154 CHAPTER 5 Infections and inflammatory conditions
Chronic pyelonephritis
Chronic pyelonephritis is a confusing term. It can be a radiological or pathological diagnosis or a description. It is not a specifically clinically based diagnosis. The appearance, either pathologically or radiologically, is one of renal scarring. The scarring can be due to previous infection or it can occur from the long-term effects of reflux (with or without superimposed infection).
A child with reflux, particularly where there is reflux of infected urine, will develop reflux nephropathy (if bilateral, it may cause renal impairment or renal failure). If the child’s kidneys are examined radiologically (or pathologically if they are removed by nephrectomy), the radiologist or pathologist will describe the appearances as those of “chronic pyelonephritis.”
An adult may also develop radiological and pathological features of chronic pyelonephritis, due to the presence of reflux, or bladder outlet obstruction combined with high bladder pressures, again particularly when the urine is infected. This was a common occurrence in male patients with spinal cord injuries and detrusor-sphincter dyssynergia before the advent of effective treatments for this condition.
Essentially, chronic pyelonephritis is the end result of longstanding reflux (nonobstructive chronic pyelonephritis) or of obstruction (obstructive chronic pyelonephritis). These processes damage the kidneys, leading to scarring. The degree of damage and subsequent scarring is more marked if infection has supervened.
The scars are closely related to a deformed renal calyx. Distortion and dilatation of the calyces are due to scarring of the renal pyramids. These scars typically affect the upper and lower poles of the kidneys, because these sites are more prone to intrarenal reflux. The cortex and medulla in the region of a scar are thin. The kidney may be so scarred that it becomes small and atrophic. Scars can be seen radiologically on a renal ultrasound, an IVP, renal isotope scan, or a CT.
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156 CHAPTER 5 Infections and inflammatory conditions
Septicemia and urosepsis
Urosepsis is a form of sepsis that results from bacterial, fungal, or other infections originating from the genitourinary system Urosepsis accounts for approximately 25% of all sepsis cases and may develop from a community or nosocomial acquired urinary tract infection.
Bacteremia is the presence of pathogenic organisms in the blood stream. True rigors with fever and chills almost always indicate bacteremia and can lead to sepsis.
Septicemia or sepsis, the clinical syndrome caused by bacterial infection of the blood, is confirmed by positive blood cultures for a specific organism and accompanied by a systemic response to the infection known as the systemic inflammatory response syndrome (SIRS)1
SIRS is defined by at least two of the following:
•Fever (>38°C) or hypothermia (<36°C)
•Tachycardia (>90 beats/min in patients not on B-blockers)
•Tachypnea (respiratory >20/min or PaCO2 <4.3 kPa or a requirement for mechanical ventilation)
•White cell count >12,000cells/mm3, <4000cells/mm3 or 10% immature (band) forms
Severe sepsis is sepsis associated with organ dysfunction.
Septic shock is sepsis, plus hypotension despite adequate fluid resuscitation, plus hypoperfusion changes, such as lactic acidosis, oliguria, or alteration in mental status.
Septicemia is often accompanied by endotoxemia, the presence of circulating bacterial endotoxins. Hypotension in septic shock is defined as a sustained systolic BP <90 mmHg, or a drop in systolic pressure of >40 mmHg for >1 hour, when the patient is normovolemic and other causes have been excluded or treated.
It results from gram-positive bacterial toxins or gram-negative endotoxins that trigger release of cytokines (TNF, IL-1), vascular mediators, and platelets, resulting in vasodilatation (manifest as hypotension) and disseminated intravascular coagulation (DIC).
Causes of urosepsis
In the hospital setting, the most common causes are the presence or manipulation of indwelling urinary catheters, urinary tract surgery (particularly endoscopic procedures such as TURP, TURBT, ureteroscopy, PCNL), and urinary tract obstruction (particularly that due to stones obstructing the ureter).
Septicemia has been reported to occur in up to 1.5% of men undergoing TURP. Diabetic patients, patients in ICUs, and patients on chemotherapy and steroids are more prone to urosepsis.
Common causative organisms in urosepsis
•E. coli, enterococci (Streptococcus faecalis), staphylococci, Pseudomonas aeruginosa, Klebsiella, and Proteus mirabilis.
1 Bone R, Back RA, Cerra FB, et al. (1992). Definition for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest 101(6):1644–1655.
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Management
The principles of management include early recognition, resuscitation, localization of the source of sepsis, early and appropriate antibiotic administration, and removal of the primary source of sepsis. From a urological perspective, the clinical scenario is a de novo presentation of patient with a clinical picture of sepsis or, as is sometimes seen, a postoperative patient who has undergone TURP or surgery for stones.
On return to the floor bed, they become febrile, develop rigors, and are tachycardic and tachypnea, resulting in initial respiratory alkalosis. They may be confused and oliguric and initially be peripherally vasodilatated (flushed appearance with warm peripheries).
