Avoidance of host defense mechanisms - General: phagocytosis (E. coli). M. tuberculosis resists phagocytosis by preventing phagoly sosome fusion. Toxins: pathogenic effect on host erythrocytes. Enzyme production: breakdown of urea in urine to ammonia, which then contributes to disease processes (struvite stone f ormation). an extracellular capsule reduces immunogenicity and resists E. coli species have haemolysin activity which has a direct Proteus species produce ureases which cause the Antimicrobial resistance - Enzyme inactivation: produce B-lactamase which hydrolyzes the B- lactam bond within the structure of some antibiotics so inactivating them. The B-lactam ant ibiotics are penicillins, cephalosporins, and carbapenems. Altered permeability: prevented by alterations in receptor activity or transportation mechanisms. Alteration of binding sit e: genetic variations may alter the antibiotic target, leading to drug resistance. S. aureus, N. gonorrhoeae, and enterobacteria can access of the antibiotic to the bacteria is Host defenses: factors that protect against UTI include the following. General - Commensal \202 ora: protect by competing for nutrients, bacteriocin production, stimulati on of immune system, and altering pH. Mechanical integrity of mucous membranes. Mucosal sec retions: lysozymes split muramic acid links in cell walls of Gram-positive organisms; lacto ferrin disrupts normal metabolism of bacteria. Urinary immunoglobulin A (IgA) inhibits bact erial adherence. URINARY TRACT INFECTION: MICROBIOLOGY 181 Speci \201 c - Mechanical \202 ushing effect of urine through the urinary tract (i.e. antegrade \202 o w of urine). A mucopolysaccharide coating of bladder (Tamm \200\223Horsfall protein) helps prevent bacterial attachment. Bladder surface mucin: glycosaminoglycan (GAG) layer is an an ti-adherent factor, preventing bacterial attachment to mucosa. Low urine pH and high osmola rity reduces bacterial growth. Female commensal \202 ora: glycogen into lactic acid, caus ing a drop in pH. Increased rates of bladder mucosal cell exfoliation are seen during infec tion, which accelerates cell removal with adherent bacteria. Lactobacillus acidophilus metabolizes CHAPTER 6 Infections and in \202 ammatory conditions 182 Lower urinary tract infection: cystitis and investigation of UTI Cystitis: is infection and/or in \202 ammation of the bladder. Presentation: frequent voiding of small volumes, dysuria, urgency, offensive urine, suprapu bic pain, haematuria, fever 9 incontinence. General investigation of UTI Dipstick of MSU specimen White blood cells (indirect testing f or pyuria) Leukocyte esterase activity detects the presence of white blood cells (WBC) in t he urine. Leukocyte esterase is produced by neutrophils and causes a color change in a chro mogen salt on the dipstick. Not all patients with bacteriuria have signi \201 cant pyuria (sensitivity of 75 \200\22395% for detection of infection, i.e. 5 \200\22325% of patients w ith infection will have a negative leuko- cyte esterase test, erroneously suggesting that t hey have no infection). - False positives (pyuria present, negative dipstick test) \200\224concentrated urine, glycos uria, presence of urobilinogen, consumption of large amounts of ascorbic acid. False negati ves (pyuria absent, positive dipstick test) \200\224contamination. Remember, there are many causes for pyuria (and, therefore, a positive leukocyte esterase t est occurring in the absence of bacteria on urine microscopy). This is so-called sterile py uria and it occurs with TB infec- tion, renal calculi, bladder calculi, glomerulonephritis, interstitial cystitis, and carcinoma in situ. Thus, the leukocyte esterase dipstick test m ay be truly positive in the absence of infection. Nitrite testing (indirect testing for bacteriuria) Nitrites are not normally found in urine and their presence suggests the possibility of bacteriuria. Many species of Gram-negative bacteria can con- vert nitrates to nitrites and these are detected in the urine by a reacti on with the reagents on the dipstick which form a red azo dye. The speci \201 city of the nitrite dipstick for detecting bacteriuria is >90% (false positive nitrite testing can occu r with contamination). The sensitivity is 35 \200\22385% (i.e. false negatives are common \200\224a negative dipstick in the presence of active infec- tion) and is less accurate in urine containing <105 organisms/mL. Hence, if the nitrite