Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections
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  • 英文篇名:Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections
  • 作者:Lynne ; Vernice ; Mc ; Farland ; Metehan ; Ozen ; Ener ; Cagri ; Dinleyici ; Shan ; Goh
  • 英文作者:Lynne Vernice Mc Farland;Metehan Ozen;Ener Cagri Dinleyici;Shan Goh;Department of Medicinal Chemistry,School of Pharmacy,University of Washington;Faculty of Medicine,Department of Pediatrics,Division of Pediatric Infectious Disease,atakent acibadem University Hospital;Faculty of Medicine,Department of Pediatrics,Pediatric Intensive Care Unit,Eskisehir Osmangazi University;Department of Pathology and Pathogen Biology,Royal Veterinary College;
  • 英文关键词:Antibiotics;;Antibiotic-associated diarrhea;;Clostridum difficile infections;;Adults;;Pediatrics;;Diarrhea;;Risk factors;;Treatments;;Prevention
  • 中文刊名:ZXXY
  • 英文刊名:世界胃肠病学杂志(英文版)
  • 机构:Department of Medicinal Chemistry,School of Pharmacy,University of Washington;Faculty of Medicine,Department of Pediatrics,Division of Pediatric Infectious Disease,atakent acibadem University Hospital;Faculty of Medicine,Department of Pediatrics,Pediatric Intensive Care Unit,Eskisehir Osmangazi University;Department of Pathology and Pathogen Biology,Royal Veterinary College;
  • 出版日期:2016-03-21
  • 出版单位:World Journal of Gastroenterology
  • 年:2016
  • 期:v.22
  • 语种:英文;
  • 页:ZXXY201611003
  • 页数:27
  • CN:11
  • 分类号:24-50
摘要
Antibiotic-associated diarrhea(AAD) and Clostridum difficile infections(CDI) have been well studied for adult cases, but not as well in the pediatric population. Whether the disease process or response to treatments differs between pediatric and adult patients is an important clinical concern when following global guidelines based largely on adult patients. A systematic review of the literature using databases Pub Med(June 3, 1978-2015) was conducted to compare AAD and CDI in pediatric and adult populations and determine significant differences and similarities that might impact clinical decisions. In general, pediatric AAD and CDI have a more rapid onset of symptoms, a shorter duration of disease and fewer CDI complications(required surgeries and extended hospitalizations) than in adults. Children experience more community-associated CDI and are associated with smaller outbreaks than adult cases of CDI. The ribotype NAP1/027/BI is more common in adults than children. Children and adults share some similar risk factors, but adults have more complex risk factor profiles associated with more co-morbidities, types of disruptive factors and a wider range of exposures to C. difficile in the healthcare environment. The treatment of pediatric and adult AAD is similar(discontinuing or switching the inciting antibiotic), but other treatment strategies for AAD have not been established. Pediatric CDI responds better to metronidazole, while adult CDI responds better to vancomycin. Recurrent CDI is not commonly reported for children. Prevention for both pediatric and adult AAD and CDI relies upon integrated infection control programs, antibiotic stewardship and may include the use of adjunctive probiotics. Clinical presentation of pediatric AAD and CDI are different than adult AAD and CDI symptoms. These differences should be taken into account when rating severity of disease and prescribing antibiotics.
        Antibiotic-associated diarrhea(AAD) and Clostridum difficile infections(CDI) have been well studied for adult cases, but not as well in the pediatric population. Whether the disease process or response to treatments differs between pediatric and adult patients is an important clinical concern when following global guidelines based largely on adult patients. A systematic review of the literature using databases Pub Med(June 3, 1978-2015) was conducted to compare AAD and CDI in pediatric and adult populations and determine significant differences and similarities that might impact clinical decisions. In general, pediatric AAD and CDI have a more rapid onset of symptoms, a shorter duration of disease and fewer CDI complications(required surgeries and extended hospitalizations) than in adults. Children experience more community-associated CDI and are associated with smaller outbreaks than adult cases of CDI. The ribotype NAP1/027/BI is more common in adults than children. Children and adults share some similar risk factors, but adults have more complex risk factor profiles associated with more co-morbidities, types of disruptive factors and a wider range of exposures to C. difficile in the healthcare environment. The treatment of pediatric and adult AAD is similar(discontinuing or switching the inciting antibiotic), but other treatment strategies for AAD have not been established. Pediatric CDI responds better to metronidazole, while adult CDI responds better to vancomycin. Recurrent CDI is not commonly reported for children. Prevention for both pediatric and adult AAD and CDI relies upon integrated infection control programs, antibiotic stewardship and may include the use of adjunctive probiotics. Clinical presentation of pediatric AAD and CDI are different than adult AAD and CDI symptoms. These differences should be taken into account when rating severity of disease and prescribing antibiotics.
引文
1 Mc Farland LV,Brandmarker Sa,Guandalini S.Pediatric Clostridium difficile:a phantom menace or clinical reality?J Pediatr Gastroenterol Nutr 2000;31:220-231[PMID:10997362]
    2 Surawicz CM,Brandt LJ,Binion DG,ananthakrishnan a N,Curry SR,Gilligan PH,Mc Farland LV,Mellow M,Zuckerbraun BS.Guidelines for diagnosis,treatment,and prevention of Clostridium difficile infections.Am J Gastroenterol 2013;108:478-498;quiz499[PMID:23439232]
    3 Cheng AC,Ferguson JK,Richards MJ,Robson JM,Gilbert GL,Mc Gregor a,Roberts S,Korman TM,Riley TV.australasian Society for Infectious Diseases guidelines for the diagnosis and treatment of Clostridium difficile infection.Med J Aust 2011;194:353-358[PMID:21470086]
    4 Wendt JM,Cohen Ja,Mu Y,Dumyati GK,Dunn JR,Holzbauer SM,Winston LG,Johnston HL,Meek JI,Farley MM,Wilson LE,Phipps EC,Beldavs ZG,Gerding DN,Mc Donald LC,Gould CV,Lessa FC.Clostridium difficile infection among children across diverse US geographic locations.Pediatrics 2014;133:651-658[PMID:24590748 DOI:10.1542/peds.2013-3049]
    5 Zilberberg MD,Tillotson GS,Mc Donald C.Clostridium difficile infections among hospitalized children,United States,1997-2006.Emerg Infect Dis 2010;16:604-609[PMID:20350373 DOI:10 .3201/eid1604.090680]
    6 Sammons JS,Toltzis P.Recent trends in the epidemiology and treatment of C.difficile infection in children.Curr Opin Pediatr 2013;25:116-121[PMID:23241874 DOI:10.1097/MOP.obo13e32835bf6c0]
    7 Zilberberg MD,Tabak YP,Sievert DM,Derby KG,Johannes RS,Sun X,Mc Donald LC.Using electronic health information to risk-stratify rates of Clostridium difficile infection in US hospitals.Infect Control Hosp Epidemiol 2011;32:649-655[PMID:21666394 DOI:10.1086/660360]
    8 Evans CT,Safdar N.Current Trends in the Epidemiology and Outcomes of Clostridium difficile Infection.Clin Infect Dis 2015;60 Suppl 2:S66-S71[PMID:25922403 DOI:10.1093/cid/civ140]
    9 Lessa FC,Winston LG,Mc Donald LC.Burden of Clostridium difficile infection in the United States.N Engl J Med 2015;372:2369-2370[PMID:26061850 DOI:10.1056/NEJMc1505190]
