G Model
ARTICLE IN PRESS
MAT 6398 1–5
Maturitas xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Maturitas journal homepage: www.elsevier.com/locate/maturitas
1
Review
2
The management of urinary tract infections in octogenarian women Dudley Robinson ∗ , Ilias Giarenis, Linda Cardozo
3
Q1
4
Q2 Department of Urogynaecology, Kings College Hospital, Suite 8, 3rd Floor, Golden Jubilee, London SE5 9RS, United Kingdom
5
6 19
a r t i c l e
i n f o
a b s t r a c t
7 8 9 10 11 12
Article history: Received 18 April 2015 Received in revised form 23 April 2015 Accepted 25 April 2015 Available online xxx
13
18
Keywords: Oestrogen Investigation Urogenital atrophy Urinary tract infection
20
Contents
14 15 16 17
21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45
Urinary Tract Infections are common in women of all ages and the incidence increases with age. Whilst they are a common cause of lower urinary tract symptoms in all women they may be associated with increased morbidity in the elderly. Appropriate investigation and treatment in primary and secondary care are essential to effectively manage urinary tract infection and decrease morbidity and hospitalisation rates. Loss of endogenous oestrogen at the time of the menopause is associated with the urogenital atrophy and an increased incidence of urinary tract infection. Consequently vaginal oestrogen therapy may offer a rationale for treatment and prevent of urinary tract infection. The aim of this paper is to review the clinical management of elderly women presenting with primary and recurrent urinary tract infection. © 2015 Published by Elsevier Ireland Ltd.
1. 2. 3. 4. 5.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Recurrent lower urinary tract infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Management of urinary tract infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1. Symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2. Signs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6. Investigations: Basic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7. Investigations: Complex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.1. Management: General measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2. Management: Asymptomatic bacteriuria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.3. Management: Antimicrobials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8. Management: Duration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.1. Recurrent urinary tract infections: Prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.2. Recurrent urinary tract infections: Role of oestrogens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.3. Oestrogens in the management of urogenital atrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10. Practice points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11. Research agenda . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conflict of interest statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Competing interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Provenance and peer review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
∗ Corresponding author. Tel.: +44 203 2993568; fax: +44 203 2993449. E-mail address: [email protected] (D. Robinson). http://dx.doi.org/10.1016/j.maturitas.2015.04.014 0378-5122/© 2015 Published by Elsevier Ireland Ltd.
Please cite this article in press as: Robinson D, et al. The management of urinary tract infections in octogenarian women. Maturitas (2015), http://dx.doi.org/10.1016/j.maturitas.2015.04.014
G Model MAT 6398 1–5
ARTICLE IN PRESS D. Robinson et al. / Maturitas xxx (2015) xxx–xxx
2
Box 1: Definitions of urinary tract infection. Bacteruria This is used to describe the presence of small numbers of bacteria in the urine. In a clean-catch freshly voided sample, this represents 10 000 colony-forming units(CFU)/mL. Significant bacteruria This term is used to describe the presence of at least 100 000 CFU/mL of urine in a voided midstream clean-catch specimen, or at least 100 CFU/mL of urine from a catheterised specimen.1 While 20–40 per cent of women with symptomatic UTIs may present with bacterial counts of 100 000 CFU/mL,2 bacterial counts of 100–10 000 CFU/mL have also been associated with symptoms of cystitis. This may represent the early stages of infection. Asymptomatic bacteruria This is used to describe the presence of bacteria in the urine of an asymptomatic woman. Asymptomatic bacteruria is common, the prevalence depends on age, sex, sexual activity and the presence of urological abnormalities. In women it is only diagnosed if the same organism is present in quantities of at least 100 000 CFU/mL of urine in at least two consecutive voided specimens.
Table 1 Common uropathogens in general practice and hospital. Organism
Community (%)
Hospital (%)
Escherichia coli Proteus mirabilis Enterococcus faecalis Klebsiella pneumoniae Pseudomonas aeruginosa
77.3 4.3 3.8 3.5 1.8
56.3 6.3 8.4 6.9 3.8
Box 2: Aims of treatment. • • • • •
Symptomatic relief, microbiological cure, detection of predisposing factors, revention of upper urinary tract involvement, and management of recurrence.
age range between 17 and 82 years with Escherichia coli cystitis, 44 per cent had a recurrence within one year, and recurrence is more common in older than younger women [8].
