Urological infections in men

Transcription

1 Infections Urological infections in men Luke A McGuinness, Urology Clinical Fellow; Robert C Calvert, Consultant Urologist, Royal Liverpool and Broadgreen University Hospitals; Frederick Banks, Consultant Urologist, Watford General Hospital; Although urinary tract infections occur predominantly in women, men also suffer. Some features are similar to both genders, but certain anatomical sites, risk factors and treatment are unique to men. These are explored in this review of the commonly encountered urological infections in men. Urinary tract infection (UTI) describes an inflammatory response to bacterial infection within the urinary tract. It is the second most common indication for empirical antibiotics. Although predominantly affecting women, 20% of UTIs occur in men, with an annual incidence of approximately 2300 per With a low prevalence in younger men (<1%) it dramatically increases with age, affecting 6 7% of those over 65. 2,3 Different definitions further characterise UTI and assist the subsequent treatment. Asymptomatic bacteriuria describes the presence of bacteria on two consecutive urine cultures without symptoms of upper or lower UTI. Treatment is only required if an invasive genitourinary procedure is planned. An uncomplicated UTI occurs in patients with a structurally and functionally normal urinary tract without comorbidity that might precipitate a serious outcome. A complicated UTI occurs in the presence of another condition (structural/functional urinary tract abnormality or medical comorbidity), Escherichia coli is the most commonly encountered uropathogen, accounting for 80% of community UTIs that increases risk of persistent infection, recurrent infection or treatment failure. A positive urine culture with a risk factor (listed in Table 1) is required to diagnose a complicated UTI. 4 NICE defines recurrent UTI as more than two UTIs within six months or three within 12 months. 5 Re-infection occurs with different bacteria, while bacterial persistence is infection with the same organism. UTIs are usually classified by anatomical site; urethra (urethritis), bladder (cystitis/lower UTI), prostate (bacterial prostatitis), kidneys and ureters (pyelonephritis/upper UTI), blood stream (urosepsis) and testes and epididymis (epididymo-orchitis). Pathogenesis Urological infections tend to result from enteric micro-organisms colonising the urogenital tract. Faecal flora, normally gram-negative organisms, colonise the perineum, with UTI usually resulting from retrograde ascent of these microorganisms from the urethra. Bacteria adhere to the urothelium and can release toxins. Adhesion stimulates urothelial cells to release chemokines and an inflammatory response ensues. 6 The degree of virulence of uropathogens varies - the more virulent factors expressed, the more severe the infection. Equally, the more compromised the host s natural defences (eg obstruction, catheterisation), the fewer virulent factors need to be expressed to cause infection. Escherichia coli is the most commonly encountered uropathogen, accounting for 80% of community UTIs. 6 Other gram-negative trendsinmenshealth.com Trends in Urology & Men s Health November/December

2 Infections uropathogens include Klebsiella, Proteus and Pseudomonas species. Gram-positive organisms include Enterococcus faecalis and occasionally Staphylococcus. Cystitis/lower UTI Assessment and diagnosis The majority of male lower UTIs will be complicated. Classically, symptoms of cystitis include dysuria, urgency, frequency and polyuria. Signs include suprapubic tenderness, offensive smelling or cloudy urine and haematuria. Elderly men and those with an indwelling catheter may not describe classical symptoms, and nausea, vomiting, general malaise, worsening confusion or new delirium may be the only indicator of UTI. Febrile symptoms may indicate concomitant prostate infection and flank pain may signify pyelonephritis. If urethral discharge is present, a sexual history should be considered to assess for urethritis. Measurement of temperature, blood pressure and heart rate may identify urosepsis requiring hospital admission. Abdominal examination should elucidate signs of pyelonephritis or urinary retention and rectal examination should be considered to assess for bacterial prostatitis or concurrent prostatic hypertrophy. Nitrites and leucocyte esterase on urine dipstick in men have positive and negative predictive values of 90% and 50%, respectively. 