By Richard R. Watkins, MD, MS, FACP, FIDSA

Professor of Internal Medicine, Northeast Ohio Medical University; Division of Infectious Diseases, Cleveland Clinic Akron General, Akron, OH

Dr. Watkins reports no financial relationships relevant to this field of study.

SYNOPSIS: In a retrospective study from Canada, researchers reported several risk factors for serious Staphylococcus aureus infections, including bacteremia and vertebral osteomyelitis, in patients with S. aureus bacteriuria.

SOURCE: Stokes W, Parkins MD, Parfitt ECT, et al. Incidence and outcomes of Staphylococcus aureus bacteriuria: A population-based study. Clin Infect Dis 2019;69:963-969.

Staphylococcus aureus bacteriuria (SABU) is a frequent clinical conundrum. It rarely causes urinary tract infections and usually represents urinary colonization, especially in patients with indwelling Foley catheters. However, SABU can be an ominous sign of a serious infection, such as S. aureus bacteremia (SAB) or an occult abscess. Therefore, Stokes and colleagues sought to identify characteristics associated with SABU that establish a higher risk for systemic infection.

The study included all urine cultures from patients ≥ 18 years of age reported positive for S. aureus between Jan. 1, 2010, and Dec. 31, 2013, from a centralized laboratory in Calgary. Researchers excluded urine cultures within three months of each other and of the same antibiogram because these were presumed to be recurrences of the original infection. Researchers included blood cultures and cultures from sterile fluid, tissue, hardware, catheter tips, and deep abscesses in the analysis if they occurred within three months of any SABU. Because of incomplete data, investigators excluded laboratory data from the multivariate regression analysis.

Of the more than 800,000 urine cultures collected during the study period, 3,739 (0.4%) grew S. aureus. After exclusion, 2,540 cultures from 2,054 patients were included in the analysis. Compared to the general population in Calgary, SABU occurred at a higher rate among males and in older patients (i.e., 60 years to > 85 years, median age 74). Diabetes was twice as common in the SABU patients compared to the general population, and even higher in those with SABU and SAB. Compared to those with SABU, those with SABU and SAB were more likely to be younger, be hospitalized, recently have a urological procedure, and have a pure S. aureus culture (i.e., not mixed).

Additional risk factors associated with SABU and SAB included the presence of immature neutrophils, serum platelets < 120, serum WBC > 15,000, inpatient status, urinary procedure, male sex, and pure S. aureus urine culture. The most common source of bacteremia identified were osteomyelitis of the spine or pelvis (23% of cases) and infective endocarditis (11% of cases).

Factors that were protective against SAB were dementia, urine WBC > 10 cells/hpf, persistent SABU, age > 65 years, and presence of urine nitrites. In evaluating for SAB in outpatients with SABU, a WBC > 15,000 was associated with a higher risk, along with diabetes and the presence of a urinary catheter. Living in a nursing home was associated with a lower risk, but dementia, age > 65 years, and recent urologic procedure had no impact on the rate of SAB among outpatients with SABU. Finally, an increased C-reactive protein level was identified as a predictor of SAB with SABU on univariate analysis, but not on multivariate analysis because of infrequent testing.

COMMENTARY

This is the largest study to evaluate the association between SABU and SAB. The risk factors that were identified should help clinicians in determining the significance of SABU and the need for further work-up. It was notable that SABU detected ≥ 48 hours before SAB was associated with a higher risk of death compared to those who had SAB and SABU diagnosed concurrently. This finding highlights the importance of identifying SAB quickly when SABU is detected. As the authors mentioned, microbiology laboratories should play an active role in commu-nicating the significance of SABU, especially the first time it is detected.

The detection of SABU is especially challenging in outpatients. In this patient population, clinicians do not have the luxury of careful investigation and monitoring that is available in the inpatient setting. It is interesting that the presence of a urinary catheter was a risk factor for SAB in outpatients but not in inpatients. The likely explanation is that the use of urinary catheters in hospitalized patients is a temporary measure more often compared to outpatients, for whom the catheter is more likely to be chronic. Thus, there is an increased risk for complications, such as ascending urinary tract infection.

Of the patients with SABU and SAB, a large number of them had spine infections. Previous studies have documented an increased risk for osteomyelitis due to gram-negative urinary pathogens, especially among the elderly with bacteriuria. This phenomenon is believed to be because of the connection of venous networks between the pelvis, spine, and bladder. Therefore, when SABU is detected, a detailed history and physician examination for vertebral osteomyelitis should be performed.

The study had a couple of limitations. As with all retrospective studies, unmeasured confounding variables may have affected the observed morbidity and mortality rates. It is unclear if an elevated CRP is truly associated with SAB in patients with SABU because of the small number of test results (n = 39). This could be answered by further investigation. Finally, death was defined as occurring during hospitalization, so those who died outside of the hospital would not have been detected.

Despite these shortcomings, this study provides useful data that should be helpful to clinicians when they are pondering the significance of SABU. Microbiology laboratories should consider adding to the culture report that SABU might represent severe systemic disease and that clinical correlation is advised.