Urinary Tract Infections

Etiology ?

- A large proportion of these infections are sexually transmitted - especially in men below 35. - However, there is overlap between the age groups depending on sexual history etc.) - The common causative organisms for sexually transmitted cases are: • Chlamydia trachomatis - accounts for over half of all testes and epididymis infections in men under 35. • Neisseria gonorrhoeae - second most common cause. - These infections start in the urethra and move upwards towards the testes. - In men over 35, or pre-pubescent boys, it is more common to stem from non-sexually transmitted causes such as a urinary tract infection. In this case, the organism is likely to be gram negative enteric bacteria e.g. Escherichia coli, klebsiella, and pseudomonas. - Risk factors for infection in this age group include recent instrumentation, catheterisation and bladder outlet obstruction.

Treatment?

- Treatment depends on the cause of the infection, and the likely organism involved. - In infections caused by chlamydia/other gonococcal infections (usually in sexually active men under 35 years old), first line treatment is CEFTRIAXONE 250mg IM & DOXYCYLINE 100mg PO BD for 14 days. - Patients are also advised not to have unprotected sex until treatment is completed. Infections likely not sexually transmitted - These infections (often in men over 35 years old with UTI/bladder obstruction), are usually caused by enteric bacteria. Therefore they are treated with Quinolone antibiotics: OFLOXACIN 300mg PO BD for 10 days OR LEVOFLOXACIN 500mg PO OD for 10 days All cases including viral causes - Bed rest is advised, along with scrotal elevation until symptoms have resolved. - Analgesics such as paracetamol can be taken for the pain and fever. NSAIDs can be taken and may be of some benefit in reducing inflammation. - If patients become systemically unwell due to the infection and show signs of sepsis, IV fluid replacement can be given and consider IV antibiotics.

What are the two ways in which the infection spreads in acute pyelonephritis spreads?

1) Ascending infection: bacteria from the gut enter the kidney from the lower urinary tract if there is an incompetent vesicoureteric valve. This permits vesicoureteric reflux (VUR) and results in ascending transmission of infection 2) Hematogenous spread: seen in patients with septicaemia or infective endocarditis. The pathogens include fungi, bacteria (staphylococci and Escherichia coli) and viruses. The kidney is often affected in septicaemic diseases because of its large blood supply.

What is urethral syndrome?

Also called abacterial cystitis. It is the presence of characterstic symptoms but no bacteriuria

Define: epididymitis and orchitis

Epididymitis: An infection of the epididymis (coiled tube at the back of testicle which delivers sperm to the vas deferens.) → This is usually a bacterial infection rather than viral. Orchitis: An infection of the testicle - often arising from epididymitis.

Complications of acute pyelonephritis?

Risk factors for complications → age>65, renal tract structural abnormality, DM, pregnancy, transplant • Sepsis • Perinephric abscess • Renal abscess - emphysematous pyelonephritis: rare, life-threatening form with tissue necrosis and accumulation of gas in the renal parenchyma, perinephric space and collecting systems ; particularly occurs in obese, elderly women who have diabetes and develop urinary tract obstruction • Acute papillary necrosis (suggested by associated symptoms of renal colic). • Pyonephrosis (obstruction of the pelvicalyceal system)

Define pyuria

The presence of pus in the urine, can be sterile or not sterile (bacteriuria). Causes of sterile pyruia include - TB - treated UTI - appendicitis - calculi - TIN - papillary necrosis - polycystic kidney disease - chemical cystitis.

Define UTI

This implies the presence of characteristic symptoms and significant bacteriuria from kidneys to bladder. Many laboratories regard 105 colony-forming units per millilitre (cfu/ml) as the threshold for diagnosing significant bacteriuria. Bacteriuria does NOT equate to a UTI, especially in the population aged over 65.

Define bacteruria

This refers to the presence of bacteria in the urine. This may be symptomatic or asymptomatic. Asymptomatic bacteriuria should be confirmed by two consecutive urine samples.

