Polymicrobial Urine Cultures: Reconciling Contamination with the Urobiome while Recognizing the Pathogens

Polymicrobial or mixed urine cultures of more than one predominant microbe confound clinical urinary tract infection diagnosis. The current College of American Pathologists clinical laboratory standard states that a urine sample cultured with more than two isolates with >10,000 colony forming units/ml is to be considered contaminated. However, the presence of urinary sample bacteria in individuals without urinary symptoms (referred to as asymptomatic bacteriuria) is common especially in older people and in pregnant individuals. Furthermore, the discovery of an indigenous urinary microbiome (urobiome) in healthy humans throughout life from shortly after birth to death conflicts with the long-standing notion that urine derived from sterile filtered blood should be sterile above the urethral sphincter. Polymicrobial infections clash with Koch’s postulates that a single pathogen is causal for disease. In this review, we will discuss current standards of contamination, how to reconcile the sterility of urine with the existence of the urobiome, a history of polymicrobial infections, and why re-examining current practices is essential for the practice of medicine, improving quality of life, and potentially saving lives.