Surgery Where conservative treatments have failed, surgery can be considered for selected c ases. - In women, options include colposuspension (particularly if associated with anterior compart ment prolapse), suburethral slings/tapes or periurethral bulking agents for SUI, and surger y for POP. In men, sphincter incompetence can be treated with bulbourethral tapes and arti \201 cial urinary sphincter in appropriately selected cases. 1 Royal College of Physicians (1995) Incontinence: causes, management and provision of serv ices, Report of a working party. London: RCP 1995 [online]. Available from: M www.rcplondon .ac.uk. 1 6 0 Initial management of urinary incontinence in women C H A P T E R 5 Initial Management of Urinary Incontinence in Women Incontinence with mixed symptoms Incontinence on physical activity Incontinence / frequency with urgency Complicated incontinence \200 Recurrent incontinence \200 Incontinence associated with: I n c o n t i n e n c e HISTORY Pain - Hematuria - Recurrent infection - Significant voiding General assessment (see relevant chapter) \200 Urinary symptom assessment (including freq uency- volume chart and questionnaire) Assess quality of life and desire for treatment \200 Physical examination: abdominal, pel vic and perineal \200 Cough test to demonstrate stress incontinence if appropriate \200 Urinalysis urine culture -> if infected, treat and reassess symptoms Pelvic irradiation - Radical pelvic surgery - Suspected fistula CLINICAL ASSESSMENT If appropriate Assess estrogen status and treat as appropriate \200 Assess voluntary pelvic floor muscle contraction \200 Assess post-void residual urine a n d f e m a l e PRESUMED DIAGNOSIS OAB -with or without URGENCY INCONTINENCE presumed due to detrusor overactivity STRESS INCONTINENCE presumed due to sphincteric incompetence MIXED INCONTINENCE (treat most bothersome symptom first) If other abnormality found e.g. \200 Significant post void residual \200 Significant pelvic organ prolapse Life style interventions. \200 Pelvic floor muscle training for SUI or OAB \200 Bladder retraining for OAB \200 Duloxetine* (SUI) or antimuscarinic (OAB urgency incontinence ) u r o l o g y Pelvic mass MANAGEMENT Other adjuncts, such as electrical stimulation \200 Vaginal devices, urethral inserts Subject to local Failure regulatory approval (see black box worning). SPECIALIZED MANAGEMENT Fig. 5.7 International Continence Society (ICS) recommendations. Reproduced with permission from 4th International Consultation on Incontinence. Incontinence, 4th edition 2009. Ed. A brams P, Cardozo L, Khoury S, Wein A. Health Publications Ltd 2009, p. 1785. Specialized management of urinary incontinence in women Specialized Management of Urinary Incontinence in Women M A N A G E M E N T O F Incontinence with mixed symptoms Incontinence on physical activity Incontinence with urgency / frequency HISTORY/ SYMPTOM ASSESSMENT \200\234Complicated \200\235 incontinence: \200 Recurrent incontinence \200 Incontinen ce associated with: - Pain - Hematuria - Recurrent infection - Voiding symptoms - Pelvic irradiation - Ra dical pelvic surgery - Suspected fistula Assess for pelvic organ mobility / prolapse \200 Consider imaging of the UT/ pelvic floor \200 Urodynamics (see notes) CLINICAL ASSESSMENT U R N A R Y I INCONTINENCE associated with poor bladder emptying DETRUSOR OVERACTIVITY INCONTINENCE (DOI) MIXED INCONTINENCE (USI/DOI) (Treat. most bother- some symptom first) URODYNAMIC STRESS INCONTINENCE (USI) Consider: \200 Urethrocystoscopy \200 Further imaging \200 Urodynamics I N C O N T N E N C E DIAGNOSIS Underactive detrusor Bladder outlet obstruction Lower urinary tract anomaly / pathology I Correct anatomic bladder outlet obstruction (e.g. genito-urinary prolapse) \200 Intermitt ent TREATMENT If initial therapy fails : \200 Stress incontinence If initial therapy fails : \200 Botulinum toxin \200 Neuromodulation \200 Bladder aug mentation I surgery N W O M E N bulking agents - tapes and slings - colposuspension Correct anomaly \200 Treat pathology catheterization Fig. 5.8 International Continence Society (ICS) recommendations. Reproduced with permission from 4th International Consultation on Incontinence. Incontinence, 4th edition 2009. Ed. A brams P, Cardozo L, Khoury S, Wein A. Health Publications Ltd 2009, p. 1787. 