Presentation of epididymitis and orchitis?

o Gradual onset of pain and swelling over a few days, usually unilateral - this distinguishes it from a testicular torsion, (which is a surgical emergency), where there is a sudden onset of pain. o Tenderness of the epididymis - the tubular structure can be felt posterior to the testis o Hot, erythematous and swollen scrotum o Groin pain o Painful urination - common if UTI cause o Painful ejaculation o Blood in semen o Symptoms do not usually last more than 6 weeks (but usually resolves in less than a week) - if they do this is chronic inflammation o Pyrexia - a slight fever may be seen with the infection o If STI cause → possible urethral discharge and symptoms of urethritis

Imaging in acute pyelonephritis?

o Useful if the clinical picture or biochemical markers are ambivalent, as structural problems are not uncommon. Ultrasonography is usually the first-line investigation. o Normally recommended in men and children; it is mandatory in patients with recurrent pyelonephritis and may help to identify obstruction or stones. o Contrast-enhanced helical/spiral CT (CECT) scan is the best investigation in adults where diagnosis is in doubt, improvement does not occur after 72 hours of treatment, or deterioration occurs.

Define recurrent UTI

this may be due to relapse or re-infection. A recurrence is with a new organism while a relapse is with the same organism. The number of recurrences regarded as clinically significant depends on age and sex (usually >3 infections a year).

Define complicated UTI

this occurs where anatomical, functional, or pharmacological factors predispose the person to persistent infection, recurrent infection or treatment failure - ex, abnormal urinary tract, outflow obstruction, impaired host defence etc.

Define uncomplicated UTI

this refers to infection of the urinary tract by a usual pathogen in a person with a normal urinary tract and with normal kidney function.

What is urethritis?

• Acute inflammation of the urethra, usually occurs from infection with a sexually transmitted disease • It can be related to urethral diverticuli, urethral carbuncles or phimosis and can result in urethral stricture. • The most common symptom is painful or difficult urination. • Classified as either gonococcal urethritis (caused by Neisseria gonorrhoeae) or non-gonococcal urethritis (most commonly caused by Chlamydia trachomatis) • Other organisms include → E.choli, herpes simplex, CMV and much more • Treated with antibiotics and advice on hygiene is important.

What is acute pyelonephritis?

• Acute pyelonephritis is infection within the renal pelvis, usually accompanied by infection within the renal parenchyma. • The usual organisms are the same as for lower urinary tract infection (UTI) - ex. Escherichia coli, Klebsiella spp., Proteus spp., Enterococcus spp. • Unusual organisms are occasionally seen - ex. mycobacteria, yeasts, fungi, opportunistic pathogens such as Corynebacterium urealyticum.

Risk factors for chronic pyelonephritis?

• Any structural renal tract anomalies, obstruction or calculi. • VUR & Intrarenal reflux in neonates • Diabetes • Any factors predisposing to recurrent urinary infection - ex, neurogenic bladder

Epidemiology of acute pyelonephritis?

• Can occur at any age. • Incidence is highest in women aged 15-29, followed by infants and older people. • It is relatively uncommon in men until the age of 65+ when incidence rises to match that of women. • In neonates it is more common in boys & tends to be associated with abnormalities of the renal tract.

Presentation of chronic nephritis?

• Chronic pyelonephritis is often asymptomatic. • There may be features of acute or recurrent infection, or of complications of significant renal damage → fever, malaise, loin pain, nausea, vomiting, dysuria, hypertension, failure to thrive and feature of CKD

Management of cystitis?

• Drink plenty • ? Cranberry juice • Treat with antibiotics for 3-6d, examples of ones that are used:- o Trimethoprim 100-200mg BD → most commonly used o Nitrofurantoin 50-100mg QDS (not in RF) o Cefalexin 500mg BD (good in RF) o Co-amoxiclav 625mg TDS

Referral indications for acute pyelonephritis?

