URINARY SEPTICAEMIA: TREATMENT

Sepsis as a result of a urinary tract infection is a serious condition that can lead to septic shock and death. Septicaemia or sepsis is the clinical syndrome caused by bacterial infection of the blood, confirmed by positive blood cultures for a speci.c organism. There should be a documented source of infection with a systemic response to the infection. The systemic response is known as the systemic inflammatory response syndrome (SIRS) and is de.ned by as at least two of the following:

- Fever (>38°C) or hypothermia (<36°C)
- Tachycardia (>90 beats/min in patients not on beta-blockers)
- Tachypnoea (respiratory rate >20/min or PaCO2 < 4.3 kPa or a requirement for mechanical ventilation)
- White cell count >12,000 cells/mm3, <4000 cells/mm3, or 10% immature (band) forms

Severe sepsis or sepsis syndrome is a state of altered organ perfusion or evidence of dysfunction of one or more organs, with at least one of the following: hypoxaemia, lactic acidosis, oliguria, or altered mental status. Septic shock is severe sepsis with refractory hypotension, hypoperfusion, and organ dysfunction. This is a life-threatening condition.

There are many causes of urinary sepsis, but in the hospital setting the commonest causes from a urological perspective are the presence of or manipulation of indwelling urinary catheters, urinary tract surgery, particularly endoscopic [transurethral resection of the prostate (TURP), transurethral resection of bladder tumor (TURBT), ureteroscopy, percutaneous nephrolithotomy (PCNL)] and urinary tract obstruction, particularly that due to stones obstructing the ureter. In the National Prostatectomy Audit and the European Collaborative Study of Antibiotic Prophylaxis for TURP, septicaemia occurred in approximately 1.5% of men undergoing TURP. Diabetic patients, patients in the intensive care units (ICU), and patients on chemotherapy and steroids are more prone to urosepsis. The commonest causative organisms of urinary sepsis are Escherichia coli, enterococci (Streptococcus faecalis), staphylococci, Pseudomonas aeruginosa, Klebsiella, and Proteus mirabilis.

The principles of management include early recognition, resuscitation, localisation of the source of sepsis, early and appropriate antibiotic administration, and removal of the primary source of sepsis. The clinical scenario is usually a postoperative patient who has undergone TURP or surgery for stone. Having returned to the ward, the patient becomes pyrexial, starts to shiver and shake, is tachycardic, and may be confused. On inspection the patient may initially show signs of peripheral vasodilatation (may appear flushed and warm to the touch). Look for symptoms and signs of a non-urological 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 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 disseminated intravascular coagulopathy (DIC). - Coagulation screen. This is important if surgical or radiological drainage of the source of infection is necessary. - Urea and electrolytes as a baseline determination of renal function. - Arterial blood gases to identify hypoxia and the presence of metabolic acidosis. - Blood cultures. - Chest x-ray (CXR), looking for pneumonia, atelectasis, and effusions. Depending on the clinical situation, a renal ultrasound may be helpful to demonstrate hydronephrosis or pyonephrosis and CT urography (CTU) may be used to establish the presence or absence of a ureteric stone.

Treatment - Remember A (airway), B (breathing), C (circulation). - Administer 100% oxygen via a face mask. - Establish intravenous access with a wide-bore intravenous cannula, e.g., 16 or 18 gauge. - Start an intravenous infusion of crystalloid e.g., normal saline or colloid e.g., Gelofusin. - Catheterise the patient to monitor urine output. - Start empirical antibiotic therapy (see below). This should be adjusted later when cultures are available. - If there is septic shock, the patient needs to be transferred to the ICU. Inotropic support may be needed. Steroids may be used as adjunctive therapy in gram-negative infections. Naloxone may help revert endotoxic shock. This should all be done under the supervision of an intensivist. - Treat the underlying cause. Drain any obstruction and remove any foreign body. If there is a stone obstructing the ureter, then either ask the radiologist to insert a nephrostomy tube to relieve the obstruction or take the patient to the operating room and insert a JJ stent. Send any urine specimens obtained for microscopy and culture.

Empirical Treatment

Empirical antibiotic treatment is the ‘blind’ use of antibiotics based on an educated guess of the most likely pathogen that has caused the sepsis. In urinary sepsis, the cause is often a gramnegative rod. Gram-negative aerobic rods include the enterobacteria, e.g., E. coli, Klebsiella, Citrobacter, Proteus, and Serratia. The enterococci (gram-positive aerobic nonhaemolytic streptococci) may sometimes cause urosepsis. In urinary tract operations involving bowel, anaerobic bacteria may be the cause of urospesis and in wound infections staphylococci, e.g., staphylococcus aureus and staphylococcus epidermidis are the usual cause. The recommendations for treatment of urosepsis include (Naber 2001):

- A third-generation cephalosporin, e.g., cefotaxime IV, ceftriaxone IV. These are active against gram-negative bacteria, but less active against staphylococci and gram-positive bacteria. Ceftazidime also has activity against Pseudomonas aeruginosa. It is therefore important to get an urgent gram stain on any .uid sample sent to the laboratory. About 5% of patients who are allergic to penicillin are also allergic to cephalosporins, so enquire about penicillinallergy and consider alternative antibiotics.

- Fluoroquinolones, e.g., cipro.oxacin, can be used instead of cephalosporins. They exhibit good activity against enterobactaria and P. aeruginosa, but less activity against staphylococci and enterococci. Cipro.oxacin can be given both orally and intravenously. It is well absorbed from the gastrointestinal tract.

- Metronidazole is used if there is suspicion of an anaerobic source of sepsis. - Other drugs that can be used if there is no clinical response to the above include a combination of piperacillin and tazobactam. This combination is active against enterobacteria, enterococci, and Pseudomonas. - Gentamicin is used in conjunction with other antibiotics because it 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 b-lactam antibiotics, e.g., cotrimoxazole but can be combined with ciprofloxacin instead.

If there is clinical improvement, intravenous treatment should continue for at least 48 hours with oral medication thereafter. Make appropriate adjustments when the sensitivity results are available from the urine cultures that were sent. It may take about 48 hours for sensitivity results to become available.