1 6 1 1 6 2 Initial management of urinary incontinence in men C H A P T E R 5 Initial Management of Urinary Incontinence in Men Incontinence on physical activity (usually post- prostatectomy) Urgency / frequency, with or with- out urgency incontinence Post- micturition dribble I n c o n t i n e n c e \200\234Complicated \200\235 incontinence \200 Recurrent or \200\234total \200\235 Incontinence with mixed symptoms HISTORY incontinence Incontinence associated with: - Pain - Hematuria - Recurrent infection - Prostate irradiation - Radical pelvic surg ery General assessment (see relevant chapter) \200 Urinary Symptom Assessment and symptom sco re (including frequency-volume chart and questionnaire) CLINICAL ASSESSMENT Assess quality of life and desire for treatment \200 Physical examination: abdominal, rec tal, sacral, neurological \200 Urinalysis urine culture -> if infected, treat and reas sess \200 Assessment of pelvic floor muscle function \200 Assess post-void residual uri ne a n d Any other abnormality detected e.g. significant post void residual f e m a l e STRESS INCONTINENCE presumed due to sphincteric incompetence MIXED INCONTINENCE (treat most bothersome symptom first) URGENCY INCONTINENCE presumed due to detrusor overactivity PRESUMED DIAGNOSIS DISCUSS TREATMENT OPTIONS WITH THE PATIENT \200 Lifestyle interventions \200 Pelvic flo or muscle training biofeedback \200 Scheduled voiding (bladder training) \200 Incont inence products \200 Antimuscarinics (OAB urgency incontinence) and -adrenergic anta gonists (if also bladder outlet obstruction) Urethral milking u r o l o g y Pelvic floor MANAGEMENT muscle contraction Failure SPECIALIZED MANAGEMENT Fig. 5.9 International Continence Society (ICS) recommendations. Reproduced with permission from 4th International Consultation on Incontinence. Incontinence, 4th edition 2009. Ed. A brams P, Cardozo L, Khoury S, Wein A. Health Publications Ltd 2009, p.1781. Specialized management of urinary incontinence in men Specialized Management of Urinary Incontinence in Men Incontinence with urgency / frequency \200\234Complicated \200\235 Incontinence : \200 Recurrent incontinence \200 Incontine nce associated with: - Prostate or pelvic irradiation - Radical pelvic surgery Post-prostatectomy incontinence HISTORY/ SYMPTOM ASSESSMENT M A N A G E M E N T O F Consider urodynamics and imaging of the urinary tract \200 Urethrocystoscopy (if indicate d) CLINICAL ASSESSMENT Consider: \200 Urethrocystoscopy \200 Further imaging \200 Urodynamics U R N A R Y URGENCY INCONTINENCE due to detrusor overactivity (during filling) MIXED INCONTINENCE Treat major component first STRESS INCONTINENCE due to sphincteric incompetence I DIAGNOSIS I N C O N T N E N C E with coexisting underactive detrusor (during voiding) with coexisting bladder outlet obstruction Lower urinary tract anomaly/ pathology -blockers, 5ARI \200 Correct anatomic bladder outlet obstruction \200 Antimuscarinics I If initial therapy fails: \200 Artificial urinary sphincter \200 Male sling (see chapte r) If initial therapy fails: \200 Neuromodulation Intermittent catheteri- sation \200 Antimus- carinics Correct anomaly \200 Treat pathology TREATMENT I (See note) N M E N Fig. 5.10 International Continence Society (ICS) recommendations. Reproduced with permissio n from 4th International Consultation on Incontinence. Incontinence, 4th edition 2009. Ed. Abrams P, Cardozo L, Khoury S, Wein A. Health Publications Ltd 2009, p. 1783. 1 6 3 1 6 4 Management of urinary incontinence in frail older persons C H A P T E R 5 Management of Urinary Incontinence in Frail Older Persons HISTORY/SYMPTOM ASSESSMENT Active Case Finding in Frail Elderly UI associated with: \200 Pain \200 Haematuria \200 Recurrent symptomatic I n c o n t i n e n c e UTI CLINICAL ASSESSMENT Assess, treat and reassess potentially treatable conditions, Pelvic mass \200 Pelvic irradiation \200 Pelvic / LUT surgery \200 Prolapse beyond hy men (women) including relevant comorbidities and ADLs (see text) Assess Qol, desire for Rx, goals for Rx, pt & caregiver preference \200 Targeted physical exam including cognition, mobility, Delirium \200 Infection \200 Pharmaceuticals \200 Psychological \200 Excess urine o utput \200 Reduced Mobility \200 Stool impaction and neurological and rectal exams Urinalysis \200 Consider frequency volume chart or wet checks, especially if Suspected fistula nocturia present Other a n d SIGNIFICANT PVR* STRESS UI* URGENCY UI* other factors Avoid overtreatment of asymptomatic bacteriura f e m a l e Treat constipation \200 Review medications \200 Consider trial of Lifestyle interventions \200 Behavioral therapies \200 Consider addition and trial of a ntimuscarinic drug Lifestyle interventions \200 Pelvic floor muscle CLINICAL DIAGNOSIS exercises alpha-blocker (men) \200 Catheter drainage if These diagnoses may PVR 200-500 ml, then reassess (see text) overlap in various combinations, e.g., Mixed UI, DHIC (see text) u r o l o g y INITIAL MANAGEMENT If insufficient improvement, reassess for treatment of contributing comorbidity function al impairment (if Mixed UI, initially treat most bothersome symptoms) ONGOING If continued insufficient improvement, or severe associated symptoms are present, consider specialist referral as appropriate per patient preferences and comorbidity (see tex) MANAGEMENT and REASSESSMENT Fig. 5.11 International Continence Society (ICS) recommendations. Reproduced with permissio