dipstick test is positive, the pa tient probably has a UTI, but a negative test often occurs in the presence of infection. Cloudy urine, which is positive for WBCs on dipstick and is nitrite- positive, is very likely to be infected. Blood Hemoglobin has a peroxidase-like activity, causing oxidation of a chro- mogen indicat or on the dipstick, which changes color when oxidized. False positives are seen with menstr ual blood and dehydration. LOWER URINARY TRACT INFECTION: CYSTITIS 183 pH Urinary pH usually lies between 5.5 and 6.5 (range 4.5 \200\2238). A persistent alka- li ne pH associated with UTI indicates a risk of stones. Urease-producing bacteria (such as Pr oteus mirabilis) hydrolyze urea to ammonia and carbon dioxide, leading to the formation of magnesium, calcium, ammonium phos- phate stones (triple phosphate or struvite calculi). Microscopy of MSU - False negative: low bacterial counts may make it very dif \201 cult to identify bacteria a nd the specimen of urine may, therefore, be deemed to be negative for bacteriuria when, in fact, there is active infection. False positive: bacteria may be seen in the infection. Thi s is most often due to contamination with commensals from the distal urethra and perineum ( urine from a woman may contain thousands of lactobacilli and corynebacteria derived from th e vagina). These bacteria are readily seen under the microscope and although they are Gram- positive, they often appear Gram-negative (Gram-variable) if stained. MSU in the absence of If the urine specimen contains large numbers of squamous epithelial cells (cells which are derived from the foreskin, vaginal, or distal urethral epithelium), this suggests contamina tion of the specimen and the presence of bacteria in this situation may indicate a false po sitive result. The \201 nding of pyuria and red blood cells suggests the presence of acti ve infection. Further investigation Determined by the clinical scenario. If this is a one-off infection i n an oth- erwise healthy individual, no further investigations are required. However, furth er investigations are required if: - The patient develops symptoms and signs of upper tract infection (loin pain, malaise, fever ) and, therefore, acute pyelonephritis, a pyonephrosis or perinephric abscess is suspected. UTIs develop (see b p. 186). Recurrent The patient is pregnant. Unusual infecting organism (e.g. an infection stone. - Proteus), suggesting the possibility of These further investigations will include a KUB X-ray 9 IVU (looking for infection stones i n the kidney; avoid in pregnant women), renal USS 9 cystoscopy. Non-infective cystitis Symptoms of cystitis can also be caused by: - Pelvic radiotherapy (radiation cystitis \200\224bladder capacity is reduced and multiple ar eas of mucosal telangiectasia are seen cystoscopically). Drug-induced cystitis (e.g. cyclop hosphamide, ketamine). CHAPTER 6 Infections and in \202 ammatory conditions 184 Urinary tract infection: general treatment guidelines Antimicrobial drug therapy The aim is to eliminate bacterial growth from the urine. Empirical treat- ment involves the administr ation of antibiotics according to the clinical presentation and most likely causative organ ism before culture sensitivities are available (Table 6.4). Men are often affected by compl icated UTI and may require longer treatments as may patients with uncorrectable struc- tura l or functional abnormalities (e.g. indwelling catheters, neuropathic bladders). Bacterial resistance to drug therapy Organisms susceptible to concentrations of an antibiot ic in the urine (or serum) after the recommended clinical dosing are termed \200\230sensit ive \200\231 and those that do not respond are \200\230resistant \200\231. Bacterial resis tance may be intrinsic (e.g. Proteus is intrinsically resistant to nitrofurantoin) via sele c- tion of a resistant mutant during initial treatment or genetically transferred between b acteria by R plasmids. Antibiotic-resistant organisms that cause complicated UTI include Gr am-negative bacteria that produce AmpC enzymes or extended spectrum B-lactamases (ESBLs) (w hich are often multidrug resistant) and Gram-positive cocci such as methicillin-resistant S taphylococcus aureus (MRSA), methicillin-resistant coagulase-negative staphylococci (MRCoNS ), and vancomycin-resistant enterococci (VRE). To avoid increasing resistance, it is not ad visable to commence antibiot- ics without clinical