The causes of the increased susceptibility to UTI in the elderly are multiple: decline in cell-mediated immunity, altered bladder defenses due to obstructive uropathy, neurogenic bladder dysfunction, increased bacterial receptivity of uroepithelial cells (Reid 1984), increased risk of contamination due to fecal and urinary incontinence as well as urethral instrumentation and catheterization, and decrease in prostatic and vaginal antibacterial factors associated with changes in zinc levels, urinary and vaginal pH, and hormones (Sant 1987).
The bacteriological features of UTI also differ between elderly and young patients. Escherichia coli and Staphylococcus saprophyticus are the most common causative organisms of UTI in young adults, accounting for 80 to 90% of all cases (Winickoff 1981). Escherichia coli is also the most common pathogen in elderly women, varying from 90% in outpatients to 45% in hospitalized patients. In contrast with younger people, Proteus, Klebsiella, Enterobacter, Serratia, Pseudomonas spp., and other gram-negative bacteria as well as enterococci are also encountered frequently (Kunin 1987). Staphylococcus saprophyticus is almost never isolated in the elderly. In elderly ambulatory men, the predominant organisms were gram-positive enterococci followed by Escherichia coli (Boscia 1986), whereas in elderly institutionalized men, Proteus mirabilis is the most frequently found (Nicolle 1993).
In addition to the differences mentioned above, i.e. prevalence, microbiology and outcome of UTI, elderly patients often also show a different response to treatment. The most important factors that affect pharmacokinetic and pharmacodynamic drug response in elderly patients are a decline in renal function, reduced body weight, decreased response to homeostatic changes, presence of multiple underlying disease, and polypharmacy, which lead to an increased risk of drug interactions and toxicity (Borrego 1997). However many drugs are tested only in young people, and are then frequently prescribed for the elderly (Rochon 1993), although this age group may need a different treatment approach.
We recently performed a critical quality assessment of the many published review articles on urinary tract infections in the elderly. We identified 28 articles or book chapters on urinary tract infections in the elderly (unpublished results). The overall methodological quality was low (mean score 2.0 ± 1.1 on a scale of 9) according to criteria adapted from Oxman and Guyatt (Oxman 1988). None of the identified reviews specified the methods of identifying, selecting and validating the included information. The reference section of most review articles cited mainly other review articles and only a few clinical trials for treatment recommendations. Only 41% of these clinical trials included mainly elderly patients, and the resulting treatment recommendations varied enormously, especially for the treatment duration for uncomplicated lower UTI in elderly women, which varied between 3 to 10 days (Wood 1996).
In young women, many trials have shown that short-term treatments (i.e. 1 to 3 days) are as effective as the traditional longer treatments (i.e. 7 to 14 days), while being less expensive and associated with fewer side effects, and better compliance. However, the results from more recent trials have shown that single dose treatments are less effective than longer treatments. One systematic review found that the optimal treatment duration is three days for cotrimoxazole and the quinolones, but five days for beta-lactam antibiotics (Norrby 1990).
Many authors do not recommend single dose treatments in elderly women because these seem to be less effective (Nicolle 1992, Stamm 1993, Nygaard 1996, Humbert 1992, Baldassarre 1991). However, this attitude is based on either previous review articles or on results from three trials which did not specifically assess efficacy in women over 60 with symptomatic uncomplicated UTI. Indeed, two of these trials compared women over and under 40 years old, and the mean age of the trial populations were 26 and 36 years, respectively (Saginur 1992, Pfau 1984). The third trial included only women with urinary catheters, i.e. complicated UTI (Harding 1991). As mentioned above, no author used a systematic approach for their review.
Because the optimal treatment duration for uncomplicated lower UTI in elderly women is not clear, we decided to carry out a comprehensive overview of available trial evidence on the benefits and harm of different antibiotic treatment durations in elderly women with symptomatic lower urinary tract infections. Men and patients with upper or complicated UTI will be excluded from this review because they usually need longer and more aggressive treatment (Baldassare 1991, Nicolle 1994, Wood 1996, Childs 1996). Patients with asymptomatic bacteriuria will also be excluded, because there is consensus in the medical literature that elderly patients without symptoms should not be treated (Humbert 1992).