• Hospital admission → many patients can be managed in the community, providing they are otherwise healthy. Referral indications: o Pregnancy o Comorbidity such as diabetes. o Signs of sepsis (ex. tachypnoea, tachycardia, hypotension). o Failure of response to treatment within 24 hours or relapse of symptoms when antibiotics are stopped o Urinary tract obstruction. o Oliguria or anuria.

Organisms that cause cystitis?

• In the majority of UTIs the infecting organism comes from the patient's own faecal flora • Non-infective cystitis can be caused by radiation, drugs (ex. cyclophosphamide, ketamine).

Histopathology of acute pyelonephritis?

• Infection spreads into the renal pelvis and papillae and causes abscess formation throughout the cortex and medulla. • With retrograde ureteric spread the kidney characteristically contains areas of wedge-shaped suppuration especially at the upper and lower poles. • In septicemia there is hematogenous seeding within the kidney and minute abscesses are distributed randomly in the cortex. • On histological examination there is: o Polymorphic infiltration of the tubules o Interstitial edema o Focal inflammation.

What is Schistosomiasis (bilharzia)?

• Most common helminth infection worldwide, although it is rare in the UK. o It is endemic in the Middle East, Africa, the Far East and in parts of South America. • The pathogen is a blood fluke (Schistosoma haematobium). • Freshwater snails are also part of its complicated life cycle. • The schistosomes penetrate intact skin to enter the venous system, & migrate to the liver & bladder. • They settle in the bladder to lay eggs causing chronic irritation of the transitional cells of the bladder. • The eggs are excreted into local water supplies and transmitted through freshwater snails • Can present with an itchy papular rash accompanied by myalgia, abdominal pain and headache. • The most common presentation of infection with S. haematobium is recurrent haematuria. • Eventually, urinary tract obstruction, bladder calcification (risk for squamous carcinoma) and CKD can occur. • Investigations o Urine sample to detect the eggs in the urine o ELISA on serum to detect an antibody response to infection. • Treatment → praziquantel given once daily.

What is chronic non-bacterial prostatitis?

• Most common type of prostatitis and results in enlargement of the prostate, which can obstruct the urethra. • The usual pathogen is C. trachomatis so, typically, sexually active men are affected. • Often there is no history of recurrent UTIs. • Presentation is similar to that of chronic prostatitis and histological examination shows fibrosis as a result of chronic inflammation. • Diagnosis is confirmed by the presence of 15 white blood cells per high-power field (this indicates inflammation) and repeated negative bacterial cultures (excludes infection).

Rarer causes?

• Mumps - most common viral cause (followed by Coxackie A, Varicella and Echo-viral). • TB - extra-pulmonary TB can occasionally manifest as epididymo-orchitis. However, this is more likely to be seen in countries with a higher prevalence of TB or in patients with an immunodeficiency. It is often associated with renal TB, but can be seen alone. • Brucellosis - highly contagious zoonosis caused by ingesting unpasteurised milk/ eating uncooked meat. • Coccidioidomycosis - fungal infection, endemic in parts of the southern American states and Mexico • Blastomycosis - parasitic fungal infection

What is interstitial cystitis?

• Often associated with SLE, so is thought to be an autoimmune condition. • As with all autoimmune conditions, it has a much higher incidence in women than in men. • It can also result from recurrent and persistent infection that leads to fibrosis of all the layers of the bladder wall. There is often localized ulceration of the mucosa.

Presentation of acute pyelonephritis?

• Onset is usually rapid with symptoms appearing over a day or two. • There is unilateral or bilateral loin pain, suprapubic pain or back pain. • Fever is variable but can be high enough to produce rigors. • Malaise, nausea, vomiting, anorexia and occasionally diarrhea occur. • There may be accompanying lower urinary tract symptoms ex. frequency, dysuria, gross hematuria or hesitancy. • The patient looks ill and there is commonly pain on firm palpation of one or both kidneys and moderate suprapubic tenderness without guarding. • Presentation in children, especially when young, can be much less specific and culture of urine should be a routine investigation in pyrexial and unwell infants.