46Q4
1. Introduction
3. Pathogenesis
47Q5
The organisms responsible for UTI are well-established and consistent. E. coli is responsible for almost 80 per cent of acute community-acquired uncomplicated infections. Klebsiella, Proteus and enterococci are infrequent causes of uncomplicated UTI. The commonly occurring organisms in community practice differ when compared to those found within the hospital environment (Table 1) [9]. In addition, in those women with persistent, or recurrent infections it is also important to consider the fastidious organisms (Mycoplasma hominis, Ureaplasma urealyticum and Chlamydia trachomatis).
77
Urinary tract infections (UTI) are common medical conditions accounting for 7–8 million clinic visits, with more than 100 000 hospital admissions in the United States [1] and 21.4% of hospital admissions attributable to infection in Israel [2]. They are more common in women than men with a ratio of 14:1; the reasons being related to anatomical and functional differences. The female urethra is shorter with the distal third contaminated by bacteria from the vagina and rectum. In addition, during intercourse, bacteria are introduced into the urethra and bladder, and voiding may be impaired with increasing age. A woman’s lifetime risk of at least one UTI is around 20 per cent, with a prevalence that is age related, and this increases by 1% per decade of life. The increased incidence of UTI in post menopausal women has been shown to be associated with urinary incontinence, cystocele and post-void residual urine [3]. Urinary tract infections are common in the elderly with a reported incidence of 20% in the community and over 50% in institutionalised patients [4,5]. Pathophysiological changes such as impairment of bladder emptying, poor perineal hygiene and both anal and urinary incontinence may partly account for the high prevalence observed. In addition, changes in the vaginal flora due to oestrogen depletion lead to colonisation with gram negative bacilli which in addition to causing local overactive bladder type symptoms also act as uropathogens. These microbiological changes may be reversed with oestrogen replacement following the menopause, offering a rationale for treatment and prophylaxis. Lower urinary tract infection represents a spectrum of disease from asymptomatic bacteriuria to acute pyelonephritis [Box 1], may involve the lower or upper urinary tract and may be complicated, associated with an underlying structural abnormality, or uncomplicated.
78
2. Recurrent lower urinary tract infection
48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76
79 80 81 82 83 84 85
This is defined as three or more episodes of UTI during a 12month period [6] or two infections in a six-month period. Recurrent UTI with the same organism following adequate therapy is termed a relapse. Reinfection is a recurrent UTI caused by bacteria previously isolated after treatment and a negative intervening urine culture or a recurrent UTI caused by a second isolate [7]. The risk of recurrence of UTI is also age related. In a study of women with
4. Management of urinary tract infection The management of lower urinary tract infection is aimed at treating the current infection and preventing further recurrences [Box 2].
86 87 88
89
90 91 92 93 94 95 96 97 98 99
100
101 102 103
5. Diagnosis
104
5.1. Symptoms
105
Women with lower urinary tract infections typically complain of symptoms of cystitis such as dysuria, suprapubic discomfort, frequency, urgency and nocturia and these may be associated with haematuria. While the diagnostic accuracy of clinical assessment of UTI is uncertain, the presence of both dysuria and frequency increases the probability of UTI by 90%. Of these women, approximately 30 per cent will also have an upper urinary tract infection, which may present as loin pain and tenderness. Importantly, in the elderly, urinary tract infections may present with atypical symptoms, such as confusion, deliruim [10] and falls. In addition incomplete bladder emptying secondary to chronic constipation may be associated with recurrent infections and it is essential to enquire about bowel function as well as sexual function if intercourse is recognized as a precipitating factor. 5.2. Signs Physical examination is usually unremarkable although, in more severe infections there may be pyrexia. Suprapubic or loin tenderness may be the only physical signs. In addition a pelvic
Please cite this article in press as: Robinson D, et al. The management of urinary tract infections in octogenarian women. Maturitas (2015), http://dx.doi.org/10.1016/j.maturitas.2015.04.014
106 107 108 109 110 111 112 113 114 115 116 117 118 119
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G Model MAT 6398 1–5
ARTICLE IN PRESS D. Robinson et al. / Maturitas xxx (2015) xxx–xxx
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examination should be performed to exclude a significant urinary residual, constipation, pelvic mass, urogenital prolapse and to assess the degree of urogenital atrophy.
