Probiotics for Treatment of C. difficile in Older Patients

Abstract and Introduction

Abstract

Clostridium difficile infection (CDI) is the leading cause of nosocomial diarrhoea in older people, causing substantial morbidity and mortality. The fact that CDI is almost exclusively a disease of older people and the debilitated indicates that patient susceptibility is a major determinant of who gets CDI. It would help efforts to combat this disease if we better understood and could reduce patient susceptibility. In this regard, several strategies are currently under investigation. The use of probiotics for CDI has received particular attention in the medical and lay media. Patients and their carers often ask doctors about them. In this review article, we describe the pathogenesis of CDI before looking at the ageing host in more detail. We discuss how probiotics may work and review the current evidence for their use in CDI.

Introduction

Huge efforts are being made to combat the spread of Clostridium difficile infection (CDI) in hospitals. Although rates have fallen markedly in the UK, it remains the leading healthcare-associated infection affecting older people.^[1]

Clostridium difficile was described as a cause of antibiotic-associated diarrhoea (AAD) in 1978.^[2] Rates of CDI increased through the 1990s, but the disease emerged dramatically after around 2000, when two major changes in epidemiology occurred. First, CDI rates rose exponentially throughout North America and Europe. In the UK, rates peaked in 2007 with over 50,000 cases reported, 80% being in patients aged over 65.^[3] Second, the clinical syndrome associated with CDI changed. Initial reports of increased severity and mortality came from Quebec in Canada.^[4] Novel strains of C. difficile ribotype 027 which were resistant to fluoroquinolone antibiotics became rapidly dispersed across North America and Europe and were linked to severe disease.^[5] In the UK, ribotype 027 C. difficile was associated with notorious outbreaks at Stoke Mandeville and Maidstone Hospitals and came to account for over 40% of C. difficile isolates from English hospitals by 2007.^[6,7] A huge effort across the NHS backed by the Department of Health has been made to reduce CDI rates. Key components include improved infection control practice, rapid diagnosis and isolation of cases, use of 'root-cause analysis' and antibiotic stewardship policies focused on reducing use of 'high-risk' antibiotics. Nevertheless, there were still over 20,000 cases of CDI in the NHS in 2010. While the prevalence of ribotype 027 strains is now falling in the UK, other virulent ribotypes are now being described.^[8]

Table 1. Clinical presentation of HBV-related membranous nephropathy
Author	n	Probiotic strain used	Study design	CDI rate probiotic (%)	CDI rate placebo (%)	Comments
Gao et al. [31]	255	Lactobacillus acidophilus CL1285® + Lactobacillus casei LBC80R®	50–70 years of age Product given for the duration of antibiotics + 5 days Follow-up: 21 days post-cessation of product	1.2^a	23.8	Probiotic blend showed positive dose-ranging effect (100 billion c.f.u. versus 50 billion); study only single-centred and only recruited patients receiving high-risk antibiotics
Sampalis et al. [33]	437	Lactobacillus acidophilus CL1285® + Lactobacillus casei LBC80R®	>18years of age Product given for the duration of antibiotics + 5 days Follow-up: 21 days post cessation of product	6.2	13.3	Multi-centre study in Canada. Patients in the active group had a shorter duration of AAD and a significantly reduced incidence (P = 0.067)
Safdar et al. [34]	40	Lactobacillus acidophilus	>18 years of age Product given for the duration of antibiotics + 14 days Follow-up: not defined	0(0/3)	25 (1/4)	This was a small pilot study and therefore underpowered. Only one CDT positive case of diarrhoea out of total of seven tested
Beausoleil et al. [36]	89	Lactobacillus acidophilus CL1285® + Lactobacillus casei	Age limits not defined; mean age in the active group 68.8 ± 14.5 Product given for the duration of antibiotics only Follow-up: 21 days post-cessation of product	2.3	15.6	Although there was a significant difference in the rate of AAD between the groups, this was not seen for CDI due to the small numbers of patients with CDI
Hickson et al. [32]	135	Lactobacillus casei DN114001, Lactobacillus Bulgaricus, Streptococcus thermophilus	≥50 years of age Product given for the duration of antibiotics + 7 days Follow-up: 4 weeks post-discharge	0	17	The NNT was six and there was a significant difference in the rate of CDI (P = 0.001) Only 8% of the screened population were recruited; therefore, it is difficult to generalise these findings to the wider hospital population
Plummer et al. [51]	138	Lactobacillus acidophilus, Bifidobacterium bifidum	Elderly patientsPrimary outcome was the rate of CDIProduct given for 20 daysFollow-up: patients were not followed up	3	7	Lower rate of CDI in the probiotic group (2.9 versus 7.25% placebo); poor recruitment to trial resulted in reduced statistical power
Surawicz et al. [52]	180	Saccharomyces boulardii	Only mean age reported in study (47.8 years ± 21) Product given for the duration of antibiotics + 2 weeks Follow-up: mean duration of 17.3 ± 8.6 days	3	5	Lower rate of CDI in the probiotic group (9.4 versus 31% placebo; P = 0.07). Intervention tested in much younger population

