This article is more than 5 years old. Information may no longer be current.
Optimizing treatment for patients with staph bacteremia
Click Here to Manage Email Alerts
Treatment of gram-positive bloodstream infections often is a clinical challenge, especially those caused by staphylococci. Staphylococci are one of the most commonly identified pathogens associated with both community- and hospital-acquired bloodstream infections. The incidence of Staphylococcus aureus bacteremia (SAB) ranges from 10 to 30 per 100,000 person-years, with case fatality rates of 15% to 50%, which has not really improved over the past few decades. Much of the current data for management of SAB are based on low-quality evidence, and the optimal duration of therapy has not yet been established with prospective clinical trials. In general, uncomplicated SAB is treated for 14 days following negative blood cultures whereas complicated infections require 4 to 6 weeks of treatment. With the exception of S. lugdunensis, coagulase-negative staphylococci (CoNS) are of lower virulence compared with S. aureus. However, CoNS infections pose therapeutic dilemmas because they are common contaminants, therefore if isolated from cultures, providers must determine whether it is a true infection. When treatment is necessary, CoNS also have a high rate of methicillin resistance; moreover, increasing numbers are becoming less susceptible to glycopeptides. In addition, the duration of therapy for CoNS is also based on limited evidence, ranging from no treatment for contamination, up to 5 to 7 days for uncomplicated infections, and several weeks for complicated bacteremia such as those with retained foreign bodies or endocarditis.
Two recent studies provided important evidence of how to optimize treatment for patients with staphylococci bacteremia. One uses pharmacists to assist providers through recommendations in management of these infections; the other uses an algorithm for treatment of staphylococci bloodstream infections.
Pharmacist-driven protocol
In a retrospective study of hospitalized patients at The Ohio State University Wexner Medical Center, Wenzler and colleagues evaluated an automated pharmacist-driven initiative for SAB. Before the implementation of the automated protocol, an evidence-based guideline was developed by a multidisciplinary team and was then made available to clinicians. The antimicrobial stewardship program (ASP) used this guideline when evaluating patients with SAB and would consult with providers as necessary on a case-by-case basis to improve adherence to the guideline. However, there was no formalized procedure to ensure guideline adherence.
To help to provide a formalized process of care, a scoring tool for SAB was developed and integrated into the electronic medical record. Pharmacists were required to evaluate a patient list generated by this tool at least once per shift to identify patients with SAB. In addition to the scoring tool, an educational session that focused on a comprehensive care bundle was developed that adhered to the Infectious Diseases Society of America’s MRSA quality of care guidelines. Clinical pharmacists received real-time alerts for patients with blood cultures positive for S. aureus via the scoring tool. After review, pharmacists communicated their guideline-based recommendations to providers both verbally and through written progress notes in the electronic medical record. Notably, clinical pharmacists were utilized to perform these tasks to expand the reach of the ASP.
There were 84 patients in the study: 45 in the pre-intervention period and 39 in the intervention group. The primary outcome was a composite of adherence of four quality of care components, including ID consult, repeat blood cultures, echocardiogram and targeted antibiotic therapy initiation. Adherence to all four measures was significantly higher in the intervention group compared with the pre-intervention period (92.3% vs. 68.9%; P = .015). In addition, ID consultation improved by approximately 20%, which is significant because ID consultation has been shown to improve clinical outcomes in those with SAB. Also important, all patients in the intervention group were started on targeted antibiotic therapy almost 40 hours sooner than those in the pre-intervention group. This study highlights the benefit clinical pharmacists can have on the management of those with SAB by using technology and non-ID trained pharmacists.
Algorithm-based therapy
In a recent multicenter open-label randomized study, Holland and colleagues compared an algorithm protocol with standard of care to define treatment duration for staphylococcal bacteremia. The algorithm group had predefined diagnostic evaluation, antibiotic selection and duration of therapy (Table), whereas treating providers caring for those in the usual practice group were able to care for patients as they would according to their normal practice. Patients were eligible for the study if they had blood cultures positive for S. aureus or CoNS. Patients with complicated infections at the time of randomization, polymicrobial bacteremia with at least one nonstaphyloccal pathogen, or those with renal insufficiency were excluded. Patients remained in the study if they were found to have a complicated infection after randomization and were then managed for complicated bacteremia. The primary outcome measures were clinical success, which was determined by a blinded adjudication committee, and serious adverse event rates.
They enrolled 255 patients in the algorithm group and 254 in the usual care group. Clinical success was similar between the groups, 82% vs. 81.5%. Serious adverse events also were not significantly different. One of the significant outcomes reported in this study was that for those included in the per-protocol analysis for simple or uncomplicated bacteremia, duration of antibiotic therapy was shorter in the algorithm-based therapy group than the usual practice group (4.4 days vs. 6.2; days, 95% CI, –3.1 to –0.6 days). The shorter duration of therapy was primarily explained by a 3-day shorter duration of therapy in those treated for uncomplicated CoNS bacteremia in the algorithm treatment group. Although this study was not powered to detect a difference in complicated SAB, those treated using the algorithm had higher treatment success rates (82.6% vs. 35.7%), which may indicate that following standard treatment principles can improve outcomes in this group of patients.
Overall, this study can help change practice in that using an algorithm-based approach can reduce the use of antibiotics such as vancomycin for the treatment of CoNS bacteremia. This is important because vancomycin is one of the most commonly prescribed antibiotics for these infections and can lead to adverse effects such as nephrotoxicity, as well as increase the overall pressure on the host’s normal microbiome. Although the results of this study are impressive and will likely help change treatment guidelines, there were some limitations. Most of the infections were caused by CoNS and the study was not powered to compare subgroups such as those with SAB. Additionally, all sites were academic centers that had access to ID physicians, which may limit generalizability in settings that do not have this expertise.
There are several management strategies for staphylococcal bacteremia that are well established. As the above mentioned studies highlight, using a well-defined protocol can help improve adherence to these measures and may also decrease the total duration of antibiotic therapy, especially for CoNS bloodstream infections. In my perspective, I feel that pharmacists can play a vital role in optimizing care for these patients, especially in institutions that may not have infectious disease physician expertise readily available. This can be achieved by developing guidelines or protocols for management of these patients and pharmacist review and feedback to providers to ensure adherence to the guidelines, especially when it comes to initiating targeted antibiotic therapy. We are all well aware of the implications of overusing broad-spectrum antibiotics, so ensuring the use of targeted antibiotics is vital. Development of an algorithm or guideline for staphylococci bacteremia treatment should be considered by ASPs to direct treatment for these patients.
Even though the above mentioned studies add to the available evidence, there is a need for additional clinical trials in this area, specifically to address optimal antimicrobial therapy, as well as to define the optimal duration of therapy for these infections.
- References:
- Becker K, et al. Clin Microbiol Rev. 2014;doi:10.1128/CMR.00109-13.
- Holland TL, et al. JAMA. 2018;doi:10.1001/jama.2018.13155.
- Holland TL, et al. JAMA. 2014;doi:10.1001/jama.2014.9743.
- Tong SYC, et al. Clin Microbiol Rev. 2015;doi:10.1128/CMR.00134-14.
- Wenzler, E, et al. Clin Infect Dis. 2017;doi:10.1093/cid/cix315.
- For more information:
- Jeff Brock, PharmD, MBA, BCPS AQ-ID, is an infectious disease pharmacy specialist at Mercy Medical Center in Des Moines, Iowa. He can be reached at JBrock@mercydesmoines.org.
Disclosure: Brock reports no relevant financial disclosures.