    10 Kwon JH,Olsen Ma,Dubberke ER.The morbidity,mortality,and costs associated with Clostridium difficile infection.Infect Dis Clin North Am 2015;29:123-134[PMID:25677706 DOI:10.1016/j.idc.2014.11.003]
    11 Mc Farland LV.antibiotic-associated diarrhea:epidemiology,trends and treatment.Future Microbiol 2008;3:563-578[PMID:18811240 DOI:10.2217/17460913.3.5.563]
    12 Crews JD,Koo HL,Jiang ZD,Starke JR,Du Pont HL.a hospitalbased study of the clinical characteristics of Clostridium difficile infection in children.Pediatr Infect Dis J 2014;33:924-928[PMID:25361022 DOI:10.1097/INF.0000000000000338]
    13 Na JY,Park JM,Lee KS,Kang JO,Oh SH,Kim YJ.Clinical Characteristics of Symptomatic Clostridium difficile Infection in Children:Conditions as Infection Risks and Whether Probiotics Is Effective.Pediatr Gastroenterol Hepatol Nutr 2014;17:232-238[PMID:25587523 DOI:10.5223/pghn.2014.17.4.232]
    14 Nylund CM,Goudie a,Garza JM,Fairbrother G,Cohen MB.Clostridium difficile infection in hospitalized children in the United States.Arch Pediatr Adolesc Med 2011;165:451-457[PMID:21199971 DOI:10.1001/archpediatrics.2010.282]
    15 Jangi S,Lamont JT.asymptomatic colonization by Clostridium difficile in infants:implications for disease in later life.J Pediatr Gastroenterol Nutr 2010;51:2-7[PMID:20512057 DOI:10.1097/MPG.0b013e3181d29767]
    16 World Health Organization.WHO definition of diarrhea.accessed on November 13,2015.available from:URL:http://www.who.int/topics/diarrhoea/en/
    17 Khanna S,Pardi DS,aronson SL,Kammer PP,Orenstein R,St Sauver JL,Harmsen WS,Zinsmeister a R.The epidemiology of community-acquired Clostridium difficile infection:a populationbased study.Am J Gastroenterol 2012;107:89-95[PMID:22108454 DOI:10.1038/ajg.2011.398]
    18 Dul?ba K,Paw?owska M,Wietlicka-Piszcz M.Clostridium difficile infection in children hospitalized due to diarrhea.Eur J Clin Microbiol Infect Dis 2014;33:201-209[PMID:24213847DOI:10.1007/s10096-013-1946-1]
    19 Mc Farland LV,Goh S.Preventing Pediatric antibiotic-associated Diarrhea and Clostridium difficile Infections with Probiotics:a meta-analysis.World J Meta-analysis 2013;1:102-120[DOI:10 .13105/wjma.v1.i3.102]
    20 Alam S,Mushtaq M.antibiotic associated diarrhea in children.Indian Pediatr 2009;46:491-496[PMID:19556659]
    21 Arvola T,Laiho K,Torkkeli S,Mykk?nen H,Salminen S,Maunula L,Isolauri E.Prophylactic Lactobacillus GG reduces antibiotic-associated diarrhea in children with respiratory infections:a randomized study.Pediatrics 1999;104:e64[PMID:10545590]
    22 Asha NJ,Tompkins D,Wilcox MH.Comparative analysis of prevalence,risk factors,and molecular epidemiology of antibioticassociated diarrhea due to Clostridium difficile,Clostridium perfringens,and Staphylococcus aureus.J Clin Microbiol 2006;44:2785-2791[PMID:16891493]
    23 Dietrich CG,Kottmann T,alavi M.Commercially available probiotic drinks containing Lactobacillus casei DN-114001 reduce antibiotic-associated diarrhea.World J Gastroenterol 2014;20:15837-15844[PMID:25400470 DOI:10.3748/wjg.v20.i42.15837]
    24 Pituch H,Obuch-Woszczatyński P,Wultańska D,van Belkum A,Meisel-Miko?ajczyk F,?uczak M.Laboratory diagnosis of antibiotic-associated diarrhea:a Polish pilot study into the clinical relevance of Clostridium difficile and Clostridium perfringens toxins.Diagn Microbiol Infect Dis 2007;58:71-75[PMID:17300901]
    25 Peled N,Pitlik S,Samra Z,Kazakov a,Bloch Y,Bishara J.Predicting Clostridium difficile toxin in hospitalized patients with antibiotic-associated diarrhea.Infect Control Hosp Epidemiol2007;28:377-381[PMID:17385141]
    26 H?genauer C,Langner C,Beubler E,Lippe IT,Schicho R,Gorkiewicz G,Krause R,Gerstgrasser N,Krejs GJ,Hinterleitner Ta.Klebsiella oxytoca as a causative organism of antibioticassociated hemorrhagic colitis.N Engl J Med 2006;355:2418-2426[PMID:17151365]
    27 Ackermann G,Thomalla S,ackermann F,Schaumann R,Rodloff a C,Ruf BR.Prevalence and characteristics of bacteria and host factors in an outbreak situation of antibiotic-associated diarrhoea.J Med Microbiol 2005;54:149-153[PMID:15673508]
    28 Cohen SH,Gerding DN,Johnson S,Kelly CP,Loo VG,Mc Donald LC,Pepin J,Wilcox MH.Clinical practice guidelines for Clostridium difficile infection in adults:2010 update by the society for healthcare epidemiology of america(SHEa)and the infectious diseases society of america(IDSa).Infect Control Hosp Epidemiol 2010;31:431-455[PMID:20307191 DOI:10 .1086/651706]
    29 Lübbert C,John E,von Müller L.Clostridium difficile infection:guideline-based diagnosis and treatment.Dtsch Arztebl Int 2014;111:723-731[PMID:25404529 DOI:10.3238/arztebl.2014.0723]
    30 Mc Farland LV.[Risk factor for antibiotic-associated diarrhea.a review of the literature].Ann Med Interne(Paris)1998;149:261-266[PMID:9791558]
    31 Wistr?m J,Norrby SR,Myhre EB,Eriksson S,Granstr?m G,Lagergren L,Englund G,Nord CE,Svenungsson B.Frequency of antibiotic-associated diarrhoea in 2462 antibiotic-treated hospitalized patients:a prospective study.J Antimicrob Chemother2001;47:43-50[PMID:11152430]
    32 Benno Y,Sawada K,Mitsuoka T.The intestinal microflora of infants:composition of fecal flora in breast-fed and bottle-fed infants.Microbiol Immunol 1984;28:975-986[PMID:6513816]
    33 Penders J,Vink C,Driessen C,London N,Thijs C,Stobberingh EE.Quantification of Bifidobacterium spp.,Escherichia coli and Clostridium difficile in faecal samples of breast-fed and formulafed infants by real-time PCR.FEMS Microbiol Lett 2005;243:141-147[PMID:15668012]
    34 Vanderhoof JA,Whitney DB,antonson DL,Hanner TL,Lupo JV,Young RJ.Lactobacillus GG in the prevention of antibioticassociated diarrhea in children.J Pediatr 1999;135:564-568[PMID:10547243]
    35 Xie C,Li J,Wang K,Li Q,Chen D.Probiotics for the prevention of antibiotic-associated diarrhoea in older patients:a systematic review.Travel Med Infect Dis 2015;13:128-134[PMID:25805164DOI:10.1016/j.tmaid.2015.03.001]
    36 Lusk RH,Fekety FR,Silva J,Bodendorfer T,Devine BJ,Kawanishi H,Korff L,Nakauchi D,Rogers S,Siskin SB.Gastrointestinal side effects of clindamycin and ampicillin therapy.J Infect Dis 1977;135 Suppl:S111-S119[PMID:850084]
    37 Elseviers MM,Van Camp Y,Nayaert S,DuréK,annemans L,Tanghe a,Vermeersch S.Prevalence and management of antibiotic associated diarrhea in general hospitals.BMC Infect Dis 2015;15:129[PMID:25888351 DOI:10.1186/s12879-015-08690]
    38 Sathyendran V,Mcauliffe GN,Swager T,Freeman JT,Taylor SL,Roberts Sa.Clostridium difficile as a cause of healthcareassociated diarrhoea among children in auckland,New Zealand:clinical and molecular epidemiology.Eur J Clin Microbiol Infect Dis 2014;33:1741-1747[PMID:24810967 DOI:10.1007/s10096-014-2139-2]
    39 Matsuki S,Ozaki E,Shozu M,Inoue M,Shimizu S,Yamaguchi N,Karasawa T,Yamagishi T,Nakamura S.Colonization by Clostridium difficile of neonates in a hospital,and infants and children in three day-care facilities of Kanazawa,Japan.Int Microbiol 2005;8:43-48[PMID:15906260]
    40 Khanna S,Baddour LM,Huskins WC,Kammer PP,Faubion Wa,Zinsmeister a R,Harmsen WS,Pardi DS.The epidemiology of Clostridium difficile infection in children:a population-based study.Clin Infect Dis 2013;56:1401-1406[PMID:23408679DOI:10.1093/cid/cit075]
    41 Kim K,Du Pont HL,Pickering LK.Outbreaks of diarrhea associated with Clostridium difficile and its toxin in day-care centers:evidence of person-to-person spread.J Pediatr 1983;102:376-382[PMID:6827409 DOI:10.1016/S0022-3476(83)80652-0]