n from 4th International Consultation on Incontinence. Incontinence, 4th edition 2009. Ed. Abrams P, Cardozo L, Khoury S, Wein A. Health Publications Ltd 2009, p. 1798. This page intentionally left blank CHAPTER 5 Incontinence and female urology 166 Female urethral diverticulum (UD) An epithelialized outpouching of urethral mucosa with a s ingle connec- tion (ostium) entering the urethral lumen. Affects women in the 3rd to 5th de cades of life, with an incidence of 1 \200\2236%. The UK incidence has increased from 74 ca ses in 1998 \200\2231999 to 174 in 2009 \200\2232010, likely due to improved detected cases .1 Some report a predilection in Afro-Caribbean races. Etiology - - Congenital (rare). Acquired. \200 Periurethral (Skene \200\231s) gland infection (by Neis seria gonorrhea, Escherichia coli, other coliform bacteria, or normal vaginal \202 ora) c auses abscess formation and subsequent rupture into the urethral lumen. Repeated \201 lli ng and stasis of urine in the cavity causes expansion of the diverticulum, recurrent infect ion, and epithelialization. Trauma associated with childbirth (forceps delivery). \200 Previous urethral or vaginal s urgery. \200 Repeated urethral instrumentation. Classi \201 cation - - - Simple (most common). Horseshoe (or saddlebag). Circumferential types. UD are single or multiple (10%) and located in the distal, middle (most common), or proxima l urethra, usually seen as a midline anterior vaginal cystic swelling. Presentation The classical \200\230three Ds \200\231 (dysuria, post-void dribble, and dysp areunia) are only found in 23% of patients.2 Patients report a wide array of symptoms, incl uding urinary frequency, urgency, urethral discharge, recurrent UTI, incontinence, pain, ob structive symptoms, urinary retention, vaginal mass, and haematuria. Twenty percent of pati ents are asymptomatic. Differential diagnoses Skene \200\231s gland cysts or abscess, Gartner \200\231s duct cysts , vaginal wall inclusion cysts, vaginal leiomyoma, ectopic ureterocele, urethral carcinoma, and en- dometrioma. Complications of UD - - - - Malignancy (5%). Stones (4 \200\22310%). Endometriosis. Rupture (can lead to \201 stula f ormation). FEMALE URETHRAL DIVERTICULUM (UD) 167 Assessment History: voiding symptoms, dyspareunia, and urethral or vaginal discharge. It is common to have coexisting detrusor overactivity or SUI. Examination: a midline anterior vaginal wall mass may be visualized or palpable in 80%2 (Fi g. 5.12). Gentle pressure can express urethral discharge in up to 40%.2 Investigation - - - - - Bladder diary. MSU Urethral pressure \202 owmetry may show a classical biphasic recording . Rigid cystourethroscopy to exclude concomitant bladder pathology. Twin channel urodynamic s are recommended for patients with signi \201 cant voiding symptoms or incontinence. . Imaging - MRI with up to 100% sensitivity. UD are identi \201 ed as hyperdense areas on T2 -weighted images (Fig. 5.13). Micturating cystourethrography: UD and useful for assessing c oncomitant voiding dysfunction. USS (transvaginal, transrectal, or transperineal): UD is se en as an anechoic or hypoechoic lesion with through-transmission of signal. Double balloon high pressure urethrography: involves infusion of contrast via a double balloon urethral ca theter to delineate the UD cavity. It is up to 90% sensitive, but invasive and so is rarely used. (endoluminal or surface coil): is the gold standard investigation is up to 95% sensitive at detecting Treatment Symptomatic UD requires surgery. The aims are dissection and excision of the dive rticulum, identi \201 cation and closure of the connection to the ure- thra (ostium), and a three-layered watertight closure 9 an interpositional \202 ap (Martius fat pad). Some a dvocate marsupialization for small distal third UD. A urethral catheter is placed for up to 14 days 9 cystourethrogram prior to catheter removal (depending on the complexity of the r epair). The concomitant insertion of a pubovaginal sling or tape for SUI remains controversial. Man y authors advocate initial UD surgery and reassessment of symptoms before proceeding with i ncontinence surgery.2 Complications and outcomes of surgery - - - - - - - - UTI Recurrent Incontinence. Recurrence of de novo LUTS. Persistent or Urethrovaginal \201 stula (2%). Persistent pain or dyspareunia. Urinary retention. (up to 40%). UTI (23%). UD. Contemporary series report overall success rates for primary and redo surgery of 70 \200 \22397%. Success rates for primary surgery are approximately 89%. 