UEU-co logo

Ovid: Oxford Handbook of Urology

Authors: Reynard, John; Brewster, Simon; Biers, Suzanne Title: Oxford Handbook of Urology, 1st Edition Copyright ©2006 Oxford University Press > Table of Contents > Chapter 6 – Infections and inflammatory conditions Chapter 6 Infections and inflammatory conditions P.136
Urinary tract infection: definitions, incidence, and epidemiology Definitions Urinary tract infection A diagnosis of urinary tract infection (UTI) used to be based on finding >105 bacteria/ml of urine, whether or not there were associated symptoms of infection. However, 20–40% of women with symptomatic UTIs present with bacteria counts of 102–104 bacteria/ml of urine (the low counts are due to frequent voiding due to the irritation caused by the infection and also represent the slow doubling time of many bacteria in urine). Furthermore, contamination of urine from perineal bacteria or those on the foreskins of uncircumcised men can often lead to bacterial counts of >105. UTI is currently defined as the inflammatory response of the urothelium to bacterial invasion. This inflammatory response causes a constellation of symptoms. In bladder infection this is described as ‘cystitis’—frequent small volume voids, urgency, suprapubic pain or discomfort, urethral ‘burning’ on voiding (dysuria). In acute kidney infection (acute pyelonephritis) the symptoms are 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 urine is no longer required to make a diagnosis of UTI. In symptomatic patients many clinicians will now make a diagnosis of UTI with bacterial counts of >102/ml. Bacteriuria is the presence of bacteria in the urine. Bacteriuria may be asymptomatic or symptomatic. Bacteriuria without pyuria indicates the presence of bacterial colonization of the urine, rather than the presence of active infection (‘active’ implies an inflammatory response to bacterial invasion of the urothelium). Pyuria is the presence of white blood cells in the urine (implying an inflammatory response of the urothelium to bacterial infection or, in the absence of bacteriuria, some other pathology such as carcinoma in situ, TB infection, bladder stones, or other inflammatory conditions). An uncomplicated UTI is one occurring in a patient with a structurally 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 the presence of an underlying anatomical or functional abnormality (e.g. functional problems causing incomplete bladder emptying, such as BPO, DSD in spinal cord injury), stones in the kidney or bladder, fistula between bladder and bowel, etc. Most UTIs in men occur in association with a structural or functional abnormality and are therefore defined as complicated UTIs. Complicated UTIs take longer to respond to antibiotic treatment than uncomplicated UTIs, and if there is an underlying anatomical or structural abnormality they will usually recur within days, weeks, or months. Urinary tract infection may be isolated, recurrent or unresolved.

  • Isolated UTI: an interval of at least 6 months between infections.

P.137
Prevalence of bacteriuria

Age Female Male
Infants (<1 year) 1% 3%
School (<15 years old) 1–3% <1%
Reproductive 4% <1%
Elderly 20–30% 10%
  • Recurrent UTI: >2 infections in 6 months, or 3 within 12 months.Recurrent UTI may be due to reinfection (i.e. infection by a different bacteria) or bacterial persistence (infection by the same organism originating from a focus within the urinary tract). Bacterial persistence is caused by the presence of bacteria within calculi (e.g. struvite calculi), within a chronically infected prostate (chronic bacterial prostatitis), within an obstructed or atrophic infected kidney, or occurs as a result of a bladder fistula (with bowel or vagina) or urethral diverticulum.
  • Unresolved infection: implies inadequate therapy and is caused by natural or acquired bacterial resistance to treatment, infection by different organisms, or rapid reinfection.

Risk factors for bacteriuria Female sex; increasing age; low oestrogen states (menopause); pregnancy; diabetes mellitus; previous UTI; the institutionalized elderly; indwelling catheters; stone disease (kidney, bladder); genitourinary malformation and voiding dysfunction (including obstruction). P.138
Urinary tract infection: microbiology Most UTIs are caused by faecal-derived bacteria which are facultative anaerobes (i.e. they can grow under both anaerobic and non-anaerobic conditions)—see Table 6.1. Uncomplicated UTI Most UTIs are bacterial in origin. The most common cause is Escherichia coli (E. coli), a gram-negative bacillus, which accounts for 85% of community acquired and 50% of hospital acquired infection. Other common causative organisms include Staphylococcus saprophyticus and Enterococcus faecalis (also known as Streptococcus faecalis—gram +ve), Proteus mirabilis, and Klebsiella (gram-negative enterobacteriacae). Complicated UTI E. coli is responsible for up to 50% of cases. Other causes include Enterococci (e.g. Streptococcus faecalis), Staph. aureus, Staph. epidermidis (gram +ve), Pseudomonas aeruginosa (gram -ve). Route of infection Ascending The vast majority of UTIs result from infection ascending retrogradely up the urethra. The bacteria, derived from the large bowel, colonize the perineum, vagina, and distal urethra. They ascend along the urethra to the bladder (increased risk in females as urethra shorter) causing cystitis, and from the bladder they may ascend, via the ureters, to involve the kidneys (pyelonephritis). Reflux is not necessary for infection to ascend to the kidneys, but the presence of reflux will encourage ascending infection, as will any process that impairs ureteric peristalsis (e.g. ureteric obstruction, gram-negative organisms and endotoxins, pregnancy). Infection which ascends to involve the kidneys is also more likely where the infecting organism has P pili (filamentous protein appendages—also known as fimbriae—which allow binding of bacteria to the surface of epithelial cells). Haematogenous Uncommon, but is seen with Staph. aureus, candida fungaemia, and TB. Infection via lymphatics Seen rarely in inflammatory bowel disease, retroperitoneal abscess. Factors increasing bacterial virulence Adhesion factors Many gram-negative bacteria contain pili on their surface, which aid attachment to urothelial cells of the host. A typical piliated cell may contain 100–400 pili. Pili are 5–10nm in diameter and up to 2µm long. E. coli produces a number of antigenically and functionally different types of pili on the same cell; other strains may produce only a single type, and, in some isolates, no pili are seen. Pili are defined functionally by their ability to mediate hemagglutination (HA) of specific types of erythrocytes. Mannose-sensitive (type 1) pili are produced by all strains of E. coli. Certain pathogenic types of E. coli also produce mannose-resistant (P) pili (associated with pyelonephritis). P.139
P.140
Avoidance of host defense mechanisms An extracellular capsule reduces immunogenicity and resists phagocytosis (E. coli). M. tuberculosis resists phagocystosis by preventing phagolysosome fusion. Toxins E. coli species release cytokines which have a direct pathogenic effect on host tissues. Enzyme production Proteus species produce ureases, which causes breakdown of urea in the urine to ammonia, which then contributes to disease processes (struvite stone formation). Host defences Factors which protect against UTI are:

  • Mechanical flushing effect of urine through the urinary tract (i.e. antegrade flow of urine).
  • A mucopolysaccharide coating of bladder (Tamm–Horsfall protein) helps prevent bacterial attachment.
  • Low urine pH and high osmolarity reduces bacterial growth.
  • Urinary immunoglobulin (IgA) inhibits bacterial adherence.
Table 6.1 Bacterial classification: uropathogens
COCCI Gram-positive
Staphylococcus, Enterococcus faecalis (also known as Streptococcus faecalis) e.g. S. saprophyticus causes approximately 10% of symptomatic lower UTIs in young, sexually active women)
Gram-negative
Aerobes: Neisseria
BACILLI (RODS) Gram-positive
Anaerobes*: Clostridium, Lactobacillus (usually a vaginal commensal)
Gram-negative
Aerobes: Enterobacteria (Escherichia, Klebsiella, Proteus), Pseudomonas
Anaerobes*: Bacteroides
OTHERS Filamentous bacteria: Mycobacterium (M. tuberculosis—acid-fast, aerobic, gram-positive)
Chlamydiae: Chlamydia trachomatis Fungi: Candida albicans
Mycoplasma: Mycoplasma species, Ureaplasma urealyticum (cause UTI in patients with indwelling catheters)
*Anaerobic infections of the bladder and kidney are uncommon—anaerobes are normal commensals of the perineum, vagina, and distal urethra. However, infections of the urinary system which produce pus (e.g. scrotal, prostatic, or perinephric abscesses) are often caused by anaerobic organisms (e.g. Bacteroides species such as Bacteroides fragilis, Fusobacterium species, anaerobic cocci, and Clostridium perfringens).

P.141
P.142
Lower urinary tract infection Cystitis infection and/or inflammation of the bladder. Presentation: frequent voiding of small volumes, dysuria, urgency, offensive urine, suprapubic pain, haematuria, fever, and incontinence. Investigation Dipstick of midstream specimen of urine (MSU) White blood cells (indirect testing for pyuria) Leukocyte esterase activity detects the presence of white blood cells in the urine. Leukocyte esterase is produced by neutrophils and causes a colour change in a chromogen salt on the dipstick. Not all patients with bacteriuria have significant pyuria (sensitivity of 75–95% for detection of infection—i.e. 5–25% of patients with infection will have a -ve leukocyte esterase test suggesting, erroneously, that they have no infection).

