Xanthogranulomatous pyelonephritis (XGP) A severe renal infection, usually (although not al ways) occurring in asso- ciation with underlying renal calculi and renal obstruction. Three forms exist: focal (XGP in the renal cortex with no pelvic communication), seg- mental, an d diffuse. The severe infection results in the destruction of renal tissue, leading to a no n-functioning kidney. E. coli and Proteus are common causative organisms. Lipid-laden, \200\230foamy \200\231 macrophages become deposited around abscesses within the parenchyma of the kidney. The infection may be con \201 ned to the kidney or extend to the perinephri c fat. The kidney becomes grossly enlarged and macroscopically contains yellowish nodules ( pus) and areas of haemorrhagic necrosis. It can be very dif \201 cult to distin- guish the radiological \201 ndings from a renal cancer on imaging studies such OTHER FORMS OF PYELONEPHRITIS 195 as CT. Indeed, in most cases, the diagnosis is made after nephrectomy for what was presumed to be a renal cell carcinoma. Presentation Acute \202 ank pain, fever, haematuria, LUTS, and a tender \202 ank mass. It affects all age groups, females more often than males. Complications Fistula (nephrocutaneous, nephrocolonic), paranephric abscess, psoas abscess. Investigation Blood tests show anemia and leukocytosis. Bacteria (E. coli, Proteus) may be found on culture urine. Renal USS shows an enlarged kidney containing echogenic material. C T may identify (obstructing) renal or urinary tract calculi, hydronephrosis, renal cortical thinning, and perinephric fat in \202 am- mation. Non-enhancing cavities are seen, contai ning pus and debris. On radioisotope scanning (DMSA, MAG3 renogram), there may be some or n o function in the affected kidney. Management On presentation, these patients are usually commenced on antibiotics as the cons tellation of symptoms and signs suggest infection. If systemically unwell, transfer to ITU/ HDU for treatment. When imaging studies are done, such as CT, the appearances usually sugge st the possibility of a renal cell carcinoma and, therefore, when signs of infection have r esolved, the majority of patients will proceed to nephrectomy. Often, only following pathol ogical examination of the removed kidney will it become apparent that the diagnosis was one of infection (XGP) rather than tumor. Fig. 6.1 Enhanced axial CT scan demonstrating emphysematous pyelonephritis (type I) affecti ng the left kidney. Image kindly provided with permission from Professor S. Reif. 1 Aswathaman K, Gopalakrishnan G, Gnanaraj L, et al. (2008) Emphysematous pyelonephritis: O utcome of conservative management. Urology 71:1007 \200\2239. CHAPTER 6 Infections and in \202 ammatory conditions 196 Chronic pyelonephritis In essence, this describes renal scarring which may or may not be re lated to previous UTI. It is a radiological, functional, or pathological diagnosis or descr iption. Causes - - Renal scarring due to previous infection. Long-term effects of VUR, with or without superimposed infection. A child with VUR, particularly where there is re \202 ux of infected urine, will develop r e \202 ux nephropathy (which, if bilateral, may cause renal impairment or renal failure). If the child \200\231s kidneys are examined radio- logically (or pathologically if they are removed by nephrectomy), the radi- ologist or pathologist will describe the appearances as those of \200\230chronic pyelonephritis \200\231. An adult may also develop radiological and pathological features of chronic pyelonephritis due to the presence of re \202 ux or BOO combined with high bladder pressures, again parti cularly where the urine is infected. This was a common occurrence in male patients with SCI and DSD before the advent of effective treatments for this condition. Pathogenesis Chronic pyelonephritis is essentially the end result of longstanding re \202 ux (non-obstructive chronic pyelonephritis) or of obstruction (obstructive chronic pyelonep hritis). These processes damage the kidneys, leading to scarring and the degree of damage a nd subsequent scarring is more marked if infection has supervened. Presentation Patients may be asymptomatic or present with symptoms secondary to renal failu re. Diagnosis is often from incidental \201 ndings during general investigation. There is usually no active infection. Appearances on imaging Scars can be \200\230seen \200\231 radiologically on a renal USS, I VU, renal isotope scan, or CT. The scars are closely related to a deformed renal calyx. Dis tortion 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 pro ne to intrarenal re \202 ux. The cortex and medulla in the region of a scar is thin. The k idney may be so scarred that it becomes small and atrophic. Management Aim to investigate and treat any infection, prevent further UTI, and moni- tor a nd optimize