127
6. Investigations: Basic
124 125
140
• Urine appearance. Whilst urine turbidity has been shown to have a specificity of 66.4% and sensitivity of 90.4% predicting symptomatic UTI, it is prone to observer error [11]. • Urine microscopy has a sensitivity of 60–100% and specificity of 49–100% of predicting significant bacteruria in women [12]. • Urine dipstick for nitrites and leukocytes. If the test is positive for both, then the probability of UTI is higher than each alone; however if both are negative, the likelihood of UTI is less than 20 per cent [13]. • Urine culture will isolate the causative organism and provide antibiotic sensitivities that should guide antimicrobial treatment. • Vaginal swabs for culture and sensitivity may also be indicated in presence of significant urogenital atrophy and atrophic vaginitis.
141
7. Investigations: Complex
128 129 130 131 132 133 134 135 136 137 138 139
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• In women who have recurrent or complicated urinary infections, renal function should be assessed with serum creatinine, urea and electrolytes. • For persistent or recurrent infections, urine should be sent for culture of fastidious organisms (M. hominis, U. urealyticum and C. trachomatis) to rule out less common causes of infection. • Ultrasound of the upper urinary tract will exclude renal causes, such as hydronephrosis or calculi, and a post-micturition bladder scan will rule out a significant urinary residual. • An alternative is radiological imaging using an intravenous urogram or computed tomography urogram. These involve exposure to ionising radiation and influence treatment in limited cases. • A transvaginal ultrasound can exclude the possibility of a pelvic mass. • Urodynamic investigations may be useful in those women who also complain of concomitant lower urinary tract symptoms. • Cystourethroscopy will exclude an intravesical lesion, such as a bladder tumour, and anomalies, such as diverticula and calculi. Cystoscopy is essential in women with a history of infection following a previous continence procedure to exclude a tape erosion into the bladder or urethra. A bladder biopsy may show evidence of chronic follicular or interstitial cystitis.
164
7.1. Management: General measures
142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162
3
Table 2 Recommended treatment for acute uncomplicated cystitis. 1st choice 2nd choice 3rd choice
4th choice
Nitrofurantointoin 50 mg every 6 h for 7 days Trimethoprim 200 mg twice daily for 5 days (if local E. coli resistance is
ARTICLE IN PRESS
MAT 6398 1–5
Maturitas xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Maturitas journal homepage: www.elsevier.com/locate/maturitas
1
Review
2
The management of urinary tract infections in octogenarian women Dudley Robinson ∗ , Ilias Giarenis, Linda Cardozo
3
Q1
4
Q2 Department of Urogynaecology, Kings College Hospital, Suite 8, 3rd Floor, Golden Jubilee, London SE5 9RS, United Kingdom
5
6 19
a r t i c l e
i n f o
a b s t r a c t
7 8 9 10 11 12
Article history: Received 18 April 2015 Received in revised form 23 April 2015 Accepted 25 April 2015 Available online xxx
13
18
Keywords: Oestrogen Investigation Urogenital atrophy Urinary tract infection
20
Contents
14 15 16 17
21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45
Urinary Tract Infections are common in women of all ages and the incidence increases with age. Whilst they are a common cause of lower urinary tract symptoms in all women they may be associated with increased morbidity in the elderly. Appropriate investigation and treatment in primary and secondary care are essential to effectively manage urinary tract infection and decrease morbidity and hospitalisation rates. Loss of endogenous oestrogen at the time of the menopause is associated with the urogenital atrophy and an increased incidence of urinary tract infection. Consequently vaginal oestrogen therapy may offer a rationale for treatment and prevent of urinary tract infection. The aim of this paper is to review the clinical management of elderly women presenting with primary and recurrent urinary tract infection. © 2015 Published by Elsevier Ireland Ltd.
