Authors: Andrew Parfitt / Editor: John P Sloan / Reviewer: Suzy Connor, Pragya Mallick / Codes: SLO1, SLO2, UC6, UC7, UP5 / Published: 25/05/2021

 

Context

Urinary tract infections (UTIs) are among the most common infectious conditions seen in the emergency department (ED) [1]. A half of all females will have experienced a UTI during their lifetime, with one third having done so by the age of 24. The changing pattern of antibiotic resistance requires regular review of their assessment and management.

UTIs in males suggest obstructive pathology such as benign prostate enlargement or urethral stricture.

Definition

The term UTI encompasses a number of clinical conditions that result from the presence of microbial pathogens in the urinary tract. This may involve the upper tract (kidneys and ureters), lower tract (bladder, prostate in men), or both. More commonly, the terms pyelonephritis, cystitis and prostatitis are used.

Pyelonephritis

Pyelonephritis refers to infection specifically in the renal pelvis, parenchyma and upper ureters.

Cystitis

Cystitis refers to the inflammatory response of the bladder to infection.

Acute prostatitis

Acute prostatitis may occur as a distinct condition, but is often associated with infection in other parts of the urinary tract.

UTIs that occur in otherwise healthy, young, non-pregnant women with no genitourinary abnormalities are ‘uncomplicated’. ‘Complicated’ UTIs occur in certain patient populations. These include UTIs in the elderly (>65), men, in the presence of structural or functional abnormality such as obstruction and neurogenic bladder. They also include the presence of renal stones or foreign body (catheter), pregnancy, recent instrumentation or presence of comorbidity (diabetes, malignant disease). ED physicians must be aware of the increased morbidity and mortality of the complicated group.

The vast majority of UTIs arise from bacteria ascending the urinary tract. Women, because of the shorter distance from the urethra to bladder, proximity of the vagina and rectal area, are more prone to them. Men tend to develop UTIs in conjunction with prostatic hypertrophy (majority), renal stones, catheterisation, recent cystoscopy and anal intercourse.

In the majority of patients (between 75-95%) with uncomplicated cystitis and pyelonephritis, the infection is monobacterial with Escherichia coli [2]. Staphylococcus saprophyticus is isolated in 5-15%, enterococci, klebsiella and proteus account for the remaining 5-10%. It is important to note that the virulence of the infecting organism is less important than host factors in complicated infections [3].

E.coli remains the dominant pathogen in complicated UTIs. However, patients at risk from complicated UTIs are more likely to culture less common antibiotic resistant organisms. The choice of empiric antibiotic employed in these patients must take this into account.

UTIs present with variable symptoms related not only to the site of infection but also to patient factors.

Cystitis

Cystitis commonly presents with one or more of dysuria, urinary frequency, haematuria, urgency and suprapubic discomfort, especially in the young adult woman.

Pyelonephritis

Pyelonephritis is characterised by fever, flank pain or tenderness with or without the symptoms of lower urinary tract infection. Studies reveal younger patients lacking a fever (defined as less than 37.8°C) to often have an alternative diagnosis such as PID, cholecystitis or renal colic [4]. Unusual presentations of pyelonephritis are often seen with pain in the epigastric area or either hypochondrium. The vast majority of patients with uncomplicated UTI will be systemically well.

The elderly merit special mention. They often have complicated UTIs and the symptoms and signs are often less well localised. They may be afebrile or have only a low grade fever. Verbalisation of their symptoms may be difficult because of acute confusion, as well as from existing medical conditions. The diagnosis should be considered in the elderly presenting with reduced level of consciousness, lethargy and generalised weakness [4].

The differentiation between cystitis and pyelonephritis is important in terms of resulting morbidity, choice of antibiotic and length of treatment. Pyelonephritis will most often require a 7-10 day course of antibiotics. It also always requires a renal ultrasound to be performed. This may be done acutely on admission or as part of follow-up after discharge.

It is difficult to be dogmatic regarding admission criteria. In a select group of immunocompetent patients who respond to initial treatment and can easily return to hospital, the outpatient management of pyelonephritis appears safe and cost effective [5]. The most common indications for admission are nausea and vomiting, comorbidity (especially pregnancy) and obviously severe sepsis or shock.

Introduction

The bedside and laboratory investigations performed for suspected UTIs are urine dipstick, urine microscopy and culture. Imaging including US and CT are indicated in certain complicated cases of UTI.

However, before considering these investigations, it is worth considering evidence for patients treated on history alone.

One study assessed the likelihood of UTI on the basis of signs and symptoms alone [6]. The combination of dysuria and frequency in the absence of vaginal discharge and irritation had a likelihood ratio for UTI of 24.6. This supported the authors’ premise that female patients with uncomplicated cystitis could be treated on history alone.