2 CHAPTER 5 Incontinence and female urology 168 Urethral diverticulum Fig. 5.12 Picture of a urethral diverticulum in a catheterized patient prior to surgery. (K indly provided with permission from Tamsin Greenwell). Urethral diverticulum Fig. 5.13 T2-weighted axial magnetic resonance image demonstrating a horseshoe-shaped ureth ral diverticulum. (Kindly provided with permission from Tamsin Greenwell). FEMALE URETHRAL DIVERTICULUM (UD) 169 1 Department of Health, UK. Hospital Episode Statistics [online]. Available from: M http:// www. hesonline.nhs.uk. 2 Ockrim JL, Allen DJ, Shah PJ, Greenwell TJ (2009) A tertiary experience of urethral diver ticulec- tomy: diagnosis, imaging and surgical outcomes. BJU Int 103:1550 \200\2234. CHAPTER 5 Incontinence and female urology 170 Pelvic organ prolapse (POP) De \201 nitions Anterior wall prolapse: is herniation of the bladder (cystocele) or urethra (urethrocele) t hrough the anterior vaginal wall due to weakened puboce- rvical ligaments. Posterior wall prolapse: is protrusion of the rectum through the posterior vaginal wall due to weakened perirectal fascia (rectocele) or protrusion of peritoneum (small intestine or omentum) into the vagina (enterocele). Middle compartment prolapse: includes uterine prolapse (descent of the uterus secondary to weak cardinal or uterosacral ligaments), vault prolapse (descent of the vaginal cuff after hysterectomy) and procidentia (prolapse of the entire uterus). Incidence Approximately 50% of women develop prolapse after childbirth (20% is symptomatic) . Lifetime risk of requiring POP or incontinence surgery is 711% with 29% requiring repeat procedures.1 Fifty percent are anterior, 30% posterior, and 20% uterine or vault prolapse. Etiology Congenital: secondary to connective tissue abnormalities (spina bi \201 da, exstr ophy, Ehlers \200\223Danlos syndrome). Acquired (multifactorial): related to previous vaginal surgery (prolapse repair, colposuspe nsion, hysterectomy); vaginal delivery; older age (decreased estrogen levels), obesity, con stipation, and chronic straining. Staging Pelvic organ prolapse quanti \201 cation (POPQ) is a validated system which allows standardized and accurate prolapse description by measuring distances between de \201 ned anatomical points and the hymen (Fig. 5.14; Tables 5.4 and 5.5). An alternative is the Bad en \200\223Walker classi \201 cation (Table 5.3).2 Table 5.3 Baden \200\223Walker classi \201 cation of POP2 Grade 0 No prolapse Grade 1 Descent halfway to the hymen Grade 2 Descent to hymen Grade 3 Descent halfway past the hymen Grade 4 Maximal descent/eversion PELVIC ORGAN PROLAPSE (POP) 171 Uterus bladder D Aa C B a Bp tvL Ap Aa Ba C gh pb tvl gh pb Ap Bp D Fig. 5.14 Anatomical reference points used for POPQ. Table 5.4 Description of anatomical points used in POPQ Anatomical point Description Range of values Anterior wall, Aa Anterior vaginal wall 3cm proximal to the external meatus \200\2233cm to + 3cm Anterior wall, Ba Most distal part of remaining upper anterior vaginal wall \200\2233cm to + tvl Cervix or cuff, C Most distal edge of cervix or vaginal cuff (vault) Posterior wall, Ap Posterior vaginal wall 3cm proximal to the hymen \200\2233cm to + 3cm Posterior wall, Bp Most distal position of the remaining upper posterior vaginal wall \200\2233cm to + tvl Posterior fornix, D Genital hiatus, gh Measured from middle of external urethral meatus to posterior midline hymen Perineal body, pb Measured from posterior margin of gh to middle of anal ori \201 ce Total vaginal length, tvl Depth of vagina when point D or C is returned to normal position CHAPTER 5 Incontinence and female urology 172 Table 5.5 ICS staging of POP based on POPQ Stage Leading edge of POP in relation to hymen Description 0 < \200\2233cm No prolapse 1 < \200\2231cm Prolapse >1cm above the level of the hymen \211 +1 and \211 +1cm 2 Prolapse between 1cm above or 1cm below the hymen 3 >+1cm Prolapse >1cm below the hymen, but without complete vaginal eversion \211 tvl \200\2242cm 4 Complete vaginal eversion. Protrusion minimally extends beyond hymen further than tvl \200 \2242cm Presentation History - - - - - - Vaginal pressure or bulge. Urinary frequency, urgency, incomplete emptying, incontinence. B owel dysfunction (urgency, dif \201 culty defecating, fecal soiling). Symptoms aggravated by prolonged standing. May need to manually reduce prolapse to void or defecate. Sexual dys function (dyspareunia, lack of sensation). Examination - Examine in lithotomy, left lateral position using a Sims \200\231 speculum, and standing. C ough or bear down when retracting the posterior wall to demonstrate anterior or middle comp artment prolapse. Anterior prolapse may be due to a central fascial defect (vagina wall loo ks smooth) or lateral defects (vaginal has rugae). Retract anterior wall to visualize poste rior compartment prolapse. Cough test for SUI. Should repeat with prolapse reduced as may u nmask occult SUI. Investigation - . - - - MSU Bladder diary. PVR Urodynamics (if concomitant voiding dysfunction or incontinence; rec ommends it for prolapse > stage II where surgery is planned). MRI Defaecography (isotope or contrast). . ICS (selected cases). PELVIC ORGAN PROLAPSE (POP) 173 