7 A midstream urine (MSU) sample for culture should be taken in all men with suspected UTI before commencing antibiotic therapy. Catheter specimen urine should only be sent for culture if symptoms are present. A culture is considered positive if there are >10 4 colony forming units per millilitre (CFU/ml) of a single organism with >10 4 /ml of leucocytes in the presence of urinary symptoms or >10 3 CFU/ml of E.coli. 5 False positive culture results caused by contamination are indicated by the presence of epithelial cells, Risk factor for complicated UTI Anatomic or functional urinary tract abnormality Iatrogenic (surgical modification, foreign body) Obstructive uropathy Neurological bladder dysfunction Medical comorbidity multiple micro-organisms or bacteria without leucocytes. Treatment Empirical antibiotic therapy should be directed by local guidelines; however, nitrofurantoin is often used as the first-line agent. The length of treatment of male cystitis is not well studied. No difference has been shown between 7 and 14 days of therapy and expert consensus states that seven days should be sufficient. 8,9 In men with indwelling urethral catheters, their position and patency should be checked to ensure that there is no obstruction. If symptoms are mild, antibiotic treatment can be withheld until culture results are available as asymptomatic bacteriuria does not require treatment. Catheters in situ for more than seven days should be changed. 10 Acute pyelonephritis or upper urinary tract infection Assessment and diagnosis Pyelonephritis describes inflammation of the kidney and renal pelvis. It is a Example Pelvicoureteric junction obstruction Vesicoureteric reflux Ileal conduit urinary diversion Indwelling urethral catheter Ureteric stent Intermittent urethral catheterisation Urological instrumentation/procedure Chemoradiotherapy to urothelium Urolithiasis Bladder outlet obstruction Post-void residual volume >100ml Ureteral tumour/stricture Spinal cord injury Stroke Multiple sclerosis Diabetes mellitus Immunosupression Renal insufficiency Renal transplantation Table 1. Risk factors for complicated urinary tract infections clinical diagnosis of loin pain with fever and culture-proven UTI. 11 Careful history is important to exclude other diagnoses (eg appendicitis, renal colic, cholecystitis, pancreatitis, diverticulitis and abdominal aortic aneurysm). Both kidneys can be affected and it is usually preceded by symptoms of cystitis. Nausea and vomiting are common. Urine dipstick can be useful if diagnostic uncertainty exists, but formal urine culture is mandatory. Pyelonephritis can be accompanied by bacteraemia and is potentially life-threatening. Initial assessment identifies those with systemic compromise requiring hospitalisation. Treatment For those with pyrexia but who are systemically stable, management in the community is reasonable. Empirical therapy is usually a fluoroquinolone or co-amoxiclav, given their broad spectrum and excellent penetration into renal parenchyma. 8 Patients who are haemodynamically compromised or who fail to respond 16 Trends in Urology & Men s Health November/December 2018 trendsinmenshealth.com

3 Infections to antibiotics after 24 hours require hospital admission. Blood cultures should be taken and intravenous antibiotics commenced according to local policy. Upper tract abnormalities should be assessed using X-ray or ultrasound imaging. Patients not responding to antibiotic therapy, or with signs of severe sepsis, require CT scanning to investigate possible pyonephrosis (pus in the renal pelvis) or perinephric abscess. Both require urgent drainage by percutaneous drain, nephrostomy or ureteric stent insertion depending on available facilities. The recommended duration of treatment is seven days if using a fluoroquinolone or co-amoxiclav. 8,12 Bacterial prostatitis Bacterial prostatitis is inflammation of the prostate secondary to infection and is separate from chronic pelvic pain syndrome (CPPS). It is classified as acute or chronic depending on its duration and requires high dosages of potent antibiotics to treat successfully. Acute bacterial prostatitis Acute bacterial prostatitis (ABP) is a potentially serious infection often accompanied by lower UTI. Symptoms usually include those of cystitis along with intense localised pain to the perineum, scrotum, rectum or lower back. Systemic symptoms of fevers, rigors and myalgia are also present. Rectal examination reveals a smooth, swollen and tender prostate gland, and palpable fluctuance may indicate an abscess. The most important investigation is urine culture. Prostate massage is contraindicated in ABP as it is painful and may cause bacteraemia. 4,13 Although sexually transmitted diseases are rare, screening in those under 35 years or with suggestive history (eg multiple sexual partners, recent partner change) is recommended. 