Table 1. Clinical presentation of HBV-related membranous nephropathy

Author

Probiotic strain used

Study design

CDI rate probiotic (%)

CDI rate placebo (%)

Comments

Gao et al. [31]

255

Lactobacillus acidophilus CL1285® + Lactobacillus casei LBC80R®

50–70 years of age
Product given for the duration of antibiotics + 5 days
Follow-up: 21 days post-cessation of product

1.2^a

23.8

Probiotic blend showed positive dose-ranging effect (100 billion c.f.u. versus 50 billion); study only single-centred and only recruited patients receiving high-risk antibiotics

Sampalis et al. [33]

437

Lactobacillus acidophilus CL1285® + Lactobacillus casei LBC80R®

>18years of age
Product given for the duration of antibiotics + 5 days
Follow-up: 21 days post cessation of product

6.2

13.3

Multi-centre study in Canada. Patients in the active group had a shorter duration of AAD and a significantly reduced incidence (P = 0.067)

Safdar et al. [34]

Lactobacillus acidophilus

>18 years of age
Product given for the duration of antibiotics + 14 days
Follow-up: not defined

0(0/3)

25 (1/4)

This was a small pilot study and therefore underpowered. Only one CDT positive case of diarrhoea out of total of seven tested

Beausoleil et al. [36]

Lactobacillus acidophilus CL1285® + Lactobacillus casei

Age limits not defined; mean age in the active group 68.8 ± 14.5 Product given for the duration of antibiotics only
Follow-up: 21 days post-cessation of product

2.3

15.6

Although there was a significant difference in the rate of AAD between the groups, this was not seen for CDI due to the small numbers of patients with CDI

Hickson et al. [32]

135

Lactobacillus casei DN114001, Lactobacillus Bulgaricus, Streptococcus thermophilus

≥50 years of age
Product given for the duration of antibiotics + 7 days
Follow-up: 4 weeks post-discharge

The NNT was six and there was a significant difference in the rate of CDI (P = 0.001) Only 8% of the screened population were recruited; therefore, it is difficult to generalise these findings to the wider hospital population

Plummer et al. [51]

138

Lactobacillus acidophilus, Bifidobacterium bifidum

Elderly patientsPrimary outcome was the rate of CDIProduct given for 20 daysFollow-up: patients were not followed up

Lower rate of CDI in the probiotic group (2.9 versus 7.25% placebo); poor recruitment to trial resulted in reduced statistical power

Surawicz et al. [52]

180

Saccharomyces boulardii

Only mean age reported in study (47.8 years ± 21)
Product given for the duration of antibiotics + 2 weeks
Follow-up: mean duration of 17.3 ± 8.6 days

Lower rate of CDI in the probiotic group (9.4 versus 31% placebo; P = 0.07). Intervention tested in much younger population

Probiotics for the Prevention and Treatment of Clostridium difficile in Older Patients

Abstract and Introduction

Abstract

Introduction

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