Treatment Conservative - - - Lifestyle intervention (treat constipation, chronic cough). PFMT Vaginal pessary \200\224in dividually \201 tted and changed in clinic initially every 3 \200\2236 months with inspec tion for vaginal ulceration or \201 stulae. Treat any vaginal atrophy. . Surgery Repair may be with absorbable interrupted buttress sutures, with an on- lay mesh st rip cut to size or with pre-designed mesh (i.e. AMS Elevate and Gynecare Prolift ).There is controversy as to whether SUI should be treated at the same time as prolapse. This will be addressed by RCT CUPIDO. Anterior compartment Interrupted sutures are placed in remnant fascia, excise surplus vagin al skin, and close. Gynecare Prolift is a tension-free vaginal mesh system using a trocar delivery system to guide placement of a pre-shaped mesh. AMS Elevate has pre-shaped mesh which is positioned with a slim needle device and then held in place by self- \201 xing t ips and also supports the middle compartment. If there is coexisting SUI, options include prolapse repair and insertion of a tension-free vaginal tape or alternatively, a primary colposuspension (15% risk of posterior wall prola pse). Posterior compartment Repair with suture or mesh as above. Middle compartment prolapse - Uterine prolapse: An alternative for women wishing to preserve the uterus is sacrohysterope xy. An open or laparoscopic approach may be taken. A strip of mesh encircles the cervix and is then sutured to the sacrum. Vault prolapse: \200 Sacrospinous \201 xation involves (unilateral) suspension of the vaginal vault (or cervix) to the sacrospinous ligament with two sutures via a posterior vaginal approach. options include vaginal or abdominal hysterectomy. options include: Sacrocolpopexy involves suspension of the anterior and posterior aspects of the vaginal vau lt to the sacrum by strips of mesh and non-absorbable sutures which are then covered with p eritoneum to avoid bowel adhesion. Uterosacral ligament suspension where the uterosacral ligament is sutured to the vaginal apex. 1 Olsen AL, Smith VJ, Bergstrom JO, Colling JC, Clark AL (1997) Epidemiology of surgically man- aged pelvic organ prolapse and urinary incontinence. Obstet Gynecol 89:501-6. 2 Baden WF, Walker TA, Lindsay HJ (1968) The vaginal pro \201 le. Tex Med J 64:56 \200\223 8. This page intentionally left blank 175 Chapter 6 Infections and in \202 ammatory conditions Urinary tract infection: de \201 nitions and epidemiology 176 Urinary tract infection: mic robiology 178 Lower urinary tract infection: cystitis and investigation of UTI 182 Urinary tract infection: general treatment guidelines 184 Recurrent urinary tract infection 186 Upper urinary tract infection: acute pyelonephritis 190 Pyonephrosis and perinephric a bscess 192 Other forms of pyelonephritis 194 Chronic pyelonephritis 196 Septicaemia 198 Fou rnier \200\231s gangrene 202 Peri-urethral abscess 204 Epididymitis and orchitis 206 Prosta titis: classi \201 cation and pathophysiology 208 Bacterial prostatitis 210 Chronic pelvic pain syndrome 212 Bladder pain syndrome (BPS) 214 Urological problems from ketamine misuse 218 Genitourinary tuberculosis 220 Parasitic infections 222 HIV in urological surgery 226 Phimosis 228 In \202 ammatory disorders of the penis 230 CHAPTER 6 Infections and in \202 ammatory conditions 176 Urinary tract infection: de \201 nitions and epidemiology De \201 nitions Urinary tract i nfection (UTI) UTI is currently de \201 ned as the in \202 ammatory response of the uroth elium to bacterial invasion. This in \202 ammatory response causes a constellation of symp toms. Bladder infection (cystitis) causes frequent small volume voids, urgency, suprapubic pain or discomfort, and urethral \200\230burning \200\231 on void- ing (dysuria). Acute ki dney infection (acute pyelonephritis) causes symp- toms of fever, chills, malaise, and loin pain, often with associated LUTS of frequency, urgency, and urethral pain on voiding. The strict requirement for >105 bacteria/mL of MSU specimen is no longer required to make a dia gnosis of UTI. In symptomatic patients, many clinicians will now make a diagnosis of UTI wi th bacterial counts of >102/mL. Current recommenda- tions for diagnosing UTI from MSU cultu re is shown in Table 6.2. Bacteriuria: is the presence of bacteria in the urine. Bacteriuri a may be asymptomatic or symptomatic. Bacteriuria without pyuria indicates the presence of bacterial colonization of the urine rather than the presence of active infection. Pyuria: i s the presence of white blood cells in the urine (implying an in \202 am- matory response of the urothelium to bacterial infection or in the absence of bacteriuria (sterile pyuria), some other pathology such as carcinoma in situ, TB infection, bladder stones, or other in \202 ammatory conditions. An uncomplicated UTI: is one occurring in a patient with a struc turally