Frontiers in Clinical Drug Research-Anti Infectives

Volume: 7

Bioactive Substances as Anti-infective Strategies Against Clostridioides Difficile

Author(s): Joana Barbosa* and Paula Teixeira

Pp: 72-102 (31)

DOI: 10.2174/9789814998093121070005

* (Excluding Mailing and Handling)

Abstract

The incidence and severity of diarrhea associated with Clostridioides difficile increased exponentially worldwide until 2004. But during the last few years, a downward trend has been observed globally, except in some European countries and Asia.

Until recently, C. difficile was the primary cause of nosocomial infection following antibiotic exposure, presenting a high rate of mortality and morbidity. However, the emergence and spread of a hypervirulent strain (BI/NAP1/027) and an increase in the incidence of community-acquired C. difficile infection (CDI), especially in populations not previously considered at high risk, have contributed to alterations in the infection epidemiology. After initial treatment with broad-spectrum antibiotics, CDI recurrence is the cause of substantial morbidity, indicating that alternative strategies to the usual therapeutics are urgently needed.

Several studies have investigated probiotics to assess their preventative and/or prophylactic effects on CDI, but their use is still controversial. Other anti-infective alternatives, such as bacteriocins and phage therapy, appear as promising answers for CDI treatment.

This review explores the current therapy approaches and the advances in searching for alternative solutions to inhibit the opportunistic pathogen C. difficile.


Keywords: Antibiotics, Antimicrobials, Bacteriocins, Bacteriophages, Clostridioides difficile infection (CDI), Fecal microbiota transplantation, Fidaxomicin, Monoclonal antibodies, Metronidazole, Non-toxigenic spores, Probiotics, Recurrent CDI, Synthetic polymers, Vaccines, Vancomycin.

