October 17, 2017
7 min read
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The critical role of antimicrobial susceptibility testing in medical decision-making

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Medical decision-making remains challenging despite the unprecedented advances in technology over the past several decades. This is most apparent when it comes to empirical and targeted treatment with antibiotics. Years of antibiotic misuse and overuse have led to global resistance and the rise of new bacterial resistance threats that defy treatment with conventional therapies.

Elliot J.C. Goldstein

Although new agents are sorely needed to address multidrug-resistant (MDR) gram-negative bacteria, this is only one part of the solution. Alongside new antimicrobial agents, rapid diagnostics must be developed to precisely target priority pathogens. Collaboration between infectious disease physicians with a comprehensive antimicrobial stewardship (AMS) team can improve innovation of the tools that are available and in development to help achieve this goal.

Antimicrobial susceptibility testing contributes to AMS efforts

Antimicrobial susceptibility testing (AST) confirms susceptibility, detects resistance and guides the selection of patient therapy. Microbiology labs are essential to stewardship programs by ensuring quality specimen collection, appropriate testing, implementation of rapid diagnostics, AST and data analysis. AST helps preserve antibiotics and target therapy but is an underused strategy. Recognizing the value of this tool and working collaboratively with laboratories — particularly in high-risk patients — is a cornerstone of appropriate and targeted therapy.

This is not always easy for a variety of reasons. First are the challenges of the physical location of the lab itself. In the not-too-distant past, labs were centrally located in every hospital. Today, labs operate at an off-site location, perhaps 1 or 2 miles from the hospital. This means issues of specimen transport, as well as gaps in training fellows who are not regularly going to the lab on rounds, not looking at plates and not learning about testing procedures. What was formerly considered routine is missing, and what was once considered basic knowledge — understanding the lab process and the technologists’ work flow and capabilities — has been lost. The lack of opportunity to build personal relationships with the lab staff, including microbiologists and lab techs, within the lab environment diminishes collegiality and subsequent communications. The off-site location belies the essential role of the lab in AMS efforts.

Secondly, we are really talking about microbiology and diagnostic stewardship. Physicians must understand the quality and appropriateness of cultures that they are requesting. When specialists are called in the middle of the night, they are also removed from the patient and often follow the nurse’s suggestion for a “pan-culture,” regardless of what else is going on with the patient. We need to think of cultures in terms of microbiology stewardship: the more cultures you take, the more likely something will grow. Inappropriate cultures lead to unnecessary treatment that can inadvertently add complexity to an already complicated case. When something grows, one feels obligated to treat the patient, often with an overly broad selection of antibiotics because of the presence of bacteria that are not causing an infection, and these antibiotics can sometimes cause serious side effects.

Maximizing the use of antibiograms

Hospitals are now required to have annual antibiograms, which summarize the proportion of organisms that are susceptible to specific antimicrobials during a specific period of time, for their AMS programs. More frequent reports may be necessary to keep up with resistance trends. Targeting specific patient populations (inpatient vs. outpatient), hospital units (ICU vs. non-ICU) and infection sites (blood vs. urine vs. sputum) may provide valuable insights to resistance trends. Resistance has “hot spots” in local areas that depend on what else is going on in the community. This is also true for specific areas of your hospital. For example, the level of carbapenem resistance to Pseudomonas aeruginosa varies depending on whether you work at a tertiary hospital that performs transplants or in a community hospital.

The mortality rate of patients with hospital-onset P. aeruginosa infection was nearly twice as high among those with MDR Pseudomonas infections compared with non-MDR infections, according to recent data presented at ASM Microbe and reported in Infectious Disease News. Researchers found that the mortality rate was 20.1% among patients with MDR Pseudomonas infections vs. 11.5% among those without MDR infections. Patients with MDR infections spent an additional 6 days in the hospital compared with those with susceptible infections. Therefore, the antimicrobial stewardship program (ASP) team of physicians, pharmacists, nurses and microbiologists needs to be aware not just of resistance rates in general, but of rates in their specific environment.

Successful antimicrobial stewardship programs require a sustained and seamless level of monitoring and decision-making regarding antimicrobial therapy.
Source: Shutterstock

This can be used as a tool for making formulary decisions, developing guidelines for empiric therapy and monitoring resistance rates over time. When dealing with MDR organisms such as MDR P. aeruginosa, delayed treatment — and incorrect treatment — lead to higher mortality. Selecting the right treatment early on leads to improved survival outcomes. Antibiograms also help support empirical decisions, which are especially important when there is a paucity of AST data for newer agents.

