Alternative to antibiotics for managing asymptomatic and non-symptomatic bacteriuria in older persons: a review

Incidence of UTIs

Around 10–20% of women experience a symptomatic UTI in their lifetime (Foxman, 2002; 2014). However, a comprehensive literature review of seven different medical databases found this value to be even higher, at 33% (Salvatore et al, 2011), showing that one in three women will experience at least one episode of UTI during their lifetime. Men commonly have more complicated UTIs, which means they have structural or function abnormalities of the urinary tract that impede urinary flow and underlying disease that interferes with the immune system (Melekos and Naber, 2000; Foxman, 2014; Kelly-Fatemi, 2015; NICE, 2018a).

A qualitative study conducted by Prakash and Saxena (2013) in India showed a considerably higher prevalence of UTIs among women (73.57%) than men (35.14%). Recurrent UTI, too, is certainly more common in women, but it has is no universally accepted definition (Barclay, 2017). Some studies have defined it as a single individual experiencing two episodes of UTI in 6 months or three episodes in a 1-year period (Gupta and Trautner, 2013; NICE, 2018b).

The incidence of UTI is known to increase with age in both sexes (NICE, 2018a), but studies conducted so far have reported conflicting results regarding the age group most susceptible to UTIs. Prakash and Saxena (2013) found that the occurrence of UTI recorded among older individuals (≥48 years, 63.51%) was higher than that recorded in young (26–37 years, 58.11%; 15–25 years, 54.55%) and middle-aged individuals (37–47 years, 39.19%). These findings corresponded with those of a large-scale Japanese study conducted over a 20-year period, which identified an increasing trend of complicated UTI in older adults (Shigemura et al, 2005). However, they differed considerably from those reported in a Kuwaiti study by Dimitrov et al (2004) and a large-scale retrospective Nigerian study by Omigie et al (2009), both of which suggested that the highest incidence of UTIs was recorded in individuals from the age group of 20–50 years.

Several large meta-analyses and reviews have identified factors that predispose older people to UTIs, including the use of urinary catheters; neurological conditions such as dementia, which are associated with impaired bladder emptying; impaired autoimmune response as observed in individuals with diabetes mellitus; prostate problems; and oestrogen deficiency after menopause (Beveridge et al, 2011; Matthews and Lancaster, 2011). General aging, declining physical ability and mental decline can affect bladder emptying and increase the risk of UTIs (McMurdo and Gillespie, 2000; Benton et al, 2006). Certainly, in older men, prostate enlargement and bladder prolapse can limit urine flow (Benton et al, 2006; Beveridge et al, 2011). Incontinence and the use of incontinence pads also increase the rates of UTIs, particularly if there is poor hygiene practice and/or faecal incontinence (Wilson et al, 2001).

Antimicrobial resistance

Older men and women are commonly prescribed long-term antibiotics to prevent recurrent UTIs (NICE, 2018b). UTIs and recurrent UTIs are also over-diagnosed in older people, as seen in the large retrospective case series of emergency hospital admissions in an acute general hospital in northwest England (Woodford and George, 2009). Although significant, this case series was only undertaken in one region, in which most clinicians would have received similar education and would consequently make similar clinical decisions. Nonetheless, it does reflect the evidence from George et al's large qualitative study in India (2015) and Alanazi's smaller retrospective study in Saudi Arabia (2018), which found that the prevalence of inappropriate antibiotic prescriptions was 47% in older adults.

Within the community setting, repeated exposure to antibiotics is a strong causative factor of antibiotic-resistant Escherichia coli infection (Hillier et al, 2007). Antimicrobial resistance is certainly a major concern for UK healthcare professionals, with the increasing prevalence of healthcare-associated infections due to organisms like Clostridioides difficile (Gopal Rao and Patel, 2009; While, 2016). NICE (2018a) suggests that these can be minimised by adhering to regional or local best practice guidelines such as the Scottish Intercollegiate Guidelines Network and the National Institute of Health and Social Care Board guidelines (NICE, 2018b), as well as collation of local antimicrobial resistance data (NICE, 2018b). Local guidelines that should be used for prescribing antimicrobials are based on local resistance patterns and available agents (Beveridge et al, 2011).

