We are perched on a global time bomb. Antibiotics, once considered the “magic bullet” for infections, are turning against us. Philip M. Tierno, Jr, in his book “The Secret Life of Germs: Observations and Lessons from a Microbe Hunter,” noted, “The world’s antibiotic use has been a fifty-year experiment in self-sabotage. … the selective toxicity of antibiotics has bred more and more dangerous germs. Wonder drugs have produced super bugs. … Modern medicine is running out of magic bullets.”1
Antibiotic stewardship must be pursued vigorously and relentlessly. Otherwise we risk returning to a time when people die of diarrhea or a simple cut on the finger. Anyone who has ever taken an antibiotic is potentially a source of antibiotic-resistant organisms. We shed, excrete, or otherwise spread bacteria constantly, wherever we go. We can spread antibiotic-resistant organisms to others unwittingly and easily. With global travel, antibiotic resistance knows no boundaries.
Responsible use of antibiotics is a vital first step in the battle against antibiotic resistance. Infection-screening strategies and better diagnostic tools are becoming increasingly important in the battle against antibiotic resistance. The faster clinicians can diagnose infection, the faster they can be matched to the appropriate antibiotic. In his book “The Antibiotic Paradox: How Miracle Drugs Are Destroying the Miracle,” Stuart B. Levy, MD, advised, “Knowing the kind of bacteria causing the disease helps the physician decide what kind of disease symptoms and signs to expect and what kind of drug to use.”2 Armed with this knowledge, physicians can determine whether an antibiotic is in order at all or can prescribe the correct antibiotic, which can cut down on unnecessary use of antibiotics.
Point-of-care testing
One of the weapons in our antimicrobial-stewardship arsenal is point-of-care (POC) testing. The offending bacteria can be identified quickly, so that the appropriate antibiotic can be used from the get-go. When cultures have to be sent to a laboratory, precious time is lost. It is not unusual for a doctor to make an educated guess as to what ails a patient and which antibiotic is appropriate, only to find a mistake has been made once laboratory results are available. This just-in-case scenario can lead to antibiotic resistance. If the time ever comes when the patient truly needs that antibiotic, it may not work due to having developed resistance to it. One instance of how this can happen is with influenza. Influenza is a virus, and antibiotics do not work on viruses. Unfortunately, the patient’s symptoms could initially be mistaken for a bacterial infection of the respiratory tract. A rapid test can determine which illness is the cause of the symptoms, so that antibiotics could be either ruled out or prescribed appropriately.
Alan Wright, MD, MPH, Chief Medical Officer, Roche Diagnostics Corporation, talked to Healthcare Purchasing News about how misdiagnosis and inappropriate use of antibiotics set the scene for resistance. “For respiratory infections like flu and strep, numerous studies have shown that today’s rapid antigen tests have less-than-optimal sensitivity, and the results often need to be sent to a laboratory for confirmation via polymerase chain reaction (PCR)-based molecular tests or viral culture. This results in the loss of precious time when someone is sick and spreading the virus. In addition, misdiagnosis can lead to the inappropriate use of antibiotics.
“One of the best examples of diagnostic testing that contributes to the fight against antimicrobial resistance is real-time PCR testing at the POC, which can deliver highly accurate lab-quality results for flu, strep, respiratory syncytial virus (RSV), and more at the emergency room or physician’s office in 20 minutes or less,” explained Wright. “This gives the clinician definitive answers while the patient is still present. Providing greater certainty about whether antibiotics are needed and ensuring the right antibiotic is delivered can lead to more appropriate antibiotic use. More precise and accurate use of antibiotics is the heart of the antibiotic-stewardship philosophy.”
Wright talked further about advantages of POC diagnostics. “The new generation of compact, Clinical Laboratory Improvement Amendments (CLIA)-waived molecular diagnostics for POC environments offers significant advantages. Real-time PCR is ideally suited for laboratory diagnosis of influenza A/B because of its high sensitivity, high specificity, and fast turnaround compared to culture. Traditionally, most PCR tests had to be performed in moderate- or high-complexity labs and required pre-analytic DNA extraction and subsequent interpretation by trained staff. These tradeoffs, plus the need for transportation of samples to the testing lab, created challenges for emergency department physicians and retail clinic staff who need to make fast patient-management decisions. New technologies have changed that. Roche’s new cobas Liat PCR system, for example, is a closed, sample-to-result, in-vitro diagnostic system with CLIA-waived cartridges for flu, strep, and flu A/B plus respiratory syncytial virus that performs a PCR-based analysis in 20 minutes or less.