    42 Mc Farland LV,Surawicz CM,Greenberg RN,Bowen KE,Melcher Sa,Mulligan ME.Possible role of cross-transmission between neonates and mothers with recurrent Clostridium difficile infections.Am J Infect Control 1999;27:301-303[PMID:10358237]
    43 S?es LM,Holt HM,B?ttiger B,Nielsen HV,Torpdahl M,Nielsen EM,Ethelberg S,M?lbak K,andreasen V,Kemp M,Olsen KE.The incidence and clinical symptomatology of Clostridium difficile infections in a community setting in a cohort of Danish patients attending general practice.Eur J Clin Microbiol Infect Dis 2014;33:957-967[PMID:24352841 DOI:10.1007/s10096-013-2033-3]
    44 Sammons JS,Localio R,Xiao R,Coffin SE,Zaoutis T.Clostridium difficile infection is associated with increased risk of death and prolonged hospitalization in children.Clin Infect Dis2013;57:1-8[PMID:23532470]
    45 McFarland LV,Mulligan ME,Kwok RY,Stamm WE.Nosocomial acquisition of Clostridium difficile infection.N Engl J Med 1989;320:204-210[PMID:2911306]
    46 Chopra T,Goldstein EJ.Clostridium difficile Infection in Long-term Care Facilities:a Call to action for antimicrobial Stewardship.Clin Infect Dis 2015;60 Suppl 2:S72-S76[PMID:25922404]
    47 Ferroni A,Merckx J,ancelle T,Pron B,abachin E,Barbut F,Larzul J,Rigault P,Berche P,Gaillard JL.Nosocomial outbreak of Clostridium difficile diarrhea in a pediatric service.Eur J Clin Microbiol Infect Dis 1997;16:928-933[PMID:9495676]
    48 Cartwright CP,Stock F,Beekmann SE,Williams EC,Gill VJ.PCR amplification of r RNA intergenic spacer regions as a method for epidemiologic typing of Clostridium difficile.J Clin Microbiol1995;33:184-187[PMID:7699038]
    49 Delmée M,Verellen G,avesani V,Francois G.Clostridium difficile in neonates:serogrouping and epidemiology.Eur J Pediatr1988;147:36-40[PMID:3338476]
    50 Toltzis P,Kim J,Dul M,Zoltanski J,Smathers S,Zaoutis T.Presence of the epidemic North american Pulsed Field type 1 Clostridium difficile strain in hospitalized children.J Pediatr 2009;154:607-608[PMID:19324222 DOI:10.1016/j.jpeds.2008.10.016]
    51 von Müller L,Mock M,Halfmann a,Stahlmann J,Simon a,Herrmann M.Epidemiology of Clostridium difficile in Germany based on a single center long-term surveillance and German-wide genotyping of recent isolates provided to the advisory laboratory for diagnostic reasons.Int J Med Microbiol 2015;305:807-813[PMID:26341328 DOI:10.1016/j.ijmm.2015.08.035]
    52 Stoesser N,Crook DW,Fung R,Griffiths D,Harding RM,Kachrimanidou M,Keshav S,Peto TE,Vaughan a,Walker a S,Dingle KE.Molecular epidemiology of Clostridium difficile strains in children compared with that of strains circulating in adults with Clostridium difficile-associated infection.J Clin Microbiol 2011;49:3994-3996[PMID:21940476 DOI:10.1128/JCM.05349-11]
    53 Rousseau C,Poilane I,De Pontual L,Maherault a C,Le Monnier A,Collignon A.Clostridium difficile carriage in healthy infants in the community:a potential reservoir for pathogenic strains.Clin Infect Dis 2012;55:1209-1215[PMID:22843784 DOI:10.1093/cid/cis637]
    54 Hart J,Putsathit P,Knight DR,Sammels L,Riley TV,Keil a.Clostridium difficile infection diagnosis in a paediatric population:comparison of methodologies.Eur J Clin Microbiol Infect Dis 2014;33:1555-1564[PMID:24781004 DOI:10.1007/s10096-014-2108-9]
    55 Gaynes R,Rimland D,Killum E,Lowery HK,Johnson TM,Killgore G,Tenover FC.Outbreak of Clostridium difficile infection in a long-term care facility:association with gatifloxacin use.Clin Infect Dis 2004;38:640-645[PMID:14986246]
    56 Johnson S,Samore MH,Farrow Ka,Killgore GE,Tenover FC,Lyras D,Rood JI,De Girolami P,Baltch a L,Rafferty ME,Pear SM,Gerding DN.Epidemics of diarrhea caused by a clindamycinresistant strain of Clostridium difficile in four hospitals.N Engl J Med 1999;341:1645-1651[PMID:10572152]
    57 Loo VG,Poirier L,Miller Ma,Oughton M,Libman MD,Michaud S,Bourgault a M,Nguyen T,Frenette C,Kelly M,Vibien a,Brassard P,Fenn S,Dewar K,Hudson TJ,Horn R,RenéP,Monczak Y,Dascal a.a predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality.N Engl J Med 2005;353:2442-2449[PMID:16322602]
    58 Pépin J,Valiquette L,Cossette B.Mortality attributable to nosocomial Clostridium difficile-associated disease during an epidemic caused by a hypervirulent strain in Quebec.CMAJ 2005;173:1037-1042[PMID:16179431]
    59 Muto CA,Pokrywka M,Shutt K,Mendelsohn a B,Nouri K,Posey K,Roberts T,Croyle K,Krystofiak S,Patel-Brown S,Pasculle a W,Paterson DL,Saul M,Harrison LH.a large outbreak of Clostridium difficile-associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased fluoroquinolone use.Infect Control Hosp Epidemiol 2005;26:273-280[PMID:15796280]
    60 Jump RL,Riggs MM,Sethi a K,Pultz MJ,Ellis-Reid T,Riebel W,Gerding DN,Salata Ra,Donskey CJ.Multihospital outbreak of Clostridium difficile infection,Cleveland,Ohio,USA.Emerg Infect Dis 2010;16:827-829[PMID:20409374 DOI:10.3201/eid1605.071606]
    61 Lam TS,Yuk MT,Tsang NC,Wong MH,Chuang SK.Clostridium difficile infection outbreak in a male rehabilitation ward,Hong Kong Special administrative Region(China),2011.Western Pac Surveill Response J 2012;3:59-60[PMID:23908942 DOI:10 .5365/wpsar.2012.3.4.001]
    62 Miller M,Gravel D,Mulvey M,Taylor G,Boyd D,Simor a,Gardam M,Mc Geer a,Hutchinson J,Moore D,Kelly S.Health care-associated Clostridium difficile infection in Canada:patient age and infecting strain type are highly predictive of severe outcome and mortality.Clin Infect Dis 2010;50:194-201[PMID:20025526 DOI:10.1086/649213]
    63 Turck D,Bernet JP,Marx J,Kempf H,Giard P,Walbaum O,Lacombe a,Rembert F,Toursel F,Bernasconi P,Gottrand F,Mc Farland LV,Bloch K.Incidence and risk factors of oral antibiotic-associated diarrhea in an outpatient pediatric population.J Pediatr Gastroenterol Nutr 2003;37:22-26[PMID:12827001]
    64 Mc Farland LV,Surawicz CM,Stamm WE.Risk factors for Clostridium difficile carriage and C.difficile-associated diarrhea in a cohort of hospitalized patients.J Infect Dis 1990;162:678-684[PMID:2387993]
    65 Huang H,Wu S,Chen R,Xu S,Fang H,Weintraub a,Nord CE.Risk factors of Clostridium difficile infections among patients in a university hospital in Shanghai,China.Anaerobe 2014;30:65-69[PMID:25219941 DOI:10.1016/j.anaerobe.2014.08.015]
    66 Sandora TJ,Fung M,Flaherty K,Helsing L,Scanlon P,PotterBynoe G,Gidengil Ca,Lee GM.Epidemiology and risk factors for Clostridium difficile infection in children.Pediatr Infect Dis J 2011;30:580-584[PMID:21233782 DOI:10.1097/INF.0b013e31820bfb29]
    67 Tai E,Richardson LC,Townsend J,Howard E,Mcdonald LC.Clostridium difficile infection among children with cancer.Pediatr Infect Dis J 2011;30:610-612[PMID:21206395 DOI:10.1097/INF.0b013e31820970d1]
    68 Samady W,Bush R,Pong a,andrews a,Fisher ES.Predictors of Clostridium difficile infections in hospitalized children.J Hosp Med 2014;9:94-98[PMID:24343932 DOI:10.1002/jhm.2135]
    69 de Blank P,Zaoutis T,Fisher B,Troxel a,Kim J,aplenc R.Trends in Clostridium difficile infection and risk factors for hospital acquisition of Clostridium difficile among children with cancer.J Pediatr 2013;163:699-705.e1[PMID:23477996 DOI:10 .1016/j.jpeds.2013.01.062]
    70 Benson L,Song X,Campos J,Singh N.Changing epidemiology of Clostridium difficile-associated disease in children.Infect Control Hosp Epidemiol 2007;28:1233-1235[PMID:17926272]
