Faecal pharmacokinetics of orally administered vancomycin in patients with suspected Clostridium difficile infection

Gonzales, Milagros; Pépin, Jacques; Frost, Éric; Carrier, Julie; Sirard, Stéphanie; Fortier, Louis‐Charles; Valiquette, Louis

doi:10.1186/1471-2334-10-363

Cited by 117 publications

(66 citation statements)

References 33 publications

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“…We found all 403 isolates to be fully susceptible to metronidazole with MICs of Յ4 g/ml. All but two isolates were susceptible to vancomycin, and only one vancomycin-resistant isolate was a toxigenic strain; that particular isolate carried toxin A, toxin B, and binary toxin genes and had a MIC for vancomycin of 4 g/ml, still orders of magnitude below fecal levels of vancomycin achieved during treatment (17). No vancomycin-or metronidazole-resistant clones were found among 100 clinical isolates from South Korea during 2006 to 2008 (23).…”

Section: Discussionmentioning

confidence: 99%

Characterizations of Clinical Isolates of Clostridium difficile by Toxin Genotypes and by Susceptibility to 12 Antimicrobial Agents, Including Fidaxomicin (OPT-80) and Rifaximin: a Multicenter Study in Taiwan

Liao

et al. 2012

Antimicrob Agents Chemother

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A total of 403 nonduplicate isolates of Clostridium difficile were collected at three major teaching hospitals representing northern, central, and southern Taiwan from January 2005 to December 2010. Of these 403 isolates, 170 (42.2%) were presumed to be nontoxigenic due to the absence of genes for toxins A or B or binary toxin. The remaining 233 (57.8%) isolates carried toxin A and B genes, and 39 (16.7%) of these also had binary toxin genes. The MIC 90 of all isolates for fidaxomicin and rifaximin was 0.5 g/ml (range, <0.015 to 0.5 g/ml) and >128 g/ml (range, <0.015 to >128 g/ml), respectively. All isolates were susceptible to metronidazole (MIC 90 of 0.5 g/ml; range, <0.03 to 4 g/ml). Two isolates had reduced susceptibility to vancomycin (MICs, 4 g/ml). Only 13.6% of isolates were susceptible to clindamycin (MIC of <2 g/ml). Nonsusceptibility to moxifloxacin (n ‫؍‬ 81, 20.1%) was accompanied by single or multiple mutations in gyrA and gyrB genes in all but eight moxifloxacin-nonsusceptible isolates. Two previously unreported gyrB mutations might independently confer resistance (MIC, 16 g/ml), Ser416 to Ala and Glu466 to Lys. Moxifloxacin-resistant isolates were cross-resistant to ciprofloxacin and levofloxacin, but some moxifloxacinnonsusceptible isolates remained susceptible to gemifloxacin or nemonoxacin at 0.5 g/ml. This study found the diversity of toxigenic and nontoxigenic strains of C. difficile in the health care setting in Taiwan. All isolates tested were susceptible to metronidazole and vancomycin. Fidaxomicin exhibited potent in vitro activity against all isolates tested, while the more than 10% of Taiwanese isolates with rifaximin MICs of >128 g/ml raises concerns.

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Section: Discussionmentioning

confidence: 99%

Characterizations of Clinical Isolates of Clostridium difficile by Toxin Genotypes and by Susceptibility to 12 Antimicrobial Agents, Including Fidaxomicin (OPT-80) and Rifaximin: a Multicenter Study in Taiwan

Liao

et al. 2012

Antimicrob Agents Chemother

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“…to 4 g/ml, which is the EUCAST epidemiologic cutoff for vancomycin resistance, for all adult isolates resistant to vancomycin (19), and because vancomycin has poor systemic absorption and achieves fecal concentrations well above this MIC (22), this difference is unlikely to be clinically significant. The significantly higher proportion of moxifloxacin-resistant isolates in adult patients is likely related to the significantly higher proportion of BI/NAP1/ 027 strains in the adult cohort.…”

Section: Discussionmentioning

confidence: 99%

Differences in the Molecular Epidemiology and Antibiotic Susceptibility of Clostridium difficile Isolates in Pediatric and Adult Patients

Kociolek

Gerding

Osmolski

et al. 2016

Antimicrob Agents Chemother

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fThe rising incidence of Clostridium difficile infections (CDIs) in adults is partly related to the global spread of fluoroquinoloneresistant strains, namely, BI/NAP1/027. Although CDIs are also increasingly diagnosed in children, BI/NAP1/027 is relatively uncommon in children. Little is known about the antibiotic susceptibility of pediatric CDI isolates. C. difficile was cultured from tcdB-positive stools collected from children diagnosed with CDI between December 2012 and December 2013 at an academic children's hospital. CDI isolates were grouped by restriction endonuclease analysis (REA). MICs were measured by agar dilution method for 7 antibiotics. Susceptibility breakpoints were based on guidelines from CLSI and/or the European Committee on Antimicrobial Susceptibility Testing (EUCAST). MICs and REA groupings of C. difficile isolates from 74 adult patients (29 isolates underwent REA) from a temporally and geographically similar adult cohort were compared to those of pediatric isolates. Among 122 pediatric and 74 adult isolates, respectively, the rates of resistance were as follows: metronidazole, 0% and 0%; vancomycin, 0% and 8% (P ‫؍‬ 0.003); rifaximin, 1.6% and 6.7% (P ‫؍‬ 0.11); clindamycin, 18.9% and 25.3% (P ‫؍‬ 0.29); and moxifloxacin, 2.5% and 36% (P ‫؍‬ <0.0001). Only 1 of 122 (0.8%) BI/NAP1/027 isolates was identified among the children, compared to 9 of 29 (31%) isolates identified among the adults (P ‫؍‬ <0.0001). The 3 moxifloxacin-resistant pediatric isolates were of REA groups BI and CF and a nonspecific group. The 2 rifaximin-resistant pediatric isolates were of REA groups DH and Y. The 21 clindamycin-resistant pediatric isolates were distributed among 9 REA groups (groups A, CF, DH, G, L, M, and Y and 2 unique nonspecific REA groups). These data suggest that a diverse array of relatively antibiotic-susceptible C. difficile strains predominate in a cohort of children with CDI compared to adults. T he increased frequency, morbidity, and mortality of Clostridium difficile infections (CDI) in adults over the past 2 decades are primarily attributable to the emergence and global spread of a fluoroquinolone-resistant strain known as BI/NAP1/027 (1, 2). CDI is now the most frequently encountered health care-associated infection in the United States (3), causing nearly 500,000 infections and 30,000 deaths each year (4). These troubling trends in the clinical and molecular epidemiology of CDI recently prompted the Centers for Disease Control and Prevention (CDC) to classify CDI among the most serious immediate antibiotic-resistant diseases representing "public health threats that require urgent and aggressive action" (5).The molecular epidemiology (6-8) and antibiotic resistance (7-9) patterns of CDI in adults over the past 3 decades have been well described. Although the prevalence of BI/NAP1/027 is declining, recent data from the United States (4) and the United Kingdom (10) indicate that BI/NAP1/027 is still an important cause of CDI in adults. Limited investigation of the molecular epidemiology of...