evidence of a UTI (exceptions include as ymptomatic bacteriuria in pregnancy) and local microbiology guidelines should be followed. De \201 nitive treatment Once urine or blood culture results are available, antimicrobial therapy should be adjusted according to bacterial sensitivities. Underlying abnor- mality s hould be corrected if feasible (i.e. extraction of infected calculus; removal of catheter; nephrostomy drainage of an infected, obstructed kidney). Post-menopausal women may bene \201 t from topical estrogen treatment. General preventative advice Encourage a good \202 uid intake, cranberry juice, double voi ding, avoid constipation. In women \200\224voiding before and after intercourse; wiping per ineum from \200\230front to back \200\231 after voiding; avoid using bubble bath or washin g hair in the bath (as this affects the protective commensal organ- isms, the lactobacilli) . URINARY TRACT INFECTION: GENERAL TREATMENT GUIDELINES 185 Table 6.4 Recommendations for antimicrobial therapy1 Infection Bacteria Initial empirical drug Duration Nitrofurantoin E. coli, Klebsiella, Proteus, Staphylococci 55 \200\2237 days Acute, uncomplicated cystitis Alternatives: Trimethoprim 55 days Co-trimoxazole 33 days Fluoroquinolone (cipro \202 ox-acin) 33 days Acute, uncomplicated pyelonephritis E. coli, Proteus, Klebsiella, other Enterobacteriacae, Staphylococci Fluoroquinolone 7 \200\22310 days Cephalosporin Alternatives: Aminopenicillin with beta-lactamase inhibitor (BLI) (amoxicillin/clavulanic acid) Aminoglycoside (gentamicin) Complicated UTI E. coli, Enterococcus, Pseudomonas, Staphylococci Fluoroquinolone Continue for 3 \200\2235 days after control of infection/ elimination of underlying cause. Parenteral treatment is usually followed by oral antibiotics to complete course Aminopenicillin/BLI Cephalosporin Nosocomial* UTI Staphylococcus, Klebsiella, Proteus Carbapenem (meropenem) 9Aminoglycoside For Candida: Acute compli- cated pye- lonephritis Enterobacter, Pseudomonas, (Candida) \200\223Fluconazole \200\223Amphotericin B Nosocomial = hospital acquired. These are general recommendations only, adapted from EAU gu idelines, to \201 t with common UK antibi-otic use. You should be guided by your local mi crobiology department whose recommendations will be based on local and regional bacterial s ensitivities and resistance. 1 Grabe M, Bjerklund-Johansen TE, Botto H, et al. Guidelines on Urological Infections. Euro pean Association of Urology Guidelines 2011 edition. CHAPTER 6 Infections and in \202 ammatory conditions 186 Recurrent urinary tract infection Recurrent UTI is de \201 ned as >2 infections in 6 month s or 3 within 12 months. It may be due to re-infection (i.e. infection by different bac- te ria) or bacterial persistence (infection by the same organism originating from a focus with in the urinary tract). Bacterial persistence Bacterial persistence usually leads to frequent recurrence of infecti on (within days or weeks) and the infecting organism is usually the same organism as that c ausing the previous infection(s). There is often an under- lying functional or anatomical p roblem and infection will often not resolve until this has been corrected. Causes include k idney stones, the chroni- cally infected prostate (chronic bacterial prostatitis), bacteria within an obstructed or atrophic infected kidney, vesicovaginal or colovesical \201 stul a, and bacteria within a urethral diverticulum. Re-infection This usually occurs after a prolonged interval (months) from the previous infe ction and is often caused by a different organism than the previous infecting bacterium. Women: with re-infection, do not usually have an underlying functional or anatomical abnorm ality. Re-infections are associated with increased vaginal mucosal receptivity for uropatho gens and ascending colonization from fecal \202 ora. These women cannot be cured of their predisposition to recurrent UTIs, but they can be managed by a variety of techniques (see b p. 176). Men: with re-infection, may have underlying BOO (due to BPE or a ure- thral stri cture), which makes them more likely to develop a repeat infec- tion, but between infection s, their urine is sterile (i.e. they do not have bacterial persistence between symptomatic UTIs). A \202 exible cystoscopy, post-void bladder USS for residual urine volume and in s ome cases, uro- dynamics or urethrography may be helpful in establishing the potential caus