14 Prostate-specific antigen (PSA) is increased in ABP; serum levels normalise after antibiotic course in 50% and stable PSA should not be assumed until after three months. Transrectal ultrasound can be used if a prostatic abscess is suspected. Given its potential seriousness, empirical therapy is required after urine culture is obtained. Patients with signs of sepsis, unable to take oral antibiotics or with urinary retention, necessitate hospitalisation. Fluoroquinolones are the antibiotic of choice due to their high penetration into the prostate gland. For patients requiring parenteral therapy, a third-generation cephalosporins plus an aminoglycoside will cover the likely pathogens. After clinical improvement, oral therapy can be instituted. 4,8,13 Early re-review ensures no deterioration indicative of prostate abscess. Optimal duration is not well established, but UK guidelines recommend 28 days to prevent development of chronic prostatitis. 8,13 Chronic bacterial prostatitis Chronic bacterial prostatitis (CBP) refers to infection of more than three months duration. It can occur with or without symptoms, but is associated with recurrent UTIs. It is rare in comparison with chronic prostatitis/ CPPS. Typical history includes recurrent infections with voiding dysfunction. Genitourinary and pelvic pain usually flares during infective episodes and is alleviated by antibiotic therapy. Between infective episodes mild pain and voiding symptoms may persist, but some will be asymptomatic. Unlike the acute form, CBP patients are systemically well. The prostate gland can be diffusely tender but is often normal. Diagnosis is made on clinical history of relapsing symptoms for more than three months with recurrent UTIs of the same pathogen and no evidence of structural abnormality on imaging. 14 Urine cultures are usually normal unless acute infection is present, and review of historical microbiology is required to identify the causative organism. The four glass test (or Meares- Stamey Test) for expressed prostatic secretions can distinguish between CBP and CPPS, but due to its low sensitivity most clinicians will empirically treat with antibiotics. 15 Due to overlap with CPPS, CBP management should involve careful patient counselling, explaining the prostate as the focus for recurrent infection and that, although a chronic condition, most cases improve over a period of months or years. Antimicrobial treatment should be guided by available culture results, but fluoroquinolones form the mainstay. Alpha blockers used in conjunction with antibiotics may provide symptomatic benefit. 13 Typical antibiotic duration is days, but prolonged courses of up to three months may sometimes be required. 14 Owing to the risk of relapse, follow-up with repeat urine culture is mandatory. Epididymo-orchitis Epididymo-orchitis is inflammation involving the epididymis and testicle. Its pathogenesis differs slightly from the other UTIs discussed. In sexually active men under 35 years it is usually a complication of urethritis, and Neisseria gonnorhoea or Chlamydia trachomatis are the usual culprits. In older men the uropathogens discussed earlier predominate. Concurrent parotiditis should raise suspicions for mumps orchitis (paramyxovirus). Assessment and diagnosis Inflammation of the epididymis and testicle presents with acute onset of scrotal swelling and pain, particularly on movement. Usually unilateral, it starts in the epididymal tail, spreading to the upper pole in the epididymis and causing testicular inflammation. Involvement of the spermatic cord results in groin pain and a reactive hydrocele can occur. Sexual history, associated urethral discharge or UTI symptoms should indicate the trendsinmenshealth.com Trends in Urology & Men s Health November/December

4 Infections likely cause. Signs include scrotal swelling and erythema, palpable epididymal or spermatic cord swelling, and tenderness particularly over the epididymis. The most important differential is testicular torsion, which is more likely in those under 20 years and with an acute onset (under four hours) of severe pain. If any doubt persists, urgent urological referral is advised. Patients with signs of severe sepsis (particularly if immunosuppressed or diabetic) should be examined for necrotic scrotal/perineal skin tissue and Routine urology referral Two-week outpatient urology referral Urgent urology referral subcutaneous emphysema, the hallmarks of Fournier s gangrene. Sexually transmitted infection (STI) should be excluded and chlamydia polymerase chain reactio assay can be useful. Pragmatically, genitourinary medicine referral is advocated as microscopy can diagnose gonococcal infections quickly, allowing administration of appropriate antibiotics. 