We anticipate that trials will report the outcomes at different time points. If possible outcomes will be recalculated for common time points from the raw data. If this is not possible, outcomes will be pooled for short-term effects (i.e. during, immediately after or up to 2 weeks post treatment) and long-term effects ( > 2 weeks post treatment).
See: Collaborative Review Group search strategy
We will search MEDLINE, EMBASE, CINAHL, Current Contents, Science Citation Index, The Cochrane Library, the trial register of the Cochrane Renal group, Best Evidence, and other available databases. In MEDLINE, the first two sections of the optimal Medline Search Strategy (Dickersin 1994) will be applied to identify randomized controlled trials, and combined with the following specific terms:1. elderly
2. explode ""AGED""/ all subheadings
3. explode ""AGED, 80 AND OVER""/ all subheadings
4. old*
5. geriatric*
6. nursing home
7. #1 or #2 or #3 or #4 or #5 or #6
8. urinary tract infection*
9. explode ""URINARY TRACT INFECTIONS""/ all subheadings
10. cystitis
11. explode ""CYSTITIS""/ all subheadings
12. UTI
13. bacteriuria
14. explode ""BACTERIURIA""/ all subheadings
15. #8 or #9 or #10 or #11 or #12 or #13 or #14
16. explode ""ANTI-INFECTIVE AGENTS"" / all subheadings
17. explode ""ANTIBIOTICS""/ all subheadings
18. antibiotic*
19. #16 or #17 or #18
20. #7 and #15 and #19
For the other databases a similar search strategy will be used and help will be obtained from those experienced in searching these databases. The Cochrane Health Care of Older People Field will be asked for additional advice.
In addition, the reference lists of identified articles, reviews, books and book chapters on the treatment of infections in the elderly will be searched. Available abstracts of conferences in the fields of infectious diseases, geriatric medicine and pharmacology will also be screened. Unpublished data will be sought from identified authors as well as from pharmaceutical companies marketing antibiotics that are used in urinary tract infections.
No language restriction will be applied. Articles written in languages other that those familiar to the authors (that is other than English, French, German, Dutch, Spanish and Italian) will be submitted for evaluation to other Cochrane collaborators.
The level of allocation concealment will be assessed using the criteria described in the Cochrane Handbook (Mulrow 1997). Studies will be graded A if the assigned treatment was adequately concealed prior to allocation, B if there is inadequate information to judge concealment, and C if the assigned treatment was clearly not concealed prior to allocation. All data will be analyzed together, and then a sensitivity analysis will be performed to determine if the inclusion of lower quality trials (levels B and C) affects the overall result. To further test the robustness of the results, we will perform several other sensitivity analyses: blinded versus non blinded studies, trials with a high versus a low drop-out rate, and trials including only elderly persons versus trials with a mixed population.
Statistical analyses: Relative risks and 95% confidence interval will be calculated for each trial and outcome. Heterogeneity will be tested by a standard chi-square test and considered to be significant if p < 0.1. The relative risk from each trial will be combined using a fixed effects model if no heterogeneity is detected; if heterogeneity is found we will use a random effects model. The results will also be expressed as NNT (number needed to treat). If enough trials are identified, variables which are likely to influence the outcome of the trials will be assessed in subgroup analyses. Such variables include: different antibiotic classes (e.g. beta-lactams, quinolones) or molecules, place of residence (community, long-stay institution, hospital), patients age (under and over 75 years old), year and country of publication. We will also use the funnel plot approach to assess the likelihood of publication bias.
