Negative urine culture does not preclude UTI in symptomatic women

A study from Belgium has found that women with typical symptoms of urinary tract infection (UTI) may still be infected with the uropathogen Escherichia coli despite a negative culture result.

The authors enrolled 256 women with a mean age of 42.6 years presenting with dysuria and urinary urgency and/or frequency to a general practitioner in the Ghent region of Belgium between May 2014 and January 2016. Thirty-six women were excluded due to criteria such as symptoms of complicated UTI (e.g., high fever or symptoms lasting > 7 days), pregnancy, urological or neurological issues, diabetes mellitus or other predisposing factors for UTI, use of antibiotics during the 4 weeks prior to presentation, or obvious gynecological complaints. Patients with a history of recurrent UTIs were admitted into the study, which was ultimately composed of 220 symptomatic women with a mean age of 38.5 years (range 17-65 years). A control group of 86 healthy women without UTI symptoms were recruited from the Ghent University campus (mean age 37.2, range 23-65 years).

Urine samples collected midstream were used in the study and analyzed with standard culture and compared to a quantitative PCR (qPCR) assay for E. coli and Staphylococcus saprophyticus. In women with symptoms, qPCR was also conducted for four sexually transmitted pathogens.

In women with symptoms, 80.9% of urine cultures were positive for a uropathogen such as E. coli (the primary culprit in most cases), S. saprophyticus, or other Gram-negative rods and Enterococcus species, compared to 95.9% that were positive for E. coli on the qPCR assay. There were also 19 positive qPCR results for S. saprophyticus, one for Mycoplasma genitalium, and one for Trichomonas vaginalis among symptomatic women. All samples were negative for the sexually transmitted infections (STIs) Chlamydia trachomatis and Neisseria gonorrhea in women with UTI symptoms and negative culture results.

Among women in the control group, 10.5% of cultures were positive for E. coli as were 11.6% of qPCR assays. The authors noted that asymptomatic bacteriuria, which is defined as a bacterial count ≥ 10⁵ CFU/mL with no symptoms, is common in the general female population (affecting 1% to 8%) and was expected.

E. coli was found by qPCR in 25 samples that were positive for other uropathogens on culture, suggesting coinfection, although this supposition needs to be further investigated.

The authors, in a review of the literature, noted that there are several theories as to why culture might be negative in the presence of infection. One might be that the threshold for the bacterial count needs to be lowered to capture these cases. Another is that standard microbiology protocols may be inadequate to the task of finding certain uropathogens. A third is that E. coli strains may be contained in biofilms that cause inflammation and symptoms but that are not detectable on standard culture.

Clinical recommendations

Based on the results of this study, the investigators recommended that all nonpregnant women with symptoms of uncomplicated UTI and no evidence of an STI (e.g., vaginal symptoms) be treated empirically according to standard clinical guidelines. “Instead of spending time and energy to prove an uncomplicated UTI, physicians can rely on the typical symptoms and focus on acknowledging and managing the patient’s complaints,” they wrote in summary.