14 Where uropathogens are felt to be a more likely culprit (older age, low-risk sexual history, UTI history) a urine dipstick can be useful, but formal MSU culture is essential. Persistent symptoms of infection despite appropriate antibiotic therapy Suspicion of underlying urological risk factor (see Table 1) Recurrent UTI (includes chronic bacterial prostatitis) All men with episode of pyelonephritis following recovery All men with episode of acute bacterial prostatitis following recovery Men with episode of epididymo-orchitis not secondary to STI Aged under 50 with persistent microscopic haematuria and normal renal function Aged over 45 and have: - unexplained visible haematuria - visible haematuria that persists or recurs after successful treatment of a urinary tract infection Aged over 60 and have unexplained non visible haematuria and either dysuria or raised white cell count on a blood test Abdominal mass thought to arise from urinary tract Cystitis rarely required Acute pyelonephritis: - Systemic instability - Vomiting/unable to take oral antibiotics - No improvement after 24 hour oral antibiotics - Suspicion of obstructed system/pyonephrosis (eg known renal stones) Acute bacterial prostatitis: - Systemic instability - Urinary retention - Possible prostatic abscess (eg failing to respond to antibiotics, palpable fluctuance) Chronic bacterial prostatitis - rarely required Epididymo-orchitis: - Suspicion of testicular torsion (eg aged under 20, pain onset within four hours) - Signs of scrotal abscess (palpable fluctuance, failure to respond to antibiotics) - Signs of Fournier s gangrene (necrotic skin, palpable crepitus) Table 2. Referral criteria for urinary tract symptoms Treatment Simple analgesia and scrotal support help to manage the symptoms. Empirical antimicrobial therapy will depend on the suspected causative organism. In non-gonococcal infection a 14-day course of tetracycline or fluoroquinolone is recommended. It is worth noting that ciprofloxacin is not effective against chlamydial infections and ofloxacin or levofloxacin are preferred. If gonococcal infection is suspected then an intramuscular injection of ceftriaxone with 14 days of a tetracycline is usually sufficient. 8,14 Partner notification and screening for other STIs is required. Empirical antibiotics for suspected uropathogenic epididymo-orchitis vary according to the local policy, but usually include two weeks of a fluoroquinolone. 4 Patients should be reassessed to ensure treatment response and review culture results. Those with inadequate response or with palpable scrotal fluctuance warrant acute referral for management of potential scrotal abscess. Haematospermia The presence of blood in the semen often provokes anxiety in men, who will seek medical advice. The most frequent cause is urogenital infection, with an organism isolated in up to 75% of cases. 16 Cystitis, urethritis, epididymo-orchitis and bacterial prostatitis can all present with haematospermia. Urine culture and, where indicated, STI screen will usually identify the causative pathogen to guide antimicrobial treatment. Occasionally culture of ejaculate is required. When presented with haematospermia it is important to discern from co-existing haematuria, which requires a more urgent urological assessment. A rectal exam and PSA test should be performed in men with prostate cancer risk, as haematospermia can be a presenting symptom. 18 Trends in Urology & Men s Health November/December 2018 trendsinmenshealth.com

5 Infections Indications for referral Male UTI is frequently associated with risk factors that can be reversed or modified. Urological referral should be aimed at identifying and treating these. No referral is required in men who have an isolated, uncomplicated UTI; however, lower urinary tract abnormalities are present on urodynamic assessment in 80% of men with UTI. 17 Table 2 shows the UK and European recommendations for referral. 3,4,5, Further urological assessment aims to diagnose and treat any risk factors (Table 3). Treatment depends on the functional or anatomical abnormality contributing to UTI; renal stones should be removed and obstructive pathologies should be relieved. Those with recurrent infections and unmodifiable risks may require antibiotic prophylaxis. Antibiotic resistance Bacterial resistance to antibiotic overuse has risen and is an important health threat worldwide. Agents previously used as empirical therapy now have high levels of bacterial resistance among common uropathogens, with an increasing trend of extended-spectrum beta-lactamase (ESBL) resistant organisms. Figure 1 shows resistance patterns in the UK. Trimethoprim and penicillin resistance is high and they should no longer be considered as empirical therapy for UTI. Nitrofurantoin retains a low endemic resistance and is excreted in high concentrations in urine, making it the empirical antibiotic of choice in cystitis. Unfortunately its low tissue penetration means it is not efficacious in treating other forms of UTI. Perhaps more worrying is the nationwide trend of increasing fluoroquinolone resistance among common