  • False -ves (pyuria present, negative dipstick test)—concentrated urine, glycosuria, presence of urobilinogen, consumption of large amounts of ascorbic acid.
  • False +ves (pyuria absent, positive dipstick test)—contamination.

Remember, there are many causes for pyuria (and therefore a +ve leukocyte esterase test) occurring in the absence of bacteria on urine micro-scopy. This is so-called sterile pyuria and it occurs with TB infection, renal calculi, bladder calculi, glomerulonephritis, interstitial cystitis, carcinoma in situ. Thus, the leukocyte esterase dipstick test may 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 convert nitrates to nitrites and these are detected in urine by a reaction with the reagents on the dipstick which form a red azo dye. The specificity of the nitrite dipstick for detecting bacteriuria is >90% (false +ve nitrite testing can occur with contamination). Sensitivity: 35–85% (i.e. false -ves are common—a negative dipstick in the presence of active infection); less accurate in urine containing fewer than 105 organisms/ml. So, if the nitrite dipstick test is +ve, the patient probably has a UTI, but a -ve test often occurs in the presence of infection. Cloudy urine which is +ve for WBCs on dipstick and is nitrite +ve is very likely to be infected. Microscopy of midstream specimen of urine (MSU)

  • False -ves—low bacterial counts may make it very difficult to identify bacteria, and the specimen of urine may therefore be deemed to be negative for bacteriuria, when in fact there is active infection.
  • False +ves—bacteria may be seen in the MSU in the absence of infection. This is most often due to contamination of the MSU with commensals from the distal urethra and perineum (urine from a woman may contain thousands of lactobacilli and corynebacteria, and these organisms are derived from the vagina). These bacteria are readily seen under the microscope, and although they are gram-positive, they often appear gram-negative (gram-variable) if stained.

P.143
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 contamination of the specimen, and the presence of bacteria in this situation may indicate a false +ve result. The finding of pyuria and red blood cells suggests the presence of active infection. Further investigation Determined by the clinical scenario. If this is a one-off infection in an otherwise healthy individual, no further investigations are required. However, further 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
  • recurrent UTIs develop (see p.144)
  • the patient is pregnant
  • unusual infecting organism (e.g. Proteus), suggesting the possibility of an infection stone

These further investigations will include a KUB X-ray (looking for infection stones in the kidney; avoid in pregnant women) and a renal ultrasound. The investigation of recurrent UTIs is discussed on p.144). Non-infective cystitis

  • Pelvic radiotherapy (radiation cystitis—bladder capacity is reduced and multiple areas of mucosal telangectasia are seen cystoscopically)
  • Drug-induced cystitis (e.g. cyclophosphamide treatment)
  • Haemorrhagic cystitis

Urethritis is inflammation of the urethra. Urethritis in men is a sexually transmitted disease, which presents with dysuria and urethral discharge. Gonococcal urethritis (GU) is caused by the gram-negative dipplococcus Neisseria gonorrhoea (incubation 3–10 days). Diagnosis is on cultures from urethral swab. Treatment involves a single dose of cefotaxime or course of ciprofloxacin. Sexual contacts must be informed and treated. Non-gonococcal urethritis (NGU) is mainly caused by Chlamydia trachomatis (incubation 1–5 weeks). Treat with a single dose of azithromycin and 7 days of doxicycline. Transmission to females results in increased risk of pelvic inflammatory disease; abdominal pain; ectopic pregnancy; infertility; and perinatal infection. Urethral syndrome is a condition of uncertain aetiology that only affects women. It manifests as dysuria, frequency, and urgency without evidence of infection, although some cases improve with antibiotics. P.144
Recurrent urinary tract infection Recurrent UTI is defined as >2 infections in 6 months, or 3 within 12 months. It may be due to reinfection (i.e. infection by a different bacteria) or bacterial persistence (infection by the same organism originating from a focus within the urinary tract). Bacterial persistence implies the presence of bacteria within a site in the urinary tract, the presence of which leads to repeat episodes of infection. Such sites include kidney stones; the chronically infected pro-state (chronic bacterial prostatitis); bacteria within an obstructed or atrophic infected kidney; bacteria gaining access to the urinary tract via a fistula (with bowel or vagina); bacteria within a urethral diverticulum. Thus, recurrent urinary infection due to bacterial persistence implies a functional or anatomical problem, and that the recurrent UTIs will not resolve until this underlying problem has been addressed. Reinfections usually occur after a prolonged interval (months) from the previous infection and are often caused by a different organism than the previous infecting bacterium. Bacterial persistence usually leads to frequent recurrence of infection (within days or weeks) and the infecting organism is usually the same organism as that causing the previous infection(s). Women with reinfection do not usually have an underlying functional or anatomical abnormality. Reinfections in women are associated with increased vaginal mucosal receptivity for uropathogens and ascending colonization from the faecal flora. These women cannot be cured of their predisposition to recurrent UTIs, but they can be managed by a variety of techniques (see below). Men with reinfection may have underlying BOO (due to BPE or a urethral stricture), which makes them more likely to develop a repeat infection, but between infections their urine is sterile (i.e. they do not have bacterial persistence between symptomatic UTIs). A urethrogram, flexible cystoscopy, post-void bladder ultrasound for residual urine volume, and, in some cases, urodynamics may be helpful in establishing the potential causes. As stated above, both men and women with bacterial persistence usually have an underlying functional or anatomical abnormality and they can potentially be cured of their recurrent UTIs, if this abnormality can be identified and corrected. Management of women with recurrent UTIs due to reinfection Most urologists will arrange a series of screening tests (KUB X-ray, renal ultrasound, flexible cystoscopy) to double check there is no potential source of bacterial persistence (i.e. to confirm that they are dealing with a ‘simple’ case of reinfection rather than one of bacterial persistence). In the absence of finding an underlying functional or anatomic abnormality, these patients cannot be cured of their tendency to recurrent urinary infection, but they can be managed in one of the following ways: Avoidance of spermicides used with the diaphragm or on condoms Spermicides containing nonoxynol-9 reduce vaginal colonization with P.145
lactobacilli and may enhance E. coli adherence to urothelial cells. Recommend an alternative form of contraception. Estrogen replacement therapy Lack of estrogen in post-menopausal women causes loss of vaginal lactobacilli and increased colonization by E. coli. Estrogen replacement can result in recolonization of the vagina with lactobacilli and eliminate colonization with bacterial uropathogens.1 Low-dose antibiotic prophylaxis Oral antimicrobial therapy with full-dose oral tetracyclines, ampicillin, sulphonamides, amoxicillin, and cephalexin causes resistant strains in the faecal flora and subsequent resistant UTIs. However, trimethoprim, nitrofurantoin, low-dose cephalexin, and the fluoroquinolones have a minimal adverse effects on the faecal and vaginal flora.

  • Efficacy of prophylaxis. Recurrences of UTI may be reduced by as much as 90% when compared with placebo.2 Prophylactic therapy requires only a small dose of an antimicrobial agent, generally given at bedtime for 6 to 12 months. Symptomatic reinfection during prophylactic therapy is managed with a full therapeutic dose with the same prophylactic antibiotic or another antibiotic. Prophylaxis can then be restarted. Symptomatic reinfection immediately after cessation of prophylactic therapy is managed by restarting nightly prophylaxis.
  • Trimethoprim. The gut is a reservoir for organisms that colonize the periurethral area and which may subsequently cause episodes of acute cystitis in young women. Trimethoprim eradicates gram-negative aerobic flora from the gut and vaginal fluid (i.e. it eliminates the pathogens from the infective source). Trimethoprim is also concentrated in bactericidal concentrations in the urine following an oral dose. Adverse reactions: blood dyscrasias due to bone marrow depression; rarely, Stevens–Johnson syndrome; allergic reactions; rarely, erythema multiforme, toxic epidermal necrolysis (photosensitivity).
  • Nitrofurantoin is completely absorbed and/or degraded/inactivated in the upper intestinal tract and therefore has no effect on gut flora. It is present for brief periods at high concentrations in the urine and leads to repeated elimination of bacteria from the urine. Nitrofurantoin prophylaxis therefore does not lead to a change in vaginal or introital colonization with Enterobacteria. The bacteria colonizing the vagina remain susceptible to nitrofurantoin because of the lack of bacterial resistance in the fecal flora. Adverse reactions: include acute pulmonary reactions (pulmonary fibrosis has been reported), allergic reactions (angioedema, anaphylaxis, urticaria, rash and pruritus), peripheral neuropathy, blood dyscrasias (agranulocytosis, thrombocytopenia, aplastic anaemia), liver damage, lupus erythematosus-like syndrome, and chronic pulmonary reactions. The risk of an adverse reaction increases with age, with the greatest number occurring in patients older than 50 years.
  • Cephalexin at 250mg or less nightly is an excellent prophylactic agent because faecal resistance does not develop at this low dosage.
  • P.146

  • Adverse reactions: allergic reactions.
  • Fluoroquinolones (e.g. Ciprofloxacin). Short courses eradicate Enterobacteria from the faecal and vaginal flora. Adverse reactions to quinolones: tendon damage (including rupture), which may occur within 48h of starting treatment (quinolones are contraindicated in patients with a history of tendon disorders related to quinolone use; elderly patients are more prone to tendonitis; risk of tendon rupture is increased by the concomitant use of corticosteroids; discontinue quinolone immediately if tendonitis suspected). Other adverse reactions: arthropathy in children; Stevens–Johnson syndrome; allergic reactions.

