Oral fidaxomicin versus vancomycin for the treatment of Clostridioides difficile infection: A systematic review and meta-analysis of randomized controlled trials

Tashiro, Syoichi; Mihara, Takayuki; Sasaki, Moe; Shimamura, Chiaki; Shimamura, Rina; Suzuki, Shigeaki; Yoshikawa, Masahide; Hasegawa, Tatsuki; Enoki, Yuki; Taguchi, Kazuaki; Matsumoto, Kazuaki; Ohge, Hiroki; Suzuki, Hiromichi; Nakamura, Atsushi; Môri, N.; Morinaga, Yoshitomo; Yamagishi, Yuka; Yoshizawa, Sadako; Yanagihara, Katsunori; Mikamo, Hiroshige; Kunishima, Hiroyuki

doi:10.1016/j.jiac.2022.08.008

Cited by 19 publications

(12 citation statements)

References 46 publications

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“…The occurrence of antimicrobial resistance in hospital-acquired ESKAPE pathogens ( Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa , and Enterobacter species) was a major cause for concern in 2009 [ 28 ]. New classes of antibiotics have now been developed for Gram-positive bacteria, such as the tiacumicin Fidaxomicin for Clostridioides difficile [ 29 ]. However, Gram-negative bacteria (the KAPE in ESKAPE) remain a major cause for concern.…”

Section: Introductionmentioning

confidence: 99%

A 2.8 Å Structure of Zoliflodacin in a DNA Cleavage Complex with Staphylococcus aureus DNA Gyrase

Morgan

Lipka-Lloyd

Warren

et al. 2023

IJMS

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Since 2000, some thirteen quinolones and fluoroquinolones have been developed and have come to market. The quinolones, one of the most successful classes of antibacterial drugs, stabilize DNA cleavage complexes with DNA gyrase and topoisomerase IV (topo IV), the two bacterial type IIA topoisomerases. The dual targeting of gyrase and topo IV helps decrease the likelihood of resistance developing. Here, we report on a 2.8 Å X-ray crystal structure, which shows that zoliflodacin, a spiropyrimidinetrione antibiotic, binds in the same DNA cleavage site(s) as quinolones, sterically blocking DNA religation. The structure shows that zoliflodacin interacts with highly conserved residues on GyrB (and does not use the quinolone water–metal ion bridge to GyrA), suggesting it may be more difficult for bacteria to develop target mediated resistance. We show that zoliflodacin has an MIC of 4 µg/mL against Acinetobacter baumannii (A. baumannii), an improvement of four-fold over its progenitor QPT-1. The current phase III clinical trial of zoliflodacin for gonorrhea is due to be read out in 2023. Zoliflodacin, together with the unrelated novel bacterial topoisomerase inhibitor gepotidacin, is likely to become the first entirely novel chemical entities approved against Gram-negative bacteria in the 21st century. Zoliflodacin may also become the progenitor of a new safer class of antibacterial drugs against other problematic Gram-negative bacteria.

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Section: Introductionmentioning

confidence: 99%

A 2.8 Å Structure of Zoliflodacin in a DNA Cleavage Complex with Staphylococcus aureus DNA Gyrase

Morgan

Lipka-Lloyd

Warren

et al. 2023

IJMS

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“…The primary endpoint was a combination of clinical resolution and a negative toxin polymerase chain reaction at 8 weeks after allocation, and was achieved in 33% (8/24), 19% (3/16), and 71% (17/24) of patients receiving fidaxomicin, vancomycin, and FMT, respectively [ 86 ]. A recent meta-analysis pooling data also from these three small RCTs in addition to OTP-80-003, OTP-80-004, and the RCT conducted in Japan, showed a comparable clinical cure between fidaxomicin and vancomycin (risk ratio (RR) 1.02, with 95% CI from 0.98 to 1.06), and favorable associations between fidaxomicin and reduced risk of rCDI (RR 0.59, with 95% CI from 0.47 to 0.75) and improved global cure (RR 1.18, with 95% CI from 1.09 to 1.26) [ 87 ].…”

Section: Results Of Phase-3/4 Randomized Controlled Trialsmentioning

confidence: 99%

Fidaxomicin for the Treatment of Clostridioides difficile Infection in Adult Patients: An Update on Results from Randomized Controlled Trials

et al. 2022

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In recently updated international guidelines, fidaxomicin is preferentially recommended as first-line treatment over vancomycin both for the first episode of CDI and for rCDI, based on the results of different randomized controlled trials (RCTs). Although noninferiority was the rule in phase-3 RCTs with regard to the primary endpoint of clinical cure, for shaping these recommendations, particular attention was devoted to the improved global cure and reduced risk of recurrent CDI (rCDI) observed with fidaxomicin compared to vancomycin in RCTs. Overall, while the major driver of choice should remain the global benefit for the patient, consideration of available resources should be necessarily weighed in the balance, since fidaxomicin still remains more costly than vancomycin. Against this background, precisely stratifying risk groups for rCDI will represent a crucial research trajectory of future real-life studies on the treatment of first CDI episodes. In the current narrative review, we discuss the updated evidence from RCTs on the efficacy of fidaxomicin for the treatment of either the first CDI episode or rCDI, which eventually supports its positioning within current treatment algorithms and guidelines.

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“…Vancomycin and metronidazole are common treatments for CDI, but recent Infectious Diseases Society of America (IDSA) guidelines have added oral fidaxomicin, a narrow‐spectrum macrocyclic antibiotic, as a first‐line option 8 . The systematic review summarized here compared the efficacy of oral fidaxomicin and vancomycin for treatment of CDI 9 …”

Section: Narrativementioning

confidence: 99%

“…The review included randomized controlled trials (RCTs) comparing oral fidaxomicin and vancomycin for treatment of CDI 9 . Participants were ≥16 years of age.…”

Section: Narrativementioning

confidence: 99%

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Oral fidaxomicin versus vancomycin for Clostridioides difficile infection

Long

Gottlieb

2022

Academic Emergency Medicine

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Oral fidaxomicin versus vancomycin for the treatment of Clostridioides difficile infection: A systematic review and meta-analysis of randomized controlled trials

Cited by 19 publications

References 46 publications

A 2.8 Å Structure of Zoliflodacin in a DNA Cleavage Complex with Staphylococcus aureus DNA Gyrase

A 2.8 Å Structure of Zoliflodacin in a DNA Cleavage Complex with Staphylococcus aureus DNA Gyrase

Fidaxomicin for the Treatment of Clostridioides difficile Infection in Adult Patients: An Update on Results from Randomized Controlled Trials

Oral fidaxomicin versus vancomycin for Clostridioides difficile infection

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