Thus, appropriate diagnosis; a higher-dose, shorter-duration antibiotic regimen; or alterative therapy needs to be considered to reduce the risk of antimicrobial resistance and the impact of over-prescribing on older people (Beveridge et al, 2011). Certainly, NICE (2018a) recommends that the overuse of antibiotic treatment may be minimised through clear diagnostic guidelines and prudent antibiotic prescribing. There is also clear guidance about the unnecessary use of antibiotic treatment for ABU, as it is associated with a significantly increased risk of clinical adverse events, including C. difficile infection, methicillin-resistant Staphylococcus aureus infection and the development of antibiotic-resistant UTIs (Zalmanovici Trestioreanu et al, 2015; NICE, 2018a). The diagnosis of infection in those aged 65 years and older can be complicated, and often these patients have a lack of symptoms such as pyrexia and a clear history (Walker et al, 2000; Bardsley, 2017). This complexity of clinical features was also reported in Juthani-Mehta et al's (2009) prospective cohort study of nursing home residents in Connecticut.

Bardsley (2017) therefore suggested that a full clinical assessment should be made, which includes a review of the patient's medical history, physical examination, vital signs and a record of the reported symptoms. A UTI should be considered only if the patient has urgency, frequency of urination or suprapubic tenderness (Ninan et al, 2014; NICE, 2018a).

Asymptomatic bacteriuria

NICE (2018a) defines ABU as ‘significant levels of bacteria (greater than 105 colony-forming units (CFU)/ml) in the urine with no symptoms of UTI’. People over the age of 65 years show an increased prevalence of this condition: the prevalence of ABU increases with age, and up to 50% of older women and 35% of older men who reside in long-term care facilities are believed to have ABU (Walker et al, 2000). ABU showing >105 CFU/ml of a single E. coli strain can persist for years without provoking a host response (Klemm et al, 2006). This can be a concern as older people in long-term care frequently have unnecessary antibiotic treatment for ABU, as they present with non-specific symptoms, so clinicians may presume they have a UTI. Beveridge (2011) suggested that there is strong evidence that ABU should not be treated. In their more recent review, Cai et al (2017) suggest that ABU is a common clinical condition in specific risk groups like older persons and often leads to unnecessary treatment. This is something community nurses must consider.

Bacterial infections

Many bacterial organisms cause UTIs, but the most common causative agent of both ABU and non-symptomatic bacteriuria is the gram-negative uropathogen E. coli (UPEC) (Foxman, 2010; 2014; NICE, 2015). It is responsible for 80%–90% of all uncomplicated UTIs and approximately 65% of complicated UTIs (Foxman, 2010; 2014; Hooton, 2000). The second leading cause is gram-positive Enterococcus spp. (Flores-Mireles et al, 2015). These bacteria are thought to occur in the gastrointestinal tract where they are either commensal or transient members of the gut microbiota (Schwartz et al, 2013). It has also been shown that ABU-E. coli and UPEC can both exploit the human urinary system for survival, and how they do this needs to be examined in order to develop more preventative and/or therapeutic approaches (Roos et al, 2006).

Lim et al's (2014) large review of inappropriate antibiotic prescribing in the residential care setting identified several resulting complications such as prolonged antibiotic use in the absence of infection, empiric prescribing without microbiological investigation and unnecessary treatment of ABU. Multimorbidity, frailty and polypharmacy are also more common in older people and are contributory factors for potential harms such as those related to drug interactions such as renin–angiotensin system inhibitors and trimethoprim, which can increase the risk of hyperkalaemia-related hospitalisation and sudden death (Antoniou et al, 2009; Woodford and George, 2009; Lim et al, 2015). In fact, Detweiler et al (2015) suggested that differentiating between ABU and a UTI is challenging for healthcare providers, as the symptoms of UTI are highly variable. They argued that standardising definitions and ensuring a thorough assessment are important. This is summarised in Ninan et al's (2014) case series, where they reiterate that ABU is common in older people and that prescribing antibiotics confers no benefit and may cause harm, and outlined again in Cai et al's (2017) opinion piece.

