Description of the condition
Acute lower urinary tract infection (UTI), also known as cystitis, is a superficial bacterial infection of the bladder mucosa characterised by symptoms of burning on urination, urinary frequency including nocturia, and urgency. UTIs are considered uncomplicated if the patient is not pregnant or elderly, and if there are no known functional or anatomical abnormalities of the genitourinary tract (Hooton 1996).
UTIs are the most common bacterial infection presented by women in the primary care setting (Butler 2006; Foxman 2002; Little 2010). Around 40% to 50% of women experience one UTI episode during their lives (Kunin 1994). The impact of treating UTIs is substantial. UTIs were reported to account for between 1% and 3% of all consultations in general practice in the UK (Stapleton 1999), and nearly seven million office visits and one million emergency department visits, resulting in 100,000 hospitalisations in the US (Foxman 2002). The most common pathogens causing uncomplicated UTI are Escherichia coli (80% to 90%), Staphylococcus saprophyticus (5% to 10%), Proteus spp. and other gram-negative rods (Milo 2005).
Recurrent UTIs (RUTIs) are commonly defined in the literature as three UTI episodes in the last 12 months or two episodes in the last six months (Albert 2004). Between 20% and 30% of women who have had one UTI episode will have a recurrent UTI (Sanford 1975), and around 25% of these will develop subsequent recurrent episodes (Hooton 1996). RUTIs can have a significant negative effect on quality of life, and a high impact on healthcare costs as a result of outpatient visits, diagnostic tests and prescriptions. Precise estimates on the economic impact of UTIs are difficult to derive. In the US, approximately 15% of all community-prescribed antibiotics are dispensed for UTIs at an estimated annual cost of over USD 1 billion (Mazzulli 2002). The direct and indirect costs associated with community-acquired UTIs in the US are estimated at around USD 2 billion each year (Foxman 2002).
Antibiotics are currently the mainstay treatment for both acute and recurrent UTIs. Although antibiotics may be effective in reducing the duration of severe symptoms in acute episodes (Falagas 2008; Little 2010a), antibiotic resistance is currently estimated at 20% for trimethoprim and cephalosporins, and 50% for amoxicillin (Christiaens 2002). Antibiotic resistance and previous episodes of cystitis have been positively associated with an increased duration of severe symptoms of UTIs (Little 2010). It is predicted that antibiotic resistance will continue to increase (Kumarasamy 2010).
Antibiotic prophylaxis is used to prevent RUTIs. Treatment usually lasts for between six and 12 months but can be extended for up to five years (Franco 2005). A Cochrane systematic review of antibiotics used to prevent RUTIs in non-pregnant women found that antibiotics given continuously for six to 12 months were significantly more effective than placebo in preventing recurrent infection (RR 0.15, 95% CI 0.08 to 0.28; number needed to treat = 1.85, 95% CI 1.60 to 2.20) (Albert 2004). Severe side effects such as urticaria, nausea and vomiting, and less serious but unpleasant side effects including oral and vaginal candidiasis, and gastrointestinal disturbances may require treatment to be withdrawn. These side effects can cause considerable discomfort and may contribute to some women’s expressed preference to avoid using antibiotics (Leydon 2010).
Once prophylaxis is discontinued, even after extended periods of therapy, approximately 50% to 60% of women will become re-infected within three months (Car 2003; Harding 1982). Therefore, antibiotic prophylaxis does not exert a long-term effect on the baseline infection rate.
A number of complementary therapies are used to treat RUTIs. A recently revised Cochrane review of the use of cranberries for preventing UTIs (Jepson 2012) found that they had little effect in reducing the rate of recurrent infection. There is some preliminary evidence that Chinese herbal medicine (CHM) may be of use in the treatment of RUTI.
Description of the intervention
CHM is one part of a system of Traditional Chinese Medicine (TCM). CHM involves the use of complex herbal formulae usually comprising between 10 and 15 herbs that are delivered as decoctions, encapsulated herbal granules, or pills. CHM formulae may be standardised or individualised according to specific patient needs. Although biomedical diagnoses are commonly used in CHM practice to optimise treatment effectiveness, these may be differentiated into TCM syndromes according to analysis of presenting signs and symptoms.
CHM has a recorded history of use in treating the symptoms of UTIs for over 2000 years (Maciocia 1994). More recent clinical research in China suggests that CHM may alleviate UTI symptoms (Liu 1987; Xu 1989; Zhan 2007; Zhang 2005) and reduce one year post-treatment recurrence rates from 30% when antibiotics were used alone, to 4.4% when antibiotics and CHM were combined (Zhang 2005).
How the intervention might work
The herbal products used in CHM contain highly active compounds that have been extensively researched, and in some instances, developed as pharmaceutical drugs. Active compounds that have been refined to develop conventional medicines include ephedrine (Ma Huang, Radix Ephedra sinensis); artemisinin (Qing Hao, Herba Artemisiae annuae); and genistein (Glycine max).
The biological plausibility of CHM for RUTIs is supported by in vitro research suggesting that some CHM may have significant diuretic, antiblastic, immune enhancing, antipyretic, anti-inflammatory and pain relieving activities (Peng 2010; Zhu 1998). There is growing evidence that some herbal medicines can disable bacterial efflux pumps, which are an important mechanism underlying the development of bacterial resistance to antibiotic drugs (Stavri 2007) and may thereby serve as an important adjuvant treatment to conventional antibiotics.
Why it is important to do this review
There is a need to conduct a systematic review to evaluate the extent and quality of clinical evidence relating to CHM for RUTIs. If the benefits of these interventions, either as stand-alone or adjuvant treatment are confirmed by rigorous data, then CHM may make an important contribution to managing this common and problematic condition.