Natural yoghurt applied to the vulva and vagina can help restore normal vaginal flora, thereby improving the natural resistance to recurrent infections. Post-intercourse antibiotic prophylaxis Sexual intercourse has been established as an important risk factor for acute cystitis in women and women who use the diaphragm have a significantly greater risk of UTI than women who use other contraceptive methods.3 Post-intercourse therapy with antimicrobials such as nitrofurantoin, cephalexin, or tri-methoprim, taken as a single dose, effectively reduces the incidence of reinfection. Self-start therapy Women keep a home supply of an antibiotic (e.g. trimethoprim, nitrofurantoin, a fluoroquinolone) and start treatment when they develop symptoms suggestive of UTI. Management of men and women with recurrent UTIs due to bacterial persistence Investigations These are directed at identifying the potential causes of bacterial persistence, outlined above.

  • KUB X-ray to detect radio-opaque renal calculi.
  • Renal ultrasound to detect hydronephrosis and renal calculi. If hydro-nephrosis is present, but the ureter is not dilated, consider the possibility of a radio-opaque stone obstructing the PUJ (this will usually be seen as an acoustic shadow on the ultrasound; arrange a CTU if no stone is seen) or a PUJO (arrange a MAG3 renogram to determine the presence/absence of PUJO).
  • Determination of post-void residual urine volume by bladder ultrasound.
  • IVU or CTU where a stone is suspected, but not identified on plain X-ray or ultrasound.
  • Flexible cystoscopy to identify possible causes of recurrent UTIs such as bladder stones, an underlying bladder cancer (rare), urethral or bladder neck stricture, fistula.

Treatment: depends on the functional or anatomical abnormality which is identified as the cause of the bacterial persistence. If a stone is identified, this should be removed. If there is obstruction (e.g. BPO, PUJO, DSD in spinal injured patients), this should be corrected. P.147
P.148
Urinary tract infection: treatment Antimicrobial drug therapy The aim is to eliminate bacterial growth from the urine. Empirical treatment involves the administration of antibiotics according to the clinical presentation and most likely causative organism, before culture sensitivities are available (see Table 6.2). Men are often affected by complicated UTI and may require longer treatments, as may patients with uncorrectable structural or functional abnormalities (e.g. indwelling catheters, neuropathic bladders). Bacterial resistance to drug therapy Organisms susceptible to concentrations of an antibiotic in the urine (or serum) after the recommended clinical dosing are termed ‘sensitive’, and those that do not respond are ‘resistant’. Bacterial resistance may be intrinsic (e.g. Proteus is intrinsically resistant to nitrofurantoin), via selection of a resistant mutant during initial treatment, or genetically transferred between bacteria by R plasmids. Definitive treatment Once urine or blood culture results are available, antimicrobial therapy should be adjusted according to bacterial sensitivities. Underlying abnormality should be corrected if feasible (i.e. extraction of infected calculus; removal of catheter; nephrostomy drainage of an infected, obstructed kidney).

Table 6.2 Recommendations for antimicrobial therapy
Infection Bacteria Initial empirical drug Duration
Acute, uncomplicated cystitis E. coli, Klebsiella, Proteus, Staphylococcus Trimethoprim/co-trimoxazole Quinolone (ciprofloxacin)
or
Nitrofurantoin (not for Proteus)
3 days
3 days
7 days
Acute, uncomplicated pyelonephritis E. coli, Proteus, Klebsiella, other Enterobacter, Staphylococcus Ciprofloxacin Cephalosporin
or
Aminopenicillin (ampicillin) Aminoglycoside (gentamicin)
7–10 days
Complicated UTI E. coli, Enterococcus Ciprofloxacin Aminopenicillin Continue for 3–5 days after elimination of underlying factor
Nosocomial (hospital acquired) UTI Staphylococcus, Klebsiella, Proteus Cephalosporin Aminoglycoside  
Acute complicated pyelonephritis Enterobacter, Pseudomonas, Candida For Candida: Fluconazole Amphotericin B  
These are general recommendations only; you should be guided by your local microbiology department whose recommendations will be based on local and regional bacterial sensitivities and resistance.

P.149
P.150
Acute pyelonephritis A clinical diagnosis based on the presence of fever, flank pain, and tenderness, often with an elevated white count. It may affect one or both kidneys. There are usually accompanying symptoms suggestive of a lower UTI (frequency, urgency, suprapubic pain, urethral burning or pain on voiding) responsible for the ascending infection which resulted in the subsequent acute pyelonephritis. Nausea and vomiting are common. Differential diagnosis includes cholecystitis, pancreatitis, diverticulitis, appendicitis. Risk factors vesicoureteric reflux (VUR); urinary tract obstruction; calculi; spinal cord injury (neuropathic bladder); diabetes mellitus; congenital malformation; pregnancy; indwelling catheters. Pathogenesis and microbiology initially, there is patchy infiltration of neutrophils and bacteria in the parenchyma. Later changes include the formation of inflammatory bands extending from renal papilla to cortex, and small cortical abscesses. 80% of infections are secondary to E. coli (possessing P pili virulence factors). Other infecting organisms: Enterococci (Streptococcus faecalis), Klebsiella, Proteus, and Pseudomonas. Urine culture will be positive for bacterial growth, but the bacterial count may not necessarily be be >105cfu/ml of urine Thus, if you suspect a diagnosis of acute pyelonephritis from the symptoms of fever and flank pain, but there are <105cfu/ml of urine, manage the case as acute pyelonephritis. Investigation and treatment

  • For those patients who have a fever but are not systemically unwell, outpatient management is reasonable. Culture the urine and start oral antibiotics according to your local antibiotic policy (which will be based on the likely infecting organisms and their likely antibiotic sensitivity). We use oral ciprofloxacin, 500mg bd for 10 days.
  • If the patient is systemically unwell, culture urine and blood, start intravenous fluids and intravenous antibiotics, again selecting the antibiotic according to your local antibiotic policy. We use IV ampicillin 1g TDS and gentamicin 3mg/kg as a once-daily dose.
  • Arrange a KUB X-ray and renal ultrasound, to see if there is an underlying upper tract abnormality (such a ureteric stone), unexplained hydronephrosis, or (rarely) gas surrounding the kidney (suggesting emphysematous pyelonephritis).
  • P.151

  • If the patient does not respond within 3 days to this regimen of appropriate intravenous antibiotics (confirmed on sensitivities), arrange a CTU. The lack of response to treatment suggests the possibility of a pyonephrosis (i.e. pus in the kidney, which like any abscess will only respond to drainage), a perinephric abscess (which again will only respond to drainage), or emphysematous pyelonephritis. The CTU may demonstrate an obstructing ureteric calculus that may have been missed on the KUB X-ray, and ultrasound may show a perinephric abscess. A pyonephrosis should be drained by insertion of a percutaneous nephrostomy tube. A perinephric abscess should also be drained by insertion of a drain percutaneously.
  • If the patient responds to IV antibiotics, change to an oral antibiotic of appropriate sensitivity when they become apyrexial, and continue this for approximately 10–14 days.