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“…A trial of 46 patients randomized to 500 or 125 mg of vancomycin four times daily for the initial treatment of CDI showed no diff erence in duration of diarrhea, relapse rate, or microbiological cure (carriage of C. diffi cile at the end of therapy) ( 56 ). Moreover, fecal levels of vancomycin in patients with CDI with this dose achieve levels that are a minimum of 10 times the minimal inhibitory concentration reported for C. diffi cile strains ( 57 ). Given the high cost of vancomycin therapy, there is insuffi cient evidence to support the use of doses >125 mg four times daily for patients with mildto-moderate CDI, particularly for outpatients.…”

mentioning

confidence: 99%

Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections

Surawicz

Brandt

Binion

et al. 2013

American Journal of Gastroenterology

1,479

1,408

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Clostridium diffi cile infection (CDI) is a leading cause of hospital-associated gastrointestinal illness and places a high burden on our health-care system. Patients with CDI typically have extended lengths-of-stay in hospitals, and CDI is a frequent cause of large hospital outbreaks of disease. This guideline provides recommendations for the diagnosis and management of patients with CDI as well as for the prevention and control of outbreaks while supplementing previously published guidelines. New molecular diagnostic stool tests will likely replace current enzyme immunoassay tests. We suggest treatment of patients be stratifi ed depending on whether they have mild-to-moderate, severe, or complicated disease. Therapy with metronidazole remains the choice for mildto-moderate disease but may not be adequate for patients with severe or complicated disease. We propose a classifi cation of disease severity to guide therapy that is useful for clinicians. We review current treatment options for patients with recurrent CDI and recommendations for the control and prevention of outbreaks of CDI. Am J Gastroenterol 2013; 108:478-498; doi: 10.1038/ajg.2013 12. In patients in whom oral antibiotics cannot reach a segment of the colon, such as with Hartman's pouch, ileostomy, or colon diversion, vancomycin therapy delivered via enema should be added to treatments above until the patient improves. (Conditional recommendation, low-quality evidence)13. The use of anti-peristaltic agents to control diarrhea from confi rmed or suspected CDI should be limited or avoided, as they may obscure symptoms and precipitate complicated disease. Use of anti-peristaltic agents in the setting of CDI must always be accompanied by medical therapy for CDI. (Strong recommendation, low-quality evidence) Management of severe and complicated CDI14. Supportive care should be delivered to all patients and includes intravenous fl uid resuscitation, electrolyte replacement, and pharmacological venous thromboembolism prophylaxis. Furthermore, in the absence of ileus or signifi cant abdominal distention, oral or enteral feeding should be continued. 17. Vancomycin delivered orally (500 mg four times per day) and per rectum (500 mg in a volume of 500 ml four times a day) plus intravenous metronidazole (500 mg three times a day) is the treatment of choice for patients with complicated CDI with ileus or toxic colon and / or signifi cant abdominal distention. (Strong recommendation, low-quality evidence)18. Surgical consult should be obtained in all patients with complicated CDI. Surgical therapy should be considered in patients with any one of the following attributed to CDI: hypotension requiring vasopressor therapy; clinical signs of sepsis and organ dysfunction (renal and pulmonary); mental status changes; white blood cell count ≥ 50,000 cells / μ l, lactate ≥ 5 mmol / l; or failure to improve on medical therapy after 5 days. (Strong recommendation, moderate-quality evidence) Management of recurrent CDI (RCDI)19. The fi rst recurrence of CDI can be treated ...

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Faecal pharmacokinetics of orally administered vancomycin in patients with suspected Clostridium difficile infection

Cited by 117 publications

References 33 publications

Characterizations of Clinical Isolates of Clostridium difficile by Toxin Genotypes and by Susceptibility to 12 Antimicrobial Agents, Including Fidaxomicin (OPT-80) and Rifaximin: a Multicenter Study in Taiwan

Characterizations of Clinical Isolates of Clostridium difficile by Toxin Genotypes and by Susceptibility to 12 Antimicrobial Agents, Including Fidaxomicin (OPT-80) and Rifaximin: a Multicenter Study in Taiwan

Differences in the Molecular Epidemiology and Antibiotic Susceptibility of Clostridium difficile Isolates in Pediatric and Adult Patients

Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections

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