Investigations?

• Physical examination will lead you to suspect orchitis and epididymitis • A urine dipstick may show positive leukocytes • Urine culture - isolates causative organisms • Gram stain test of urethral secretions and a urethral swab to identify causative bacterial organism → this will show Chlamydia trachomatis and Neisseria gonorrhoeae. • Ultrasound imaging may also help to diagnose - will show increased blood flow to the area. This also rules out testicular torsion.

Complications of chronic pyelonephritis?

• Progressive renal scarring with reflux nephropathy and CKD • Secondary hypertension • Pyonephrosis • Focal glomerulosclerosis

Histopathology of chronic pyelonephritis?

• Reflux of urine into the renal pelvis occurs during micturition and this increases the pressure in the major calyces. The high intrapelvic pressure forces urine into the collecting ducts with intraparenchymal reflux further distorting the internal structure. • This is most predominant at the poles of the kidney and results in deep irregular scars on the cortical surface. • The tubulointerstitial inflammation heals with the formation of corticomedullary scars that overlie the deformed and dilated calyces, which are characteristic of chronic pyelonephritis • On histological examination there is interstitial fibrosis and dilated tubules containing eosinophilic casts; 10-20% of patients requiring dialysis have chronic pyelonephritis

What is chronic pyelonpehritis and its types?

• Repeated attacks of acute pyelonephritis can lead to chronic pyelonephritis, which involves destruction and scarring of renal tissue due to repeated inflammation. • There are two main types: 1. Obstructive: chronic obstruction (stones, tumors or congenital abnormalities) prevents pelvicalyceal drainage and increases the risk of renal infection. Chronic pyelonephritis develops because of recurrent infection. 2. Reflux nephropathy: this is the most common cause of chronic pyelonephritis. It is associated with VUR, which is congenital. The organisms enter the ascending portion of the ureter with refluxed urine as the valvular orifice is held open on contraction of the bladder during micturition. Reflux results from the abnormal angle at which the ureter enters the bladder wall

What is chronic cystitis?

• Results from recurrent or persistent infection of the bladder • Chronic infection leads to fibrous thickening so the bladder wall is less distensible • This affects the ability of the bladder to store urine and contract during micturition

Risk factors of acute pyelonephritis?

• Structural renal abnormalities, including vesicoureteric reflux (VUR) • Calculi and urinary tract catheterisation • Stents or drainage procedures • Primary biliary cirrhosis • Immunocompromised patients ex. Pregnancy, diabetes • Prostate enlargement

Management of chronic pyelonephritis?

• Supervening UTI may require lengthier courses of antibiotics than are normally given. • Severe underlying VUR diagnosed in children may require antibiotics prophylactically until puberty or until the reflux resolves. • Calculi may need removal. • Surgical re-implantation of the ureters may be needed in severe cases. • In severe cases, there may eventually be a need for dialysis or renal transplantation. • As with all other forms of CKD, the patient should be monitored for the development of hyperlipidaemia, hypertension, diabetes and deteriorating renal function.

Management of acute pyelonephritis?

• Support → rest, adequate fluid intake and analgesia are important. • Antibiotics → start empirical antibiotic treatment whilst awaiting culture and sensitivity. o First-line antibiotic should be either ciprofloxacin or co-amoxiclav for seven days (500 mg bd or 500/125 mg tds respectively). o Trimethoprim may be used if culture confirms sensitivity (200 mg bd for 14 days). o For children co-amoxiclav or cephalosporin is recommended for 7-10 days and may need to refer esp if under 3 months. • Surgery → this may rarely be required to drain renal or perinephric abscesses, or to relieve obstructions causing the infection.

Quick disease profile on acute prostatitis.