and functionally normal urinary tract. The majority of such patients are women who respond quickly to a short course of antibiotics. A complicated UTI: is one occurring in th e presence of an underlying ana- tomical or functional abnormality (e.g. incomplete bladder emptying sec- ondary to BOO or DSD in SCI), renal or bladder stones, colovesical \201 st ula, etc. Other factors suggesting a potential complicated UTI are diabetes mel- litus, imm unosuppression, hospital-acquired infection, indwelling catheter, recent urinary tract inte rvention, and a failure of response to appropriate treatment. Most UTIs in men occur in ass ociation with a structural or functional abnormality and are, therefore, de \201 ned as co mplicated UTIs. Complicated UTIs take longer to respond to antibiotic treatment than uncomp licated UTIs and if there is an untreated underlying abnormality, they will usually recur w ithin days, weeks, or months. UTIs may be isolated, recurrent, or unresolved. Isolated Recu rrent Recurrent UTI may be due to re-infection (i.e. infection by different bacteria) or ba cterial persistence (infection by the same organism originating from a focus within the uri nary tract). Bacterial persistence is caused by the presence of bacteria within calculi (e. g. struvite stone), within a chronically infected prostate (chronic bacterial prostatitis), within an obstructed or atrophic infected kidney, or occurs as a result of a bladder \201 stula (with bowel or vagina) or UD. UTI: an interval of at least 6 months between infections. UTI: >2 infections in 6 months or 3 within 12 months. URINARY TRACT INFECTION: DEFINITIONS AND EPIDEMIOLOGY 177 Unresolved infection: natural or acquired bacterial resistance to treatment, infection by ( multiple) different organisms, or rapid re-infection. implies inadequate therapy and is caused by Table 6.1 Prevalence of bacteriuria Age Female Male Infants (<1y) 1% 3% School (<15y) 1 \200\2233% <1% Reproductive 4% <1% Elderly 20 \200\22330% 10% General risk factors for bacteriuria - - - - - - - - - - - Female sex. Increasing age. Low estrogen states (menopause). Pregnancy. Diabetes mellitus. Previous Institutionalized elderly patients. Indwelling catheters. Stone disease (kidney, b ladder). Genitourinary tract malformation. Voiding dysfunction (including obstruction). UTI. Table 6.2 Recommended criteria for diagnosing UTI1 Type of UTI Urine culture (cfu/mL) >103 Acute uncomplicated UTI/cystitis in women >104 Acute uncomplicated pyelonephritis >105 in women; >104 in men Complicated UTI >105 in two consecutive MSU cultures >24h apart Asymptomatic bacteriuria <103 Recurrent UTI cfu/mL = colony forming units/mL; MSU = midstream urine. 1 Grabe M, Bjerklund-Jphansen TE, Botto H, et al. Guidelines on Urological Infections. Euro pean Association of Urology Guidelines 2011 edition. CHAPTER 6 Infections and in \202 ammatory conditions 178 Urinary tract infection: microbiology Most UTIs are caused by fecal-derived bacteria that a re facultative anaer- obes (i.e. they can grow under both anaerobic and non-anaerobic condi - tions) (see Table 6.3). Uncomplicated UTI Infection in a subject with a normal functional and anatomical urinary tr act. Most UTIs are bacterial in origin. The most common cause is Escherichia coli (E. coli) , a Gram-negative bacillus, which accounts for 85% of com- munity-acquired and 50% of hospi tal-acquired infections. Other common causative organisms include Staphylococcus saprophyti cus, Proteus mirabilis, and Klebsiella. Complicated UTI Infection in a subject with a functional or anatomical abnormality of the u rinary tract, underlying risk factors, or failure to respond to therapy. E. coli is respons ible for up to 50% of cases. Other causes include Enterococci, Staphylococci, Pseudomonas, Proteus, Klebsiella, and other enterobacteria. Route of infection Ascending The vast majority of UTIs result from infection ascending retr ogradely up the urethra. Bacteria, derived from the large bowel, colonize the peri- neum, v agina, and distal urethra. They ascend along the urethra to the bladder (increased risk in females as urethra shorter), causing cystitis. From the bladder, they may ascend via the ur eters to involve the kid- neys (pyelonephritis). Re \202 ux is not necessary for infection to ascend to the kidneys, but it will encourage ascending infection as will any process th at impairs ureteric peristalsis (e.g. ureteric obstruction, Gram-negative organisms and end otoxins, pregnancy). Infection that ascends to involve the kidneys is also more likely wher e the infecting organism has P pili ( \201 la- mentous protein appendages, also known as \201 mbriae, which allow binding of bacteria to the surface of epithelial cells). Haematogenous: uncommon, but is seen with Staphylococcus (S.) aureus, Candida fungaemia, an d Mycobacterium (M.) tuberculosis (causing TB). Infection via