Image via Wikimedia Commons.
Infections in the bloodstream, particularly those caused by gram-negative bacteria, are common and potentially life-threatening in patients undergoing hematopoietic cell transplantation (HCT). HCT patients are at increased risk of infection due to neutropenia and mucosal disruption from chemotherapy and must frequently undergo immunosuppressive steroid treatment to prevent donor cells from attacking the cells of the recipient, a condition known as graft-versus-host-disease (GVHD). In addition to the immunosuppressive consequences of transplantation, HCT patients on high-dose steroids present dampened symptoms of infection. This is because the glucocorticoids used to quell GVHD inhibit the antibacterial cytokines whose release leads to symptoms used to diagnose infection, such as tachycardia, flushing, and fever. Due to the potential for delayed diagnosis of bacterial blood infections, many cancer centers proactively collect blood cultures at frequent intervals to attempt to identify bacteremia events before symptoms present. However, research has shown that the effectiveness of this surveillance varies greatly between patient populations and the benefits of SBC have not been systematically analyzed, prompting Dr. Erica Stohs (University of Nebraska; formerly of the Pergam group) and Dr. Victor Chow (Seattle Cancer Care Alliance Hematology-Oncology fellow) to conduct a study to characterize the level of pathogenicity of the cultures found in surveillance blood cultures (SBC). They recently published these findings in Biology of Blood and Marrow Transplantation.
Routine SBC reveal bacteria in the blood of some HCT patients, often prompting the initiation of vancomycin or other antibiotic treatment. However, Stohs and colleagues hypothesized that the cultures detected in asymptomatic HCT patients via SBC are primarily gram-positive bacteria of low pathogenicity, which would suggest that weekly SBC in this specific subset of HCT patients are superfluous and could promote excessive prescription of antibiotics. Taking advantage of a cohort of patients from a previous study who had undergone HCT and high dose glucocorticoid treatment for GVHD, the authors analyzed data from 1015 weekly SBC samples from 127 patients. Of these patients, 97% had no positive cultures in SBCs, while 20% tested positive for one culture and 3% had more than one positive culture, usually beginning around a month after initiation of steroids. Staphylococcus, a ubiquitous commensal species, represented 60% of the organisms isolated, while deleterious gram-negative bacteria were rare in SBC and only isolated in 4 out of 1015 SBC (.4%) in three individuals. Although highly pathogenic bacteria in SBC were rare and only six patients were admitted to the hospital for treatment at any point during the study, 33 of 36 patients with positive cultures were treated with antibiotics over a cumulative 376 days. Alarmingly, vancomycin is a precious drug as it is the last line of defense in certain drug-resistant infections, and its excessive use facilitates the generation of vancomycin-resistant bacteria. However, this study found that vancomycin was the most highly prescribed antibiotic used in this cohort. Patients received vancomycin during 68% of the study days, and one vancomycin-resistant culture was isolated from an SBC.
Previous studies that have evaluated the efficacy SBC have focused on varying frequencies of collection, patient status, and presence or absence of clinical symptoms, and produced a range of results, some in support of SBC. For example, in patients presenting with symptoms of infection, SBC have proved useful for early diagnosis. However, Stohs’ work suggests that in the specific population of asymptomatic HCT outpatients receiving high doses of steroids, weekly SBC are extraneous, as species of low pathogenicity predominated in positive cultures and highly pathogenic gram-negative bacteria were detected in less than half a percent of SBC. In fact, because Staphylococcus is a common skin commensal, its detection may have been due to contamination rather than a true blood infection, potentially lowering the total of positive cultures drastically. Although the necessity of vancomycin initiation cannot be accurately assessed with a retrospective study, the low incidence and severity of bacterial-mediated disease suggests that aggressive antibiotic treatment in these patients may not be warranted and could in turn cause harm by increasing vancomycin resistance and by decreasing the healthy diversity of the gut microbiome in immunosuppressed HCT patients. Since this study, the clinic where this research was conducted has implemented an antimicrobial stewardship pharmacist to carefully assess the need for vancomycin treatment and to carefully monitor dosage and duration of antibiotic treatment. The authors suggest that although SBC may yield positive bacterial cultures in asymptomatic HCT patients on high dose steroids, expenses and time associated with microbiology workup, as well as the serious potential consequences of antibiotic use may outweigh the benefits of weekly screens in this subset of HCT patients. However, a randomized trial is needed to confirm this observation. Looking forward, the authors emphasize that research informing increased diagnostic stewardship and oversight of prescription of antibiotics is necessary in high-risk and immunocompromised HCT populations.
Cancer Consortium members Catherine Liu, Barry E. Storer, Marco Mielcarek, and Steven A. Pergam (UW/Fred Hutch) contributed to this work.
Stohs E, Chow VA, Liu C, Bourassa L, Miles-Jay A, Knight J, Sweet A, Storer BE, Mielcarek M, Pergam SA. 2019. Limited utility of outpatient surveillance blood cultures in hematopoietic cell transplant recipients on high-dose steroids for treatment of acute Graft-versus-Host-Disease. Biology of Blood and Marrow Transplantation. pii: S1083-8791(19)30089-8. doi: 10.1016/j.bbmt.2019.01.031. [Epub ahead of print]