By Richard R. Watkins, MD, MS, FACP, FIDSA, FISAC
Professor of Internal Medicine, Northeast Ohio Medical University, Rootstown, OH
SYNOPSIS: A multicenter cohort study found patients with S. aureus bacteremia (SAB) and active cancer had a lower risk for infective endocarditis (IE) than those with SAB without cancer. Persistent bacteremia and cardiomyopathy were independent risk factors for IE.
SOURCE: Grillo S, Cuervo G, Laporte-Amargós J, et al. Bloodstream infection and endocarditis caused by Staphylococcus aureus in patients with cancer: A multicenter cohort study. Infect Dis Ther 2021; Dec 2. doi: 10.1007/s40121-021-00575-8. [Online ahead of print].
The incidence of cancer is rising worldwide. Despite the fact that Staphylococcus aureus bacteremia (SAB) is common in patients with cancer, few studies have focused specifically on this patient population. Therefore, Grillo and colleagues sought to determine the epidemiology, clinical characteristics, and risk factors for infective endocarditis (IE), and outcomes in patients with active cancer (PWAC) and SAB compared to those with SAB without cancer.
The study was a retrospective cohort analysis of SAB episodes in patients at least 18 years of age who were hospitalized between January 2011 and December 2019 in two tertiary care hospitals in Barcelona, Spain. SAB was defined as at least one positive blood culture obtained from a patient with clinical signs and symptoms of infection (i.e., fever, chills, malaise, phlebitis, cellulitis, and septic emboli). Acquisition categories of SAB were defined by three mutually exclusive classes: community-acquired, nosocomial, and healthcare-related. The investigators considered the following as etiologies for the SAB: vascular catheter-related infections, IE as defined by the modified Duke criteria, skin and soft tissue infections, pneumonia; osteoarticular infections (with or without prosthetic devices), urinary tract infections, unknown; and other sources, including abdominal, head and neck, and central nervous system sources. For the purposes of the study, IE was considered both as a source of infection and as a complication of bacteremia from another source.
Persistent bacteremia was defined as having positive follow-up blood cultures after more than two days of therapy. Cases of positive blood culture after negative follow-up blood cultures were considered recurrent bacteremia. Patients with active cancer were defined as those with active solid organ cancer or hematological malignancies who underwent chemotherapy/radiotherapy and/or hematopoietic stem cell transplant in the previous three months or who had metastatic cancer. Mortality was evaluated 30 days after the onset of bacteremia.
There were 217 (22.2%) cases of SAB in PWAC during the study period compared to 761 cases (77.8%) in those without cancer. The incidence of SAB was higher in PWAC compared to those without (7.3/1,000 hospital discharges/year vs. 2.9/1,000 hospital discharges/year, respectively; P = 0.001).The PWAC were younger, had fewer comorbidities, and were less likely to receive antiplatelet drugs. The acquisition of SAB was significantly different (P < 0.001) between the two groups; community-acquired SAB was more common in patients without cancer (7.4% vs. 28.0%), while the PWAC had more healthcare-related (54.4% vs. 41.7%) and nosocomial SAB (38.2% vs. 30.4%).
Among the 89 patients (9.1%) diagnosed with IE, six were PWAC. Multivariate analysis found the presence of previous cardiopathy and persistent bacteremia were risk factors independently associated with IE. Notably, having active cancer was a protective factor (adjusted odds ratio [aOR] 0.338; 95% confidence interval [CI], 0.142-0.806; P = 0.011). The 30-day all-cause mortality among 978 episodes of SAB was 24.6%. There were no significant differences in mortality between PWAC compared to those without cancer. Risk factors independently associated with 30-day mortality included age > 65 years, Charlson score > 6 points, unknown source of infection, sepsis, infection due to methicillin-resistant S. aureus (MRSA), and persistent bacteremia. No PWAC had a relapse of SAB, while this occurred in seven patients without cancer.
COMMENTARY
Bacteremia caused by S. aureus is a common and dreaded complication in patients with cancer who are undergoing active treatment. In this retrospective cohort study, PWAC were found to have a higher rate of SAB compared to patients without cancer. This likely was because of more frequent hospital admissions, chemotherapy administration, invasive procedures, and the common use of long-term indwelling catheters. The 30-day mortality rate of approximately 25% underscores the pathogenicity of SAB and that more effective management is urgently needed.
In spite of the higher rate of SAB in PWAC, their incidence of IE was lower. This notable result could be explained by the fact that PWAC were younger (mean age 59 years vs. 66 years), had fewer comorbidities including underlying devices, and had more catheter-related, healthcare-associated, and nosocomial SAB. Moreover, PWAC had faster clearance of bacteremia and a higher prevalence of thrombocytopenia, the latter of which may be protective against the formation of vegetations.
The finding of a lower rate of IE in PWAC raises the issue of whether transesophageal echocardiography (TEE) is needed in all such cases. PWAC may have conditions that increase the risk of complications with TEE, such as thrombocytopenia, cancer of the head and neck, or inflammatory mucosal changes. Thus, further studies are needed to clarify if TEE can be safely deferred in PWAC who develop SAB. One possibility is to design a prediction score that could identify low-risk patients for whom negative follow-up blood cultures and a negative transthoracic echocardiography study would be sufficient.
The study has a few limitations. First, the retrospective design may have been influenced by unmeasured confounding variables. Second, PWAC are monitored closely such that episodes of SAB likely were detected, diagnosed, and treated earlier in the course of the infection than in the patients without cancer, thus leading to selection bias. Finally, the prevalence of IE in the PWAC group was low, which may have affected the results of the multivariate analysis.
The apparent reduced risk for IE in PWAC is an interesting finding that could have important clinical implications. However, additional confirmatory studies are needed before changes in the current management of IE in PWAC can be recommended.
A multicenter cohort study found patients with S. aureus bacteremia (SAB) and active cancer were at a lower risk for infective endocarditis (IE) than those with SAB without cancer. Persistent bacteremia and cardiomyopathy were independent risk factors for IE.
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