Reduced Acquisition and Overgrowth of Vancomycin-Resistant Enterococci and Candida Species in Patients Treated With Fidaxomicin Versus Vancomycin for Clostridium difficile Infection

Nerandzic, Michelle M.; Mullane, Kathleen M.; Miller, Mark A.; Babakhani, Farah; Donskey, Curtis J.

doi:10.1093/cid/cis440

Cited by 118 publications

(104 citation statements)

References 15 publications

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“…In comparison to vancomycin, fidaxomicin causes minimal disruption of the anaerobic microbiota and in clinical studies was associated with fewer recurrences of CDI and less frequent acquisition of VRE and Candida spp. during CDI treatment (1,6). Given the relative sparing of the microbiota during fidaxomicin treatment, we hypothesized that this agent would not lead to a loss of colonization resistance to VRE and extended-spectrum-␤-lactamaseproducing Klebsiella pneumoniae (ESBL-Kp).…”

mentioning

confidence: 99%

Effect of Fidaxomicin versus Vancomycin on Susceptibility to Intestinal Colonization with Vancomycin-Resistant Enterococci and Klebsiella pneumoniae in Mice

Deshpande

Hurless

Cadnum

et al. 2016

Antimicrob Agents Chemother

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eThe use of oral vancomycin or metronidazole for treatment of Clostridium difficile infection (CDI) may promote colonization by health care-associated pathogens due to disruption of the intestinal microbiota. Because the macrocyclic antibiotic fidaxomicin causes less alteration of the intestinal microbiota than vancomycin, we hypothesized that it would not lead to a loss of colonization resistance to vancomycin-resistant enterococci (VRE) and extended-spectrum-␤-lactamase-producing Klebsiella pneumoniae (ESBL-Kp). Mice (8 per group) received orogastric saline, vancomycin, or fidaxomicin daily for 5 days at doses resulting in stool concentrations in mice similar to those measured in humans. The mice were challenged with 10 5 CFU of orogastric VRE or ESBL-Kp on day 2 of treatment and concentrations of the pathogens in stool were monitored. The impact of drug exposure on the microbiome was measured by cultures, real-time PCR for selected anaerobic bacteria, and deep sequencing. In comparison to saline controls, oral vancomycin promoted establishment of high-density colonization by VRE and ESBL-Kp in stool (8 to 10 log 10 CFU/g; P < 0.001), whereas fidaxomicin did not (<4 log 10 CFU; P > 0.5). Vancomycin treatment resulted in significant reductions in enterococci, Bacteroides spp., and Clostridium leptum, whereas the population of aerobic and facultative Gramnegative bacilli increased; deep-sequencing analysis demonstrated suppression of Firmicutes and expansion of Proteobacteria during vancomycin treatment. Fidaxomicin did not cause significant alteration of the microbiota. In summary, in contrast to vancomycin, fidaxomicin treatment caused minimal disruption of the intestinal microbiota and did not render the microbiota susceptible to VRE and ESBL-Kp colonization.O ral vancomycin and oral metronidazole are the most commonly used antibiotics for treatment of Clostridium difficile infection (CDI). One limitation of these agents is that they are nonselective (i.e., they inhibit normal anaerobic intestinal microbiota in addition to C. difficile) (1-4). For example, oral vancomycin treatment may result in suppression of Bacteroides/Prevotella, Clostridium coccoides, and Clostridium leptum group organisms in stool (2, 3). Inhibition of the anaerobic microbiota by vancomycin and metronidazole during CDI treatment may contribute to recurrences of CDI and to colonization by health care-associated pathogens such as vancomycin-resistant enterococci (VRE) (4, 5).Fidaxomicin is a macrocycle antibiotic approved by the Food and Drug Administration for the treatment of CDI (1). In comparison to vancomycin, fidaxomicin causes minimal disruption of the anaerobic microbiota and in clinical studies was associated with fewer recurrences of CDI and less frequent acquisition of VRE and Candida spp. during CDI treatment (1, 6). Given the relative sparing of the microbiota during fidaxomicin treatment, we hypothesized that this agent would not lead to a loss of colonization resistance to VRE and extended-spectrum-␤-lactamaseproducing Kleb...

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confidence: 99%

Effect of Fidaxomicin versus Vancomycin on Susceptibility to Intestinal Colonization with Vancomycin-Resistant Enterococci and Klebsiella pneumoniae in Mice

Deshpande

Hurless

Cadnum

et al. 2016

Antimicrob Agents Chemother

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“…During the intervention period, 130 specimens were submitted to the laboratory for CDI testing. In comparison to the baseline period, the proportion of specimens rejected due to factors such as leaking, improper labeling, and wrong or insufficient specimens was reduced, but the reduction was not statistically significant (15 …”

Section: Resultsmentioning

confidence: 81%

“…For example, oral metronidazole and oral vancomycin therapy have been associated with overgrowth of pathogens such as vancomycin-resistant enterococci and Candida spp. (14,15). Interviews with physicians suggested that more rapid diagnostic testing might reduce prescription of empirical treatment for suspected CDI.…”