“Conventional rapid antigen tests only have sensitivity in the range of 50 to 60 percent, making the diagnostic call about the same as a coin toss,” continued Wright. He referred to a recent study by Nolte et al, which compared performance of the cobas Liat system and another POC nucleic-acid amplification test device to a lab reference standard in detecting influenza A and B viruses in 129 samples from adult and pediatric patients.3 “The authors found that the sensitivities and specificities for flu A and B were all 100 percent for the Liat system,” Wright said. “While this level of accuracy and reliability actually exceeds the claimed performance on the system label, it is clear that PCR-based POC tests can provide a much more definitive flu result than rapid antigen tests currently in widespread use at the POC.”
Ulcers may not be the first thought to come to mind when considering antimicrobial resistance, but there is a connection. Monika Felten, Director of Research and Development, described how Serim Research’s PyloriTek rapid test for diagnosis of Helicobacter pylori infection, which causes ulcers, can help to contain antimicrobial resistance. “Antibacterial therapy is widely accepted for all patients with H pylori infection and peptic ulcer. Factors like antimicrobial resistance affect the efficacy of eradication; so, it is imperative to avoid giving antibiotics to patients who do not need them. One PyloriTek test strip can accommodate three biopsy samples, increasing the chances of finding localized infection sites. Each test strip includes a positive urease reagent control, as well as a negative control zone, thus ensuring the user of the validity of each negative (or positive) test result.”
Felten said that histopathological examination of biopsies, the most common method to date, is frequently performed in an off-site laboratory, which means that reporting can take 24 hours or more. PyloriTek enables clinicians to get results much faster, so that treatment with the appropriate antibiotic can be started sooner. “Rapid urease tests, like Serim’s PyloriTek, allow for the detection of H pylori in up to three samples in less than 60 minutes, thus enabling the diagnosis and treatment prior to discharge within the first visit of the patient.”
There is another important reason that H pylori needs to be diagnosed quickly and accurately: it has been linked to gastric cancer. Felten said that gastric cancer is the second cause of cancer death worldwide. “Gastric cancer occurrence has been linked to previous H pylori infection in several studies. Fast and accurate detection of H pylori in patients is vital. Since the management of H pylori gastritis involves diagnosis, treatment, and confirmation of the cure, it is necessary to employ rapid-test protocols to evaluate patients at the time of their visit to the endoscopy unit.”
Surveillance systems
RL Solutions’ RL6:Infection antimicrobial-stewardship software helps to identify outbreaks of antimicrobial-resistant infection and guide decisions on utilizing the correct antibiotic for the appropriate situation. Pansy Lee, Director, Product, said, “Antibiotic resistance is a serious public-health threat that many organizations are addressing with antimicrobial stewardship. Managing antimicrobial resistance requires evidence to choose the right medication, the right dose, and the right duration for the right bug. RL’s flexible antimicrobial-stewardship software gives teams the ability to develop real-time antibiograms and monitor emerging resistances patterns. In addition, the software allows users to provide tailored measures for their patient populations.”
Lee explained that RL6:Infection delivers real-time data—on lab results, transfers, admissions, and discharges—to help prevent the spread of healthcare-associated infections. “When outbreaks happen, infection preventionists (IPs) can contain the spread with early potential identification via isolate trending, facility- and unit-specific background bioburden rates.” Lee added that RL6’s outbreak-management tools both archive and provide evidence of the effectiveness of user interventions. “Users can keep track of everyone involved with real-time staff alerts and threshold monitoring via email, telephone, and inbox notifications. Plus, the software will help prove the efficacy of an organization’s infection prevention and control program with user-defined contact tracing and reports.”