es. Both men and women with bacterial persistence usually have an under- lying functional or an atomical abnormality and they can potentially be cured of their recurrent UTIs if this abno rmality can be identi \201 ed and corrected. Management of women with recurrent UTIs due to re-infection Imaging tests, including KUB X- ray and renal USS, and \202 exible cystoscopy, can be performed to check for potential so urces of bacterial persistence (i.e. to con \201 rm this is a \200\230simple \200\231 cas e of re-infection rather than one of bacterial persistence). In the absence of \201 nding an underlying functional or anatomic abnormality, these patients cannot be cured of their tendency to recurrent urinary infection, but they can be managed in several ways. RECURRENT URINARY TRACT INFECTION 187 Preventative and conservative management - - Maintain a high \202 uid intake. Avoidance of spermicides used with the diaphragm or on c ondoms. Spermicides containing nonoxynol-9 reduce vaginal colonization with lactobacilli an d may enhance E. coli adherence to urothelial cells. Recommend an alternative form of contr aception. Cranberry juice or tablets (contains proanthocyanidins which inhibit bacterial ad herence). Estrogen replacement. A lack of estrogen in post-menopausal women causes loss of vaginal lactobacilli and increased colonization by E. coli. Estrogen replacement (topical o r systemic) can result in recolonization of the vagina with lactobacilli and help eliminate colonization with bacterial uropathogens.1 Natural yogurt applied to the vulva and vagina can help restore normal \202 ora, thereby improving the natural resistance to recurrent i nfections. Alkalinization of the urine with potassium citrate or sodium bicarbonate can hel p alleviate symptoms of cystitis. Low-dose antibiotic prophylaxis Oral antimicrobial therapy with full-dose oral tetracycline s, ampicillin, sul- phonamides, amoxicillin, and cefalexin causes resistant strains in the fecal \202 ora and subsequent resistant UTIs. However, trimethoprim, nitrofuran- toin, an d low-dose cefalexin have minimal adverse effects on the fecal and vaginal \202 ora. - recurrences of UTI may be reduced up to Ef \201 cacy of prophylaxis: 90% when compared with placebo.2 Only small doses of antimicr obial agent are required, generally given at bedtime for 6 \200\22312 months. Symptomatic r e-infection during prophylactic therapy is managed with a full therapeutic dose with the sa me prophylactic antibiotic or another antibiotic. Prophylaxis can then be restarted. Sympto matic re-infection immediately after cessation of prophylactic therapy is managed by restar ting nightly prophylaxis. Trimethoprim: the gut is a reservoir for organisms that colonize the periurethral area, which may cause episodes of acute cystitis in young women. Trimethop rim eradicates Gram-negative aerobic \202 ora from the gut and vaginal \202 uid (i.e. i t eliminates the pathogens from the infective source). Trimethoprim is also concentrated in bactericidal concentrations in the urine following an oral dose. Adverse reactions: includ e gastro-intestinal (GI) disturbance, rash, purities, depression of haematopoiesis, allergi c reactions. Rare side effects: erythema multiforme, toxic epidermal necrolysis, photosensi tivity. Use with caution in renal impairment as it can increase creatinine by competitively inhibiting tubular secretion. Nitrofurantoin: upper intestinal tract and, therefore, has n o effect on gut \202 ora. It is present for brief periods at high concentrations in the u rine and leads to repeated elimination of bacteria from the urine. Nitrofurantoin prophylax is, therefore, does not lead to a change in vaginal or introital colonization with Enteroba cteria. The bacteria colonizing is completely absorbed and/or inactivated in the CHAPTER 6 Infections and in \202 ammatory conditions 188 the vagina remain susceptible to nitrofurantoin because of the lack of bacterial resistance in the fecal \202 ora. Adverse reactions: include GI upset, chronic pulmonary reactions (pulmonary \201 brosis), peripheral neuropathy, allergic reactions (angioedema, anaphylax is, urticaria, rash, and pruritus). Rare side effects: blood dyscrasias (agranulocytosis, t hrombocytopenia, aplastic anemia), liver damage. Risk of an adverse reaction increases with age (particularly >50y old). Cefalexin: because fecal resistance does not develop at this low dosage. Adverse reactions: