A Perfect Trifecta: The Pharmacist, Antimicrobial Stewardship, and Rapid Diagnostic Technologies

Antimicrobial stewardship is a hot topic in pharmacy right now, with more overseeing bodies requiring it lately. The Obama administration first called for the establishment of antimicrobial stewardship programs (ASPs) in all acute care hospitals by 2020 as part of its National Action Plan for Combating Antibiotic-Resistant Bacteria.¹ A similar mandate has been in place in all Veterans Affairs’ hospitals since July 2014.² Currently the CMS mandate is on hold due to the change in presendential administration. The Joint Commission went into effect on January 1, 2017.³

It makes sense that institutions enforce the appropriate selection and use of antimicrobials, as the use or misuse of these medications in one individual can directly impact their efficacy in another individual. The same is not true for cholesterol or pain medications.

The CDC and the Infectious Diseases Society of America/ Society for Healthcare Epidemiology of America each has guidelines outlining key principles of ASPs.⁴ Each set of guidelines advocates for the use of advancing technology to aid in the identification of infection and de-escalation of antimicrobials. Strategies such as computerized clinical decision support at the time of ordering and rapid diagnostic technologies (RDTs) are gaining in literature support for their impact and utility in aiding ASPs. Study results have shown that the time to appropriate antimicrobial selection, duration of antimicrobial therapy, length of stay, and mortality rates can all decrease. However, these are costly endeavors for institutions to implement, often with up-front costs upwards of tens or hundreds of thousands of dollars.

Most of these studies simultaneously implemented RDTs with dedicated ASP intervention. Therefore, it is difficult to accurately assess whether all the benefits seen from implementing RDT are due to the technology itself, the ASP, or a combination of the 2. If you build it, will they come? If the technology itself is available, will the house staff be able to intervene and realize the same touted benefits without the input of a dedicated stewardship team? Several studies have recently reviewed these concepts.

Holtzman and colleagues performed a retrospective review of peptide nucleic acid fluorescence in situ hybridization (PNA FISH) implemented in their institution without any active notification or ASP intervention.⁵ The PNA FISH was batched, performed on the overnight shift, and updated in computerized microbiology reports by 5 AM. A total of 199 patients (100 pre-PNA FISH and 99 post-PNA FISH) with blood cultures positive for coagulase-negative staphylococci (CoNS) were evaluated. There were no differences in terms of hospital length of stay and vancomycin use. The authors concluded that the implementation of technology alone, without real-time notification and/or ASP support and intervention, may not translate into clinical advantages.

Another study looked at PNA FISH, this time for streptococcal and enterococcal bacteremia, also without ASP involvement. Cosgrove et al prospectively randomized 220 patients growing gram-positive cocci in their blood to either standard microbiologic methods or standard methods plus PNA FISH.⁶ They did not see differences in time to effective or optimal therapy, length of stay, or in-hospital mortality. They concluded that lack of ASP intervention may reduce the benefits of RDT.

Continuing with the gram-positive organisms, Frye and colleagues retrospectively reviewed their experience with a twice-daily (once daily on weekends) batched polymerase chain reaction (PCR) test to identify Staphylococcus aureus and detect methicillin-resistant strains.⁷ Similar to the previous studies, no change in alerts or computerized decision support was provided. Overall, 126 patients with S. aureus bacteremia (68 pre-PCR and 58 post-PCR) and 118 patients with CoNS (66 pre-PCR and 52 post-PCR) were evaluated. The time to organism identification significantly decreased post PCR; however, the time to optimal antibiotic therapy did not. These authors also concluded that the implementation of RDT alone is not enough to improve antibiotic use.

Banerjee and colleagues took these notions 1 step further. They performed a prospective, randomized, controlled trial of patients with positive blood cultures in 3 distinct arms: standard blood culture processing methods, rapid multiplex PCR (rmPCR) identification, and rmPCR with real-time ASP intervention (rmPCR/AS).⁸ For all patients receiving rmPCR, computerized reports contained templated comments guiding treatment, empiric antibiogram-led therapy, and institutional protocols, thus building on the idea that the technology must be coupled with real-time guidance.

The rmPCR detected and immediately identified a number of gram-positive, gram-negative, and Candida organisms. Susceptibility reports were not integrated into the assay, but performed by another system as soon as a culture flagged positive. In the rmPCR/AS group, an ASP pharmacist or physician was paged with positive results on a 24/7 basis; however, active interventions may have been delayed until the morning shift if they were not deemed critical.

A total of 617 patients were included in the study. Overall, patients in both rmPCR groups had a quicker time to organism identification, quicker appropriate up-escalation of therapy (eg, switched from ceftriaxone to cefepime if Pseudomonas aeruginosa identified), quicker appropriate de-escalation of therapy (eg, vancomycin to cefazolin if methicillin-susceptible S. aureus identified), and less treatment of contaminated blood cultures compared with the control groups. In regard to the impact of ASP on the rmPCR implementation, the rmPCR/AS group had more de-escalation of any antimicrobial following Gram stain or PCR identification and a faster time to de-escalation from Gram stain report. There were no differences seen in terms of clinical or microbiologic outcomes among the groups. The authors were able to prove that the availability of the technology combined with templated computerized comments reduced the treatment of contaminates and decreased the use of broad spectrum antimicrobials. However, the addition of ASP enhanced antimicrobial de-escalation.