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      • 11. app/Models/ContentAccess.php:647
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      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
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      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 222027364 and j.to_ip >=222027364 )) and ((j.from_date <= 1739988810 and j.to_date >= 1739988810 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 15069) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 222027364 and j.to_ip >=222027364 )) and ((j.from_date <= 1739988810 and j.to_date >= 1739988810 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 15069) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 222027364 and j.to_ip >=222027364 )) and ((j.from_date <= 1739988810 and j.to_date >= 1739988810 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 15069)
      620μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 3085 and `b`.`banner_from_date` <= 1739988810 and `b`.`banner_to_date` >= 1739988810 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.1msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 3085
      • 3: 1739988810
      • 4: 1739988810
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='16c09457e166a7c75d171ea1579f5941'
      230μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Keywords
    15Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        4LqVo2c5ZL2TpXXW5BC7MuBGswyWSj72mTtVuoQo
        uc_cart_id
        16c09457e166a7c75d171ea1579f5941
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/15069" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/15069
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6IklzcXhydXZzSlpFS3JIT3VjVGxDc1E9PSIsInZhbHVlIjoiN0loUE9nMzZ4WHAyOEc2aHVyNW9rbkV0T2liSzhTbjVBS1QyRk55dTdwUT0iLCJtYWMiOiI3MTc0OWRhZDg0ODIzNDUyNzcxNmIxNDcxOWExMmI4OWU2Y2EzMjYwYzc3MjYwMWM0MWJlMTcwOTg0N2I4NDljIiwidGFnIjoiIn0%3D; _ga_9F3B5VV3T3=GS1.1.1739988803.1.0.1739988803.60.0.0; _ga=GA1.1.1339051010.1739988804wayfindertarget=eyJpdiI6IklzcXhydXZzSlpFS3JIT3VjVGxDc1E9PSIsInZhbHVlIjoiN0loUE9nMzZ4WHAyOEc2aHVyNW9rbkV0T2liSzhTbjVBS1QyRk55dTdwUT0iLCJtYWMiOiI3MTc0OWRhZDg0ODIz" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        0 of 0
        array:3 [ "wayfindertarget" => null "_ga_9F3B5VV3T3" => null "_ga" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Wed, 19 Feb 2025 18:13:30 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IlEvMEkwM2g3V2NHdVF5Zk84QWd6WXc9PSIsInZhbHVlIjoidWp0czBWaTJEV3lpcXlQRlFiZVNHUjhIZklvSHRabWxibDVZWHVFWmdRQWdxRW5TbE9FN25DTUhVWUswcCtkNVBiR3h0Z01MSWFIdnNJbXlWZlZlNk9la2JqVlVnQlZ1MWVqZW40OU9QTWRXamVPZ2l3ZjJDd0kwZmFpSWxaaHYiLCJtYWMiOiI5Zjc0ZGVjYTViMGI5ZGFiZmU4NTU1NGExOTRlZTVkYmY4ODZhZWI3YTEyYmJlZTg2NDU1MGJmMDMzZjJjYTJmIiwidGFnIjoiIn0%3D; expires=Sat, 22 Feb 2025 06:13:30 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IlEvMEkwM2g3V2NHdVF5Zk84QWd6WXc9PSIsInZhbHVlIjoidWp0czBWaTJEV3lpcXlQRlFiZVNHUjhIZklvSHRabWxibDVZWHVFWmdRQWdxRW5TbE9FN25DTUhVWUswcCtkNVBiR3h0Z" 1 => "alphaeurekaselectnet_session=eyJpdiI6IlBQR1dHc280em1oQXBJSVlJVmhBS3c9PSIsInZhbHVlIjoiaythZVpMNmUwU05XM2FzRnNRbGF4TGxvbTB0UXQxcTRCclpqcU5qSlFUUTlsR1d4alNZcko5ODJZU1BPSEFIR3dINXBhVWRycEdXNnhRNWpjM1ZKUFUrN1hySVAxT0ttckY4VDdiWGkyYWo3UFF3V2NqREFUUVZPWTdUaFBkbEwiLCJtYWMiOiIxMmNlMzlmYTZlODRmOGM3YTg4NGY5NGE4ODZmMTRiYWJiNjAxNGM5NThmZTQzYTJhMDU0YTkwOTExYjlmZjIzIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IlBQR1dHc280em1oQXBJSVlJVmhBS3c9PSIsInZhbHVlIjoiaythZVpMNmUwU05XM2FzRnNRbGF4TGxvbTB0UXQxcTRCclpqcU5qSlFUUTlsR1d4alNZcko5ODJ" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IlEvMEkwM2g3V2NHdVF5Zk84QWd6WXc9PSIsInZhbHVlIjoidWp0czBWaTJEV3lpcXlQRlFiZVNHUjhIZklvSHRabWxibDVZWHVFWmdRQWdxRW5TbE9FN25DTUhVWUswcCtkNVBiR3h0Z01MSWFIdnNJbXlWZlZlNk9la2JqVlVnQlZ1MWVqZW40OU9QTWRXamVPZ2l3ZjJDd0kwZmFpSWxaaHYiLCJtYWMiOiI5Zjc0ZGVjYTViMGI5ZGFiZmU4NTU1NGExOTRlZTVkYmY4ODZhZWI3YTEyYmJlZTg2NDU1MGJmMDMzZjJjYTJmIiwidGFnIjoiIn0%3D; expires=Sat, 22-Feb-2025 06:13:30 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IlEvMEkwM2g3V2NHdVF5Zk84QWd6WXc9PSIsInZhbHVlIjoidWp0czBWaTJEV3lpcXlQRlFiZVNHUjhIZklvSHRabWxibDVZWHVFWmdRQWdxRW5TbE9FN25DTUhVWUswcCtkNVBiR3h0Z" 1 => "alphaeurekaselectnet_session=eyJpdiI6IlBQR1dHc280em1oQXBJSVlJVmhBS3c9PSIsInZhbHVlIjoiaythZVpMNmUwU05XM2FzRnNRbGF4TGxvbTB0UXQxcTRCclpqcU5qSlFUUTlsR1d4alNZcko5ODJZU1BPSEFIR3dINXBhVWRycEdXNnhRNWpjM1ZKUFUrN1hySVAxT0ttckY4VDdiWGkyYWo3UFF3V2NqREFUUVZPWTdUaFBkbEwiLCJtYWMiOiIxMmNlMzlmYTZlODRmOGM3YTg4NGY5NGE4ODZmMTRiYWJiNjAxNGM5NThmZTQzYTJhMDU0YTkwOTExYjlmZjIzIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IlBQR1dHc280em1oQXBJSVlJVmhBS3c9PSIsInZhbHVlIjoiaythZVpMNmUwU05XM2FzRnNRbGF4TGxvbTB0UXQxcTRCclpqcU5qSlFUUTlsR1d4alNZcko5ODJ" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "4LqVo2c5ZL2TpXXW5BC7MuBGswyWSj72mTtVuoQo" "uc_cart_id" => "16c09457e166a7c75d171ea1579f5941" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/15069" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-19 18:13:30GET/chapter/150691121917