Article of the Week: NICE Guidance ‐ Complicated UTIs: ceftolozane/tazobactam

Every Week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

If you only have time to read one article this week, it should be this one.

NICE Guidance ‐ Complicated urinary tract infections: ceftolozane/tazobactam

Introduction and Current Guidance

Urinary tract infection is a non‐specific term that refers to infection anywhere in the urinary tract, from the urethra to the bladder and the ureters to the kidneys. According to the European Association of Urology Guidelines on urological infections (https://uroweb.org/guideline/urological-infections/?type=archive), complicated urinary tract infections are associated with certain conditions, such as structural or functional abnormalities of the genitourinary tract, or the presence of underlying disease in the lower or upper urinary tract, which increases the risk of persistent or relapsing infection. Factors associated with complicated urinary tract infections include:

• indwelling urinary catheters
• urinary obstruction (such as stones or tumour)
• anatomical abnormalities
• peri‐ and post‐operative urinary tract infection, including renal transplantation.

Pyelonephritis is infection of the upper urinary tract and can occur in 1 or both kidneys. Acute pyelonephritis may be caused by bacteria ascending from the lower urinary tract or spreading via the bloodstream to the kidney. It is considered to be uncomplicated if it is caused by a typical pathogen in an immunocompetent person with a normal urinary tract anatomy and kidney function. As for urinary tract infections generally, acute pyelonephritis is considered to be complicated in people with increased susceptibility, for example: children or older people; people with functional or structural abnormalities of the genitourinary tract or people who are immunocompromised, such that the infection is more likely to be severe. However, most episodes are uncomplicated and are cured with no residual renal damage. Complicated urinary tract infections are a frequent cause of hospital admissions and a common healthcare associated complication. The pathogens most commonly encountered in complicated urinary tract infections are the gram‐negative bacteria Escherichia coli, other common Enterobacteriaceae (for example, Proteus spp., Klebsiella spp. or Citrobacter spp.) and Pseudomonas spp. Successful treatment has become increasingly more challenging because the majority of pathogens responsible for healthcare associated complicated urinary tract infections, including catheter‐related infections, are now commonly resistant to multiple antimicrobial agents (European public assessment report [https://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/003772/human_med_001917.jsp&mid=WC0b01ac058001d124]).

The English surveillance programme for antimicrobial utilisation and resistance (ESPAUR) report (2015) (https://www.gov.uk/government/publications/english-surveillance-programme-antimicrobial-utilisation-and-resistance-espaur-report) found that, overall, antibiotic resistant infections continue to increase. Notably, the rate of E. coli and Klebsiella pneumoniae bloodstream infections increased by 15.6% and 20.8% respectively from 2010 to 2014. Urinary tract infections are most commonly caused by E. coli (recorded in more than half of all the mandatory surveillance reports for E. coli bacteraemia when foci of infection are reported). The data indicate that 97% of E. coli isolates for urinary tract infection from GP practices, other community sources (such as care homes and outpatient clinics) and acute trusts were susceptible to nitrofurantoin. Resistance to trimethoprim was seen in over a third (35–37%) of isolates and resistance to amoxicillin was seen in over 50% of isolates, in all 3 settings. It is unclear if these data include cases of complicated urinary tract infections. Also, specialists involved in the production of this evidence summary noted that the results could be prone to bias because samples may have been be submitted from a population with a higher likelihood of antimicrobial resistance caused by, for example, failed treatments, recurrent infection or repeated courses of antibiotics.

Risk factors for resistance should be taken into consideration before prescribing antibiotics for urinary tract infection according to Public Health England guidance for primary care on managing common infections (https://www.gov.uk/government/publications/managing-common-infections-guidance-for-primary-care).

As well as some other groups, Public Health England advises performing culture and sensitivity testing in people with a higher risk of recurrent urinary tract infection (such as those aged over 65 years or with urinary catheters), and people with abnormalities of the genitourinary tract or suspected pyelonephritis.

The management of suspected community‐acquired bacterial urinary tract infection in adults aged 16 years and over is covered in the NICE quality standard on urinary tract infection in adults (https://www.nice.org.uk/guidance/qs90). This includes women who are pregnant, people with indwelling catheters and people with other diseases or medical conditions such as diabetes. The guidance was developed to contribute to a reduction in emergency admissions for acute conditions that should not usually require hospital admission, and improvements in health‐related quality of life. It does not make any recommendations around antibiotic treatment of complicated urinary tract infection, but includes 7 statements that describe high‐quality care for adults with urinary tract infection.

This evidence summary outlines the best available evidence for a new antimicrobial that is licensed for complicated urinary tract infections and acute pyelonephritis, ceftolozane/tazobactam. Ceftolozane/tazobactam was developed to address antimicrobial resistance in serious infections caused by gram‐negative pathogens.