renal function. Complications Renal impairment progressing to end-stage renal failure in bilateral cases (u sually only if chronic pyelonephritis is associated with an underlying structural or functi on urinary tract abnormality). This page intentionally left blank CHAPTER 6 Infections and in \202 ammatory conditions 198 Septicaemia Bacteraemia: is the presence of pathogenic organisms in the bloodstream. This c an lead to septicaemia or sepsis \200\224the clinical syndrome caused by bacterial infectio n of the blood. This is con \201 rmed by positive blood cul- tures for a speci \201 c org anism and accompanied by a systemic response to the infection known as the systemic in \202 ammatory response syndrome (SIRS). SIRS is de \201 ned by at least two of the followi ng: C) or hypothermia (<36 C). - - - Fever (>38 Tachycardia (>90 beats/min in patients not on Tachypnoea (respiration >20 breath s/min or PaCO requirement for mechanical ventilation). White cell count >12 000 cells/mm im mature (band) forms. B-blockers). 2 <4.3kPa or a 3, <4000 cells/mm3, or >10% Septicaemia is often accompanied by endotoxaemia \200\224the presence of circulating bacter ial endotoxins. Severe sepsis: sepsis associated with organ dysfunction (hypoperfusion or h ypotension). Hypoperfusion and perfusion abnormalities may include lac- tic acidosis, oligu ria, or acute altered mental state. Septic shock: sepsis with hypotension1 despite adequate \202 uid resuscitation with perfusion abnormalities that may include lactic acidosis, ol iguria, or acute altered mental state. It results from Gram-positive bacterial toxins or Gr am-negative endotoxins which trigger the release of cytokines (TNF, IL-1), vascular mediato rs, and platelets, resulting in vasodilatation (manifest as hypotension) and disseminated i ntravascular coagulation (DIC). Refractory shock: is de \201 ned as septic shock (lasting >1h) which fails to respond to t herapy ( \202 uids or pharmacotherapy). Causes of urinary sepsis In the hospital setting, the most common causes are the presence o r manipulation of indwelling urinary catheters, urinary tract surgery (par- ticularly endos copic \200\224TURP, TURBT, ureteroscopy, PCNL), and urinary tract obstruction (particularly that due to stones obstructing the ureter). Septicaemia occurs in approximately 1.5% of me n undergoing TURP. Diabetic patients, patients in ITU, and immunocompromised patients (on c hemotherapy and steroids) are more prone to urosepsis. Causative organisms in urinary sepsi s: E. coli, Enterococci, Staphylococci, Pseudomonas, Klebsiella, and Proteus. Management The principles of management include early recognition, resuscitation, localizat ion of the source of sepsis, early and appropriate antibiotic admin- istration, and removal of the primary source of sepsis. From a urologi- cal perspective, the clinical scenario is usually a post-operative patient who has undergone TURP or surgery for stones. On return t o the ward, they become pyrexial, start to shiver (chills) and shake, and are tachy- cardic and tachypnoea (leading initially to respiratory alkalosis). They may be confused and olig uric. They may initially be peripherally vasodilated ( \202 ushed appearance with warm per ipheries). Consider the possibility of a SEPTICAEMIA 199 non-urological source of sepsis (e.g. pneumonia). If there are no indica- tions of infectio n elsewhere, assume the urinary tract is the source of sepsis. Investigations - FBC be low \200\224a possible indication of impending DIC. Coagulation screen drainage of t he source of infection is necessary. Urea and electrolytes and CRP which is usually elevate d. Arterial blood gasses metabolic acidosis. Urine culture antibiotic to use. Blood culture s . Imaging : guided by clinical \201 ndings (i.e. CXR looking for pneumonia, atelectasis , and effusions; renal USS may be helpful to demonstrate hydronephrosis or pyonephrosis; CT if suspicious of renal calculi, urinary tract anomalies, or infected pelvic collections, e tc.). : the white blood count is usually elevated. The platelet count may : this is important if surgical or radiological : as a baseline determination of renal function : to identify hypoxia and the presence of : an immediate Gram stain may aid in deciding which Treatment - - - IV- - - A ( 100% oxygen via a face-mask. Establish I Airway), B (Breathing), C (Circulation). V access with two wide-bore cannulae. crystalloid (e.g. normal saline) or colloid (e.g. Gelofusin ). Catheterize to monitor urine output. Empirical antibiotic therapy (see later when cultures are available. If there is septic shock, the patient needs to be transferred to ITU. Inotro pic support may be needed with invasive monitoring (central line, arterial line). Steroids may be used as adjunctive therapy in Gram- negative infections. Naloxone may help revert en dotoxic shock. Blood glucose is carefully controlled and recombinant activated protein C ha s proven bene \201 t in severe sepsis. 