It is also important to consider the possibility of a nonurological source of sepsis (such as pneumonia). If there are no indications of infection elsewhere, assume the urinary tract is the source of sepsis.
Investigations
•Urine culture. An immediate gram-stain of an unspun urine may aid in deciding which antibiotic to use.
•Full blood count. The white blood count is usually elevated. The platelet count may be low—a possible indication of impending DIC.
•Coagulation screen. This is important if surgical or radiological drainage of the source of infection is necessary.
•Creatine, blood urea nitrogen (BUN), and electrolytes as a baseline determination of renal function
•Arterial blood gases to identify hypoxia and the presence of metabolic acidosis, although respiratory alkalosis may be present initially due to tachypnea.
•Blood cultures
•Chest X-ray (CXR) to evaluate for pneumonia, atelectasis, and effusions
•Depending on the clinical situation, a renal ultrasound may be helpful to demonstrate hydronephrosis or pyonephrosis, and CT urography may be used to establish the presence or absence of other urological pathology.
Treatment
Immediate support care is necessary with attention to the basic A (Airway), B (Breathing), and C (Circulation) and to prevent cardiovascular collapse through coordinated-goal directed therapy.
•Give 100% oxygen via a facemask and monitor with use of oximetry.
•Establish IV access with a wide-bore intravenous cannula.
•Intravenous crystalloid (e.g., normal saline). Maintain adequate hemoglobin levels and transfuse if needed (>10 g/dL) to normalize blood pressure.
•Catheterize to monitor urine output.
•Obtain cultures before administering antibiotic therapy. Give empiric antibiotic therapy (see below) and adjust when cultures are available.
158 CHAPTER 5 Infections and inflammatory conditions
If there is septic shock, then the patient needs to be transferred to the intensive care unit (ICU), as ionotropic support may be needed. Steroids may have an adjunctive role in gram-negative infections and refractory septic shock. All of these steps should be coordinated with an intensivist.
Treat the underlying cause. Drain any urinary obstruction and remove any foreign body if possible. If there is a stone obstructing the ureter, insert a nephrostomy tube to relieve the obstruction or take the patient to the operating room and insert a double J-stent.
Send any urine specimens obtained for microscopy and culture.
Empirical antibiotic recommendations for treatment of urosepsis
This use of antibiotics is based on an educated guess of the most likely pathogen that has caused the urosepsis. Gram-negative aerobic rods are common causes of urosepsis (e.g., E. coli, Klebsiella, Citrobacter, Proteus, and Serratia). The enterococci (gram-positive aerobic nonhemolytic streptococci) may sometimes cause urosepsis.
In urinary tract operations involving the bowel, anaerobic bacteria may be the cause of urosepsis, and in wound infections, staphylococci (e.g.,
Staph. aureus and Staph. epidermidis) are the usual cause.2
There are no uniform published guidelines to the initial and empiric treatment of urosepsis. The following are some recommendations:
•Gentamicin is used in conjunction with other antibiotics such as ampicillin. Gentamicin has a relatively narrow therapeutic spectrum against gram-negative organisms. Close monitoring of therapeutic levels and renal function is important. It has good activity against enterobacteria and Pseudomonas, with poor activity against streptococci and anaerobes and, therefore, should ideally be combined with beta-lactam antibiotics (ampicillin) or ciprofloxacin.
•A third-generation cephalosporin (e.g., IV cefotaxime or ceftriaxone). These are active against gram-negative bacteria but have less activity against staphylococci and gram-positive bacteria. Ceftazidime also has activity against Pseudomonas aeruginosa.
•Fluoroquinolones (e.g., ciprofloxacin) are an alternative to cephalosporins. They exhibit good activity against Enterobacteriaceae and P. aeruginosa but less activity against staphylococci and enterococci.
•Monotherapy with suspected enterococci (E. faecalis) is with ampicillin 2 g IV q4h or vancomycin (if penicillin-allergic).
•Add metronidazole if there is a potential anaerobic source of sepsis.
•If Candida sepsis suspected, fluconazole 6 mg/kg/d or 400 mg IV q24h should be initiated.
If there is no clinical response to the above antibiotics, consider a combination of piperacillin and tazobactam. This combination is active against enterobacteria, enterococci, and Pseudomonas.
2 Wagenlehner FM, Weidner W, Naber KG (2007). Optimal management of urosepsis from the urological perspective. Int J Antimicrob Agents 30(5):390–397.
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If there is clinical improvement, IV treatment should continue for at least 48 hours and then be changed to oral medication. Make appropriate adjustments when sensitivity results are available from urine cultures (which may take about 48 hours).
Further reading
Bugano DD, Camargo LF, Bastos JF, Silva E (2008). Antibiotic management of sepsis: current concepts. Expert Opin Pharmacother 9(16):2817–2828.
Mackenzie I, Lever A (2007). Management of sepsis. BMJ 335(7626):929–932.
Naber KG, Bergman B, Bishop MC, et al. (2001). Guidelines on urinary and male genital tract infections. European Association of Urology, Eur Urol 40:576–588.