1. 2. 3. 4. 5.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Recurrent lower urinary tract infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Management of urinary tract infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1. Symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2. Signs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6. Investigations: Basic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7. Investigations: Complex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.1. Management: General measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2. Management: Asymptomatic bacteriuria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.3. Management: Antimicrobials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8. Management: Duration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.1. Recurrent urinary tract infections: Prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.2. Recurrent urinary tract infections: Role of oestrogens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.3. Oestrogens in the management of urogenital atrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10. Practice points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11. Research agenda . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conflict of interest statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Competing interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Provenance and peer review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
∗ Corresponding author. Tel.: +44 203 2993568; fax: +44 203 2993449. E-mail address: [email protected] (D. Robinson). http://dx.doi.org/10.1016/j.maturitas.2015.04.014 0378-5122/© 2015 Published by Elsevier Ireland Ltd.
Please cite this article in press as: Robinson D, et al. The management of urinary tract infections in octogenarian women. Maturitas (2015), http://dx.doi.org/10.1016/j.maturitas.2015.04.014
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Box 1: Definitions of urinary tract infection. Bacteruria This is used to describe the presence of small numbers of bacteria in the urine. In a clean-catch freshly voided sample, this represents 10 000 colony-forming units(CFU)/mL. Significant bacteruria This term is used to describe the presence of at least 100 000 CFU/mL of urine in a voided midstream clean-catch specimen, or at least 100 CFU/mL of urine from a catheterised specimen.1 While 20–40 per cent of women with symptomatic UTIs may present with bacterial counts of 100 000 CFU/mL,2 bacterial counts of 100–10 000 CFU/mL have also been associated with symptoms of cystitis. This may represent the early stages of infection. Asymptomatic bacteruria This is used to describe the presence of bacteria in the urine of an asymptomatic woman. Asymptomatic bacteruria is common, the prevalence depends on age, sex, sexual activity and the presence of urological abnormalities. In women it is only diagnosed if the same organism is present in quantities of at least 100 000 CFU/mL of urine in at least two consecutive voided specimens.
Table 1 Common uropathogens in general practice and hospital. Organism
Community (%)
Hospital (%)
Escherichia coli Proteus mirabilis Enterococcus faecalis Klebsiella pneumoniae Pseudomonas aeruginosa
77.3 4.3 3.8 3.5 1.8
56.3 6.3 8.4 6.9 3.8
Box 2: Aims of treatment. • • • • •
Symptomatic relief, microbiological cure, detection of predisposing factors, revention of upper urinary tract involvement, and management of recurrence.
age range between 17 and 82 years with Escherichia coli cystitis, 44 per cent had a recurrence within one year, and recurrence is more common in older than younger women [8].
46Q4
1. Introduction
3. Pathogenesis
47Q5
The organisms responsible for UTI are well-established and consistent. E. coli is responsible for almost 80 per cent of acute community-acquired uncomplicated infections. Klebsiella, Proteus and enterococci are infrequent causes of uncomplicated UTI. The commonly occurring organisms in community practice differ when compared to those found within the hospital environment (Table 1) [9]. In addition, in those women with persistent, or recurrent infections it is also important to consider the fastidious organisms (Mycoplasma hominis, Ureaplasma urealyticum and Chlamydia trachomatis).
77
Urinary tract infections (UTI) are common medical conditions accounting for 7–8 million clinic visits, with more than 100 000 hospital admissions in the United States [1] and 21.4% of hospital admissions attributable to infection in Israel [2]. They are more common in women than men with a ratio of 14:1; the reasons being related to anatomical and functional differences. The female urethra is shorter with the distal third contaminated by bacteria from the vagina and rectum. In addition, during intercourse, bacteria are introduced into the urethra and bladder, and voiding may be impaired with increasing age. A woman’s lifetime risk of at least one UTI is around 20 per cent, with a prevalence that is age related, and this increases by 1% per decade of life. The increased incidence of UTI in post menopausal women has been shown to be associated with urinary incontinence, cystocele and post-void residual urine [3]. Urinary tract infections are common in the elderly with a reported incidence of 20% in the community and over 50% in institutionalised patients [4,5]. Pathophysiological changes such as impairment of bladder emptying, poor perineal hygiene and both anal and urinary incontinence may partly account for the high prevalence observed. In addition, changes in the vaginal flora due to oestrogen depletion lead to colonisation with gram negative bacilli which in addition to causing local overactive bladder type symptoms also act as uropathogens. These microbiological changes may be reversed with oestrogen replacement following the menopause, offering a rationale for treatment and prophylaxis. Lower urinary tract infection represents a spectrum of disease from asymptomatic bacteriuria to acute pyelonephritis [Box 1], may involve the lower or upper urinary tract and may be complicated, associated with an underlying structural abnormality, or uncomplicated.