    71 Pai S,aliyu SH,Enoch Da,Karas Ja.Five years experience of Clostridium difficile infection in children at a UK tertiary hospital:proposed criteria for diagnosis and management.PLo S One 2012;7:e51728[PMID:23300561 DOI:10.1371/journal.pone.0051728]
    72 Tschudin-Sutter S,Tamma PD,Naegeli a N,Speck Ka,Milstone a M,Perl TM.Distinguishing community-associated from hospitalassociated Clostridium difficile infections in children:implications for public health surveillance.Clin Infect Dis 2013;57:1665-1672[PMID:24046303 DOI:10.1093/cid/cit581]
    73 Vesteinsdottir I,Gudlaugsdottir S,Einarsdottir R,Kalaitzakis E,Sigurdardottir O,Bjornsson ES.Risk factors for Clostridium difficile toxin-positive diarrhea:a population-based prospective case-control study.Eur J Clin Microbiol Infect Dis 2012;31:2601-2610[PMID:22441775]
    74 Vardakas KZ,Konstantelias aa,Loizidis G,Rafailidis PI,Falagas ME.Risk factors for development of Clostridium difficile infection due to BI/Na P1/027 strain:a meta-analysis.Int J Infect Dis 2012;16 :e768-e773[PMID:22921930 DOI:10.1016/j.ijid.2012.07.010]
    75 Fellmeth G,Yarlagadda S,Iyer S.Epidemiology of communityonset Clostridium difficile infection in a community in the South of England.J Infect Public Health 2010;3:118-123[PMID:20869672DOI:10.1016/j.jiph.2010.07.002]
    76 Damrongmanee A,Ukarapol N.Incidence of antibiotic-associated diarrhea in a pediatric ambulatory care setting.J Med Assoc Thai2007;90:513-517[PMID:17427529]
    77 Corrêa NB,Péret Filho La,Penna FJ,Lima FM,Nicoli JR.a randomized formula controlled trial of Bifidobacterium lactis and Streptococcus thermophilus for prevention of antibiotic-associated diarrhea in infants.J Clin Gastroenterol 2005;39:385-389[PMID:15815206]
    78 Ruszczyński M,Radzikowski a,Szajewska H.Clinical trial:effectiveness of Lactobacillus rhamnosus(strains E/N,Oxy and Pen)in the prevention of antibiotic-associated diarrhoea in children.Aliment Pharmacol Ther 2008;28:154-161[PMID:18410562 DOI:10.111/j.1365-2036.2008.03714.x]
    79 Can M,Be?irbellioglu BA,Avci IY,Beker CM,Pahsa A.Prophylactic Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea:a prospective study.Med Sci Monit2006;12:PI19-PI22[PMID:16572062]
    80 Yapar N,Sener a,Karaca B,Yucesoy M,Tarakci H,Cakir N,Yuce a.antibiotic-associated diarrhea in a Turkish outpatient population:investigation of 288 cases.J Chemother 2005;17:77-81[PMID:15828448]
    81 Hickson M,D’Souza a L,Muthu N,Rogers TR,Want S,Rajkumar C,Bulpitt CJ.Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics:randomised double blind placebo controlled trial.BMJ 2007;335:80[PMID:17604300]
    82 De La Cochetière MF,Durand T,Lalande V,Petit JC,Potel G,Beaugerie L.Effect of antibiotic therapy on human fecal microbiota and the relation to the development of Clostridium difficile.Microb Ecol 2008;56:395-402[PMID:18209965]
    83 Young VB,Schmidt TM.antibiotic-associated diarrhea accompanied by large-scale alterations in the composition of the fecal microbiota.J Clin Microbiol 2004;42:1203-1206[PMID:15004076]
    84 Dethlefsen L,Huse S,Sogin ML,Relman Da.The pervasive effects of an antibiotic on the human gut microbiota,as revealed by deep 16S r RNa sequencing.PLo S Biol 2008;6:e280[PMID:19018661 DOI:10.1371/journal.pbio.0060280]
    85 Mitchell DK,Van R,Mason EH,Norris DM,Pickering LK.Prospective study of toxigenic Clostridium difficile in children given amoxicillin/clavulanate for otitis media.Pediatr Infect Dis J1996;15:514-519[PMID:8783348]
    86 Chang HT,Krezolek D,Johnson S,Parada JP,Evans CT,Gerding DN.Onset of symptoms and time to diagnosis of Clostridium difficile-associated disease following discharge from an acute care hospital.Infect Control Hosp Epidemiol 2007;28:926-931[PMID:17620239]
    87 Kutty PK,Benoit SR,Woods CW,Sena a C,Naggie S,Frederick J,Engemann J,Evans S,Pien BC,Banerjee SN,Engel J,Mc Donald LC.assessment of Clostridium difficile-associated disease surveillance definitions,North Carolina,2005.Infect Control Hosp Epidemiol 2008;29:197-202[PMID:18241032 DOI:10 .1086/528813]
    88 Walters BA,Roberts R,Stafford R,Seneviratne E.Relapse of antibiotic associated colitis:endogenous persistence of Clostridium difficile during vancomycin therapy.Gut 1983;24:206-212[PMID:6826104]
    89 Mc Farland LV,Surawicz CM,Rubin M,Fekety R,Elmer GW,Greenberg RN.Recurrent Clostridium difficile disease:epidemiology and clinical characteristics.Infect Control Hosp Epidemiol 1999;20:43-50[PMID:9927265]
    90 Figueroa I,Johnson S,Sambol SP,Goldstein EJ,Citron DM,Gerding DN.Relapse versus reinfection:recurrent Clostridium difficile infection following treatment with fidaxomicin or vancomycin.Clin Infect Dis 2012;55 Suppl 2:S104-S109[PMID:22752857 DOI:10.1093/cid/cis357]
    91 Barbut F,Richard a,Hamadi K,Chomette V,Burghoffer B,Petit JC.Epidemiology of recurrences or reinfections of Clostridium difficile-associated diarrhea.J Clin Microbiol 2000;38:2386-2388[PMID:10835010]
    92 Johnston BC,Shamseer L,da Costa BR,Tsuyuki RT,Vohra S.Measurement issues in trials of pediatric acute diarrheal diseases:a systematic review.Pediatrics 2010;126:e222-e231[PMID:20566617 DOI:10.1542/peds.2009-3667]
    93 Shan LS,Hou P,Wang ZJ,Liu FR,Chen N,Shu LH,Zhang H,Han XH,Han XX,Cai XX,Shang YX,Vandenplas Y.Prevention and treatment of diarrhoea with Saccharomyces boulardii in children with acute lower respiratory tract infections.Benef Microbes 2013;4:329-334[PMID:24311316]
    94 Gogate A,De a,Nanivadekar R,Mathur M,Saraswathi K,Jog a,Kulkarni MV.Diagnostic role of stool culture&toxin detection in antibiotic associated diarrhoea due to Clostridium difficile in children.Indian J Med Res 2005;122:518-524[PMID:16518003]
    95 Vidrine SR,Cortina C,Black M,Vidrine SB.Simultaneous acute appendicitis and pseudomembranous colitis in a pediatric patient.J La State Med Soc 2012;164:265-267[PMID:23362591]
    96 Mc Farland LV,Bauwens JE,Melcher Sa,Surawicz CM,Greenberg RN,Elmer GW.Ciprofloxacin-associated Clostridium difficile disease.Lancet 1995;346:977-978[PMID:7564771]
    97 Denno DM,Shaikh N,Stapp JR,Qin X,Hutter CM,Hoffman V,Mooney JC,Wood KM,Stevens HJ,Jones R,Tarr PI,Klein EJ.Diarrhea etiology in a pediatric emergency department:a case control study.Clin Infect Dis 2012;55:897-904[PMID:22700832DOI:10.1093/cid/cis553]
    98 Kim J,Shaklee JF,Smathers S,Prasad P,asti L,Zoltanski J,Dul M,Nerandzic M,Coffin SE,Toltzis P,Zaoutis T.Risk factors and outcomes associated with severe clostridium difficile infection in children.Pediatr Infect Dis J 2012;31:134-138[PMID:22031485DOI:10.1097/INF.0b013e3182352e2c]
    99 Castillo A,López J,Panadero E,CerdáJ,Padilla B,Bustinza a.Conservative surgical treatment for toxic megacolon due to Clostridium difficile infection in a transplanted pediatric patient.Transpl Infect Dis 2012;14:E34-E37[PMID:22726419 DOI:10 .1111/j.1399-3062.2012.00756.x]
    100 Morinville V,Mc Donald J.Clostridium difficile-associated diarrhea in 200 Canadian children.Can J Gastroenterol 2005;19:497-501[PMID:16107901]
    101 Kyne L,Merry C,O’Connell B,Kelly a,Keane C,O’Neill D.Factors associated with prolonged symptoms and severe disease due to Clostridium difficile.Age Ageing 1999;28:107-113[PMID:10350405]
    102 Wenisch JM,Schmid D,Kuo HW,Simons E,allerberger F,Michl V,Tesik P,Tucek G,Wenisch C.Hospital-acquired Clostridium difficile infection:determinants for severe disease.Eur J Clin Microbiol Infect Dis 2012;31:1923-1930[PMID:22210266 DOI:10 .1007/s10096-011-1522-5]