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, preferably arrange for nephrostomy tube inser tion to relieve the obstruction. If the patient is stable, an alternative is to take the pa tient to theater for JJ ureteric stent insertion. Send any urine specimens obtained for mic roscopy and culture. b p. 200). This should be adjusted 1 Hypotension in septic shock is de \201 ned as a sustained systolic BP <90mmHg, or a drop in systolic pressure of >40mmHg for >1h, when the patient is normovolaemic, and other caus es have been excluded or treated. CHAPTER 6 Infections and in \202 ammatory conditions 200 Empirical treatment of septicaemia This is \200\230blind \200\231 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, Proteu s, and Serratia). The enterococci (Gram-positive aerobic non-haemolytic Streptococci) may s ometimes cause urosepsis. In urinary tract operations involving the bowel, anaerobic bacter ia may be the cause of urosepsis and in wound infections, staphylococci (e.g. S. aureus and S. epidermidis) are the usual cause. Recommendations for treatment of urosepsis1 Refer to your local microbiology guidelines. Op tions include: - A third-generation cephalosporin (e.g. IV cefotaxime or ceftriaxone). These are active agai nst Gram-negative bacteria, but have less activity against staphylococci and Gram-positive bacteria. Ceftazidime also has activity against Pseudomonas. Fluoroquinolones (e.g. cipro \202 oxacin) are an alternative to cephalosporins. They exhibit good activity against enter obacteriaceae and Pseudomonas, but less activity against staphylococci and enterococci. GI tract absorption of cipro \202 oxacin is good so oral administration is as effective as IV . (Consider metronidazole if there is a potential anaerobic source of sepsis.) If no clinic al response to these antibiotics, consider a combination of antipseudomonal acylaminopenici llin and B-lactamase inhibitor (i.e. piperacillin and tazobactam; trade name Tazocin ). Th is combination is active against enterobacteriaceae, enterococci, and Pseudomonas. Carbapen ems (i.e. meropenem, imipenem, ertapenem). Broad- spectrum with good activity against Gram- positive and Gram-negative bacteria, including anaerobes. Meropenem and imipenem are also a ctive against Pseudomonas. Aminoglycoside (i.e. gentamicin) is used in conjunction with oth er antibiotics. It has a relatively narrow therapeutic spectrum against Gram-negative organ isms. Close monitoring of therapeutic levels and renal function is important. It has good a ctivity against enterobacteriaceae and Pseudomonas with poor activity against streptococci and anaerobes and, therefore, should ideally be combined with B-lactam antibiotics or cipro \202 oxacin. If there is clinical improvement, parenteral treatment (IV) should continue for 3 \200\2235 days after the infection has been controlled (or complicating fac- tor has been eliminated ), followed by a course of oral antibiotics. Make appropriate adjustments when sensitivity results are available from urine cultures (which may take about 48h). Mortality rate: 13% w ith septicaemia alone; 28% with septicaemia and shock; 43% with septicaemia followed by sep tic shock.2 SEPTICAEMIA 201 1 Grabe M, Bjerklund-Johansen TE, Botto H, et al. (2011) Guidelines on urological infection s. European Association of Urology Guidelines [online]. Available from: M http://www.uroweb .org/ gls/pdf/15_Urological_Infections.pdf. 2 Bone RC, Fisher CJ Jr, Clemmer TP, et al. (1989) Sepsis syndrome: a valid clinical entity . Methyl-prednisolone Severe Sepsis Study Group. Crit Care Med 17:389 \200\22393. CHAPTER 6 Infections and in \202 ammatory conditions 202 Fournier \200\231s gangrene A necrotizing fasciitis of the external genitalia and perineum, primarily affecting males and causing necrosis and subsequent gangrene of infected tissues . Also known as spontaneous fulminant gangrene of the genitalia, it is a urological emergen cy. Causative organisms Culture of infected tissue reveals a combination of aerobic (E. coli, e nte- rococci, Klebsiella) and anaerobic organisms (Bacteroides, Clostridium, micro-aerophil ic streptococci) which are believed to grow in a synergistic fashion. Predisposing factors - Diabetes mellitus. - Chronic alcohol excess. - Local trauma to the g enitalia and perineum (e.g. zipper injuries to the foreskin, periurethral extravasation of urine following traumatic catheterization, or instrumentation of the urethra). Surgical pro cedures such as circumcision. Paraphimosis. Perianal and perirectal infections. - Pathophysiology Fournier \200\231s gangrene is usually related to an initial genitourinary tract infec- tion, skin trauma, or from direct extension from a perirectal focus. Spread of infection is