Automated surveillance systems such as RL6:Infection have the advantage of freeing up expensive human labor, allowing staff to spend more time with patients and less on managing data. “There is a wealth of published data supporting the cost-effectiveness of active surveillance systems to support IP teams. With RL6:Infection, IPs can automate tasks and free up their time, with the software taking on their resource-intensive monitoring and reporting workload. Integrating data analytic reports with knowledgeable IPs and responsive infectious-disease pharmacists provides a comprehensive program and helps improve patient outcomes. Furthermore, RL6’s illustrative graphs and reports can help IP teams effectively present and communicate evidence showing the positive impact of their work.”
Matthew Weissenbach, MPH, CPH, CIC, Director of Clinical Operations, Wolters
Kluwer, Pharmacy OneSource, explained how their antimicrobial-stewardship offering also improves on surveillance, with their hospital customers often realizing 50 percent to 100 percent increases in clinical-intervention activity when the streamlined, data-driven workflows of clinical-surveillance technology are introduced. “Sentri7 has played a significant role in the evolution of technology-enabled workflows that improve the outlook on antimicrobial resistance,” said Weissenbach. “In fact, we just introduced a comprehensive antimicrobial-stewardship offering that provides the advanced clinical surveillance, clinical-decision support, and consulting expertise needed to move antimicrobial-stewardship programs from infancy to high performance. The key to any successful antimicrobial-stewardship initiative is the ability to operationalize best practices and empower appropriate antimicrobial selection and medication management. Because access to the right data at the right time is critical to achieving this over-arching goal, use of clinical-surveillance technology has emerged as a proven method for moving clinical response from reactive to proactive.” He provided an example: “For instance, if an inappropriate antimicrobial is ordered, a solution like Sentri7 can alert pharmacists in real-time, who can then intervene before the medication is administered.”
Weissenbach explained that Sentri7 also assists with antimicrobial stewardship by means of continuous automated and aggregated real-time data collected from electronic medical records and other disparate lab and clinical systems, flagging potential infection and antimicrobial issues. “Real-time alerts are then delivered to clinicians, opening the door to more proactive clinical response,” said Weissenbach. “Key features include actionable, risk-stratified information, drawing attention to urgent issues and the greatest opportunities for improvement; automated antimicrobial-utilization reporting and real-time antibiograms; customized dashboards, clinical rules, and reports; and evidence-based POC guidance and suggested actions.”
Sentri7 also can be cost-effective while ensuring that antibiotics are used appropriately. “Sentri7 has repeatedly proven its ability to drive cost savings in the multiple millions for many organizations. One Dallas-based community hospital used Sentri7 to power an antimicrobial-stewardship program and decreased broad-spectrum antimicrobial use by 15 percent, representing a cost savings of $1,621,730 in one year. Streamlined workflows free up clinician time for better collaboration and increased clinical intervention, driving better decision-making and focus on improvements in clinical outcomes.”
Parting thoughts
Antibiotic resistance is one of the world’s most pressing public-health problems. The Centers for Disease Control and Prevention said that, in the United States alone, at least 2 million people become infected with bacteria that are resistant to antibiotics and at least 23,000 people die each year as a direct result of these infections.4 We cannot afford to continue overusing and misusing antibiotics. We must be more responsible and more proactive. Technology and tools like these can help us to beat antibiotic resistance.
References
1. Tierno PM Jr. The Secret Life of Germs: Observations and Lessons from a Microbe Hunter. New York, NY: POCKET BOOKS, Simon & Schuster, Inc. 2001.
2. Levy SB. The Antibiotic Paradox: How Miracle Drugs Are Destroying the Miracle. New York NY: Plenum Press. 1992.
3. Nolte FS, Gauld L, Barrett SB. Direct comparison of Alere i and cobas Liat influenza A and B tests for rapid detection of influenza virus infection. J Clin Microbiol. 2016 Nov;54(11):2763-2766. Epub 2016 Aug 31.
4. Centers for Disease Control and Prevention. Antibiotic/antimicrobial resistance. https://www.cdc.gov/drugresistance. Last accessed December 29, 2016.
