter this effect. Conclusion: Progressive CKD is associated with increased TTROD, lower cure rates, and higher recurrence rates with treatment of CDI.

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Section: Discussionmentioning

confidence: 99%

Renal Impairment and Clinical Outcomes of Clostridium difficile Infection in Two Randomized Trials

et al. 2013

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“…A systematic collection of the serum samples for the PK analyses was not done in these studies. In a prospective study of 57 patients treated with 125 mg of oral vancomycin every 6 h, only one patient had a detectable concentration of 6.7 g/ml based on an assay range of 3.4 g/ml to 90 g/ml (18). The details on how the serum PK samples were collected were not reported.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of LFF571 and Vancomycin in Patients with Moderate Clostridium difficile Infections

Bhansali

Mullane

Ting

et al. 2015

Antimicrob Agents Chemother

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Clostridium difficile infection causes diarrheal disease with potentially fatal complications. Although treatments are available, including vancomycin, metronidazole, and fidaxomicin, the recurrence of disease after therapy remains a problem. LFF571 is a novel thiopeptide antibacterial that shows in vitro potency against C. difficile that is comparable to or greater than that of other clinically used antibiotics. Here, we compare the pharmacokinetics (PK) of LFF571 and vancomycin in patients with C. difficile infection as part of an early efficacy study. This multicenter, randomized, evaluator-blind, and active-controlled study evaluated the safety, efficacy, and pharmacokinetics of LFF571 in adults with primary episodes or first relapses of moderate C. difficile infections. Patients were randomized to receive 200 mg of LFF571 or 125 mg of vancomycin four times daily for 10 days. The PK parameters were calculated from drug concentrations measured in serum and fecal samples. The systemic exposure following oral administration of 200 mg of LFF571 four times per day for 10 days in patients with C. difficile infection was limited. The highest LFF571 serum concentration observed was 41.7 ng/ml, whereas the levels in feces at the end of treatment were between 107 and 12,900 g/g. In comparison, the peak vancomycin level observed in serum was considerably higher, at 2.73 g/ml; the levels of vancomycin in feces were not measured. Similar to healthy volunteers, patients with C. difficile infections exhibited high fecal concentrations and low serum levels of LFF571. These results are consistent with the retention of LFF571 in the lumen of the gastrointestinal tract. (This study has been registered at ClinicalTrials.gov under registration no. NCT01232595.)

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“…Nevertheless, the high dose of VCM induced a high serum VCM concentration (3.9 μg/mL). The systemic absorption of oral VCM is known to cause adverse effects, including maculopapular rashes (15,16), red man syndrome (13,17,18), anaphylaxis (19), leukopenia (14) and encephalopathy (20). Based on these findings and the patient's clinical course, we suspected that he developed the maculopapular rash secondary to VCM (21).…”

Section: Discussionmentioning

confidence: 99%

Continuous Administration of Vancomycin through a Long Intestinal Tube for Clostridium difficile Infection

et al. 2015

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A 76-year-old previously healthy Japanese man experienced severe diarrhea (8,000 mL per day) after undergoing laparotomy for small bowel obstruction and was diagnosed with Clostridium difficile infection. Although he developed a maculopapular rash secondary to the systemic absorption of enteral vancomycin (VCM), the patient was successfully treated with the continuous administration of VCM through a long intestinal tube placed in the terminal ileum. This method ensured the reliable delivery of VCM to the colon, while the continuous administration maintained high fecal levels of the drug. This treatment approach is an effective minimally invasive option for patients with severe diarrhea.

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Systemic absorption of oral vancomycin in patients with Clostridium difficile infection

Cited by 78 publications

References 9 publications

Renal Impairment and Clinical Outcomes of <i>Clostridium difficile</i> Infection in Two Randomized Trials

Renal Impairment and Clinical Outcomes of <i>Clostridium difficile</i> Infection in Two Randomized Trials

Pharmacokinetics of LFF571 and Vancomycin in Patients with Moderate Clostridium difficile Infections

Continuous Administration of Vancomycin through a Long Intestinal Tube for <i>Clostridium difficile</i> Infection

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