    103 Hsu MS,Wang JT,Huang WK,Liu YC,Chang SC.Prevalence and clinical features of Clostridium difficile-associated diarrhea in a tertiary hospital in northern Taiwan.J Microbiol Immunol Infect2006;39:242-248[PMID:16783456]
    104 Fujitani S,George WL,Murthy a R.Comparison of clinical severity score indices for Clostridium difficile infection.Infect Control Hosp Epidemiol 2011;32:220-228[PMID:21460506DOI:10.1086/658336]
    105 Khanafer N,Touréa,Chambrier C,Cour M,Reverdy ME,Argaud L,Vanhems P.Predictors of Clostridium difficile infection severity in patients hospitalised in medical intensive care.World J Gastroenterol 2013;19:8034-8041[PMID:24307797 DOI:10 .3748/wjg.v19.i44.8034]
    106 Pépin J,Valiquette L,alary ME,Villemure P,Pelletier a,Forget K,Pépin K,Chouinard D.Clostridium difficile-associated diarrhea in a region of Quebec from 1991 to 2003:a changing pattern of disease severity.CMAJ 2004;171:466-472[PMID:15337727]
    107 See I,Mu Y,Cohen J,Beldavs ZG,Winston LG,Dumyati G,Holzbauer S,Dunn J,Farley MM,Lyons C,Johnston H,Phipps E,Perlmutter R,anderson L,Gerding DN,Lessa FC.Na P1 strain type predicts outcomes from Clostridium difficile infection.Clin Infect Dis 2014;58:1394-1400[PMID:24604900 DOI:10.1093/cid/ciu125]
    108 Dallal RM,Harbrecht BG,Boujoukas a J,Sirio Ca,Farkas LM,Lee KK,Simmons RL.Fulminant Clostridium difficile:an underappreciated and increasing cause of death and complications.Ann Surg 2002;235:363-372[PMID:11882758]
    109 Koss K,Clark Ma,Sanders DS,Morton D,Keighley MR,Goh J.The outcome of surgery in fulminant Clostridium difficile colitis.Colorectal Dis 2006;8:149-154[PMID:16412077]
    110 Longo WE,Mazuski JE,Virgo KS,Lee P,Bahadursingh a N,Johnson FE.Outcome after colectomy for Clostridium difficile colitis.Dis Colon Rectum 2004;47:1620-1626[PMID:15540290]
    111 Mc Farland LV,Surawicz CM,Greenberg RN,Fekety R,Elmer GW,Moyer Ka,Melcher Sa,Bowen KE,Cox JL,Noorani Z.a randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease.JAMA 1994;271:1913-1918[PMID:8201735]
    112 Selinger CP,Bell a,Cairns a,Lockett M,Sebastian S,Haslam N.Probiotic VSL#3 prevents antibiotic-associated diarrhoea in a double-blind,randomized,placebo-controlled clinical trial.J Hosp Infect 2013;84:159-165[PMID:23618760 DOI:10.1016/j.jhin.2013.02.019]
    113 Song X,Bartlett JG,Speck K,Naegeli a,Carroll K,Perl TM.Rising economic impact of clostridium difficile-associated disease in adult hospitalized patient population.Infect Control Hosp Epidemiol 2008;29:823-828[PMID:18643746 DOI:10 .1086/588756]
    114 Kale-Pradhan PB,Jassal HK,Wilhelm SM.Role of Lactobacillus in the prevention of antibiotic-associated diarrhea:a meta-analysis.Pharmacotherapy 2010;30:119-126[PMID:20099986 DOI:10 .1592/phco.30.2.119]
    115 Kim J,Smathers SA,Prasad P,Leckerman KH,Coffin S,Zaoutis T.Epidemiological features of Clostridium difficile-associated disease among inpatients at children’s hospitals in the United States,2001-2006.Pediatrics 2008;122:1266-1270[PMID:19047244DOI:10.1532/peds.2008-0469]
    116 Mc Laughlin D,Friedmacher F,Puri P.The impact of Clostridium difficile on paediatric surgical practice:a systematic review.Pediatr Surg Int 2014;30:853-859[PMID:25008231 DOI:10 .1007/s00383-014-3543-5]
    117 Tabak YP,Zilberberg MD,Johannes RS,Sun X,Mc Donald LC.attributable burden of hospital-onset Clostridium difficile infection:a propensity score matching study.Infect Control Hosp Epidemiol 2013;34:588-596[PMID:23651889 DOI:10 .1086/670621]
    118 Eyre DW,Walker AS,Wyllie D,Dingle KE,Griffiths D,Finney J,O’Connor L,Vaughan a,Crook DW,Wilcox MH,Peto TE.Predictors of first recurrence of Clostridium difficile infection:implications for initial management.Clin Infect Dis 2012;55 Suppl2 :S77-S87[PMID:22752869 DOI:10.1093/cid/cis356]
    119 Gravel D,Miller M,Simor a,Taylor G,Gardam M,Mc Geer a,Hutchinson J,Moore D,Kelly S,Boyd D,Mulvey M.Health careassociated Clostridium difficile infection in adults admitted to acute care hospitals in Canada:a Canadian Nosocomial Infection Surveillance Program Study.Clin Infect Dis 2009;48:568-576[PMID:19191641 DOI:10.1086/596703]
    120 Bacci S,M?lbak K,Kjeldsen MK,Olsen KE.Binary toxin and death after Clostridium difficile infection.Emerg Infect Dis 2011;17:976-982[PMID:21749757 DOI:10.3201/eid/1706.101483]
    121 McFarland LV,Clarridge JE,Beneda HW,Raugi G J.Fluoroquinolone use and risk factors for Clostridium difficileassociated disease within a Veterans administration health care system.Clin Infect Dis 2007;45:1141-1151[PMID:17918075]
    122 Wullt M,Odenholt I.a double-blind randomized controlled trial of fusidic acid and metronidazole for treatment of an initial episode of Clostridium difficile-associated diarrhoea.J Antimicrob Chemother 2004;54:211-216[PMID:15163651]
    123 Bhangu S,Bhangu a,Nightingale P,Michael a.Mortality and risk stratification in patients with Clostridium difficile-associated diarrhoea.Colorectal Dis 2010;12:241-246[PMID:19508548DOI:10.1111/j.1463-1318.2009.01832.x]
    124 Lawrence SJ,Puzniak La,Shadel BN,Gillespie KN,Kollef MH,Mundy LM.Clostridium difficile in the intensive care unit:epidemiology,costs,and colonization pressure.Infect Control Hosp Epidemiol 2007;28:123-130[PMID:17265392]
    125 Mc Farland LV.From yaks to yogurt:the history,development,and current use of probiotics.Clin Infect Dis 2015;60 Suppl 2:S85-S90[PMID:25922406 DOI:10.1093/cid/civ054]
    126 Johnston BC,Goldenberg JZ,Vandvik PO,Sun X,Guyatt GH.Probiotics for the prevention of pediatric antibiotic-associated diarrhea.Cochrane Database Syst Rev 2011;(11):CD004827[PMID:22071814 DOI:10.1002/14651858.CD004827.pub3]
    127 Dinleyici EC,Kara a,Ozen M,Vandenplas Y.Saccharomyces boulardii CNCM I-745 in different clinical conditions.Expert Opin Biol Ther 2014;14:1593-1609[PMID:24995675 DOI:10.1517/14712598.2014.937419]
    128 Videlock EJ,Cremonini F.Meta-analysis:probiotics in antibioticassociated diarrhoea.Aliment Pharmacol Ther 2012;35:1355-1369[PMID:22531096]
    129 Hempel S,Newberry SJ,Maher a R,Wang Z,Miles JN,Shanman R,Johnsen B,Shekelle PG.Probiotics for the prevention and treatment of antibiotic-associated diarrhea:a systematic review and meta-analysis.JAMA 2012;307:1959-1969[PMID:22570464DOI:10.1001/jama.2012.3507]
    130 Pattani R,Palda Va,Hwang SW,Shah PS.Probiotics for the prevention of antibiotic-associated diarrhea and Clostridium difficile infection among hospitalized patients:systematic review and meta-analysis.Open Med 2013;7:e56-e67[PMID:24348885]
    131 Mc Farland LV.Systematic review and meta-analysis of Saccharomyces boulardii in adult patients.World J Gastroenterol2010;16:2202-2222[PMID:20458757 DOI:10.3748/wjg.v16.i18.2202]
    132 Szajewska H,Horvath A,Ko?odziej M.Systematic review with meta-analysis:Saccharomyces boulardii supplementation and eradication of Helicobacter pylori infection.Aliment Pharmacol Ther 2015;41:1237-1245[PMID:25898944 DOI:10.1111/apt.13214]
    133 Szajewska H,Ko?odziej M.Systematic review with meta-analysis:Lactobacillus rhamnosus GG in the prevention of antibioticassociated diarrhoea in children and adults.Aliment Pharmacol Ther 2015;42:1149-1157[PMID:26365389 DOI:10.1111/apt.13404]
    134 Johnston BC,Ma SS,Goldenberg JZ,Thorlund K,Vandvik PO,Loeb M,Guyatt GH.Probiotics for the prevention of Clostridium difficile-associated diarrhea:a systematic review and metaanalysis.Ann Intern Med 2012;157:878-888[PMID:23362517]