Additional references
Abrutyn 1991 Abrutyn E, Mossey J, Boscia JA, et al. Epidemiology of asymptomatic bacteriuria in elderly women. J Am Geriatr Soc 1991; 39(4): 388-393. Baldassarre 1991 Baldassarre JS, Kaye D. Special Problems of Urinary Tract Infection in the Elderly. Med Clin North Am 1991; 75: 375-390. Berlin 1997 Berlin JA. Does blinding of readers affect the results of meta-analyses? Lancet. 1997; 350: 185-186. Borrego 1997 Borrego F, Gleckman R. Principles of Antibiotic Prescribing in the Elderly. Drugs Aging 1997; 11(1): 7-18. Boscia 1986 Boscia JA, Kobasa WD, Knight RA,et al. Epidemiology of bacteriuria in an elderly ambulatory population. Am J Med 1986; 80: 208-214. Brocklehurst 1968 Brocklehurst JC, Dillane JB, Griffith L, et al. The Prevalence and symptomatology of urinary infection in an aged population. Gerontol Clin 1968; 10: 242-253. Childs 1996 Childs SJ, Egan RJ. Bacteriuria and urinary infections in the elderly. Geriatric Urology 1996; 23(1): 4354-. Dickersin 1994 Dickersin K, Scherer R, Lefebvre C. Identifying relevant studies for systematic reviews. BMJ 1994; 309(6964): 1286-91. Emori 1991 Emori TG, Banerjee SN, Culver DH, Gaynes RP, Horan TC, Edwards JR, Jarvis WR, Tolson JS, Hemderson TS, Martone WJ, Hughes JM, and the National Nosocomial Infections Surveillance System. Nosocomial Infections in Elderly Patients in the United States, 1986-1990. Am J Med 1991; 91(Suppl.3B): 289S-293S. Harding 1991 Harding GK, Nicolle LE, Ronald AR, Preiksaitis JK, Forward KR, Low DE, Cheang M. How long should catheter-acquired urinary tract infection in women be treated? A randomized controlled study. Ann Intern Med 1991; 114(9): 713-9. Humbert 1992 Humbert G. French consensus on antibiotherapy of urinary tract infections. Infection 1992; 20(Suppl.3): S171-A172. Kasviki-Charvati1982 Kasviki-Charvati P, Drolette-Kefakis B, Papanayiotou PC, et al. Turnover of bacteriuria in old age. Age Ageing 1982; 11: 169-174. Kaye 1980 Kaye D. Urinary tract infections in the elderly. Bull NY Acad Med 1980; 56: 209-220. Kunin 1987 Kunin MC: Detection, prevention and management of urinary tract infections. Philadelphia, Lea & Febiger,. 1987; : -. Michel 1991 Michel JP, Lesourd B, Conne P, Richard D, Rapin CH. Prevalence of infection and their risk factors in geriatric institutions: a one-day multicentre survey. WHO Bulletin 1991; 69: 35-41. Mulrow 1994 Naber 1990 Naber KG, Kumamoto Y. Summary of discussion for acute uncomplicated cystitis. In: Ohkoschi M, Kawada Y, eds. Clincal Evaluation of drug efficacy in UTI. Proceedings of the first International Symposium, 27-28 Oktober 1989, Tokyo, Japan. International Congress Series 938, Excerpta Medica, Amsterdam, New York, Oxford 1990; : 230-. Nicolle 1992 Nicolle LE. Urinary tract infection in the elderly. How to treat and when? Infection 1992; 20 (Suppl.4): S261-264. Nicolle 1993 Nicolle LE. Topics in long-term care: Urinary tract infections in long-term care facilities. Infect Control Hosp Epidemiol 1993; 14: 220-225. Nicolle 1994 Nicolle LE. Urinary tract infection in the elderly. J Antimicrob Chemother 1994; 33 (suppl. A): 99-109. Norrby 1990 Norrby SR. Short-term Treatment of Uncomplicated Lower Urianiry Tract Infections in Women. Rev Inf Dis 1990; 12(3): 458-467. Nygaard 1996 Nygaard IE, Johnson JM. Urinary tract infections in elderly women. Am Fam Physician 1996; 53(1): 175-182. Oxman 1988 Oxman AD, Guyatt GH. Guidelines for reading literature reviews. CMAJ 