Rapid testing needs to keep pace with newer antibiotics

AST, particularly for newer antibiotics, is critical because it helps determine where they fit into therapy, often for the sickest patients. AST must be available, rapid and accurate. In 2017, the FDA approved manual test strips to diagnose carbapenem-nonsusceptible gram-negative bacteria that can assist in the selection of optimal antibiotic treatment for highly resistant strains of P. aeruginosa and Klebsiella pneumoniae. However, automated AST tests such as Vitek (bioMérieux) and Microscan (Beckman Coulter), which are preferred by many labs, continue to slowly work their way through the process of FDA approval, software updates and finally, commercial availability.

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The most recent advances include rapid test strips for Zerbaxa (ceftolozane-tazobactam, Merck), approved by the FDA in 2014, and Avycaz (ceftazidime-avibactam, Allergan), approved in 2015. These are the only two systemic antibacterial drugs launched to date that are active against resistant P. aeruginosa, which tops WHO’s “Priority Pathogen” list for research and development of new antibiotics.

Ceftolozane-tazobactam is an antipseudomonal cephalosporin plus beta-lactamase inhibitor indicated for the treatment of complicated urinary tract infections (cUTIs) and complicated intra-abdominal infections (cIAIs). It is active against gram-negative infections, including MDR P. aeruginosa and extended-spectrum beta-lactamase (ESBL)-producing strains. Ceftolozane-tazobactam has been shown to be active against 84% of MDR P. aeruginosa. Ceftazidime-avibactam, an antipseudomonal cephalosporin plus beta-lactamase inhibitor, is indicated for the treatment of cUTIs and cIAIs. It is also active against gram-negative infections, including MDR P. aeruginosa, ESBL-producing strains and K. pneumoniae carbapenemase.

As other new automated tests for these and developing agents become available, the ASP group should support lab efforts to maintain the latest tools and act as allies to inform the hospital administration of the value of these advances. Lab techs are understaffed and resource strapped. However, MDR infections are costly from the perspective of readmittance, reinfection and increased hospital length of stay. Supported by AST, appropriate and timely prescribing can help address value vs. costs.

Antimicrobial susceptibility testing, or AST, confirms susceptibility, detects resistance and guides the selection of patient therapy.
Source: Shutterstock

Ideally, a new era of rapid identification will help overcome challenges when considering susceptibility thresholds. Currently, there are no hard data or randomized studies that help define thresholds that will help guide treatment decisions. In the future, computer-assisted decision-making may provide specific percentages about resistance rates, and when used correctly, can help physicians more precisely target infections with current resistance data at their fingertips.

Collaboration: A key component of AMS efforts

The Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) guidelines for the development of institutional ASPs highlight that a pharmacist with infectious disease training should be a core member of the ASP team. For AMS programs to be successful, a sustained and seamless level of monitoring and decision-making in relation to antimicrobial therapy is needed. Because nurses have the most consistent presence in patient care, they are in the ideal position to provide this level of service. Time is of the essence with serious MDR infections. There is inevitably a lag time between when an antibiotic is ordered and when it is administered to the patient (“hang time”). This gets even more complicated when considering the pharmacokinetic and pharmacodynamics of multiple drugs and extended infusions in an effort to limit the number of lines in a patient. It is important for hospital pharmacists and nurses alike to understand their role within the greater process and AMS program.

There is no shortage of challenges when it comes to medical decision-making for complicated, rapidly evolving and deadly infections. However, these challenges are not insurmountable. It is also important to recognize that the sole responsibility of AMS does not rest on the shoulders of the infectious disease physician alone. Indeed, an inclusive and collaborative team is perhaps the strongest tool at our disposal when confronting the emerging crisis of MDR bacteria.

Disclosure: Goldstein serves on advisory boards for Bio-K+, Daiichi Sankyo, Merck, Novartis, Paratek Pharmaceuticals, Sanofi-Aventis, Shionogi and Summit Corp., speakers bureaus for Allergan, Bayer, The Medicines Company and Merck, and has received research grants from numerous pharmaceutical companies.