Section: Discussionmentioning

confidence: 99%

Easily Modified Factors Contribute to Delays in Diagnosis of Clostridium difficile Infection: a Cohort Study and Intervention

et al. 2013

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cAlthough rapid laboratory tests are available for diagnosis of Clostridium difficile infection (CDI), delays in completion of CDI testing are common in clinical practice. We conducted a cohort study of 242 inpatients tested for CDI to determine the timing of different steps involved in diagnostic testing and to identify modifiable factors contributing to delays in diagnosis. The average time from test order to test result was 1.8 days (range, 0.2 to 10.6), with time from order to stool collection accounting for most of the delay (mean, 1.0 day; range, 0 to 10). Several modifiable factors contributed to delays, including not providing stool collection supplies to patients in a timely fashion, rejection of specimens due to incorrect labeling or leaking from the container, and holding samples in the laboratory for batch processing. Delays in testing contributed to delays in initiation of treatment for patients diagnosed with CDI and to frequent prescription of empirical CDI therapy for patients with mild to moderate symptoms whose testing was ultimately negative. An intervention that addressed several easily modified factors contributing to delays resulted in a significant decrease in the time required to complete CDI testing. These findings suggest that health care facilities may benefit from a review of their processes for CDI testing to identify and address modifiable factors that contribute to delays in diagnosis and treatment of CDI.C lostridium difficile is the most important cause of health careassociated diarrhea in developed countries (1). During the past decade, the emergence of an epidemic C. difficile strain, termed North American pulsed-field gel electrophoresis type 1, has been associated with dramatic increases in the incidence and severity of C. difficile infection (CDI) in North America and Europe (1-3). In the context of these changes in the epidemiology of C. difficile, accurate and efficient strategies to diagnose CDI are crucial to guide management and prevent transmission. Enzyme immunoassays for glutamate dehydrogenase or for toxins A and B and real-time PCR assays for toxin genes can provide rapid CDI test results in the laboratory (4-8); the enzyme immunoassays for toxins A and B are recommended only as part of multistep testing algorithms (4, 7). However, delays in completion of CDI diagnostic testing are common in clinical practice. Identification of easily modified factors that contribute to these delays could benefit infection control programs and clinicians who manage patients with CDI.Scheurer et al. (9) recently reported that the mean time from onset of symptoms to collection of samples for C. difficile testing was 2.2 days. Similarly, we reported that the mean time from onset of diarrhea to diagnosis of infection was 2 days in our hospital and 4 days in our long-term-care facility (10). In a hospital that tested for CDI using stool culture and external toxin analysis, Frenz and McIntyre (11) found that the mean time from onset of diarrhea to collection of samples for testing was ...

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“…Importantly, fidaxomicin has been shown to have a comparable safety profile to vancomycin [117] , have undetectable serum levels while achieving high fecal concentrations, averaging greater than 10000 times the MIC for C. difficile [118] , a bactericidal mechanism of action [119] , preserve the intestinal microbiome (by sparing of Bacteroides sp. ), reduce both toxin reexpression and CDI recurrence [120] , and reducing the acquisition of VRE and Candida species during CDI treatment [121,122] . Much of the attention centered on fidaxomicin has been based on findings from two prospective, multicenter, double-blind, randomized Phase Ⅲ trials demonstrating non-inferiority to vancomycin.…”

Section: Fidaxomicinmentioning

confidence: 99%

Clinical update for the diagnosis and treatment ofClostridium difficileinfection

Oldfield

Johnson

2014

WJGPT

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Clostridium difficile infection (CDI) presents a rapidly evolving challenge in the battle against hospitalacquired infections. Recent advances in CDI diagnosis and management include rapid changes in diagnostic approach with the introduction of newer tests, such as detection of glutamate dehydrogenase in stool and polymerase chain reaction to detect the gene for toxin production, which will soon revolutionize the diagnostic approach to CDI. New medications and multiple medical society guidelines have introduced changing concepts in the definitions of severity of CDI and the choice of therapeutic agents, while rapid expansion of data on the efficacy of fecal microbiota transplantation heralds a revolutionary change in the management of patients suffering multiple relapses of CDI. Through a comprehensive review of current medical literature, this article aims to offer an intensive review of the current state of CDI diagnosis, discuss the strengths and limitations of available laboratory tests, compare both current and future treatments options and offer recommendations for best practice strategies.

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Reduced Acquisition and Overgrowth of Vancomycin-Resistant Enterococci and Candida Species in Patients Treated With Fidaxomicin Versus Vancomycin for Clostridium difficile Infection

Cited by 118 publications

References 15 publications

Effect of Fidaxomicin versus Vancomycin on Susceptibility to Intestinal Colonization with Vancomycin-Resistant Enterococci and Klebsiella pneumoniae in Mice

Effect of Fidaxomicin versus Vancomycin on Susceptibility to Intestinal Colonization with Vancomycin-Resistant Enterococci and Klebsiella pneumoniae in Mice

Easily Modified Factors Contribute to Delays in Diagnosis of Clostridium difficile Infection: a Cohort Study and Intervention

Clinical update for the diagnosis and treatment ofClostridium difficileinfection

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