1988; : 697-703. Pfau 1984 Pfau A, Sacks TG, Shapiro A, Shapiro M. A randomized comparison of 1-day versus 10-day antibacterial treatment of documented lower urinary tract infection. J Urol 1984; 132: 931-3. Reid 1984 Reid G, Zorzotto ML, Bruce AW, et al. Pathogenesis of urinary tract infection in the elderly: The role of bacterial adherence to uroepithelial cells. Curr Microbiol 1984; 11: 67-72. Rochon 1993 Rochon PA, Fortin PR, Dear KB, Minaker KL, Chalmer TC. Reporting of age data in clinical trials of arthritis. Deficiencies and solutions. Arch Intern Med 1993; 163: 243-8. Rubin 1992 Rubin RH, Shapiro ED, Andriole VT, Davis RJ, Stamm WE. Evaluation of new anti-infective drugs for the treatment of urinary tract infection. Clin Infect Dis 1992; 15(Suppl.1): S216-27. Saginur 1992 Saginur R, Nicolle LE, Canadian Infectious Diseases Society Group. Single dose compared with three-day norfloxacin treatment of uncomplicated urinary tract infection in women. Arch Intern Med 1992; 152: 1233-7. Sant 1987 Sant GR: Urinary tract infection in the elderly. Semin Urol. 1987; 5(2): 126-133. Smith 1994 Smith MA, Duke WM. A retrospective review of nosocomial Infections in an acute rehabilitative and chronic population at a large skilled nursing facility. J Am Geriatr Soc 1994; 42: 45-49. Sobel 1990 Sobel JD , Kaye D. Urinary tract infections. In: Mandell Gl, Douglas RG Jr, Bennett JE (eds):Principles and Practice of Infectious Diseases. New York, Churchill Livingstone, 1990; : 582-611. Sourander 1966 Sourander LB. Urinary tract Infection in the aged - an epidemiological study. Ann Med Intern Fenn 1966; 55(suppl 45): 7-55. Sourander 1972 Sourander LB, Kasanen A. A 5-year follow-up of bacteriuria in the aged. Gerontol Clin 1972; 14: 274-281. Stamm 1992 Stamm WE. Criteria for the diagnosis of urinary tract infection and for the assessment of therapeutic effectiveness. Infection 1992; 20(Suppl.3): S151-S154. Stamm 1993 Stamm WE, Hooton TM. Management of urinary tract infections in adults. N Engl J Med 1993; 329: 1328-34. Winickoff 1981 Winickoff RN, Wilner SI, Gall G, et al. Urine culture after treatment of uncomplicated cystitis in women. South Med J 1981; 74: 165-169. Wood 1996 Wood CA, Abrutyn E. Optimal Treatment of Urinary Tract Infections in Elderly Patients. Drugs & Aging 1996; 9(5): 352-362. Extramural sources of support to the review Intramural sources of support to the reviewMulrow CD, Oxman AD (eds.). Cochrane Collaboration Handbook (updated September 1997). In: The Cochrane Library (database on disk and CDROM). The Cochrane Collaboration. Oxford: Update Software; 1994, issue 4
Reviewer(s) Lutters M, Vogt N Date of most recent amendment 24 February 1999 Date of most recent substantive amendment 10 February 1999 Date review expected 30 September 1999 Contact address Ms Monika Lutters
Research assistant
Département de Gériatrie, Unité de Gérontopharmacologie clinique
Hôpitaux Universitaires de Genève
Route de Mon Idée
THÔNEX
Geneva
Switzerland
1226
Telephone: +41-62-724 9557
Facsimile: +41-62-724 9557
E-mail: lutters@pop.agri.chCochrane Library number CD001535 Editorial group Cochrane Renal Group Editorial group code HM-RENAL This protocol should be cited as :
Lutters M, Vogt N. Duration of antibiotics for treating uncomplicated, symptomatic lower urinary tract infections in elderly women (Protocol for a Cochrane Review). In: The Cochrane Library, Issue 2, 1999. Oxford: Update Software.Sources of support