P.152
Pyonephrosis and perinephric abscess Pyonephrosis An infected hydronephrosis. Pus accumulates within the renal pelvis and calyces. The causes are essentially those of hydronephrosis, where infection has supervened (e.g. ureteric obstruction by stone, PUJ obstruction). Patients with pyonephrosis are usually very unwell, with a high fever, flank pain, and tenderness. Again, patients with this combination of symptoms and signs will usually be investigated by a renal ultrasound, where the diagnosis of a pyonephrosis is usually obvious. Treatment consists of IV antibiotics (as for pyelonephritis), IV fluids, and percutaneous nephrostomy insertion. Perinephric abscess Perinephric abscess develops as a consequence of extension of infection outside the parenchyma of the kidney in acute pyelonephritis, or more rarely, nowadays, from haematogenous spread of infection from a distant site. The abscess develops within Gerota’s fascia. These patients are often diabetic, and associated conditions such as an obstructing ureteric calculus may be the precipitating event leading to development of the perinephric abscess. Failure of a seemingly straightforward case of acute pyelonephritis to respond to intravenous antibiotics within a few days arouses the suspicion that there is an accumulation of pus in or around the kidney, or obstruction with infection. Imaging studies, such as ultrasound and more especially CT will establish the diagnosis, and allow radiographically controlled percutaneous drainage of the abscess. If the pus collection is large, formal open surgical drainage under general anaesthetic will provide more effective drainage. P.153
P.154
Other forms of pyelonephritis Emphysematous pyelonephritis A rare, severe form of acute pyelonephritis caused by gas-forming organisms. It is characterized by fever and abdominal pain, with radiographic evidence of gas within and around the kidney (on plain radiography or CT). It usually occurs in diabetics, and in many cases is precipitated by urinary obstruction by, for example, ureteric stones. The high glucose levels of the poorly controlled diabetic provides an ideal environment for fermentation by Enterobacteria, carbon dioxide being produced during this process. It presents as a severe acute pyelonephritis (high fever and systemic upset) which fails to respond within 2–3 days with conventional treatment in the form of intravenous antibiotics. Commonly caused by E. coli, less frequently Klebsiella and Proteus. On KUB X-ray a crescent or kidney-shaped distribution of gas may been seen around the kidney. Renal ultrasonography often demonstrates strong focal echoes, indicating gas within the kidney. Intra-renal gas is seen on CT scan. Patients with emphysematous pyelonephritis are usually very unwell and mortality is high. In selected cases, it can be managed conservatively, by intravenous antibiotics and fluids, percutaneous drainage, and careful control of diabetes. In those where sepsis is poorly controlled, emergency nephrectomy is required. Xanthogranulomatous pyelonephritis This is a severe renal infection usually (though not always) occurring in association with underlying renal calculi and renal obstruction. The severe infection results in destruction of renal tissue leading to a non-functioning kidney. E. coli and Proteus are common causative organisms. Macrophages full of fat become deposited around abscesses within the parenchyma of the kidney. The infection may be confined to the kidney or extend to the perinephric fat. The kidney becomes grossly enlarged and macroscopically contains yellowish nodules, pus, and areas of haemorrhagic necrosis. It can be very difficult to distinguish the radiological findings from a renal cancer on imaging studies such as CT. Indeed, in most cases the diagnosis is made after nephrectomy for what was presumed to be a renal cell carcinoma. Presentation: acute flank pain, fever and a tender flank mass. Bacteria (E. coli, Proteus) may be found on culture urine. Renal ultrasonography shows an enlarged kidney containing echogenic material. On CT, renal calcification is usually seen within the renal mass. Non-enhancing cavities are seen, containing pus and debris. On radioisotope scanning, there may be some or no function in the affected kidney. On presentation these patients are usually commenced on antibiotics as the constellation of symptoms and signs suggests infection. When imaging studies are done, such as CT, the appearances usually suggest the possibility of a renal cell carcinoma, and therefore when signs of infection have resolved, the majority of patients will proceed to nephrectomy. Only following pathological examination of the removed kidney will it P.155
become apparent that the diagnosis was one of infection (xanthogranulomatous pyelonephritis) rather than tumour. Acute pyelonephritis, pyonephrosis, perinephric abscess, and emphysematous pyelonephritis—making the diagnosis Maintaining a degree of suspicion in all cases of presumed acute pyelonephritis is the single most important thing in allowing an early diagnosis of complicated renal infection, such as a pyonephrosis, perinephric abscess, or emphysematous pyelonephritis, to be made. If the patient is very unwell, or is diabetic, or has a history suggestive of stones, they may have something more than just a simple acute pyelonephritis. Specifically ask about a history of sudden onset of severe flank pain a few days earlier, suggesting the possibility that a stone passed into the ureter, with later infection supervening. Arranging a KUB X-ray and renal ultrasound in all patients with suspected renal infection will demonstrate the presence of hydronephrosis, pus, or stones. Clinical indicators suggesting a more complex form of renal infection are length of symptoms prior to treatment and time taken to respond to treatment. Most patients with uncomplicated acute pyelonephritis have been symptomatic for <5 days; most with, for example, a perinephric abscess have been symptomatic for >5 days prior to hospitalization. Patients with acute pyelonephritis became afebrile within 4–5 days of treatment with an appropriate antibiotic, whereas those with perinephric abscesses remain pyrexial.4 P.156
Chronic pyelonephritis This is a confusing term. It can be a radiological or pathological diagnosis or description. The appearance—pathologically or radiologically—is one of renal scarring. The scarring can be due to previous infection or it can occur from the long-term effects of reflux (with or without superimposed infection). A child with reflux, particularly where there is reflux of infected urine, will develop reflux nephropathy (which if bilateral, may cause renal impairment or renal failure). If the child’s kidneys are examined radiologically (or pathologically if they are removed by nephrectomy) the radiologist or pathologist will describe the appearances as those of ‘chronic pyelonephritis’. An adult may also develop radiological and pathological features of chronic pyelonephritis, due to the presence of reflux, or bladder outlet obstruction combined with high bladder pressures, again particularly where the urine is infected. This was a common occurrence in male patients with spinal cord injuries and detrusor-sphincter dysynergia before the advent of effective treatments for this condition. Essentially, then, chronic pyelonephritis is the end result of longstanding reflux (non-obstructive chronic pyelonephritis) or of obstruction (obstructive chronic pyelonephritis). These processes damage the kidneys leading to scarring, and the degree of damage and subsequent scarring is more marked if infection has supervened. The scars are closely related to a deformed renal calyx. Distortion and dilatation of the calyces is due to scarring of the renal pyramids. These scars typically affect the upper and lower poles of the kidneys, because these sites are more prone to intrarenal reflux. The cortex and medulla in the region of a scar is thin. The kidney may be so scarred that it becomes small and atrophic. Scars can be ‘seen’ radiologically on a renal ultrasound, an IVU, renal isotope scan, or a CT. P.157
P.158
Septicaemia Bacteraemia is the presence of pathogenic organisms in the blood stream. This can lead to septicaemia or sepsis—the clinical syndrome caused by bacterial infection of the blood, confirmed by positive blood cultures for a specific organism, and accompanied by a systemic response to the infection known as the systemic inflammatory response syndrome (SIRS). SIRS is defined by at least two of the following:

  • Fever (>38°C) or hypothermia (<36°C)
  • Tachycardia (>90 beats/min in patients not on beta-blockers)
  • Tachypnoea (respiratory >20/min or PaCO2 < 4.3kPa or a requirement for mechanical ventilation)
  • White cell count >12,000cells/mm3, <4000cells/mm3 or 10% immature (band) forms

Septicaemia is often accompanied by endotoxaemia—the presence of circulating bacterial endotoxins. Severe sepsis or sepsis syndrome is a state of altered organ perfusion or evidence of dysfunction of one or more organs, with at least one of the following: hypoxaemia, lactic acidosis, oliguria, or altered mental status. Septic shock is severe sepsis with hypotension,* hypoperfusion, and organ dysfunction. It results from gram-positive bacterial toxins or gram-negative endotoxins which trigger release of cytokines (TNF, IL-1), vascular mediators, and platelets, resulting in vasodilatation (manifest as hypotension) and disseminated intravascular coagulation (DIC). Causes of urinary sepsis In the hospital setting, the most common causes are the presence of or manipulation of indwelling urinary catheters, urinary tract surgery (particularly endoscopic—TURP, TURBT, ureteroscopy, PCNL), and urinary tract obstruction (particularly that due to stones obstructing the ureter). Septicaemia occurs in approximately 1.5% of men undergoing TURP. Diabetic patients, patients in ICUs, and patients on chemotherapy and steroids are more prone to urosepsis. Causative organisms in urinary sepsis: E. coli, enterococci (Streptococcus faecalis), staphylococci, Pseudomonas aeruginosa, Klebsiella, and Proteus mirabilis. Management The principles of management include early recognition, resuscitation, localization of the source of sepsis, early and appropriate antibiotic administration, and removal of the primary source of sepsis. From a urological perspective, the clinical scenario is usually a post-operative patient who has undergone TURP or surgery for stones. On return to the ward they become pyrexial, start to shiver (chills) and shake, and are tachycardic and tachypnoea (leading initially to respiratory alkalosis). They may be confused and oliguric. They may initially be peripherally vasodilatated (flushed appearance with warm peripheries). Consider the P.159
possibility of a non-urological source of sepsis (e.g. pneumonia). If there are no indications of infection elsewhere, assume the urinary tract is the source of sepsis. Investigations

  • Urine culture. An immediate gram-stain may aid in deciding which antibiotic to use.
  • Full blood count. The white blood count is usually elevated. The platelet count may be low—a possible indication of impending DIC (disseminated intravascular coagulopathy).
  • Coagulation screen. This is important if surgical or radiological drainage of the source of infection is necessary.
  • Urea and electrolytes as a baseline determination of renal function.
  • Arterial blood gases to identify hypoxia and the presence of metabolic acidosis.
  • Blood cultures.
  • CXR—looking for pneumonia, atelectasis, and effusions.