through the local fascia (Buck \200\231s fascia in the penis, Darto \200\231s fascia in the scrotum, Colle \200\231s fascia in the perineal region, and Scarpa \200\231s fas- cia of the anterior abdominal wall). Infection produces tissue necrosis that can spre ad rapidly and pus produced by anaerobic pathogens (Bacteroides) produces the typical putri d smell. Presentation A previously well patient may become systemically unwell following a seemingly trivial injury to the external genitalia. Early clinical features include localized skin e rythema, tenderness and oedema, and sometimes with LUTS (dysuria, dif \201 culty voiding, urethral discharge). This progresses to fever and sepsis with cellulitis and palpable crepi tus in the affected tis- sues, indicating the presence of subcutaneous gas produced by gas- forming organisms. As the infection advances, blisters (bullae) appear in the skin and with in a matter of hours, areas of necrosis may develop, which spread to involve adjacent tissu es (e.g. lower abdominal wall). Diagnosis The diagnosis is a clinical one and is based on the awareness of the condi- tion and a high index of suspicion. In early stages of disease, abdominal X-ray, and scrotal USS , or CT may demonstrate the presence of air in tis- sues. CT can also indicate the extent o f disease, however, most surgeons would not delay to image the patient, but progress direct ly to surgical treatment. FOURNIER \200\231S GANGRENE 203 Management - Do not delay. - Resuscitate the patient: obtain LFT, CRP, clotting, group & sa ve) and blood cultures. Start IV \202 uids, administer oxygen, check and control blood su gars in diabetics. Broad-spectrum parenteral antibiotics are given immediately to cover bot h Gram-positive and Gram-negative aerobes and anaerobes (e.g. combination of aminopenicilli n with B-lactamase inhibitor plus gentamicin plus clindamycin or metronidazole). Refer to y our local microbiology guidelines. Inform ITU/HDU. Transfer the patient to theater as quick ly as possible for debridement of necrotic tissue until healthy bleeding tissue margins are found. Extensive areas 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. Send tissue for culture. If there is extensive perineal/perianal involvement, fecal diversion with colostomy may be req uired. Wound irrigation with hydrogen peroxide may be used at the end. A suprapubic cathete r is inserted to divert urine and allow monitoring of urine output. Repeat examination unde r anesthetic remove residual necrotic tissue is required at 24h and then guided by clinical progress. Where facilities allow, treatment with hyperbaric oxygen therapy can be bene \201 cial.1 Treat the underlying comorbidity or cause, i.e. optimize diabetic control. Vacu um-assisted closure of wounds can hasten patient recovery. Reconstruction can be contemplat ed when wound healing is complete. IV access and take bloods (FBC, U & E, 9 further debridement to Mortality is in the order of 20 \200\22330%. Mortality rates are reported to be higher in p atients with a degree of immunocompromise (diabetics, alco- hol excess) and those with anor ectal or colorectal disease/involvement. Mortality risk can be assessed by the Fournier \200\231s gangrene severity index (FGSI)2 based on nine clinical parameters: respiratory ra te, heart rate, temperature, WBC count, haematocrit, sodium, potassium, creatinine, and sod ium bicarbonate levels. Each parameter was valued between 0 and 4, with the higher value gi ven to the greatest deviation from normal. FGSI >9 correlates with increased mortality (46 \200\22375%);2,3 FGSI <9 has a reported 78 \200\22396% chance of survival.2,3 1 Pizzorno R, Bonini F, Donelli A, et al. (1997) Hyperbaric oxygen therapy in the treatment of Fournier \200\231s gangrene in 100 male patients. J Urol 158:837 \200\22340. 2 Laor E, Palmer LS, Tolia BM, et al. (1995) Outcome prediction in patients with Fournier \200\231s gan- grene. J Urol 154:89. 3 Corcoran AT, Smaldone MC, Gibbons EP, et al. (2008) Validation of the Fournier \200\231s gangrene severity index in a large contemporary series. J Urol 180:944 \200\2238. CHAPTER 6 Infections and in \202 ammatory conditions 204 Peri-urethral abscess Peri-urethral abscess can occur in patients with urethral stricture d isease following urethral catheterization and in association with gonococcal urethritis. Th e bulbar urethra is a commonly affected site in men. These conditions predispose to bacteri a (Gram-negative rods, enterococci, anaerobes, gonococcus) gaining access through Buck \200 \231s fascia to the peri- urethral tissues. If not rapidly diagnosed and treated, infection (necrotiz- ing fasciitis) can spread to the perineum, buttocks, and abdominal wall. In imm unocompromised patients (i.e. patients with HIV infection), M. tuberculosis is also a causa tive organism. Presentating features - - - - - - Scrotal swelling. Tender, in \202 amed area on the perineum or under the penis. Fever. Uri nary retention (>20%). Urethral discharge (10%). Spontaneous discharge of abscess through t he urethra (10%). Complications Extravasation of urine from the abscess cavity may result in cellulitis and a risk of \201 stula formation. Management Emergency treatment is required. The abscess should be incised and drained, a su prapubic catheter placed to divert the urine away from the urethra, and broad-spectrum pare nteral antibiotics commenced (gen- tamicin and cephalosporin) until antibiotic sensitivitie s are known. Any devitalized and necrotic tissue requires immediate surgical debridement. This page intentionally left blank CHAPTER 6 Infections and in \202 ammatory conditions 206 Epididymitis and orchitis Acute epididymitis An in \202 ammatory condition of the epididym is, often also involving the tes- tis, and usually caused by bacterial infection. It has an acute onset and a clinical course lasting <6 weeks, presenting with epididymal pain, swell ing, and tenderness. It can occur in all age groups. Pathogenesis Infection ascends from the urethra or bladder. In sexually active men aged <35 y, the infective organism is usually N. gonorrhoeae, C. trachomatis, or coliform bacteria ( causing a urethritis which then ascends to infect the epididymis). In older men and childre n, the infective organisms are usually common uropathogens (i.e. E. coli). M. tuberculosis (TB) is a rarer cause of epididymitis where the epididymis feels like a \200\230beaded \200\231 cord (see b p. 220). A rare, non-infective cause of epididymitis is the antiarrhythmic drug, amiodarone, which a ccumulates in high concentrations within the epidi- dymis, causing in \202 ammation.1 It c an be unilateral or bilateral and resolves on discontinuation of the drug. Some cases of ep ididymitis in children are also non-infective (idiopathic or as a result of trauma). Presentation Fever; testicular swelling; scrotal pain that may radiate to the groin (sper- matic cord) and lower abdomen; erythema of scrotal skin; thickening of spermatic cord; reac tive hydrocele; evidence of underlying infection (ure- thral discharge, symptoms of urethri tis, cystitis, or prostatitis). Differential diagnosis - Testicular torsion is the main differential diagnosis. In torsion, pain and swelling are mo re acute and localized to the testis whereas epididymitis is mainly preceded by infective s ymptoms with pain, tenderness, and swelling tending to be con \201 ned to the epididymis. If any doubt in the diagnosis exists, exploration is the safest option. Although radionucli de scanning can differentiate between a torsion and an epididymitis, this is not widely ava ilable. Color Doppler USS, which provides a visual image of blood \202 ow, can differenti ate between a tor- sion and epididymitis, but its sensitivity for diagnosing torsion is onl y 80% (i.e. it \200\230misses \200\231 the diagnosis in 20% of cases). Its sensitivity for diagnosing epididymitis is about 70%. - - - - Torsion of testicular appendage. Acute hemorrhage within a testicular tumor. Testicular tra uma. Mumps orchitis. Investigation - - - - FBC Urine dipstick Urethral swab/culture of any urethral discharge. Scrotal , U & E, CRP, and blood cultures (if systemically unwell). 9 culture (PCR of \201 rst void urine to detect chlamydia). USS. EPIDIDYMITIS AND ORCHITIS 207 Treatment Bed rest, analgesia, scrotal elevation, and antibiotics. Until culture sensitivities are available and where C. trachomatis is a pos- sible infectin g organism, prescribe a 14-day course of doxycycline 100mg twice daily (an alternative is a single dose of azithromycin 1g). If gonor- rhoea is suspected or con \201 rmed, prescribe cipro \202 oxacin (500mg bd for 14 days). An alternative is a single dose of oral ce \201 xime (400mg). Patients should be referred for genitourinary medicine (GUM) input and t racing of sexual contacts. For non-sexually transmitted infection of the epididymis, prescribe anti- biotics empirical ly (until culture results are available) according to your local microbiology department ad vice. Our empirical antibiotic regimen is cipro \202 oxacin for 2 weeks. When the patient is systemically unwell, we admit them for IV cephalosporin and IV gentamicin (initially 3 \200\2235mg/kg, then adjusted according to serum gentamicin concentration). When the patien t becomes apyrexial, we change to oral cipro \202 oxacin for 2 weeks. Any underlying cause of infection should be identi \201 ed and treated (i.e. BOO) to prevent further episodes. Complications These include abscess formation (requiring incision and drainage), infarc- ti on of the testis, chronic pain and infection, and infertility. Chronic epididymitis Diagnosed in patients with long-term pain in the epididymis (9 testicl e). It can