lymphatics: seen rarely in in \202 ammatory bowel disease and from retroperi toneal abscess. Table 6.3 Classi \201 cation of bacteria and other organisms associated with the urinary t ract and UTI Cocci Gram +ve Aerobes Streptococcus Non-haemolytic: Enterococcus (E. faecalis) A-haemolytic: S. viridians; -haemolytic strept ococcus S. saprophyticus (causes 710% of symptomatic lower UTIs in young, sexually active w omen) Staphylococcus S. aureus S. epidermidis N. gonorrhoeae C. urealyticium U R N A R Y Gram \200\223ve Aerobes Gram +ve Aerobes Neisseria Corynebacteria I Bacilli (rods) Acid-fast Gram +ve Anaerobes* Mycobacteria Lactobacillus M. tuberculosis (i.e. L. crispatis, L. Jensenii are common vaginal commensal organisms) T R A C T Clostridium perfringens Escherichia coli, Proteus mirabilis, Klebsiella sp. Pseudomonas aer uginosa Gram \200\223ve Aerobes Enterobacteriacaeae I N F E C T O N Non-fermenters Bacteroides Chlamydia Mycoplasma Ureaplasma Candida Gram \200\223ve Anaerobes* Bacteroides fragilis C. trachomatis M. hominus U. urealyticum (cause UTI in patients with i ndwelling catheters C. albicans I Other organisms : M C R O B O L O G Y I I Anaerobic infections of the bladder and kidney are uncommon \200\224anaerobes are normal co mmensals of the perineum, vagina, and distal urethra. However, infections of the urinary sy stem that produce pus (e.g. scrotal, prostatic, or perinephric abscesses) can be caused by anaerobic organisms (e.g. Bacteroides sp. such as Bacteroides fragilis, Fusobacterium sp., anaerobic cocci, and Clostridium perfringens). 1 7 9 CHAPTER 6 Infections and in \202 ammatory conditions 180 Factors increasing bacterial virulence Adhesion mechanisms Many Gram-negative bacteria have pili (also known as \201 mbriae) on their cell surface, which aid attachment to urotheli al cells of the host. A typical piliated cell may contain 100 \200\223400 pili. Pili are 5 \200\22310nm in diameter and up to 2 m long. E. coli produces a number of antigenically an d functionally different types of pili on the same cell; other strains may produce only a s ingle type and in some isolates, no pili are seen (such as Dr adhesin associated with UTI i n pregnant women and children). Pili are de \201 ned functionally by their ability to medi ate haemagglutination (clumping of red blood cells) of speci \201 c types of erythrocytes. Mannose-sensitive (type 1) pili are produced by all strains of E. coli and are associated with cystitis. Certain pathogenic types of E. coli also produce mannose-resistant P pili an d are associated with pyelonephritis. S pili are associated with infection of both the blad der and kidneys. Avoidance of host defense mechanisms - General: phagocytosis (E. coli). M. tuberculosis resists phagocytosis by preventing phagoly sosome fusion. Toxins: pathogenic effect on host erythrocytes. Enzyme production: breakdown of urea in urine to ammonia, which then contributes to disease processes (struvite stone f ormation). an extracellular capsule reduces immunogenicity and resists E. coli species have haemolysin activity which has a direct Proteus species produce ureases which cause the Antimicrobial resistance - Enzyme inactivation: produce B-lactamase which hydrolyzes the B- lactam bond within the structure of some antibiotics so inactivating them. The B-lactam ant ibiotics are penicillins, cephalosporins, and carbapenems. Altered permeability: prevented by alterations in receptor activity or transportation mechanisms. Alteration of binding sit e: genetic variations may alter the antibiotic target, leading to drug resistance. S. aureus, N. gonorrhoeae, and enterobacteria can access of the antibiotic to the bacteria is Host defenses: factors that protect against UTI include the following. General - Commensal \202 ora: protect by competing for nutrients, bacteriocin production, stimulati on of immune system, and altering pH. Mechanical integrity of mucous membranes. Mucosal sec retions: lysozymes split muramic acid links in cell walls of Gram-positive organisms; lacto ferrin disrupts normal metabolism of bacteria. Urinary immunoglobulin A (IgA) inhibits bact erial adherence. URINARY TRACT INFECTION: MICROBIOLOGY 181 Speci \201 c - Mechanical \202 ushing effect of urine through the urinary tract (i.e. antegrade \202 o w of urine). A mucopolysaccharide coating of bladder (Tamm \200\223Horsfall protein) helps prevent bacterial attachment. Bladder surface mucin: glycosaminoglycan (GAG) layer is an an ti-adherent factor, preventing bacterial attachment to mucosa. Low urine pH and high osmola rity reduces bacterial growth. Female commensal \202 ora: glycogen into lactic acid, caus ing a drop in pH. Increased rates of bladder mucosal cell exfoliation are seen during infec tion, which accelerates cell removal with adherent bacteria. Lactobacillus acidophilus metabolizes CHAPTER 6 Infections and in \202 ammatory