Depending on the clinical situation, a renal ultrasound may be helpful to demonstrate hydronephrosis or pyonephrosis, and CT urography (CTU) may be used to establish the presence or absence of a ureteric stone. Treatment

  • A (Airway), B (Breathing), C (Circulation).
  • 100% oxygen via a face-mask.
  • Establish intravenous access with a wide-bore intravenous cannula.
  • Intravenous crystalloid (e.g. normal saline or colloid—Gelofusin).
  • Catheterize to monitor urine output.
  • Empirical antibiotic therapy (see below). This should be adjusted later when cultures are available.
  • If there is septic shock, then the patient needs to be transferred to ICU. Inotropic support may be needed. Steroids may be used as adjunctive therapy in gram-negative infections. Naloxone may help revert endotoxic shock. This should all be done under the supervision of an intensivist.
  • Treat the underlying cause. Drain any obstruction and remove any foreign body. If there is a stone obstructing the ureter then either ask the radiologist to insert a nephrostomy tube to relieve the obstruction or take the patient to the operating room and insert a JJ-stent. Send any urine specimens obtained for microscopy and culture.

Empirical treatment of septicaemia This is ‘blind’ use of antibiotics based on an educated guess of the most likely pathogen that has caused the sepsis. Gram-negative aerobic rods are common causes of urosepsis (e.g. E. coli, Klebsiella, Citrobacter, Proteus, and Serratia). The enterococci (gram-positive aerobic non-haemolytic streptococci) may sometimes cause urosepsis. In urinary tract operations involving the bowel, anaerobic bacteria may be the cause of urosepsis, and in wound infections, staphylococci (e.g. Staph. aureus and Staph. epidermidis) are the usual cause. P.160
Recommendations for treatment of urosepsis5

  • A third-generation cephalosporin (e.g. IV cefotaxime or ceftriaxone). These are active against gram-negative bacteria, but have less activity against staphylococci and gram-positive bacteria. Ceftazidime also has activity against Pseudomonas aeruginosa.
  • Fluoroquinolones (e.g. ciprofloxacin) are an alternative to cephalosporins. They exhibit good activity against enterobactaria and P. aeruginosa, but less activity against staphylococci and enterococci. Gastrointestinal tract absorption of ciprofloxacin is good, so oral administration is as effective as IV.
  • Use metronidazole if there is a potential anaerobic source of sepsis.
  • If no clinical response to the above antibiotics, consider a combination of piperacillin and tazobactam. (This combination is active against enterobacteria, enterococci, and Pseudomonas.)
  • Gentamicin is used in conjunction with other antibiotics. It has a relatively narrow therapeutic spectrum against gram-negative organisms. Close monitoring of therapeutic levels and renal function is important. It has good activity against enterobacteria and Pseudomonas, with poor activity against streptococci and anaerobes and, therefore, should ideally be combined with β-lactam antibiotics or ciprofloxacin.

If there is clinical improvement, IV treatment should continue for at least 48h and then be changed to oral medication. Make appropriate adjustments when sensitivity results are available from urine cultures (which may take about 48h). P.161
P.162
Fournier’s gangrene A necrotizing fascitis of the genitalia and perineum primarily affecting males and causing necrosis and subsequent gangrene of infected tissues. Culture of infected tissue reveals a combination of aerobic (E. coli, enterococcus, Klebsiella) and anaerobic organisms (Bacteroides, Clostridium, microaerophilic streptococci), which are believed to grow in a synergistic fashion. Conditions which predispose to the development of Fournier’s gangrene include diabetes, local trauma to the genitalia and perineum (e.g. zipper injuries to the foreskin, periurethral extravasation of urine following traumatic catheterization or instrumentation of the urethra), and surgical procedures such as circumcision. Presentation This is often dramatic. A previously well patient may become systemically unwell over a very short time course (hours) following a seemingly trivial injury to the external genitalia. A fever is usually present, the patient looks very unwell, they may have marked pain in the affected tissues, and the developing sepsis may alter their mental state. The genitalia and perineum are oedematous and on palpation of the affected area, tenderness and crepitus may be present indicating the presence of subcutaneous gas produced by gas-forming organisms. As the infection advances, blisters (bullae) appear in the skin and, within a matter of hours, areas of necrosis may develop which spread to involve adjacent tissues (e.g. the lower abdominal wall). The condition advances rapidly—hence its alternative name of spontaneous fulminant gangrene of the genitalia. Diagnosis The diagnosis is a clinical one, and is based on awareness of the condition and a low index of suspicion. Treatment Do not delay. While intravenous access is obtained, blood taken for culture, intravenous fluids started, and oxygen administered, broad spectrum antibiotics are given to cover both gram-positive and negative aerobes and anaerobes (e.g. ampicillin, gentamicin, and metronidazole or clindamycin). Make arrangements to transfer the patient to the operating room as quickly as possible so that debridement of necrotic tissue (skin, subcutaneous fat) can be carried out. Extensive areas of tissue may have to be removed, but it is unusual for the testes or deeper penile tissues to be involved, and these can usually be spared. A suprapubic catheter is inserted to divert urine and allow monitoring of urine output. Where facilities allow, consider treatment with hyperbaric oxygen therapy. There is some evidence that this may be beneficial.7 Repeated debridements to remove residual necrotic tissue are not infrequently required. Mortality is in the order of 20–30%. There is debate about whether diabetes increases the mortality rate.8,9 P.163
P.164
Epididymitis and orchitis This is an inflammatory condition of the epididymis, often involving the testis, and caused by bacterial infection. It has a acute onsent and a clinical course lasting <6weeks. It presents with pain, swelling, and tenderness of the epididymis. It should be distinguished from chronic epididymitis where there is longstanding pain in the epididymis, but usually no swelling. Infection ascends from the urethra or bladder. In men aged <35 years, the infective organism is usually N. gonorrhoeae, C. trachomatis, or coliform bacteria (causing a urethritis which then ascends to infect the epididymis). In children and older men, the infective organisms are usually coliforms. Mycobacterium tuberculosis (TB) is a rarer cause—the epididymis feels like a ‘beaded’ cord. A rare, non-infective cause of epididymitis is the antiarrhythmic drug amiodarone, which accumulates in high concentrations within the epididymis, causing inflammation.10 It can be unilateral or bilateral and resolves on discontinuation of the drug. Differential diagnosis Torsion of the testicle is the main differential diagnosis. A preceding history of symptoms suggestive of urethritis or urinary infection (burning when passing urine, frequency, urgency, and suprapubic pain) suggest that epididymitis is the cause of the scrotal pain, but these symptoms may not always be present in epididymitis. In epididymitis pain, tenderness and swelling may be confined to the epididymis, whereas in torsion, the pain and swelling are localized to the testis. However, there may be overlap in these physical signs. Where doubt exists—where you are unsure whether you are dealing with a torsion or epididymitis—exploration is the safest option. Though radionuclide scanning can differentiate between a torsion and epididymitis, this is not available in many hospitals. Colour doppler ultrasonography, which provides a visual image of blood flow, can differentiate between a torsion and epididymitis, but its sensitivity for diagnosing torsion is only 80% (i.e. it ‘misses’ the diagnosis in as many as 20% of cases—these 20% have torsion but normal findings on doppler ultrasonography of the testis). Its sensitivity for diagnosing epididymitis is about 70%. Again, if in doubt, explore. Treatment of epididymitis Culture urine, any urethral discharge, and blood (if systemically unwell). This consists of bed rest, analgesia, and antibiotics. Where C. trachomatis is a possible infecting organism, prescribe a 10–14 day course of tetracycline 500mg 4 times a day or doxycycline 100mg twice daily. If gonorrhoeae is confirmed on a gram stain of the urethral discharge (if present) and on culture, prescribe ciprofloxacin (though check the sensitivity on culture). For non-STD related epididymitis, prescribe antibiotics empirically (until culture results are available) according to your local microbiology department advice, which will be based on local patterns of organisms isolated from urine cultures and on local patterns of antibiotic resistance. Our empirical antibiotic regimen is ciprofloxacin for 2 weeks P.165
where there is no systemic upset. When the patient is systemically unwell, we admit them for intravenous cefuroxime 1.5g tds and intravenous gentamicin 5mg/kg until apyrexial, at which time we switch to oral ciprofloxacin for 2 weeks. Complications of acute epididymitis These include abscess formation, infarction of the testis, chronic pain, and infertility. Chronic epididymitis is diagnosed in patients with long-term pain in the epididymis and testicle. It can result from recurrent episodes of acute epididymitis. Clinically, the epididymis is thickened and may be tender. Treatment is with the appropriate antibiotics (guided by cultures), or epididymectomy in severe cases. Orchitis is inflammation of the testis, although it often occurs with epididymitis (epididymo-orchitis). Causes include mumps; M. tuberculosis; syphilis; autoimmune processes (granulomatous orchitis). The testis is swollen and tense, with oedema of connective tissues and inflammatory cell infiltration. Treat the underlying cause. Mumps orchitis occurs in 30% of infected post-pubertal males. It manifests 3–4 days after the onset of parotitis, and can result in tubular atrophy. 10–30% of cases are bilateral and are associated with infertility. P.166
Peri-urethral abscess This can occur in patients with urethral stricture disease, in association with gonococcal urethritis and following urethral catheterization. These conditions predispose to bacteria (gram-negative rods, enterococci, anaerobes, gonococcus) gaining access through Buck’s fascia to the peri-urethral tissues. If not rapidly diagnosed and treated, infection can spread to the perineum, buttocks, and abdominal wall. The majority (90%) of patients present with scrotal swelling and a fever. ~20% will have presented with urinary retention, 10% with a urethral discharge, and 10% having spontaneoulsy discharged the abscess through the urethra. The abscess should be incised and drained, a suprapubic catheter placed to divert the urine away from the urethra, and broad spectrum antibiotics commenced (gentamicin and cefuroxime) until antibiotic sensitivities are known. P.167
P.168
Prostatitis: epidemiology and classification Definition Infection and/or inflammation of the prostate. Epidemiology Overall prevalence in men is 5%. Age groups at increased risk are 20–50 and >70 years old. Pathogenesis The tissues surrounding the prostatic acini become infiltrated with inflammatory cells (lymphocytes). The most common infective agents are gram-negative Enterbacteriacae (Escherichia coli, Pseudomonas aeruginosa, Klebsiella, Serratia, Enterobacter aerogenes). Both type 1 and P pili are important bacterial virulence factors that facilitate infection. 5–10% of infections are caused by gram-positive bacteria (Staphylococcus aureus and saprophyticus, Streptococcus faecalis). The aetiology of inflammatory and non-inflammatory forms of prostatitis is not well understood. Risk factors UTI; acute epididymitis; urethral catheters; transurethral surgery; intraprostatic ductal reflux; phimosis; prostatic stones (which can provide a nidus of infection for chronic prostatitis). Segmented urine cultures localize bacteria to a specific part of the urinary tract by sampling different parts of the urinary stream, with or without prostatic massage (which produces expressed prostatic secretions—EPS).