result from recurrent episodes of acute epididymitis. Clinically, the epididymis is thickened and may be tender. Treatment is with the appro- priate antibiotics (guided by cultures) and analgesia. Epididymectomy is reserved for severe refractory cases. Orchitis Orchitis is in \202 ammation of the testis, although it often occurs with epidi- dymitis (epididymo-orchitis). Causes include the mumps virus, M. tubercu- losis, syphilis, autoimmune processes (granulomatous orchitis). The testis is swollen and tense, with oedema of connective tissues and in \202 ammatory cell in \201 ltration. Treat the underlying c ause. Mumps orchitis occurs in 30% of infected post-pubertal males. It mani- fests 3 \200\2234 da ys after the onset of parotitis and can result in tubular atrophy. Ten to thirty percent of cases are bilateral and are associated with testicu- lar atrophy and infertility. 1 Gasparich JP, Mason JT, Greene HL, et al. (1984) Non-infectious epididymitis associated w ith amiodarone therapy. Lancet 2:1211 \200\2232. CHAPTER 6 Infections and in \202 ammatory conditions 208 Prostatitis: classi \201 cation and pathophysiology Prostatitis is infection and/or in \202 ammation of the prostate, which is described as acute or chronic and bacterial or abac terial. The classi \201 cation system is from the National Institute of Diabetes and Diges tive and Kidney Diseases (NIDDK), part of the National Institute of Health (NIH) in the Uni ted States. Chronic abacterial prostatitis is further divided into in \202 am- matory and non-in \202 ammatory types, guided by the results of segmented urine cultures. NIKKD/NIH classi \201 cation of prostatitis1 Acute bacterial prostatitis. I II Chronic bac terial prostatitis. III Chronic pelvic pain syndrome (CPPS): chronic abacterial prostatitis. In \202 ammatory CPPS: WBC in expressed prostatic secretions (EPS), post-pros tatic massage urine (VB3), or semen. IIIA IIIB Non-in \202 ammatory CPPS: no WBC in EPS, VB3, or semen. IV Asymptomatic in \202 amm atory prostatitis (histological prostatitis). Segmented urine cultures Technique described by Meares and Stamey (1968) to help classify t he type of prostatitis. It localizes bacteria to a speci \201 c part of the urinary tract by sampling different parts of the urinary stream with prostatic massage which produces EPS . Where cultures are negative, increased numbers of leukocytes per high powered \201 eld (>10) on microscopy favors a diagno- sis of in \202 ammatory CPPS. Thirty minutes before the test, the patient should drink 400mL of \202 uid. Retract foreskin and cleanse the glans before specimen collection. - VB1 or prostatitis. VB2 100 \200\223200mL in total). Positive culture indicates cystitis. E PS the glans to catch secretions. Positive culture indicates prostatitis. : \201 rst 10 \200\22315mL of urine voided following prostatic massage. VB3 Positive culture indicates pr ostatitis. : \201 rst 10 \200\22315mL of urine voided. Positive culture indicates urethritis : MSU collection of 10 \200\22315mL (the patient is asked to void : the prostate is massaged whilst holding a sterile container below Epidemiology Prostatitis is estimated to affect 50% of men at some point in their lives. Th e overall prevalence is reported at 5 \200\22314%. Age groups at increased risk are 20 \200 \22350y and >70y. Pathophysiology Bacterial prostatitis The most common infective pathogens are Gram-negative Entero- bacteriaceae (E. coli in 80% of cases, Klebsiella, Proteus, Pseudomonas). Both typ e 1 and P pili are important bacterial virulence factors that facilitate PROSTATITIS: CLASSIFICATION AND PATHOPHYSIOLOGY 209 infection. Five to ten percent of infections are caused by Gram-positive bacteria (S. aureu s and S. saprophyticus, E. faecalis). Acute bacterial prosta- titis is often secondary to i nfected urine re \202 uxing into prostatic ducts that drain into the posterior urethra. Th e resulting oedema and in \202 ammation may then obstruct the prostatic ducts, trapping ur opathogens and causing progression to chronic bacterial prostatitis in 75%. In \202 ammato ry and non-in \202 ammatory prostatitis The underlying etiology is not fully understood, b ut is likely to be multi- factorial. The Multidisciplinary Approach to Pelvic Pain (MAPP) r esearch project has been set up to evaluate the importance and impact of various \200\230c linical phenotypes \200\231 for CPPS. Essentially, patients may have a predomi- nance of ce rtain symptoms or conditions that feature in their disease, suggestive of the main underlyi ng etiology (i.e. neurological, endocrine, immunological, infectious, neuromuscular, and ps ychosocial components). The MAPP study aims to identify potential biomarkers relating to th ese \200\230clinical phenotypes \200\231 which will ultimately help with the diagnosis and direct patient speci \201 c management. 