However, many of these patients still have urine analysis. The consensus on patients with pyelonephritis and any complicated UTI is that investigation is essential.

Urine Analysis

Urine analysis involves the following:

Urine dipstick

Urine dipstick accuracy in predicting UTI has been widely reported [7]. Nitrite sensitivity alone is 81%, that of leucocytes (leucocyte esterase) alone is 77%. If both are present, sensitivity is 94%. Nitrites are only converted from nitrates in the presence of certain bacteria including E.coli.

Other common pathogens including staphylococcus saprophyticus are not nitrite producing. Nitrites are more specific for the diagnosis of UTI. For example, interstitial nephritis can cause pyuria. However, if the diagnosis of UTI is made purely on the dipstick result of positive nitrites and leucocytes (with positive culture taken as gold standard), the overtreatment rate has been estimated as 47% and the undertreatment rate has been estimated as 13%, illustrating its inability to predict UTI accurately [7].

Urine microscopy

Urine microscopy is also available to the ED physician. Classically, the presence of more than 10 WBCs per mm2 is consistent with a diagnosis of UTI. Most labs now use automated assays of cell counts. When compared to dipstick, the earlier reported over and undertreatment rates were similar and because of the time-consuming nature of microscopy, dipstick remains the screening test of choice in most cases [7].

Learning bite

It is important to understand that a negative urinanalysis does not exclude a UTI. This is especially the case if the pretest probability is high, for example, if there is a history of one or more symptoms or previous UTI.

Urine culture

Urine culture remains the gold standard for detection of UTI, but as discussed earlier, it is not required in all patients. However, the consensus remains that all patients with suspected pyelonephritis, and all complicated UTIs should have their urine sent for culture before initiating antibiotics. The presence of >105 per ml confirms significant bacteriuria.

Imaging

Renal ultrasound is another tool increasingly used in the ED. It is a valuable diagnostic tool in assessing loin pain. It may reveal complications of urinary tract infection such as hydronephrosis and renal abscess. It is useful in many clinical situations including renal calculi complicated by infection, patients with UTI associated with severe sepsis and where surgical intervention may be required for a complication of UTI, for example, obstruction and abscess.

Routine imaging is not required in most young women with uncomplicated infections and has an extremely low yield for detecting abnormalities. In the past, recommendations have been made to ultrasound all cases of pyelonephritis, but are probably best reserved where there is clinical suspicion of complications. Severely unwell patients, those who fail to resolve and those in whom diagnostic uncertainty exists, require urgent imaging.

CT will detect any renal calculi, hydronephrosis and abscess, yet is most usually saved for renal colic or diagnostic uncertainty.

Learning bite

Uncomplicated pyelonephritis in a well patient can usually be managed as an out-patient initially.

Introduction

Antibiotic choice is increasingly important in view of the increasing antibiotic resistance among typical UTI organisms. The choice also depends on patient characteristics (age, pregnancy status, prior history of UTI), complicated versus uncomplicated UTI, knowledge of the most likely pathogen (including local susceptibility patterns), severity of the condition and the hospital formulary.

Historically, Trimethoprim-sulfamethoxazole (TMP-SMX) was the first choice antimicrobial. However, due to adverse effects of the sulfamethoxazole, Trimethoprim is now used alone. E Coli resistance is increasing to all antibiotics, and Trimethoprim is no exception. Figures in some areas report an increase in E.coli resistance to Trimethoprim from between 0-5% pre-1990, to around 30% now [8]. Risk factors for Trimethoprim resistance include diabetes, recent hospitalisation, and current use of any antibiotic. E.coli resistance to quinolones is also increasing in the UK from 0.8% in 1990 to 3.7% in 1999 [9].

Different patients also have varying susceptibilities reflecting the need to take into account individual risk factors when choosing empiric treatment. Women older than 50 have been found to have increased rates of infection resistant to quinolones [10].

Acute Cystitis

Management of acute cystitis involves the following:

Acute uncomplicated cystitis

In young female non-pregnant patients in areas with low E.coli resistance, trimethoprim is still a reliable empiric treatment. Nitrofurantoin must not be used if pyelonephritis is suspected, as it has poor efficacy in the upper urinary tract. Cephalexin is also an option. Some clinicians discourage the use of ciprofloxacin for uncomplicated cystitis in an attempt to reduce further resistance and have implicated it in the development of C.difficile [3].