  • VB1—first 10mls of urine voided. Positive culture indicates urethritis or prostatitis.
  • VB2—midstream urine. Positive culture indicates cystitis.
  • VB3—first 10mls of urine voided following prostatic massage. Positive culture indicates prostatitis.
  • EPS—Positive culture indicates prostatitis.

Classification of prostatitis

  • Acute bacterial prostatitis (ABP)
  • Chronic bacterial prostatitis (CBP)
  • Chronic pelvic pain syndrome (CPPS) IIIA Inflammatory CPPS (chronic non-bacterial prostatitis): WBC in EPS, VB3, or semen IIIB Non-inflammatory CPPS (prostatodynia): no WBC in EPS, VB3 or semen
  • Asymptomatic inflammatory prostatitis (histological prostatitis)

P.169
P.170
Prostatitis: presentation, evaluation, and treatment; prostatic abscess Acute bacterial prostatitis Acute bacterial prostatitis is infection of the prostate associated with lower urinary tract infection and generalized sepsis. E. coli is the most common cause; Pseudomonas, Serratia, Klebsiella, and enterococci are less common causes. Acute onset of fevers, chills, nausea and vomiting; perineal and suprapubic pain; ‘irritative’ urinary symptoms (urinary frequency, urgency, and dysuria); ‘obstructive’ urinary symptoms (hesitancy, strangury, intermittent stream or urinary retention). Signs of systemic toxicity (fever, tachycardia, hypotension) may be present. Suprapubic tenderness and a palpable bladder will be present if there is urinary retention. On digital rectal examination the prostate is extremely tender. Treatment If the patient is systemically well use an oral quinolone (ciprofloxacin 500mg bd) for 2–4 weeks. For a patient who is systemically unwell, intravenous antibiotics (aminoglycoside (gentamicin) + 3rd generation cephalosporin (or ampicillin), pain relief, and relief of retention if present. Traditional teaching was that a suprapubic (rather than urethral) catheter should be inserted to avoid the potential obstruction of prostatic urethral ducts by a urethral catheter. However, in-and-out catheterization or short periods with an indwelling catheter probably does no harm and is certainly an easier way of relieving retention than suprapubic catheterization. Prostatic abscess Failure to respond to this treatment regimen (i.e. persistent symptoms and fever while on antibiotic therapy) suggests the development of a prostatic abscess. A transrectal ultrasound or CT scan (if the former proves too painful) is the best way of diagnosing a prostatic abscess. This may be drained by a transurethral incision. Chronic bacterial prostatitis History of recurrent UTI. Chronic episodes of pain and voiding dysfunction may be a feature. DRE may show a tender, enlarged, and boggy prostate. Chronic pelvic pain syndrome Both inflammatory (IIIA) and non-inflammatory (IIIB) types present with >3-month history of localized pain (perineal, suprapubic, penile, groin, or external genitalia); pain with ejaculation; LUTS (frequency, urgency, poor flow); erectile dysfunction. Symptoms can recur over time and severely affect patient’s quality of life. Asymptomatic inflammatory prostatitis Incidental histological diagnosis of prostatic inflammation from prostate tissue taken for other indications (i.e. biopsy for raised PSA). P.171
Evaluation

  • NIH-CPSI questionnaire (National Institute of Health Chronic Prostatitis Symptom Index). This scores 3 main symptom areas: pain (location, frequency, severity); voiding (obstructive and irritative symptoms), and impact on quality of life.
  • Segmented urine cultures and expressed prostatic secretions (EPS). Where cultures are negative, increased leucocytes per high-powered field (>10) favor a diagnosis of inflammatory chronic pelvic pain syndrome.

Treatment

  • Alpha-adrenoceptor blocker—acts on prostate and bladder neck α receptors, causing smooth muscle relaxation, improved urinary flow, and reduced intraprostatic ductal reflux.
  • Anti-inflammatory drugs—NSAIDs, steroids.
  • 5-α-reductase inhibitors—anti-androgens (Finasteride) with the ability to reduce prostatic glandular tissue and improve intraductal reflux and symptoms in selected cases.
  • Microwave heat therapy—only consider where severe symptoms are refractory to all treatments.

Treatment options for non-inflammatory chronic pelvic pain syndrome

  • Drugs—analgesia (consider low-dose tricyclic such as amitriptyline), anti-inflammatories, muscle relaxants (α blockers, diazepam), 5-α-reductase inhibitors.
  • Biofeedback.
  • Psychological support.

P.172
Interstitial cystitis Interstitial cystitis (IC) is a refractory bladder disorder of unknown aetiology. Patients suffer chronic urinary frequency, nocturia, urgency, and bladder/suprapubic pain, in the absence of any obvious cause. The presence of glomerulations on cystoscopic examination (petechiae seen after bladder wall distention) or Hunner’s ulcers, may help confirm clinical suspicion. IC is a diagnosis of exclusion (see Table 6.3)—it is diagnosed once other causes for these symptoms have been excluded (e.g. cyclophosphamide, drug-induced, TB, radiation; bladder tumour; OAB—presence of uninhibited bladder contractions on urodynamics excludes a diagnosis of IC). Epidemiology Predominantly affects females (~90%). Estimated female prevalence is 18.1 cases per 100,000 from European studies.12 American data suggests higher rates of 52–67 per 100,000.13 Associated disorders A higher prevalence of allergies, irritable bowel syndrome, fibromyalgia, focal vulvitis, and Sjögren’s syndrome has been reported in IC. Pathogenesis IC appears to be a multifactorial syndrome. Possible contributing factors include:

  • Increased mast cells. Studies have demonstrated increased mast cells in bladder smooth muscle (detrusor). Activated mast cells release histamine, which can cause pain, hyperaemia, and fibrosis in tissues.
  • Defective bladder epithelium. An abnormal glycosaminoglycan (GAG) layer may allow urine to leak past the luminal surface, causing inflammation in muscle layers.
  • Neurogenic mechanisms. Abnormal activation of sensory nerves causes release of neuropeptides, resulting in neurogenic inflammation.
  • Reflex sympathetic dystrophy of the bladder. Excessive sympathetic activity.
  • Urinary toxins or allergens.
  • Bladder autoimmune response.

Evaluation Exclude other causes for symptoms (see Table 6.3). History, examination (including pelvic in women and DRE in men), urinalysis, and culture are mandatory. IC symptom index questionnaire, voiding diaries, and urodynamics are useful. Diagnostic studies include:

  • Cystoscopy 10% of patients will have pink ulceration of bladder mucosa (Hunner’s ulcer). Under anaesthesia, the bladder should be distended twice (to 80–100cmH2O for 1–2min), and then inspected for diffuse glomerulations (>10 per quadrant in 3/4 bladder quadrants). Bladder biopsy is only indicated to rule out other pathologies. In conscious patients, bladder filling causes pain and reproduces symptoms.
  • Intravesical KCl challenge In 75% of IC patients, installation of KCl into the bladder will provoke pain and symptoms.