1 Krieger JN, Nyberg LJ, Nickel JC (1999) NIH consensus de \201 nition and classi \201 ca tion of prostatitis. JAMA 282:236 \200\2237. CHAPTER 6 Infections and in \202 ammatory conditions 210 Bacterial prostatitis Acute bacterial prostatitis Acute infection of the prostate associate d with lower urinary tract infec- tion and generalized sepsis. The underlying focus or caus e of initial infec- tion should be identi \201 ed and also treated (i.e. BOO, urethral str icture, voiding dysfunction, urinary tract stones). Risk factors Factors that predispose to genitourinary tract and then prostatic coloniza- ti on with bacteria are: - - - - - - - UTI Acute epididymitis. Indwelling urethral catheters. Transurethral surgery. Intraprostati c ductal re \202 ux. Phimosis. Prostatic stones. . Presentation - - - Acute onset of fevers, chills, nausea, and vomiting. Pain: perineal/prostatic, suprapubic, penile, groin, external genitalia. Urinary symptoms: \200\230irritative \200\231 \200\224f requency, urgency, dysuria; \200\230obstructive \200\231 \200\224hesitancy, strangury, int ermittent stream, urinary retention. Signs of systemic toxicity: fever, tachycardia, hypote nsion. Suprapubic tenderness and a palpable bladder if urinary retention. DRE - : prostate is usually swollen and tender (but may also be normal). Investigation - - - - - FBC, U & E, CRP. 9 cytology. Serum blood tests: Urinalysis, urine culture Blood cultures if high pyrexia/systemically un well. Urethral swabs (if indicated to exclude urine measurement (and \202 ow rate). PVR STI). Further investigation is guided by individual patient presentation and clini- cal suspicion . Although segmented urine cultures are recommended in some guidelines, prostatic massage s hould be avoided in the acute, painful phase of prostatitis. Treatment - Antibiotics \202 uoroquinolone (i.e. cipro \202 oxacin 500mg bd) for 2 \200\2234 weeks. For a patient who is systemically unwell, IV antibiotics options include a broad-spectrum p enicillin or a third-generation cephalosporin, combined with an aminoglycoside (gentamicin) for initial treatment. When infection parameters normalize, IV antibiotics can change to o ral therapy which is continued for a total of 2 \200\2234 weeks. Pain relief Treat urinary retention : if the patient is systemically well, use an oral . : urethral, suprapubic, or in-and-out catheter. BACTERIAL PROSTATITIS 211 Complications Prostatic abscess Failure to respond to treatment (i.e. persistent symptoms a nd fever while on appropriate antibiotic therapy) suggests the development of a pros- tatic abscess. The majority are due to E. coli infection. Risk factors include diabetes mellitus , immunocompromise, renal failure, transurethral instru- mentation, and urethral catheteriz ation. Rectal examination demonstrates a tender, boggy-feeling prostate or an area of \202 uctuance. A transrectal USS or CT scan (if the former proves too painful) is the best way of diagnosing a prostatic abscess. Transurethral resection or deroo \201 ng of the abs cess is the optimal treatment. Alternatively, percutaneous drainage may be attempted. Chronic bacterial prostatitis De \201 ned as bacterial prostatitis where symptoms persist for \211 3 months. Caused by recurrent UTI. Chronic episodes of pain, voiding dysfunction, and ejaculatory problems may be a feature. Assessment Enquire about factors that may be contributing to infection: urinary symp- toms, history of renal tract stones, symptoms suggesting a colovesical \201 s- tula in at-risk patients (pneumaturia, history of diverticular disease, pelvic surgery, or radiotherapy). DRE may reveal a tender, enlarged, and boggy prostate. Investigation - - - - - - 9 cytology. Urinalysis, urine culture Segmented urine cultures (see Semen culture. Urethral swabs (to e xclude Flow rate and Individualized further investigation as indicated (e.g. renal tract im aging to identify stones). b p. 208). STI). PVR urine measurement. Treatment - Prescribe a 2-week course of antibiotics ( \202 uoroquinolone or trimethoprim)* and then r eassess. If initial cultures are positive or the patient has reported positive effects from the treatment, antibiotics can be continued for a total course of 4 \200\2236 weeks. A- adrenoceptor blockers may provide some bene \201 t. They act on the prostate and bladder n eck A-receptors, causing smooth muscle relaxation, improved urinary \202 ow, and reduced intraprostatic ductal re \202 ux. The use of \202 uoroquinolones is restricted in many hospitals due to the risk of Clostri dium dif \201 cile infection. Hospitals now have their own antibiotic protocols for most i nfections, or alternative- ly, discuss with your local microbiologist. Alternative antibiot ics include trimethoprim which has good prostatic penetration. However, trimethoprim has no activity against Pseudomonas, some Enterococci, and