Preventing pediatric antibiotic-associated diarrhea and Clostridium difficile infections with probiotics: A meta-analysis

Table 2 Characteristics of enrolled pediatric population and probiotic therapies for 22 clinical trials of pediatric antibiotic-associated diarrhea and Clostridium difficile infections

Probiotic strain	Age range	Country	Setting (inpatient or outpatient)	Type of inciting infection	Type of antibiotic (s)	Diarrhea defined1	Ref.
S. boulardii lyo	1-5 yr	France	Out	Resp	Mixed: amox (19%), ceph (11%)	> 3	Benhamou et al[30], 1999
S. boulardii lyo	1-15 yr	Turkey	Out	Nr	Sulbactam-ampicillin only	> 2	Erdeve et al[34], 2004
S. boulardii lyo	1-15 yr	Turkey	Out	Nr	Azithromycin only	> 2	Erdeve et al[34], 2004
S. boulardii lyo	6 mo-14 yr	Poland	In and Out	OM, Resp	Mixed: ceph (41%), amox (29%)	> 3/2 d	Kotowska et al[36], 2005
S. boulardii lyo	6 mo-14 yr	China	In	Resp	IV only: ceph (52%), amox (26%)	> 3/2 d	Shan et al[43], 2014
L. rhamnosus GG	5 mo-11 yr	Finland	Out	OM	Amox only	"by parents"	Vaisanen et al[47], 1998
L. rhamnosus GG	2 wk-12.8 yr	Finland	Out	Resp	Mixed: amox (66%)	> 3/2 d	Arvola et al[29], 1999
L. rhamnosus GG	6 mo-10 yr	United States	Out	Resp, UTI, skin	Mixed: amox (52%)	> 2	Vanderhoof et al[48], 1999
L. rhamnosus GG	5-17 yr	Poland	In	H. pylori +	Amox and clarithromycin only	> 3/2 d	Szajewska et al[44], 2009
L. sporogenes (aka Bacilllus sporogenes) + FOS	4 mo-15 yr	Italy	Out	Resp	Mixed: ceph (41%), amox (30%)	> 2	La Rosa et al[37], 2003
C. butyricum MIYAIRI	1 mo-15 yr	Japan	Nr	Resp, GI	Mixed: ceph (48%)	> 3	Seki et al[42], 2003
L. acidophilus	1 mo-18 yr	Bulgaria	In	Resp, Pyel	Mixed: b-lactams, clinda, amino	Nr	Pancheva-dimitrova et al[39], 2004
B. clausii	6 mo-12 yr	Philippines	In and Out	Resp, GU, Skin	Mixed beta-lactams: pen (47%), ceph (35%)	"otherwise unexplained"	Destura et al[33], 2008
Mixes
L. acidophilus +L. bulgaricus	5 mo-6 yr	United States	Out	OM, pharyn, etc.	Amox only	> 1	Tankanow et al[46], 1990
L. acidophilus + Bifido infantis	1-36 mo	Thailand	In	Sepsis or meningitis	Mixed: cefotaxime (89%)	Nr	Jirapinyo et al[35], 2002
Bifido lactis + Strept thermophilus	6-36 mo	Brazil	In	Nr	Mixed: amp (76%), amox (58%)	> 3/2 d	Corrêa et al[32], 2005
Bifido longum PL03 + L. rhamnosus KL53A + L. plantarum PL02	5 mo-16 yr	Poland	In and Out	Resp, OM, UTI	Mixed: amox (43%), ceph (26%)	> 3/2 d	Szymański et al[45], 2008
L. rhamnosus (3 strains) E/N, Pen and Oxy	3 mo-14 yr	Poland	In and Out	Resp, OM, UTI, skin	Mixed: amp or pen (50%), ceph (37%)	> 3/2 d	Ruszczyński et al[40], 2008
Kefir (mix of 9 strains)1	1-5 yr	United States	Out	Resp	Nr	Nr	Merenstein et al[38], 2009
C. butyricum + Bifido. infantis	3 mo-3 yr	China	In	Pneumonia	Mixed: ceph (46%)	> 2	Investigating Group for Prevention of AAD in Children with Pneumonia by Clostridium Butyricum and Bifidobacterium[49], 2012
Bifido animalis +L. acidophilus +Strept thermophilus	1-17 yr	United Kingdom	Out	Resp, skin, UTI	Mixed: pen (71%)	> 3/2 d	Conway et al[31], 2007
L. casei + L. acidophilus + L. reuteri + L. bulgaricus + Strept. cremoris + Bifido. bifidum + Bifido. infantis + FOS	4-14 yr	Iran	Out	H. pylori +	Amox and clarithromycin only	> 3/2 d	Saneeyan et al[41], 2011
L. casei + L. rhamnosus + L. bulgaricus + L. acidophilus + Strept. thermophilus + Bifido. breve + Bifido. infantis	3-14 yr	Iran	Out	H. pylori +	Amox and furazolidone only	> 3/2 d	Ahmad et al[28], 2013

Diarrhea defined as > 3/2 d: indicates 3 or more loose/watery stools for at least 2 consecutive days; > 3: 3 or more loose or watery stools/day; > 2: 2 or more watery stools/day; "by parents": Defined by parents; "otherwise unexplained": Diarrhea with no other explanation associated with antibiotic use. Amino: Aminoglycosides; Amp: Ampicillin; Amox: Amoxicillin +/- clavulanic acid; Ceph: Cephalosporins; Clinda: Clindamycin; GU: Genito-urinary; FOS: Fructooligosaccharide (990 mg/d); H. pylori: Helicobacter pylori; In: Inpatient; Nr: Not reported; OM: Otitis media; Out: Outpatient; Pharyn: Pharyngitis; Pyel: Pyelonephritis; Resp: Upper or lower respiratory tract infection; UTI: Urinary tract infection.

¹Kefir contains: Lactococcus plantarum, L. rhamnosus, L. acidophilus, L. casei, L. lactis subspecies diacetylactis, Leuconostoc cremoris, Bifido. longum, Bifido. breve, Saccharomyces florentinus.