GI upset, allergic reactions. Fluoroquinolones Enterobacteri a from fecal and vaginal \202 ora. The (longer term) use of cipro \202 oxacin is increas ingly discouraged, with some hospitals not allowing its routine use in an attempt to reduce the incidence of symptomatic Clostridium dif \201 cile. \200 Adverse reactions: tendon damage (including rupture) which may at 250mg or less nightly is an excellent prophylactic agent (e.g. cipro \202 oxacin): short courses eradicate occur within 48h of starting treatment. The risk of tendon rupture is increased by the conc omitant use of corticosteroids. Contraindicated: in patients with a history of tendon disorders related to quinolone use. D iscontinue quinolone immediately if tendonitis suspected (elderly patients are most prone t o tendonitis). Other adverse reactions: GI upset, Stevens \200\223Johnson syndrome, allergic reactions. Post-intercourse antibiotic prophylaxis Sexual intercourse has been established as an impor tant risk factor for acute cystitis in women and women using the diaphragm have a signi \201 - cantly greater risk of UTI those using other contraceptive methods.3 Post- intercour se therapy with antimicrobials, such as nitrofurantoin, cefalexin, or trimethoprim, taken a s a single dose effectively reduces the incidence of re-infection. Self-start therapy Women keep a home supply of an antibiotic (e.g. trimethoprim, nitro- fur antoin, or a \202 uoroquinolone) and start treatment when they develop symptoms suggestiv e of UTI. Management of men and women with recurrent UTIs due to bacterial persistence Investigation These are directed at identifying the potential causes of bacterial persist- ence outlined on b p. 186. - - KUB Renal hydronephrosis is present, but the ureter is not dilated, consider the possibilit y of a radio-opaque stone obstructing the pelviureteric junction (PUJ) or a PUJ obstruction (PUJO). Determination of X-ray to detect radio-opaque renal calculi. USS to detect hydronephrosis and renal calculi. If IVU- PVR volume by bladder USS. or CTU where a stone is suspected, but not identi \201 ed on plain X-ray or USS. RECURRENT URINARY TRACT INFECTION 189 Flexible cystoscopy to identify possible causes of recurrent as bladder stones, an underlyi ng bladder cancer (rare), urethral or bladder neck stricture, or \201 stula. UTIs such Treatment This depends on the functional or anatomical abnormality that is identi \201 ed as the cause of the bacterial persistence. If a stone is identi \201 ed, this should be re moved. If there is obstruction (e.g. BOO, PUJO, DSD in spinal injured patients), this shoul d be corrected. 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 urinar y tract infection. JAMA 254:240. CHAPTER 6 Infections and in \202 ammatory conditions 190 Upper urinary tract infection: acute pyelonephritis De \201 nition: pyelonephritis is an i n \202 ammation of the kidney and renal pelvis. Presentation Clinical diagnosis is based on the presence of fever, \202 ank pain, bacteri uria, pyuria, often with an elevated white cell count. Nausea and vomiting are common. It m ay affect one or both kidneys. There are usually accompany- ing symptoms suggestive of a lo wer UTI (frequency, urgency, suprapubic pain, urethral burning or pain on voiding) responsi ble for the subsequent ascending infection to the kidney. Differential diagnosis: includes cholecystitis, pancreatitis, diverticulitis, appendicitis. Risk factors: females > males, VUR, urinary tract obstruction, calculi, SCI (neuropathic bl adder), diabetes mellitus, congenital malformation, pregnancy, indwelling catheters, urinar y tract instrumentation. Pathogenesis and microbiology: initially, there is patchy in \201 ltration of neutrophils and bacteria in the parenchyma. Later changes include the formation of in \202 ammatory ba nds extending from the renal papilla to cortex and small cortical abscesses. Eighty percent of infections are secondary to E. coli (possessing P pili virulence factors). Other infect ing organisms: Enterococci (E. faecalis), Klebsiella, Proteus, Staphylococci, and Pseudomon as. Any process interfering with ureteric peristalsis (i.e. obstruction) may assist in retr ograde bacterial ascent from bladder to kidney. 