    135 Goldstein EJ,Johnson S,Maziade PJ,Mc Farland LV,Trick W,Dresser L,Millette M,Mazloum H,Low DE.Pathway to Prevention of Nosocomial Clostridium difficile Infection.Clin Infect Dis 2015;60 Suppl 2:S148-S158[PMID:25922401 DOI:10 .1093/cid/civ142]
    136 Srigley JA,Brooks a,Sung M,Yamamura D,Haider S,Mertz D.Inappropriate use of antibiotics and Clostridium difficile infection.Am J Infect Control 2013;41:1116-1118[PMID:23932828 DOI:10 .1016/j.ajic.2013.04.017]
    137 Johnson S,Maziade PJ,Mc Farland LV,Trick W,Donskey C,Currie B,Low DE,Goldstein EJ.Is primary prevention of Clostridium difficile infection possible with specific probiotics?Int J Infect Dis 2012;16:e786-e792[PMID:22863358 DOI:10.1016/j.ijid.2012.06.005]
    138 Mc Farland LV.Probiotics for the primary and secondary prevention of C.difficile infections:a meta-analysis and systemic review.Antibiotics 2015;4:160-178[DOI:10.3390/antibiotics4020160]
    139 Souza DN,Jorge MT.The effect of Lactobacillus casei and Bifidobacterium breve on antibiotic-associated diarrhea treatment:randomized double-blind clinical trial.Rev Soc Bras Med Trop 2012;45:112-116[PMID:22370839 DOI:10.1590/S0037-86822012000100021]
    140 Ligny G.Le traitement par l’ultra-levure des troubles intestinaux secondaires a l’antibiotherapie etude en double aveugle et etude clinique simple.[Ultra-Levure treatment of intestinal disorders secondary to antibiotics,a double-blind study and an open clinical study]In French.Revue Fran?aise de Gastroentérologie 1975;114:45-50
    141 Cornely OA,Crook DW,Esposito R,Poirier a,Somero MS,Weiss K,Sears P,Gorbach S.Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe,Canada,and the USa:a double-blind,non-inferiority,randomised controlled trial.Lancet Infect Dis 2012;12:281-289[PMID:22321770 DOI:10 .1016/S1473-3099(11)70374-7]
    142 Surawicz CM,Mc Farland LV,Greenberg RN,Rubin M,Fekety R,Mulligan ME,Garcia RJ,Brandmarker S,Bowen K,Borjal D,Elmer GW.The search for a better treatment for recurrent Clostridium difficile disease:use of high-dose vancomycin combined with Saccharomyces boulardii.Clin Infect Dis 2000;31:1012-1017[PMID:11049785]
    143 Mc Farland LV,Elmer GW,Surawicz CM.Breaking the cycle:treatment strategies for 163 cases of recurrent Clostridium difficile disease.Am J Gastroenterol 2002;97:1769-1775[PMID:12135033]
    144 Vardakas KZ,Polyzos Ka,Patouni K,Rafailidis PI,Samonis G,Falagas ME.Treatment failure and recurrence of Clostridium difficile infection following treatment with vancomycin or metronidazole:a systematic review of the evidence.Int J Antimicrob Agents 2012;40:1-8[PMID:22398198 DOI:10.1016/j.ijantimicag.2012.01.004]
    145 Zar FA,Bakkanagari SR,Moorthi KM,Davis MB.a comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea,stratified by disease severity.Clin Infect Dis 2007;45:302-307[PMID:17599306]
    146 Lowy I,Molrine DC,Leav Ba,Blair BM,Baxter R,Gerding DN,Nichol G,Thomas WD,Leney M,Sloan S,Hay Ca,ambrosino DM.Treatment with monoclonal antibodies against Clostridium difficile toxins.N Engl J Med 2010;362:197-205[PMID:20089970 DOI:10.1056/NEJMoa0907635]
    147 Cornely OA,Miller Ma,Louie TJ,Crook DW,Gorbach SL.Treatment of first recurrence of Clostridium difficile infection:fidaxomicin versus vancomycin.Clin Infect Dis 2012;55 Suppl 2:S154-S161[PMID:22752865 DOI:10.1093/cid/cis462]
    148 Surawicz CM,Elmer GW,Speelman P,Mc Farland LV,Chinn J,van Belle G.Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii:a prospective study.Gastroenterology1989;96:981-988[PMID:2494098]
    149 Borody T,Fischer M,Mitchell S,Campbell J.Fecal microbiota transplantation in gastrointestinal disease:2015 update and the road ahead.Expert Rev Gastroenterol Hepatol 2015;9:1379-1391[PMID:26414076]
    150 Jarrad AM,Karoli T,Blaskovich Ma,Lyras D,Cooper Ma.Clostridium difficile drug pipeline:challenges in discovery and development of new agents.J Med Chem 2015;58:5164-5185[PMID:25760275 DOI:10.1021/jm5016846]
    151 Jirapinyo P,Densupsoontorn N,Thamonsiri N,Wongarn R.Prevention of antibiotic-associated diarrhea in infants by probiotics.J Med Assoc Thai 2002;85 Suppl 2:S739-S742[PMID:12403254]
    152 Ahmad K,Fatemeh F,Mehri N,Maryam S.Probiotics for the treatment of pediatric helicobacter pylori infection:a randomized double blind clinical trial.Iran J Pediatr 2013;23:79-84[PMID:23446685]
    153 Saneeyan H,Samira L,Hamid R.[Effectiveness of probiotic on treatment of Helicobacter pylori infection in children].Iranian.J Isfahan Med School 2011;29:882-889
    154 Seki H,Shiohara M,Matsumura T,Miyagawa N,Tanaka M,Komiyama a,Kurata S.Prevention of antibiotic-associated diarrhea in children by Clostridium butyricum MIYa IRI.Pediatr Int 2003;45:86-90[PMID:12654076]
    155 La Rosa M,Bottaro G,Gulino N,Gambuzza F,Di Forti F,InìG,TornambèE.[Prevention of antibiotic-associated diarrhea with Lactobacillus sporogens and fructo-oligosaccharides in children.a multicentric double-blind vs placebo study].Minerva Pediatr2003;55:447-452[PMID:14608267]
    156 Fox MJ,ahuja KD,Robertson IK,Ball MJ,Eri RD.Can probiotic yogurt prevent diarrhoea in children on antibiotics?a doubleblind,randomised,placebo-controlled study.BMJ Open 2015;5:e006474[PMID:25588782 DOI:10.1136/bmjopen-2014-006474]
    157 Kotowska M,albrecht P,Szajewska H.Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea in children:a randomized double-blind placebo-controlled trial.Aliment Pharmacol Ther 2005;21:583-590[PMID:15740542]
    158 Duman DG,Bor S,Ozütemiz O,Sahin T,O?uz D,I?tan F,Vural T,Sandkci M,I?ksal F,Sim?ek I,Soytürk M,Arslan S,Sivri B,Soykan I,Temizkan A,Be??k F,Kaymako?lu S,Kalayc C.Efficacy and safety of Saccharomyces boulardii in prevention of antibioticassociated diarrhoea due to Helicobacterpylori eradication.Eur J Gastroenterol Hepatol 2005;17:1357-1361[PMID:16292090]
    159 Allen SJ,Wareham K,Wang D,Bradley C,Sewell B,Hutchings H,Harris W,Dhar a,Brown H,Foden a,Gravenor MB,Mack D,Phillips CJ.a high-dose preparation of lactobacilli and bifidobacteria in the prevention of antibiotic-associated and Clostridium difficile diarrhoea in older people admitted to hospital:a multicentre,randomised,double-blind,placebo-controlled,parallel arm trial(PLa CIDE).Health Technol Assess 2013;17:1-140[PMID:24309198 DOI:10.3310/hta17570]
    160 Pozzoni P,Riva a,Bellatorre a G,amigoni M,Redaelli E,Ronchetti a,Stefani M,Tironi R,Molteni EE,Conte D,Casazza G,Colli a.Saccharomyces boulardii for the prevention of antibiotic-associated diarrhea in adult hospitalized patients:a single-center,randomized,double-blind,placebo-controlled trial.Am J Gastroenterol 2012;107:922-931[PMID:22472744 DOI:10 .1038/ajg.2012.56]
    161 Li D,Wang H,Tan M,Shao Y.Use of probiotics for prevention of antibiotic-associated diarrhea in elderly patients.Weichang Bingxue2010;15:154-156
    162 Surawicz CM,Mc Farland LV,Elmer G,Chinn J.Treatment of recurrent Clostridium difficile colitis with vancomycin and Saccharomyces boulardii.Am J Gastroenterol 1989;84:1285-1287[PMID:2679049]
    163 Ouwehand AC,Dong Lian C,Weijian X,Stewart M,Ni J,Stewart T,Miller LE.Probiotics reduce symptoms of antibiotic use in a hospital setting:a randomized dose response study.Vaccine 2014;32:458-463[PMID:24291194 DOI:10.1016/j.vaccine.2013.11.053]
    164 Hirschhorn LR,Trnka Y,Onderdonk a,Lee ML,Platt R.Epidemiology of community-acquired Clostridium difficileassociated diarrhea.J Infect Dis 1994;169:127-133[PMID:8277174]