Potential diagnostic markers under investigation include antiproliferative factor (APF), heparin-binding epidermal growth factor (HB-EGF), and insulin-like growth factor 1 (IGF1).14 Treatment

  • Oral medications. Tricyclics (amitriptyline) have anticholinergic, antihistamine, and sedative effects. Pentosan polysulphate (Elmiron) is an anti-inflammatory synthetic GAG analogue. Long-term analgesia P.173
    (NSAIDs, paracetamol). Opiates may be prescribed and monitored via pain clinics.
  • Repeated intravesical drug installation. Dimethyl sulphoxide (DMSO) ± local anaesthetic; GAG analogues (pentosan polysulphate and hyaluronic acid/Cystostat); BCG; capsaicin, resiniferotoxin.
  • Nerve stimulation. Transcutaneous electrical nerve stimulation (TENS); neuromodulation.
  • Surgery. Transurethral resection, laser coagulation or diathermy of Hunner’s ulcers, and bladder hydrodistention may be beneficial, otherwise surgery should only be considered after failed conservative treatments. Ultimately, urinary diversion ± cystectomy may be required.
Table 6.3 NIDDK* diagnostic criteria for interstitial cystitis
Diagnosis criteria
  1. Cystoscopic evidence of Hunner’s ulceroorp etchiae(glomerulations)
  2. Bladder/pelvic pain or urinary urgency
Exclusion criteria
  1. Bladder capacity >350ml, measured by awake cystometry
  2. Lack of urgency with a 150ml injection in cystometry
  3. Uninhibited contractions during cystometry
  4. <9 months from onset
  5. Absence of nocturia
  6. Symptoms improved by antibiotics, anticholinergics, or antispasmodics
  7. Daytime voids <8
  8. Bacterial cystitis or prostatitis within 3 months
  9. Bladder or ureteral calculi
  10. Genital herpes
  11. Uterine, cervical, vaginal, or urethral cancer
  12. Urethral diverticulum
  13. Cyclophosphamide- or drug-induced cystitis
  14. Tuberculous cystitis
  15. Radiation cystitis
  16. Bladder tumour
  17. Vaginitis
  18. <18 years old
* National Institute of Diabetes and Digestive and Kidney Diseases.

P.174
Tuberculosis Tuberculosis (TB) of the genitourinary (GU) tract is caused by Mycobacterium tuberculosis. TB predominantly affects Asian populations, with a higher incidence in males than females. Pathogenesis Primary TB The primary granulomatous lesion forms in the mid to upper zone of the lung. It consists of a central area of caseation surrounded by epitheloid and Langhans’ giant cells, accompanied by caseous lesions in the regional lymph nodes. There is early spread of bacilli via the bloodstream to the GU tract; however, immunity rapidly develops, and the infection remains quiescent. Acute diffuse systemic dissemination of tubercle bacilli can result in symptomatic miliary TB. Post primary TB Reactivation of infection is triggered by immune compromise (including HIV). It is at this point that patients develop clinical manifestations. Kidney Haematogenous spread causes granuloma formation in the renal cortex, associated with caseous necrosis of the renal papillae and deformity of the calyces, leading to release of bacilli into the urine. This is followed by healing fibrosis and calcification, which causes destruction of renal architecture and autonephrectomy. Ureters Spread is directly from the kidney, and can result in stricture formation (vesicoureteric junction, pelvi-ureteric junction, and mid-ureteric) and ureteritis cystica. Bladder Usually secondary to renal infection, although iatrogenic TB can be caused by intravesical BCG treatment for carcinoma in situ. The bladder wall becomes oedematous, red, and inflamed, with ulceration and tubercles (yellow lesions with a red halo). Disease progression causes fibrosis and contraction (resulting in a small capacity ‘thimble’ bladder), obstruction, and calcification. Prostate and seminal vesicles Haematogenous spread causes cavitation and calcification, with palpable, hard-feeling structures. Fistulae may form to the rectum or perineum. Epididymis Haematogenous spread results in a ‘beaded’ cord. Infection may spread to the testis. Presentation Early symptoms include fever, lethargy, weight loss, night sweats, and UTI not responding to treatment. Later manifestations include LUTS, haematuria, and flank pain. Investigations

  • Urine: at least 3 early morning urines (EMUs) are required, but often many more EMU specimens will be needed before a positive culture for TB is obtained. A typical finding is sterile pyuria (leucocytes, but no growth). Ziehl–Neelsen staining will identify these acid- and alcohol-fast bacilli (cultured on Lowenstein–Jensen medium).
  • CXR and sputum.
  • Tuberculin skin test.
  • P.175

  • IVU: findings include renal calcification, irregular calyces, infundibular stenosis, cavitation, pelviureteric and vesicoureteric obstruction, and a contracted, calcified bladder.
  • Cystoscopy and biopsy.

Treatment 6 months of isoniazid, rifampicin, and pyrizinamide (see BNF). Regular follow-up imaging with IVU is recommended to monitor for ureteric strictures, which may need stenting, nephrostomies, or ureteric reimplantation. Severe bladder disease may require surgical augmentation, reconstruction, or urinary diversion. P.176
Parasitic infections Schistosomiasis (bilharzia) Urinary schistosomiasis is caused by a trematode (or fluke) called Schistoma haematobium. It occurs in Africa, Egypt, and the Middle East. Fresh water snails release the infective form of the parasite (cercariae), which can penetrate skin, and migrate to the liver (as schistosomules), where they mature. Adult flukes couple, migrate to vesical veins, and lay eggs (containing miracidia larvae), which leave the body by penetrating the bladder and entering the urine. The disease has two stages: active (when adult worms are actively laying eggs) and inactive (when the adult has died, and there is a reaction to the remaining eggs). Presentation The first clinical sign is ‘swimmer’s itch’—a local inflammatory response. Other early manifestations include Katayama fever, a generalized allergic reaction, which includes fever, urticaria, lymphadenopathy, hepatosplenomegaly, and eosinophilia. Active inflammation results in haematuria, frequency, and terminal dysuria. Investigation

  • Midday urine specimen; bladder and rectal biopsies may contain eggs (distinguished by having a terminal spine).
  • Serology tests (ELISA).
  • Cystoscopy identifies eggs in the trigone (‘sandy patches’).
  • IVU may show a calcified, contracted bladder, and obstructive uropathy.
  • USS demonstrates hydronephrosis and a thickened bladder wall.

Treatment Praziquantel 40mg/kg in 2 divided doses 4–6h apart. Complications Chronic infection can lead to obstructive uropathy, ureteric stenosis, renal failure, and bladder contraction, ulceration, or squamous cell carcinoma. Hydatid disease Infection occurs after ingestion of the dog parasite, Echinococcus granulosus (tapeworm). Sheep are the intermediate hosts. Cases occur in the Middle East, Australia, and Argentina. 3% affect the kidneys. Large cysts form, which can be asymptomatic or present with flank pain. A peripheral eosinophilia is seen with a positive hydatid complement-fixation test. X-rays and CT scans show a thick-walled, fluid-filled spherical cyst with a calcified wall. Medical treatment is with albendazole. Where surgical excision is indicated, cysts can be first sterilized with formalin or alcohol. Praziquantel is also recommended pre-operatively or if cyst contents are spilt (which can provoke systemic anaphylaxis). P.177
Genital filariasis Lymphatic filariasis is caused by Wuchereria bancrofti nematode infection, and is common in the tropics. Manifestations include funiculoepididymitis, orchitis, hydrocoele, scrotal and penile elephantitis, and lymph scrotum (oedema). Diagnosis is on thick film and serology. Medical treatments include diethylcarbamazine, ivermectin, and albendazole. P.178
HIV and hepatitis in urological surgery Human immunodeficiency virus (HIV) Causes a spectrum of illness related to immune system deficiency (see Table 6.4). HIV-1 is pandemic, and accounts for significant mortality in developing countries. HIV-2 has less pathogenicity and is predominant in West Africa. Transmission is via sexual intercourse, contaminated needles, mother-to-fetus transmission, and infected blood and blood pro-ducts (blood transfusion risks are now minimal). Pathogenesis HIV is a retrovirus. It possesses the enzyme reverse transcriptase that enables viral RNA to be transcribed into DNA, which is then incorporated into the host cell genome. HIV binds to CD4 receptors on helper T-lymphocytes (CD4 cells), monocytes, and neural cells. After an extended latent period (8–10 years), CD4 counts decline. Acquired immunodeficiency syndrome (AIDS) is defined as HIV positivity and CD4 lymphocyte counts <200 × 106/l. The associated immunosuppression increases the risk of opportunistic infections and tumours (see Table 6.5). Diagnosis ELISA2 testing of serum detects antibodies against HIV antigens. The second confirmatory test is Western blot. Informed consent is required for the test. Urological sequelae

  • Kidneys—Cytomegalovirus, Aspergillus, Toxoplasma gondii infections, which can cause acute tubular necrosis and abscess formation; renal failure (HIV and AIDS-associated nephropathy); renal stones (secondary to Indinavir treatment).
  • Ureters—calculi.
  • Bladder—voiding dysfunction (urinary retention, bladder overactivity, outflow obstruction); UTI (opportunistic organisms); squamous cell carcinoma.
  • Urethra—Reiter’s syndrome (urethritis, conjunctivitis, arthritis); bacterial urethritis.
  • Prostate—bacterial prostatitis and abscesses (opportunisitic organisms).
  • External genitalia—chronic or recurrent genital herpes; atypical syphilis; opportunistic infections of testicle and epididymis; testicular cancers (germ cell and non-germ cell, lymphoma); scrotal and penile Kaposi’s sarcoma; Fournier’s gangrene.