Acute complicated cystitis

In cases of acute complicated cystitis, avoid trimethoprim. Instead, ciprofloxacin or cephalexin may be used. Take account of local antimicrobial resistance data and follow NICE guidance and/or local guidance when prescribing antibiotics. [11,12]

Acute Pyelonephritis

Management of acute pyelonephritis involves the following:

Acute uncomplicated pyelonephritis

Ciprofloxacin is the initial treatment of choice for uncomplicated pyelonephritis. Many UK hospitals advocate Trimethoprim as the first choice (taking into account the associated risk of Clostridium difficile from Ciprofloxacin).

If intravenous treatment is required, a single dose of gentamicin followed by Ciprofloxacin is a reasonable approach. The intravenous dose can be given in the ED allowing the patient to be discharged on oral antibiotics.

Learning bite

Uncomplicated pyelonephritis in a well patient can usually be managed as an out-patient initially.

Acute complicated pyelonephritis

Patients with acute complicated pyelonephritis usually require admission and intravenous Ciprofloxacin, Piperacillin-tazobactam or Co-amoxiclav. Gentamycin may also be used. It is always worth checking with your local guidelines before prescribing. Intravenous therapy may be required initially if patients are vomiting or unable to take oral antibiotics. A 2 week course of antibiotics is usually advocated in cases of pyelonephritis.[13]

UTI in Pregnancy

Asymptomatic bacteriuria is treated with antibiotics in pregnancy. UTIs in pregnancy are complicated. Cystitis may be treated with nitrofurantoin, cephalexin or amoxicillin. In pyelonephritis, Cephalexin is first choice of oral antibiotic and Cefuroxime is an intra venous option [13].

Hospital formularies tend to overestimate the occurrence of antibiotic resistance in a community, as uncomplicated UTIs are often not cultured and complicated UTIs are more likely to be infected with resistant organisms [8]. This inherent selection bias often leads to clinicians avoiding standard antibiotics for uncomplicated UTIs.

‘Subclinical’ pyelonephritis has been described in patients who present with predominantly cystitis symptoms without characteristic pyelonephritis symptoms. It is often a diagnosis made in retrospect after a failure of initial cystitis treatment. Patients at higher risk of subclinical pyelonephritis include those with symptoms greater than 1 week, males, diabetic patients, pregnancy and if immunosuppression is present.

Although bacterial counts of >105 are indicative of significant bacteriuria in uncomplicated pyelonephritis (80-95%), a significant proportion of patients may present with counts as low as 102 bacteria per ml in the setting of fever, loin pain and pyuria in catheterised patients.

Bacterial counts of >105 are occasionally seen in asymptomatic patients, especially young women. Asymptomatic bacteriuria does not require treatment except in pregnant women.

Learning bite

Hospital formulary for antibiotic choice for UTI may have inherent selection bias.

  1. Foxman B. The epidemiology of urinary tract infection. Nat Rev Urol. 2010;7:653–60.
  2. Shallcross, L.J. Diagnostic uncertainty and urinary tract infection in the emergency department: a cohort study from a UK hospital. BMC Emerg Med 20, 40 (2020).
  3. Norris DL 2nd, Young JD. Urinary tract infections: diagnosis and management in the emergency department. Emerg Med Clin North Am. 2008; 26(2): 413-30.
  4. Johnson JR. Acute Pyelonephritis in Adults. N Engl J Med 2018; 378:48-59.
  5. Safrin S, Siegel D, Black D. Pyelonephritis in adult women inpatient versus outpatient treatment. Am J Med 1988; 85(6): 793-798.
  6. Bent S, Nallamothu BK, Simel DL, Fihn SD, Saint S. Does this woman have an acute uncomplicated urinary tract infection? JAMA. 2002; 287(20): 2701-10.
  7. Lammers RL, Gibson S, Kovacs D, Sears W, Strachan G. Comparison of test characteristics of urine dipstick and urinalysis at various test cutoff points. Ann Emerg Med. 2001; 38(5): 505-12.
  8. Gian Carlo S. The ARESC study: an international survey on the antimicrobial resistance of pathogens involved in uncomplicated urinary tract infections, International Journal of Antimicrobial Agents, Volume 34, Issue 5, 2009, 407-413.
  9. Livermore DM, James D, Reacher M et al. Trends in fluoroquinolone (ciprofloxacin) resistance in enterobacteriaceae from bacteremias, England and Wales, 1990-1999. Emerg Infect Dis. 2002; 8(5): 473-8.
  10. Gupta K, Sahm DF, Mayfield D et al. Antimicrobial resistance among uropathogens that cause community-acquired urinary tract infections in women: a nationwide analysis. Clin Infect Dis. 2001; 33(1): 89-94. Epub 2001 Jun 5.
  11. NICE, Urinary tract infections overview. NICE Pathway.
  12. NICE, Lower urinary tract infection visual summary. [NG 109].
  13. NICE, Pyelonephritis (acute): antimicrobial prescribing. NICE Visual summary.