    165 Levy DG,Stergachis a,Mc Farland LV,Van Vorst K,Graham DJ,Johnson ES,Park BJ,Shatin D,Clouse JC,Elmer GW.antibiotics and Clostridium difficile diarrhea in the ambulatory care setting.Clin Ther 2000;22:91-102[PMID:10688393]
    166 Meropol SB,Localio AR,Metlay JP.Risks and benefits associated with antibiotic use for acute respiratory infections:a cohort study.Ann Fam Med 2013;11:165-172[PMID:23508604]
    167 Chen KT,Stephens DJ,anderson E,acton R,Saltzman D,Hess DJ.Clostridium difficile infection in the pediatric surgery population.J Pediatr Surg 2012;47:1385-1389[PMID:22813801]
    168 Kim MN,Kim N,Lee SH,Park YS,Hwang JH,Kim JW,Jeong SH,Lee DH,Kim JS,Jung HC,Song IS.The effects of probiotics on PPI-triple therapy for Helicobacter pylori eradication.Helicobacter 2008;13:261-268[PMID:18665934 DOI:10.1111/j.1523-5378.2008.00601.x]
    169 Deshpande A,Pant C,anderson MP,Donskey CJ,Sferra TJ.Clostridium difficile infection in the hospitalized pediatric population:increasing trend in disease incidence.Pediatr Infect Dis J 2013;32:1138-1140[PMID:23546535]
    170 Boenning DA,Fleisher GR,Campos JM,Hulkower CW,Quinlan RW.Clostridium difficile in a pediatric outpatient population.Pediatr Infect Dis 1982;1:336-338[PMID:7155966]
    171 Hyams JS,Feder H,Krause PJ,Frick J,Mc Laughlin JC,Furth T,Hine P.Occurrence of Clostridium difficile toxin-associated gastroenteritis following antibiotic therapy for otitis media in young children.Pediatr Infect Dis 1984;3:433-436[PMID:6333674]
    172 Destura RV.Bacillus clausii in preventing antibiotic-associated diarrhea among Filipino infants and children:a multi-center,randomized,open-label clinical trial of efficacy and safety.2008.Accessed June 3,2013.Available from:URL:http://en.sanofi.com/img/content/study/ENTER_L_01125_summary.pdf
    173 Stevens V,Dumyati G,Fine LS,Fisher SG,van Wijngaarden E.Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection.Clin Infect Dis 2011;53:42-48[PMID:21653301 DOI:10.1093/cid/cir301]
    174 Kuntz JL,Chrischilles Ea,Pendergast JF,Herwaldt La,Polgreen PM.Incidence of and risk factors for community-associated Clostridium difficile infection:a nested case-control study.BMC Infect Dis 2011;11:194[PMID:21762504 DOI:10.1186/1471-2334-11-194]
    175 Jarvis WR,Schlosser J,Jarvis aa,Chinn RY.National point prevalence of Clostridium difficile in US health care facility inpatients,2008.Am J Infect Control 2009;37:263-270[PMID:19278754]
    176 Schwartz KL,Darwish I,Richardson SE,Mulvey MR,Thampi N.Severe clinical outcome is uncommon in Clostridium difficile infection in children:a retrospective cohort study.BMC Pediatr2014;14:28[PMID:24485120 DOI:10.1186/1471-2431-14-28]
    177 Kociolek LK,Patel SJ,Shulman ST,Gerding DN.Molecular epidemiology of Clostridium difficile infections in children:a retrospective cohort study.Infect Control Hosp Epidemiol 2015;36:445-451[PMID:25782900 DOI:10.1017/ice.2014.89]
    178 Garg S,Mirza YR,Girotra M,Kumar V,Yoselevitz S,Segon a,Dutta SK.Epidemiology of Clostridium difficile-associated disease(CDa D):a shift from hospital-acquired infection to long-term care facility-based infection.Dig Dis Sci 2013;58:3407-3412[PMID:24154638 DOI:10.1007/s10620-013-2848-x]
    179 Leung J,Burke B,Ford D,Garvin G,Korn C,Sulis C,Bhadelia N.Possible association between obesity and Clostridium difficile infection.Emerg Infect Dis 2013;19:1791-1798[PMID:24188730DOI:10.3201/eid1911.130618]
    180 Kazakova SV,Ware K,Baughman B,Bilukha O,Paradis a,Sears S,Thompson a,Jensen B,Wiggs L,Bessette J,Martin J,Clukey J,Gensheimer K,Killgore G,Mc Donald LC.a hospital outbreak of diarrhea due to an emerging epidemic strain of Clostridium difficile.Arch Intern Med 2006;166:2518-2524[PMID:17159019]
    181 Nylund CM,Eide M,Gorman GH.association of Clostridium difficile infections with acid suppression medications in children.J Pediatr 2014;165:979-984.e1[PMID:25112692 DOI:10.1016/j.jpeds.2014.06.062]
    182 El Feghaly RE,Stauber JL,Deych E,Gonzalez C,Tarr PI,Haslam DB.Markers of intestinal inflammation,not bacterial burden,correlate with clinical outcomes in Clostridium difficile infection.Clin Infect Dis 2013;56:1713-1721[PMID:23487367 DOI:10 .1093/cid/cit147]
    183 Carignan A,allard C,Pépin J,Cossette B,Nault V,Valiquette L.Risk of Clostridium difficile infection after perioperative antibacterial prophylaxis before and during an outbreak of infection due to a hypervirulent strain.Clin Infect Dis 2008;46:1838-1843[PMID:18462108 DOI:10.1086/588291]
    184 Crabtree TD,Pelletier SJ,Gleason TG,Pruett TL,Sawyer RG.Clinical characteristics and antibiotic utilization in surgical patients with Clostridium difficile-associated diarrhea.Am Surg 1999;65:507 -511;discussion 511-512[PMID:10366203]
    185 See I,Bagchi S,Booth S,Scholz D,Geller a I,anderson L,Moulton-Meissner H,Finks JL,Kelley K,Gould CV,Patel PR.Outbreak of Clostridium difficile Infections at an Outpatient Hemodialysis Facility-Michigan,2012-2013.Infect Control Hosp Epidemiol 2015;36:972-974[PMID:25913501 DOI:10.1017/ice.2015.90]
    186 Scardina T,Labus z ewski L,Pa che co SM,Adams W,Schreckenberger P,Johnson S.Clostridium difficile infection(CDI)severity and outcome among patients infected with the Na P1/BI/027 strain in a non-epidemic setting.Infect Control Hosp Epidemiol 2015;36:280-286[PMID:25695169 DOI:10.1017/ice.2014.45]
    187 Hourigan SK,Oliva-Hemker M,Hutfless S.The prevalence of Clostridium difficile infection in pediatric and adult patients with inflammatory bowel disease.Dig Dis Sci 2014;59:2222-2227[PMID:24788321 DOI:10.1007/s10620-014-3169-4]
    188 Kelsen JR,Kim J,Latta D,Smathers S,Mc Gowan KL,Zaoutis T,Mamula P,Baldassano RN.Recurrence rate of clostridium difficile infection in hospitalized pediatric patients with inflammatory bowel disease.Inflamm Bowel Dis 2011;17:50-55[PMID:20722068DOI:10.1002/ibd.21421]
    189 Hu MY,Katchar K,Kyne L,Maroo S,Tummala S,Dreisbach V,Xu H,Leffler Da,Kelly CP.Prospective derivation and validation of a clinical prediction rule for recurrent Clostridium difficile infection.Gastroenterology 2009;136:1206-1214[PMID:19162027 DOI:10.1053/j.gastro.2008.12.038]
    190 Beaulieu M,Williamson D,Pichette G,Lachaine J.Risk of Clostridium difficile-associated disease among patients receiving proton-pump inhibitors in a Quebec medical intensive care unit.Infect Control Hosp Epidemiol 2007;28:1305-1307[PMID:17926283 DOI:10.1086/521664]
    191 Marwick CA,Yu N,Lockhart MC,Mc Guigan CC,Wiuff C,Davey PG,Donnan PT.Community-associated Clostridium difficile infection among older people in Tayside,Scotland,is associated with antibiotic exposure and care home residence:cohort study with nested case-control.J Antimicrob Chemother2013;68:2927-2933[PMID:23825381 DOI:10.1093/jac/dkt257]
    192 Dubberke ER,Reske Ka,Yan Y,Olsen Ma,Mc Donald LC,Fraser VJ.Clostridium difficile--associated disease in a setting of endemicity:identification of novel risk factors.Clin Infect Dis2007;45:1543-1549[PMID:18190314 DOI:10.1086/523582]
    193 Zerey M,Paton BL,Lincourt a E,Gersin KS,Kercher KW,Heniford BT.The burden of Clostridium difficile in surgical patients in the United States.Surg Infect(Larchmt)2007;8:557-566[PMID:18171114 DOI:10.1089/sur.2006.062]
    194 Brown KE,Knoderer Ca,Nichols KR,Crumby a S.acidSuppressing Agents and Risk for Clostridium difficile Infection in Pediatric Patients.Clin Pediatr(Phila)2015;54:1102-1106[PMID:25644650 DOI:10.1177/0009922815569201]