conditions 182 Lower urinary tract infection: cystitis and investigation of UTI Cystitis: is infection and/or in \202 ammation of the bladder. Presentation: frequent voiding of small volumes, dysuria, urgency, offensive urine, suprapu bic pain, haematuria, fever 9 incontinence. General investigation of UTI Dipstick of MSU specimen White blood cells (indirect testing f or pyuria) Leukocyte esterase activity detects the presence of white blood cells (WBC) in t he urine. Leukocyte esterase is produced by neutrophils and causes a color change in a chro mogen salt on the dipstick. Not all patients with bacteriuria have signi \201 cant pyuria (sensitivity of 75 \200\22395% for detection of infection, i.e. 5 \200\22325% of patients w ith infection will have a negative leuko- cyte esterase test, erroneously suggesting that t hey have no infection). - False positives (pyuria present, negative dipstick test) \200\224concentrated urine, glycos uria, presence of urobilinogen, consumption of large amounts of ascorbic acid. False negati ves (pyuria absent, positive dipstick test) \200\224contamination. Remember, there are many causes for pyuria (and, therefore, a positive leukocyte esterase t est occurring in the absence of bacteria on urine microscopy). This is so-called sterile py uria and it occurs with TB infec- tion, renal calculi, bladder calculi, glomerulonephritis, interstitial cystitis, and carcinoma in situ. Thus, the leukocyte esterase dipstick test m ay be truly positive in the absence of infection. Nitrite testing (indirect testing for bacteriuria) Nitrites are not normally found in urine and their presence suggests the possibility of bacteriuria. Many species of Gram-negative bacteria can con- vert nitrates to nitrites and these are detected in the urine by a reacti on with the reagents on the dipstick which form a red azo dye. The speci \201 city of the nitrite dipstick for detecting bacteriuria is >90% (false positive nitrite testing can occu r with contamination). The sensitivity is 35 \200\22385% (i.e. false negatives are common \200\224a negative dipstick in the presence of active infec- tion) and is less accurate in urine containing <105 organisms/mL. Hence, if the nitrite dipstick test is positive, the pa tient probably has a UTI, but a negative test often occurs in the presence of infection. Cloudy urine, which is positive for WBCs on dipstick and is nitrite- positive, is very likely to be infected. Blood Hemoglobin has a peroxidase-like activity, causing oxidation of a chro- mogen indicat or on the dipstick, which changes color when oxidized. False positives are seen with menstr ual blood and dehydration. LOWER URINARY TRACT INFECTION: CYSTITIS 183 pH Urinary pH usually lies between 5.5 and 6.5 (range 4.5 \200\2238). A persistent alka- li ne pH associated with UTI indicates a risk of stones. Urease-producing bacteria (such as Pr oteus mirabilis) hydrolyze urea to ammonia and carbon dioxide, leading to the formation of magnesium, calcium, ammonium phos- phate stones (triple phosphate or struvite calculi). Microscopy of MSU - False negative: low bacterial counts may make it very dif \201 cult to identify bacteria a nd the specimen of urine may, therefore, be deemed to be negative for bacteriuria when, in fact, there is active infection. False positive: bacteria may be seen in the infection. Thi s is most often due to contamination with commensals from the distal urethra and perineum ( urine from a woman may contain thousands of lactobacilli and corynebacteria derived from th e vagina). These bacteria are readily seen under the microscope and although they are Gram- positive, they often appear Gram-negative (Gram-variable) if stained. MSU in the absence of If the urine specimen contains large numbers of squamous epithelial cells (cells which are derived from the foreskin, vaginal, or distal urethral epithelium), this suggests contamina tion of the specimen and the presence of bacteria in this situation may indicate a false po sitive result. The \201 nding of pyuria and red blood cells suggests the presence of acti ve infection. Further investigation Determined by the clinical scenario. If this is a one-off infection i n an oth- erwise healthy individual, no further investigations are required. However, furth er investigations are required if: - The patient develops symptoms and signs of upper tract infection (loin pain, malaise, fever ) and, therefore, acute pyelonephritis, a pyonephrosis or perinephric abscess is suspected. UTIs develop (see b p. 186). Recurrent The patient is pregnant. Unusual infecting organism (e.g. an infection stone. - Proteus), suggesting the possibility of These further investigations will include a KUB X-ray 9 IVU (looking for infection stones i n the kidney; avoid in pregnant women), renal USS 9 cystoscopy. Non-infective cystitis Symptoms of cystitis can also be caused by: -