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 antibi otic policy (which will be based on the likely infecting organisms and their likely antibio tic sensitivity). EAU guidelines1 give several suggestions, including \202 uoroquinolones (i.e. oral cipro \202 oxacin, 500 mg bd) for 7 \200\22310 days. Aminopenicillin with B-la ctamase inhibitor (i.e. co-amoxiclav) is an alternative. If the patient is systemically unw ell, resuscitate, culture urine and blood, start intravenous (IV) \202 uids and IV antibi otics, again selecting the antibiotic according to your local antibiotic policy. EAU guidel ine1 options include IV aminopenicillin with B-lactamase inhibitor 9 aminoglycoside (gentam icin) with monitoring of levels. Alternatives include cephalosporins (i.e. ceftazidime) and carbapenems (i.e. meropenem). Arrange a upper tract abnormality (such as a ureteric stone) , unexplained KUB X-ray and renal USS to see if there is an underlying UPPER URINARY TRACT INFECTION: ACUTE PYELONEPHRITIS 191 hydronephrosis, or (rarely) gas surrounding the kidney (suggesting emphysematous pyelonephr itis). If the patient does not respond within 3 days to a regimen of appropriate IV antibio tics (con \201 rmed on sensitivities), arrange a computed tomography urogram (CTU). Failur e of response to treatment suggests possible pyonephrosis (i.e. pus in the kidney which wil l only respond to drainage), a perinephric abscess (which again will only respond to draina ge), or emphysematous pyelonephritis. The CTU may demonstrate an obstructing ureteric calcu lus that may have been missed on the KUB X-ray and USS may show a perinephric abscess. A py onephrosis 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 resp onds to of appropriate sensitivity when they become apyrexial (3 \200\2235 days after contr ol of infection or after elimination of underlying problem) and continue this for approxima tely 10 \200\22314 days. IV antibiotics, change to an oral antibiotic 1 Grabe M, Bjerklund-Johansen TE, Botto H, et al. (2011) Guidelines on urological infection s. European Association of Urology Guidelines 2011 [online]. Available from: M http://www. uroweb.org/gls/pdf/15_Urological_Infections.pdf. CHAPTER 6 Infections and in \202 ammatory conditions 192 Pyonephrosis and perinephric abscess Pyonephrosis An infected hydronephrosis where pus accu mulates within the renal pelvis and calyces. It is associated with damage to the parenchyma , resulting in loss of renal function. The causes are essentially those of hydronephrosis w here infection has supervened (e.g. ureteric obstruction by stone, PUJ obstruction). Presentation Patients with pyonephrosis are usually very unwell with a high fever, \202 a nk pain, and tenderness. Risk factors Stone disease, previous UTI, or surgery. Investigation - KUB infecting pathogens). USS collecting system, \202 uid \200\223debris levels or air in the collecting system. X-ray: may show an air urogram (secondary to gas produced by : shows evidence of obstruction (hydronephrosis) with a dilated CT- : shows hydronephrosis, stranding of perinephric fat, and thickening of renal pelvis. Treatment IV \202 uids and antibiotics (as for pyelonephritis) with urgent percutaneous d rainage (nephrostomy) or ureteric drainage (via ureteric catheter under endoscopic and X-ra y guidance). Perinephric abscess Perinephric abscess develops as a consequence of extension of infec- ti on outside the parenchyma of the kidney in acute pyelonephritis, from rupture of a cortical abscess, or if obstruction in an infected kidney (i.e. pyonephrosis) is not drained quickl y enough. More rarely, it is due to haematogenous spread of infection from a distant site o r infection from adjacent organs (i.e. bowel). The abscess develops within Gerota \200\231s fascia. Risk factors Diabetes mellitus; immunocompromise; obstructing ureteric calculus may precipi tate the development of a perinephric abscess. Causes Perinephric abscesses are caused by S. aureus (Gram-positive), E. coli, and Proteus (Gram-negative organisms). Presentation Patients present with fever, unilateral \202 ank tenderness, and \211 5 day history of milder symptoms. Failure of a seemingly straightforward case of acute pyeloneph ritis to respond to IV antibiotics within a few days also arouses suspicion that there is a n accumulation of pus in or around the kidney or obstruction with infection. PYONEPHROSIS AND PERINEPHRIC ABSCESS 193 A \202 ank mass with overlying skin erythema and oedema may be observed. Extension of the thigh (stretching the psoas) may trigger pain and psoas spasm may cause a reactive scolios is. Investigation - - - FBC Urine analysis