uropathogens. E.coli resistance to ciprofloxacin has increased from 1% to 19% in two decades This is particularly concerning given the large number of urological infective conditions that Investigations Imaging KUB X-ray Renal ultrasound CT KUB/urogram Urodynamic studies Uroflowmetry + post-void bladder residual Multichannel cystometry Micturating cystogram Endoscopic Flexible cystoscopy rely on fluoroquinolones as the mainstay of antibiotic treatment. The rise of ESBL-resistant organisms has reduced the efficacy of parenteral antibiotics such as third-generation cephalosporins and gentamicin in treating UTI. Declaration of interests: none declared. Risk factor Table 3. Further investigations to identify risk factors Antibiotic resistance (%) Trimethoprim Ampicillin Nitrofurantoin Ciprofloxacin Renal calculi Pelvic uteric junction obstruction Ureteric stricture/tumour Bladder outlet obstruction Benign prostatic hypertrophy Neuropathic bladder Detrusor sphincter dyssynergia Vesico-ureteric reflux Bladder stones Bladder tumour Urethral/bladder neck stricture Fistula Co-amoxiclav Cephalosporins Gentamicin Carbapenems Figure 1. E.coli antibiotic resistance trends in the UK and Ireland References 1. Ronald AR, Nicolle LE, Stamm E, et al. Urinary tract infection in adults: research priorities and strategies. Int J Antimicrob Agents 2001;17: Griebling TL. Urologic diseases in America project: trends in resource use for urinary tract infections in men. J Urol 2005;173: Scottish Intercollegiate Guidelines trendsinmenshealth.com Trends in Urology & Men s Health November/December

6 Infections Network. SIGN 88: Management of suspected bacterial urinary tract infection in adults a national clinical guideline. Updated July 2012 ( sign88.pdf; accessed 4 October 2018). 4. EAU Guidelines. Urological Infections, 2018 ( urological-infections/#3; accessed 4 October 2018). 5 NICE Clinical Knowledge Summaries. Urinary tract infection (lower) men. National Institute of Clinical Excellence, 2014 ( accessed 4 October 2018). 6. Grabe M. Diagnosis and management of infections of the urinary tract. In: Rane A, Dasgupta R, eds. Urinary tract infection. London: Springer-Verlag, 2013; den Heijer CD, van Dongen MC, Donker GA, Stobberingh EE. Diagnostic approach to urinary tract infections in male general practice patients: a national surveillance study. Br J Gen Pract 2012;62:e Public Health England. Management of infection guidance for primary care for consultation and local adaptation. London: Department of Health, Drekonja DM, Rector TS, Cutting A, Johnson JR. Urinary tract infection in male veterans: treatment patterns and outcomes. JAMA Intern Med 2013;173: Hooton TM, Bradley SF, Cardenas DD, et al. Diagnosis, prevention and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infec Dis 2010;50: NICE Clinical Knowledge Summaries. Pyelonephritis acute. National Institute of Clinical Excellence, 2013 ( nice.org.uk/pyelonephritis-acute; accessed 4 October 2018). 12. Eliakim-Raz N, Yahav D, Paul M, Leibovici L. Duration of antibiotic treatment for acute pyelonephritis and septic urinary tract infection - 7 days or less versus longer treatment: systematic review and meta-analysis of randomized controlled trials. J Antimicrob Chemother 2013;68: Clinical Effectiveness Group (BASHH). National guidelines for the management of prostatitis. British Association for Sexual Health and HIV, Lazaro N. Sexually transmitted infections in primary care 2013 (RCGP/ BASHH). Royal College of General Practitioners, British Association for Sexual Health and HIV, 2013 ( bashhguidelines.org/media/1089/ sexually-transmitted-infections-in-primarycare-2013.pdf; accessed 4 October 2018). 15. Meares EM, Stamey TA. Bacterial localization patterns in bacterial prostatitis and urethritis. Invest Urol 1968;5: Ramsden AR, Williams J. Haematospermia. Trends in Urology & Men s Health 2011;2(2): Booth CM, Whiteside CG, Milroy EJ, Turner-Warwick RT. Unheralded urinary tract infection in the male. A clinical and urodynamic assessment. Br J Urol 1981;53(3): Public Health England. English surveillance programme for antimicrobial utilisation and resistance (ESPAUR) report. Department of Health, 2014; updated 3 November 2017 ( gov.uk/government/publications/ english-surveillance-programmeantimicrobial-utilisation-and-resistanceespaur-report; accessed 4 October 2018). 19. Health Protection Agency. Antimicrobial resistance and prescribing in England, Wales and Northern Ireland. London: Health Protection Agency, Cullen IM, Manecksha RP, McCullagh E, et al. The changing pattern of antimicrobial resistance within 42,033 Escherichia coli isolates from nosocomial, community and urology patient-specific urinary tract infections, Dublin, BJU Int 2012;109: Trends in Urology & Men s Health November/December 2018 trendsinmenshealth.com