some Enterobacteriaceae. CHAPTER 6 Infections and in \202 ammatory conditions 212 Chronic pelvic pain syndrome Chronic prostatitis / chronic pelvic pain syndrome (CP/ CPPS) Refers to abacterial prostatitis (i.e. in \202 ammatory (IIIA) and non-in \202 am- matory (IIIB) types of prostatitis). Also referred to as \200\230prostate pain syn- drome \200 \231. The etiology and pathophysiology is unknown. Presentation (cid:116)- 3 months of localized pelvic pain (prostate/perineum, suprapubic, penile, groin, external genitalia, lower back). Pain with ejaculation. LUTS May be associat ed with erectile dysfunction. Symptoms can be dif \201 cult to treat. They can recur over time and severely affect the patient \200\231s quality of life. Younger men have a higher r isk of suffering severe symptoms. - - (dysuria, frequency, urgency, poor \202 ow). Basic evaluation - History, including enquiry into associated disorders and psychosocial assessment. Physical exam, pelvic \202 oor assessment (including tenderness), and DRE. NIH-CPSI Prostatitis Sy mptom Index). This scores three main symptom areas: pain (location, frequency, severity), v oiding (obstructive and irritative symptoms), and impact on quality of life. Uro \202 owme try and Segmented urine cultures and not reveal leucocytes, but for the diagnosis, EPS and post-prostatic massage urine (VB3) cultures should not identify any bacteria. questionnaire (National Institute of Health Chronic PVR urine volume. EPS. These specimens may or may Further evaluation (where clinically indicated) - - - - - Semen analysis and culture. Urethral swab for culture (to exclude Urine cytology (if suspic ion of bladder malignancy). Urodynamics (to investigate voiding dysfunction). Cystoscopy (i f suspicion of urethral stricture, pathology). TRUS PSA STI). BOO, or bladder Treatment Some groups of patients will bene \201 t more from speci \201 c therapies than others. Patients require a multimodal approach to treatment, guided by their main clinical features.1 Options include: - Conservative therapy stress reduction, psychotherapy, focused pelvic physiotherapy for tend erness of skeletal muscles, gentle exercise, avoid aggravating factors (i.e. certain foods or activities). : counseling, biofeedback, education, anxiety/ - adrenoceptor blockers: most useful for those with associated voiding symptoms and in newly diagnosed disease. CHRONIC PELVIC PAIN SYNDROME 213 Antibiotics diagnosis of in \202 ammatory CPPS (i.e. cipro \202 oxacin, levo \202 oxacin for 4 \200\2236 weeks). Antibiotics do not appear effective for longstanding, refractory d isease. Anti-in \202 ammatory drugs : some bene \201 t in patients presenting early with a new 5- -reductase inhibitors: anti-androgens (i.e. \201 nasteride, dutasteride) have the ab ility to reduce prostatic glandular tissue and improve intraductal re \202 ux and symptoms in selected cases. Phytotherapies and anti-in \202 ammatory properties); Cernilton (polle n abstract). Pentosan polysulphate sodium ( Analgesics Neuromodulatory therapies (pregabali n) \200\224shown to improve mean NIH-CPSI and pain scores. Muscle relaxants Prostatic massa ge therapy Local heat therapy : NSAIDs (i.e. ibuprofen). : Quercetin (polyphenolic bio \202 avonoid with antioxidant - PPS). : opioids may be trialed in collaboration with the pain team. : amitriptyline, gabapentinoid : diazepam. : 2/3 times per week for 6 weeks with antibiotic If no pathology is identi \201 ed and there is no response to initial treatments, referral to the pain team is advised. 1 Nickel JC, Shoskes DA (2010) Phenotypic approach to the management of the chronic prostat itis/chronic pelvic pain syndrome. BJU Int 106:1252 \200\22363. CHAPTER 6 Infections and in \202 ammatory conditions 214 Bladder pain syndrome (BPS) A chronic and debilitating disorder characterized by urinary fr equency, urgency, nocturia, and bladder and pelvic pain. It remains a diagnosis of exclusio n after all other causes for the symptoms have been ruled out (Table 6.5). The \200\230cla ssic \200\231 form is associated with bladder ulceration (Hunner \200\231s ulcers) and dest ructive in \202 ammation, with some developing a small-capacity \201 brotic bladder or u pper urinary tract out \202 ow obstruction. \200\230Non-ulcer \200\231 forms do not show the same progression. De \201 nitions Terminology has changed a number of times. It was formally known as inters titial cystitis (IC). The ICS, the European Society for the Study of Bladder Pain Syndrome/ Interstitial Cystitis (ESSIC), and the EAU use the term \200\230BPS \200\231.1,2 The AUA u se the term \200\230IC/BPS \200\231.2,3 ESSIC: \200\230chronic (>6 months) pelvic pain, pressure, or discomfort perceived to be re lated to the urinary bladder, accompanied by at least one other urinary symptom such as per sistent urge to void or frequency \200\231. 1,2