• The main pathogens are E. coli, Proteus and Staphylococcus species, and sexually transmitted pathogens including C. trachomatis and Neisseria gonorrhoeae. • Inflammation can be focal or diffuse. • Infection is usually spread from an acute infection in the urethra or bladder because of: o Intraprostatic reflux of urine o Intraprostatic catheterization o Surgical manipulation of the urethra (e.g. cystoscopy). • Occasionally, acute prostatitis is caused by a blood-borne infection. • On histological examination there is an acute inflammatory infiltrate of neutrophils and damaged cells, often resulting in abscess formation. • Patients present with: o General symptoms: malaise, rigours and fever o Local symptoms: difficulty in passing urine, dysuria and perineal tenderness. • Rectal examination reveals a soft, tender and enlarged prostate. • Diagnosis is based on the clinical features and a positive urine culture. • Treatment is with antibiotics (PO ciprofloxacin 500 mg BD), alpha blockers and NSAIDs

Diagnosis of cystitis?

• The typical irritative symptoms of cystitis are dysuria (pain on passing urine), frequency and urgency of micturition and suprapubic pain. • A diagnosis of UTI requires over 105 organisms/mL from a midstream urine specimen.

Define cystitis

• This is inflammation of the bladder. • If it involves loin pain and fever this indicates pyelonephritis. • UTIs rarely progress to renal damage in adults if the renal tract is normal.

Quick disease profile on chronic prostatitis.

• This results from inadequately treated acute infection. This can occur because some antibiotics cannot penetrate the prostate effectively. • There is often a history of recurrent prostatic and urinary tract infections. • Patients present with dysuria and low back and perineal pain, with no preceding acute phase. • Some patients are asymptomatic. • Chronic prostatitis is difficult to diagnose and treat. Diagnosis is confirmed by: o Histological examination showing neutrophils, plasma cells and lymphocytes o A positive culture from a sample of prostatic secretion. • Tuberculosis is a cause of chronic infection and can affect the kidneys or epididymis. • Histological examination reveals focal areas of caseation and giant cell infiltrates.

Epidemiology of cystitis?

• UTIs are more common in boys in infancy because of congenital abnormalities; this reverses at puberty, with more females being affected thereafter because of urethral trauma and pregnancy. • Women are particularly at risk of cystitis because they have a short urethra, but further investigation is required if infections are recurrent. • Any UTI in children and men should be investigated to exclude an underlying renal tract abnormality. • After the age of 40, UTI again becomes more common in men because of prostatic disease, causing bladder outflow obstruction.

Risk factors of cystitis?

• Urethral catheterization • Diabetes mellitus • Impaired voiding (due to obstruction) • Pregnancy • Sexual intercourse • Tumors • Immunosuppression

Investigations in acute pyelonephritis?

• Urinalysis → the urine is often cloudy with an offensive smell. It may be positive on dipstick urinalysis for blood, protein, leukocyte esterase and nitrite. A midstream specimen of urine (MSU) should always be sent off for microscopy and culture. Microscopy of urine shows pyuria. • Inflammatory markers → CRP, ESR, and plasma viscosity may be raised. • FBC → elevated white cell count with neutrophilia. • Blood cultures → these are positive in approximately 15-30% of cases.

Investigations in chronic pyelonephritis?

• Urine microscopy, culture and sensitivity → may be helpful in identifying the organism involved in recurrent infection but negative urine culture does not exclude diagnosis. • Imaging o Renal ultrasound may show small kidneys with a thin cortex. o Intravenous pyelogram (IVP) may show small kidneys, ureteric and caliceal dilatation/blunting with cortical scarring. o Micturating cystourethrogram (MCUG) may help to identify reflux. o Ultrasound and KUB X-ray may show stones but are not sensitive for reflux nephropathy. o Technetium-99m Tc-DMSA scan is the most sensitive for demonstration of renal scars. o Renal biopsy may be required to rule out other causes of damage.

What is Malakoplakia Vesicae?

• Very rare form of chronic bacterial cystitis, but it is important because it can mimic a tumour. • Raised mucosal plaques of inflammation cells develop on the bladder and ureteric mucosa. • These plaques are soft, yellow, 3-5 cm in diameter and are prone to ulceration.