D-mannose

D-mannose is a simple sugar that is closely related to glucose and is rapidly absorbed to reach the organs within 30 minutes, after which it is excreted by the urinary tract as it cannot be stored in the body. It is not classified as a drug (Cusumano et al, 2011; NICE, 2018b). For some time now, D-mannose powder has been recommended as an alternative antimicrobial for the treatment of UTIs, as when applied locally, it reduces the ability of UPEC to bind to bladder epithelial cells (Hung et al, 2002; Bouckaert et al, 2005; Cusumano et al, 2011; Altarac and Papeš, 2014). Certainly NICE (2018b) suggests the use of D-mannose for recurrent UTIs.

In Altarac and Papeš's study (2014), the use of D-mannose was reviewed for the prophylaxis of recurrent UTIs in women. The primary outcome measure of the trial was the reduction in microbiologically proven UTI, and the study showed that D-mannose can be an effective prophylactic agent in women. This finding agrees with those of Kranjčec et al's (2014) study, which compared D-mannose with prophylactic nitrofurantoin and found that D-mannose powder significantly reduced the risk of recurrent UTI and to a similar extent as nitrofurantoin did. Thus, D-mannose may be used instead of prophylactic antibiotics for preventing recurrent UTIs. D-mannose was also compared to the prophylactic regime of trimethoprim/sulfamethoxazole for the treatment and prevention of frequent UTIs in 60 women by Porru et al (2014), who found that D-mannose appeared to be a safe and effective treatment for recurrent UTIs in adult women. In Domenici et al's pilot study (2016), they found that D-mannose can be used as an effective treatment for cystitis and as a prophylactic agent for recurrent UTIs. Similarly, Vicariotto (2014) reported that women who experienced symptoms of cystitis found their symptoms to be improved on using D-mannose and cranberry extract-based compounds. Barclay (2017) suggested that although the evidence for non-antibiotic treatments is variable, the use of vaginal oestrogens, D-mannose, immunotherapy and methenamine for recurrent UTIs in women seems effective.

Undoubtedly, D-mannose is a viable alternative to prophylactic antibiotic use, but whether it is appropriate for the older age group or is an effective prophylactic agent in women alone (as indicated by Altarac and Papeš (2014)) are questions that still need answering. Additionally, there is an overall call to further investigate and clearly define de novo and recurrent UTI.

Cranberry products

Altarac and Papeš (2014) suggested that more studies are needed to examine the use of D-mannose in conjunction with cranberry products in UTI prevention. A Cochrane Database review on the use of cranberry products, however, concluded that cranberry products cannot at present be recommended for the prevention of recurrent UTIs (Jepson et al, 2012), although it did suggest that the lack of positive research could be because of discrepancies in the clinical studies, as many of the various cranberry products tested had no clearly defined potency, dosing and active ingredient contents.

Micali et al (2011) also reviewed clinical studies that evaluated the efficacy of cranberry products in the prevention of new or recurrent UTI episodes in young and middle-aged women. Their review does not, however, recommend cranberry products for a different age range.

Conclusion

It is well documented that UTI recurrence is one of the most common reasons for long-term antibiotic use in frail older adults (McClean et al, 2011; 2012; NICE, 2015). Antibiotic prophylaxis may also be wrongly prescribed for these patients. The author found little evidence of the management of recurrent UTIs in older men or any research in frail care home residents. This finding mirrors the conclusions of Ahmed et al's systematic review and meta-analysis of randomised trials (2017). Most research in this area concerns women, particularly postmenopausal women, and recurrent UTIs. There is certainly a call to provide a clear definition for ABU and UTI. Research about D-mannose also appears to be focused on women experiencing recurrent UTIs. Further research on the use of D-mannose and other alternatives to antibiotics for ABU and non-symptomatic bacteriuria in older adults would be worth considering.

KEY POINTS

CPD REFLECTIVE QUESTIONS