    195 Lee KS,Shin WG,Jang MK,Kim HS,Kim HS,Park CJ,Lee JY,Kim KH,Park JY,Lee JH,Kim HY,Cho SJ,Yoo JY.Who are susceptible to pseudomembranous colitis among patients with presumed antibiotic-associated diarrhea?Dis Colon Rectum 2006;49:1552-1558[PMID:17028914]
    196 Enoch DA,Butler MJ,Pai S,aliyu SH,Karas Ja.Clostridium difficile in children:colonisation and disease.J Infect 2011;63:105-113[PMID:21664931 DOI:10.1016/j.jinf.2011.05.016]
    197 James AH,Katz VL,Dotters DJ,Rogers RG.Clostridium difficile infection in obstetric and gynecologic patients.South Med J 1997;90:889-892[PMID:9305296]
    198 Morrow LE,Kollef MH,Casale TB.Probiotic prophylaxis of ventilator-associated pneumonia:a blinded,randomized,controlled trial.Am J Respir Crit Care Med 2010;182:1058-1064[PMID:20522788 DOI:10.1164/rccm.200912-1853OC]
    199 Bruns AH,Oosterheert JJ,Kuijper EJ,Lammers JW,Thijsen S,Troelstra a,Hoepelman a I.Impact of different empirical antibiotic treatment regimens for community-acquired pneumonia on the emergence of Clostridium difficile.J Antimicrob Chemother 2010;65:2464-2471[PMID:20823105 DOI:10.1093/jac/dkq329]
    200 Leekha S,aronhalt KC,Sloan LM,Patel R,Orenstein R.asymptomatic Clostridium difficile colonization in a tertiary care hospital:admission prevalence and risk factors.Am J Infect Control2013;41:390-393[PMID:23622704 DOI:10.1016/j.ajic.2012.09.023]
    201 McFarland LV,Elmer GW,Stamm WE,Mulligan ME.Correlation of immunoblot type,enterotoxin production,and cytotoxin production with clinical manifestations of Clostridium difficile infection in a cohort of hospitalized patients.Infect Immun1991;59:2456-2462[PMID:2050409]
    202 Ramanathan S,Johnson S,Burns SP,Kralovic SM,Goldstein B,Smith B,Gerding DN,Evans CT.Recurrence of Clostridium difficile infection among veterans with spinal cord injury and disorder.Am J Infect Control 2014;42:168-173[PMID:24485372DOI:10.1016/j.ajic.2013.08.009]
    203 Qualman SJ,Petric M,Karmali Ma,Smith CR,Hamilton SR.Clostridium difficile invasion and toxin circulation in fatal pediatric pseudomembranous colitis.Am J Clin Pathol 1990;94:410-416[PMID:1699407]
    204 Rivlin J,Lerner a,augarten a,Wilschanski M,Kerem E,Ephros Ma.Severe Clostridium difficile-associated colitis in young patients with cystic fibrosis.J Pediatr 1998;132:177-179[PMID:9470027]
    205 Nicholson MR,Thomsen IP,Slaughter JC,Creech CB,Edwards KM.Novel risk factors for recurrent Clostridium difficile infection in children.J Pediatr Gastroenterol Nutr 2015;60:18-22[PMID:25199038 DOI:10.1097/MPG.0000000000000553]
    206 Jardin CG,Palmer HR,Shah DN,Le F,Beyda ND,Jiang Z,Garey KW.assessment of treatment patterns and patient outcomes before vs after implementation of a severity-based Clostridium difficile infection treatment policy.J Hosp Infect 2013;85:28-32[PMID:23834988 DOI:10.1016/j.jhin.2013.04.017]
    207 Bartlett JG.Clinical practice.antibiotic-associated diarrhea.N Engl J Med 2002;346:334-339[PMID:11821511]
    208 Rubin MS,Bodenstein LE,Kent KC.Severe Clostridium difficile colitis.Dis Colon Rectum 1995;38:350-354[PMID:7720439]
    209 Khanna S,Pardi DS,aronson SL,Kammer PP,Baddour LM.Outcomes in community-acquired Clostridium difficile infection.Aliment Pharmacol Ther 2012;35:613-618[PMID:22229532DOI:10.1111/j.1365-2036.2011.04984.x]
    210 Sailhamer EA,Carson K,Chang Y,Zacharias N,Spaniolas K,Tabbara M,alam HB,De Moya Ma,Velmahos GC.Fulminant Clostridium difficile colitis:patterns of care and predictors of mortality.Arch Surg 2009;144:433-439;discussion 439-440[PMID:19451485 DOI:10.1001/archsurg.2009.51]
    211 van der Wilden GM,Chang Y,Cropano C,Subramanian M,Schipper IB,Yeh DD,King DR,de Moya Ma,Fagenholz PJ,Velmahos GC.Fulminant Clostridium difficile colitis:prospective development of a risk scoring system.J Trauma Acute Care Surg 2014;76:424-430[PMID:24458048 DOI:10.1097/Ta.0000000000000105]
    212 Drudy D,Harnedy N,Fanning S,Hannan M,Kyne L.Emergence and control of fluoroquinolone-resistant,toxin a-negative,toxin B-positive Clostridium difficile.Infect Control Hosp Epidemiol2007;28:932-940[PMID:17620240]
    213 Dubberke ER,Butler a M,Reske Ka,agniel D,Olsen Ma,D’angelo G,Mc Donald LC,Fraser VJ.attributable outcomes of endemic Clostridium difficile-associated disease in nonsurgical patients.Emerg Infect Dis 2008;14:1031-1038[PMID:18598621DOI:10.3201/eid1407.070867]
    214 Halabi WJ,Nguyen VQ,Carmichael JC,Pigazzi a,Stamos MJ,Mills S.Clostridium difficile colitis in the United States:a decade of trends,outcomes,risk factors for colectomy,and mortality after colectomy.J Am Coll Surg 2013;217:802-812[PMID:24011436DOI:10.1016/j.jamcollsurg.2013.05.028]
    215 Kamdeu Fansi AA,Guertin JR,Le Lorier J.Savings from the use of a probiotic formula in the prophylaxis of antibiotic-associated diarrhea.J Med Econ 2012;15:53-60[PMID:22023067 DOI:10 .3111/13696998.2011.629015]
    216 Dubberke ER,Schaefer E,Reske Ka,Zilberberg M,Hollenbeak CS,Olsen Ma.attributable inpatient costs of recurrent Clostridium difficile infections.Infect Control Hosp Epidemiol 2014;35:1400-1407[PMID:25333435 DOI:10.1086/678428]
    217 Dubberke ER,Reske Ka,Olsen Ma,Mc Donald LC,Fraser VJ.Short-and long-term attributable costs of Clostridium difficileassociated disease in nonsurgical inpatients.Clin Infect Dis 2008;46:497-504[PMID:18197759]
    218 Abdelsattar ZM,Krapohl G,alrahmani L,Banerjee M,Krell RW,Wong SL,Campbell Da,aronoff DM,Hendren S.Postoperative burden of hospital-acquired Clostridium difficile infection.Infect Control Hosp Epidemiol 2015;36:40-46[PMID:25627760 DOI:10 .1017/ice.2014.8]
    219 You E,Song H,Cho J,Lee J.Reduction in the incidence of hospital-acquired Clostridium difficile infection through infection control interventions other than the restriction of antimicrobial use.Int J Infect Dis 2014;22:9-10[PMID:24583565 DOI:10.1016/j.ijid.2014.01.011]
    220 Kallen AJ,Thompson a,Ristaino P,Chapman L,Nicholson a,Sim BT,Lessa F,Sharapov U,Fadden E,Boehler R,Gould C,Limbago B,Blythe D,Mc Donald LC.Complete restriction of fluoroquinolone use to control an outbreak of Clostridium difficile infection at a community hospital.Infect Control Hosp Epidemiol2009;30:264-272[PMID:19215193 DOI:10.1086/595694]
    221 Kim YS,Jeon H,Nam S,Cho BM,Park SH,Oh SM.analysis of clinical characteristics and risk factors to neurosurgical patients with C.difficile-associated diarrhea.J Kor Neurotraumatol Soc2011;7:92-98
    222 Wenisch C,Parschalk B,Hasenhündl M,Hirschl a M,Graninger W.Comparison of vancomycin,teicoplanin,metronidazole,and fusidic acid for the treatment of Clostridium difficile-associated diarrhea.Clin Infect Dis 1996;22:813-818[PMID:8722937]
    223 Wullt M,Hagsl?tt ML,Odenholt I.Lactobacillus plantarum 299v for the treatment of recurrent Clostridium difficile-associated diarrhoea:a double-blind,placebo-controlled trial.Scand J Infect Dis 2003;35:365-367[PMID:12953945]
    224 van Nood E,Dijkgraaf MG,Keller JJ.Duodenal infusion of feces for recurrent Clostridium difficile.N Engl J Med 2013;368:2145[PMID:23718168]
    225 Cammarota G,Masucci L,Ianiro G,BibbòS,Dinoi G,Costamagna G,Sanguinetti M,Gasbarrini a.Randomised clinical trial:faecal microbiota transplantation by colonoscopy vs.vancomycin for the treatment of recurrent Clostridium difficile infection.Aliment Pharmacol Ther 2015;41:835-843[PMID:25728808 DOI:10.1111/apt.13144]

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