and cultures . Blood cultures: haematogenous spread of infection (i.e. S . aureus). USS or CTU: can identify size, site, and extension of retroperitoneal abscesses and allow radiographically controlled percutaneous drainage of the abscess. : shows raised white cell count and CRP. are required to identify organisms responsible for the Treatment Commence broad-spectrum IV antibiotics (i.e. aminoglycoside and ami- nopenicillin with B-lactamase inhibitor) until culture sensitivities are available. Drainage of the col lection should be performed, either radio- graphically or by formal open incision and drain age if the pus collection is large. IV antibiotics should be used initially and followed by a course of oral antimicrobials until clinical review and re-imaging con \201 rms resolut ion of infection. Nephrectomy may be required for extensive renal involve- ment or a non-fu nctioning infected kidney. Acute pyelonephritis, pyonephrosis, perinephric abscess, and emphysematous pyelonephritis \200\224making the diagnosis Maintaining a degree of suspicion in all cases of presumed acu te pyelone- phritis is the single most important thing in allowing an early diagnosis of co mplicated renal infection such as a pyonephrosis, perinephric abscess, or emphysematous pye lonephritis to be made. If the patient is very unwell, is diabetic, or has a history sugges tive of stones, they may have something more than just a simple acute pyelonephritis. Speci \201 cally ask about a his- tory of sudden onset of severe \202 ank pain a few days ear lier, suggesting the possibility that a stone passed into the ureter, with later infection supervening. Arranging a KUB X-ray and renal USS in all patients with sus- pected renal inf ection will demonstrate the presence of hydronephrosis, pus, or stones. Clinical indicators suggesting a more complex form of renal infection are length of symptom s prior to treatment and time taken to respond to treatment. Most patients with uncomplicat ed acute pyelonephritis have been symptomatic for <5 days. Most with, for example, a perine - phric abscess have been symptomatic for >5 days prior to hospitaliza- tion. Patients with acute pyelonephritis became afebrile within 4 \200\2235 days of treatment with an appropri ate antibiotic whereas those with perinephric abscesses remained pyrexial.1 1 Thorley JD, Jones SR, Sanford JP (1974) Perinephric abscess. Medicine 53:441. CHAPTER 6 Infections and in \202 ammatory conditions 194 Other forms of pyelonephritis Emphysematous pyelonephritis (EPN) A rare severe form of acut e necrotizing 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 pla in radi- ography or CT) (Fig. 6.1). It usually occurs in diabetics (93% in a contem- porary series)1 and, in many cases, is precipitated by urinary obstruction by, for example, urete ric stones. The high glucose levels associated with poorly controlled diabetes provides an ideal environment for fermenta- tion by Enterobacteria, carbon dioxide being produced durin g this proc- ess. EPN is commonly caused by E. coli, less frequently by Klebsiella and Prot eus. Presentation Severe acute pyelonephritis (high fever and systemic upset) that fails to resp ond to IV antibiotics within 2 \200\2233 days. Investigation KUB X-ray may show a crescent or kidney-shaped distribution of gas around the kidney. Renal USS often demonstrates strong focal echoes, indicating gas within the kidney . CT can help classify the disease. Type I shows parenchymal destruction, an absence of \202 uid collection, or streaky gas from the medulla to cortex \200\224this has a poorer pr ognosis. Type II shows intrarenal gas and renal or perirenal \202 uid, or collecting syst em gas \200\224this has a better prognosis. Management Patients with EPN are usually very u nwell (to the extent that many are not \201 t enough for emergency nephrectomy) and morta lity is high. Resuscitate and transfer to ITU/HDU. In recent years, management has moved aw ay from emergency nephrectomy to an approach with IV antibiotics, IV \202 uids, percutane ous drainage, and careful control of diabetes.1 Where there is no symptomatic improvement, have a low threshold for rescanning (CT) and consider additional percutaneous drainage for \200\230pockets \200\231 of infection that have not been adequately drained.1 In those whe re sepsis is poorly controlled, emergency nephrectomy may be required. 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.