78
2. Recurrent lower urinary tract infection
48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76
79 80 81 82 83 84 85
This is defined as three or more episodes of UTI during a 12month period [6] or two infections in a six-month period. Recurrent UTI with the same organism following adequate therapy is termed a relapse. Reinfection is a recurrent UTI caused by bacteria previously isolated after treatment and a negative intervening urine culture or a recurrent UTI caused by a second isolate [7]. The risk of recurrence of UTI is also age related. In a study of women with
4. Management of urinary tract infection The management of lower urinary tract infection is aimed at treating the current infection and preventing further recurrences [Box 2].
86 87 88
89
90 91 92 93 94 95 96 97 98 99
100
101 102 103
5. Diagnosis
104
5.1. Symptoms
105
Women with lower urinary tract infections typically complain of symptoms of cystitis such as dysuria, suprapubic discomfort, frequency, urgency and nocturia and these may be associated with haematuria. While the diagnostic accuracy of clinical assessment of UTI is uncertain, the presence of both dysuria and frequency increases the probability of UTI by 90%. Of these women, approximately 30 per cent will also have an upper urinary tract infection, which may present as loin pain and tenderness. Importantly, in the elderly, urinary tract infections may present with atypical symptoms, such as confusion, deliruim [10] and falls. In addition incomplete bladder emptying secondary to chronic constipation may be associated with recurrent infections and it is essential to enquire about bowel function as well as sexual function if intercourse is recognized as a precipitating factor. 5.2. Signs Physical examination is usually unremarkable although, in more severe infections there may be pyrexia. Suprapubic or loin tenderness may be the only physical signs. In addition a pelvic
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106 107 108 109 110 111 112 113 114 115 116 117 118 119
120
121 122 123
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examination should be performed to exclude a significant urinary residual, constipation, pelvic mass, urogenital prolapse and to assess the degree of urogenital atrophy.
127
6. Investigations: Basic
124 125
140
• Urine appearance. Whilst urine turbidity has been shown to have a specificity of 66.4% and sensitivity of 90.4% predicting symptomatic UTI, it is prone to observer error [11]. • Urine microscopy has a sensitivity of 60–100% and specificity of 49–100% of predicting significant bacteruria in women [12]. • Urine dipstick for nitrites and leukocytes. If the test is positive for both, then the probability of UTI is higher than each alone; however if both are negative, the likelihood of UTI is less than 20 per cent [13]. • Urine culture will isolate the causative organism and provide antibiotic sensitivities that should guide antimicrobial treatment. • Vaginal swabs for culture and sensitivity may also be indicated in presence of significant urogenital atrophy and atrophic vaginitis.
141
7. Investigations: Complex
128 129 130 131 132 133 134 135 136 137 138 139
163
• In women who have recurrent or complicated urinary infections, renal function should be assessed with serum creatinine, urea and electrolytes. • For persistent or recurrent infections, urine should be sent for culture of fastidious organisms (M. hominis, U. urealyticum and C. trachomatis) to rule out less common causes of infection. • Ultrasound of the upper urinary tract will exclude renal causes, such as hydronephrosis or calculi, and a post-micturition bladder scan will rule out a significant urinary residual. • An alternative is radiological imaging using an intravenous urogram or computed tomography urogram. These involve exposure to ionising radiation and influence treatment in limited cases. • A transvaginal ultrasound can exclude the possibility of a pelvic mass. • Urodynamic investigations may be useful in those women who also complain of concomitant lower urinary tract symptoms. • Cystourethroscopy will exclude an intravesical lesion, such as a bladder tumour, and anomalies, such as diverticula and calculi. Cystoscopy is essential in women with a history of infection following a previous continence procedure to exclude a tape erosion into the bladder or urethra. A bladder biopsy may show evidence of chronic follicular or interstitial cystitis.
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7.1. Management: General measures
142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162
3
Table 2 Recommended treatment for acute uncomplicated cystitis. 1st choice 2nd choice 3rd choice
4th choice
Nitrofurantointoin 50 mg every 6 h for 7 days Trimethoprim 200 mg twice daily for 5 days (if local E. coli resistance is