Last, MacVane and Nolte performed a pre-post quasiexperimental study with 3 groups of patients presenting with bloodstream infections: standard organism identification (control), standard identification plus ASP intervention (AS), and rmPCR plus ASP intervention (BCID). The overall study cohort included 364 patients. The AS and the BCID groups had higher rates of de-escalation compared with the control group. Additionally, the BCID arm had significantly faster organism identification time, shorter time to effective therapy, and faster de-escalation time compared with the other two groups. No differences were seen in mortality, 30-day readmission rates, lengths of stay, or costs.⁹

These study results highlight the importance of a dedicated, knowledgeable team integrated with the implementation of RDT. Employing RDT alone will not result in tangible clinical benefits. A recent survey of infectious diseases (ID)-interested pharmacists¹⁰ indicated that most institutions employ some form of RDT, although the type varied greatly from one institution to another. Pharmacists were the most likely healthcare professional to receive alerts of positive RDT results. Familiarity with different types of RDT changed depending on the technology in question. However, pharmacists with ID training (residency, fellowship, or stewardship certificate training) self-reported an increased rate of familiarity with any RDT compared with non-ID-trained pharmacists (P ≤ .05).

Where does this leave us? Technology is a vital component of delivering rapid, cutting-edge medicine to our patients. If institutions are to follow recommendations to implement ASP and utilize RDT, they should optimally employ ID-trained pharmacists. As the need would far exceed the supply, educational programs should focus on the instruction of non- ID—trained pharmacists in the utility of RDT. General clinical pharmacy meetings and on-demand/home study continuing education programs would be a perfect venue for disseminating this information to a wide-reaching audience. Together, the combination of RDT and an antimicrobial stewardship pharmacist can have immediate, positive benefits on the management of bloodstream infections.

MONICA V. MAHONEY, PHARMD, BCPS AQ-ID, graduated from MCPHS-University (Boston) and completed PGY1 and PGY2 specialty training at Tufts Medical Center. She is the Clinical Pharmacy Coordinator in Infectious Diseases at Beth Israel Deaconess Medical Center in Boston, MA.

References

• National Action Plan for Combating Antibiotic-Resistant Bacteria. March 2015. White House website. whitehouse.gov/sites/default/files/docs/national_ action_plan_for_combating_antibotic-resistant_bacteria.pdf. Accessed September 28, 2016.
• Department of Veterans Affairs. VHA Directive 1031. Veterans Affairs website. va.gov/vhapublications/ViewPublication.asp?pub_ID=2964. Published January 22, 2014. Accessed September 28, 2016.
• Approved: new antimicrobial stewardship standard. Joint Commission website. jointcommission.org/assets/1/6/New_Antimicrobial_Stewardship_ Standard.pdf. Published July 2016. Accessed September 30, 2016.
• Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an antibiotic stewardship program: guidelines by the infectious diseases society of America and the society for healthcare epidemiology of America. Clin Infect Dis. 2016;62(10):e51-e77. doi: 10.1093/cid/ciw118.
• Holtzman C, Whitney D, Barlam T, Miller NS. Assessment of impact of peptide nucleic acid fluorescence in situ hybridization for rapid identification of coagulase-negative staphylococci in the absence of antimicrobial stewardship intervention. J Clin Microbiol. 2011;49(4):1581-1582. doi: 10.1128/ JCM.02461-10.
• Cosgrove SE, Li DX, Tamma PD, et al. Use of PNA FISH for blood cultures growing Gram-positive cocci in chains without a concomitant antibiotic stewardship intervention does not improve time to appropriate antibiotic therapy. Diagn Microbiol. Infect Dis. 2016;86(1):86-92. doi: 10.1016/j.diagmicrobio. 2016.06.016.
• Frye AM, Baker CA, Rustvold DL, et al. Clinical impact of a real-time PCR assay for rapid identification of a staphylococcal bacteremia. J Clin Microbiol. 2012;50(1):127-133. doi: 10.1128/JCM.06169-11.
• Banarjee R, Teng CB, Cunningham SA, et al. Randomized trial of rapid multiplex polymerase chain reaction-based blood culture identification and susceptibility testing. Clin Infect Dis. 2015;61(7):1071-1080. doi: 10.1093/cid/civ447.
• MacVane SH, Nolte FS. Benefits of adding a rapid PCR-based blood culture identification panel to an established antimicrobial stewardship program. J Clin Microbiol. 2016;54(10):2455-2463. doi:10.1128/JCM.00996-16.
• Mahoney MV, Bland CM, Kuper K, Bookstaver PB. Familiarity and utilization of rapid diagnostic technologies for antimicrobial stewardship. Presented at: 2016 IDWeek; October 26-30, 2016. New Orleans, LA. Abstract 1883.