Needle stick injury The risk of seroconversion following needle stick injury from a seropositive patient is ~0.3%. Risks are increased if patient has terminal ARC illness; needle is hollow bore with visible blood contamination, inserted deeply or directly into a vein. The seroconversion rate after cutaneous exposure to HIV-infected blood is 0.09%. Immediately wash the area well, report to occupational health, and where appropriate, commence antiviral prophylaxis as soon as possible (AZT, ddi, ddc).

Table 6.4 Clinical syndromes of HIV infections and AIDS*
Group I Acute seroconversion illness. Self-limiting, glandular fever-like illness ~6 weeks after infection.
Group II Asymptomatic. Latent period (up to 10 years).
Group III Persistent generalized lymphadenopathy (PGL). Nodes >1cm at >2 extra-inguinal sites.
Group IV (AIDS) AIDS-related complex (ARC):

  1. constitutional disease (fever >1 month, weight loss >10%, diarrhoea >1 month).
  2. neurological disease (dementia, peripheral neuropathy, myelopathy).
  3. secondary infectious disease.
  4. secondary cancers (Kaposi’s sarcoma, non-Hodgkin’s lymphoma, primary cerebral lymphoma).
  5. other conditions (lymphoid interstitial pneumonia, thrombocytopenia)
* Communicable Disease Center, USA.
Table 6.5 Examples of opportunistic infections and AIDS-defining illnesses*
Bacterial infections (multiple or recurrent in children <12 years)
Candidiasis of oesophagus, traches, bronchi
Coccidioidomycosis
Cryptococcosis
Cryptosporidiosis
Histoplasmosis
Isosporiasis
Mycobacteriosis—disseminated or extrapulmonary
Pneumocystis carinii pneumonia
Toxoplasmosis gondii
Salmonellosis—recurrent septicaemia
Cytomegalovirus
Herpes simplex virus >1 month, or bronchi, lung, or oesophageal involvement
Progressive multifocal leucoencephalopathy
Oral hairy leukoplakia
Multidermatomal herpes zoster
Nocardiasis
* Valid after excluding other causes of immunodeficiency.

P.179
P.180
Hepatitis B Transmission is via sexual intercourse, infected blood, contaminated needles, and mother-to-child during parturition. The virus is carried in semen and saliva. Incubation period is 6 months. Surface antigen (HBsAg) is initially detected on blood testing from 6–12 weeks; persistence indicates carrier status. Antibodies to HBsAg indicates vaccination. The e-antigen (HBeAg) rises early in disease and then declines; persistence correlates with increased infectivity and severity. Antibodies to the core antigen (HBcAg) indicate past infection. Sequelae include chronic hepatitis, which may cause cirrhosis and hepatocellular carcinoma. Glomerulonephritis is a rare complication. Prophylaxis The risk of hepatitis B infection from a contaminated needle stick injury is 12%. Hospital health care workers receive vaccination with active immunization injections at 0, 1, and 6 months. Antibodies are checked at 7–9 months, and booster doses given after 3–5 years. Passive immunization with antihepatitis B immunoglobulin may be given to non-immune contacts after high-risk exposure. Full universal theatre precautions are utilized; place patient at end of operating lists. Footnote 2 Enzyme-linked immunosorbant assay. P.181
P.182
Phimosis Where the foreskin cannot be retracted behind the glans. A physiological phimosis is present at birth due to adhesions between the foreskin and glans. As the penis develops, epithelial debris (smegma) accumulates under the foreskin, causing gradual separation. 90% of foreskins are retractile at age 3; few persist into adulthood (<1% phimosis at age 17). Recurrent balanitis in uncircumcised males can cause new phimosis. Treatment Older children with phimosis, suffering recurrent infection (balanitis), can be treated with a 6-week course of topical 0.1% dexamethasone cream, which acts to soften the phimosis and allow foreskin retraction (avoid circumcision where possible). Adults may require a dorsal slit or circumcision for recurrent balanitis, voiding obstruction, or difficulties with sexual intercourse. Complications Recurrent balanitis; balanoprosthitis (severe balanitis where inflammatory secretions and pus are trapped in the foreskin by the phimotic band); paraphimosis; chronic inflammation; squamous cell carcinoma. P.183
P.184
Inflammatory disorders of the penis See also Table 6.6. Psoriasis Chronic papulosquamous inflammatory skin disease, presenting with itchy pink plaques covered in silver-white scales in hair-bearing areas and extensor surfaces (knees and elbows). It also causes pitting of the nails. Lesions may be guttate (raindrop-shaped), circinate (rings), or geographic. Genital psoriasis may involve the glans, which can be treated with topical emollients and short courses of topical low-dose steroid creams. Lichen planus Presents as an itchy, papular rash. It consists of mauve papules, which have a flat top covered in white streaks (Wickham’s striae). It affects flexor surfaces (wrists, elbows); genitalia (appearing as a white annular lesion on the glans penis); buccal mucosa; lumbar region; and ankles. Erosions may occur on vulva and vagina causing pain. It is self-limiting and usually resolves spontaneously. Topical steroids may be prescribed for symptomatic lesions. Lichen sclerosis et atrophicus Chronic dermatitis which presents as itchy, flat-topped white papules that coalesce to form white patches. It commonly affects the genitalia (vulva and penis). On the penis it is called balanitis xerotica obliterans (BXO), which can result in urethral meatal stenosis and phimosis. It is a pre-malignant condition, although progression to squamous cell carcinoma is rare. Close follow-up is recommended, with biopsy if lesions change. General treatment includes topical 2% testosterone proprionate ointment (for females) or short courses of topical steroids. Men may require circumcision and urethral meatal dilatation. Reiter’s syndrome The typical triad of symptoms is urethritis, conjunctivitis, and seronegative arthritis. Genital mainfestations include circinate balanitis (ring-shaped eroded lesions on the glans penis), which is self-limiting and responds well to topical steroid treatment.

Table 6.6 Descriptions of skin lesions
Blister, bulla Vesicle >1cm
Crust Lesion covered with drying exudate (serum, blood, pus)
Erosions Loss of epidermis
Erythema Redness of skin (usually blanches on pressure)
Macule Flat, discrete lesion, different colour to surrounding skin, <1cm diameter
Maculo-papular Raised spots different in colour to surrounding skin
Papule Raised palpable lesion <0.5cm
Patch Macule >1cm diameter
Plaque Coalesced papules (larger, raised, flat areas)
Pustule Circumscribed pus-filled lesion
Nodule Solid dermal or hypodermal lesion >0.5cm
Scale Flake of hard skin
Ulcer Break in epithelium (+superficial dermis)
Vesicle Small, fluid-filled lesion <1cm

References 1 Raz R, Stamm WE (1993) A controlled trial in intravaginal estriol in postmenopausal women with recurrent urinary tract infection. N Engl J Med 329:753. 2 Nicolle LE, Ronald AR (1987) Recurrent urinary tract infection in adult women: diagnosis and treatment. Infect Dis Clin North Am 1:793. 3 Fihn SD, Latham RH, Roberts P, et al. (1985) Association between diaphragm use and urinary tract infection. JAMA 254:240. 4 Thorley JD, Jones SR, Sanford JP (1974) Perinephric abscess. Medicine 53:441. 5 Naber KG, Bergman B, Bishop MC, et al. (2001) Guidelines on urinary and male genital tract infections. European Association of Urology, http://www.eau.org 6 Bone RC, Fisher CJ Jr, Clemmer TP, et al. (1989) Sepsis syndrome: a valid clinical entity. Methylprednisolone Severe Sepsis Study Group. Crit Care Med 17:389–93. 7 Pizzorno R, Bonini F, Donelli A, et al. (1997) Hyperbaric oxygen therapy in the treatment of Fournier’s gangrene in 100 male patients. J Urol 158:837–40. 8 Nisbet AA, Thompson IM (2002) Impact of diabetes mellitus on the presentation and outcomes of Fournier’s gangrene. Urology 60:775–79. 9 Chawla SN, Gallop C, Mydlo JH (2003) Fournier’s gangrene: an anlysis of repeated surgical debridement. Eur Urol 43:572–75. 10 Gasparich JP, Mason JT, Greene HL, et al. (1984) Non-infectious epididymitis associated with amiodarone therapy. Lancet 2:1211–12. 11 Krieger JN, Nyberg LJ, Nickel JC (1999) NIH consensus definition and classification of prostatitis. JAMA 282:236–37. 12 Oravisto KJ (1975) Epidemiology of interstitial cystitis. Ann Chir Gynaecol Fenn 64(2):75–77. 13 Curhan GC, Speizer FE, Hunter DJ, et al. (1999) Epidemiology of interstitial cystitis: a population based study. J Urol 161(2):549–52. 14 Keay S, Takeda M, Tamaki M, et al. (2003) Current and future directions in diagnostic markers in interstitial cystitis. Int J Urol 10:S27–S30.

Leave a Reply


Time limit is exhausted. Please reload the CAPTCHA.

Categories

apply_now Pepperstone Group Limited