Barbara Rutkowski, EdD, MSN, CCM – Vice President, Clinical Operations, Advanced Plan for Health
A lot has happened since Alexander Fleming accidentally discovered Penicillin in 1928 after a chance exposure of staphylococcus to penicillin mold. For his discovery, he won the Nobel Prize after penicillin was commercialized in 1945, used successfully for war wounds and surgery in World War II and hailed as the “miracle drug”. In his acceptance speech, Fleming admonished the world to beware that bacteria would become resistant in time.
Fast forward to today where there are several classes of antibiotics including: Penicillins, Tetracyclines, Cephalosporins, Quinolones, Lincomycins, Macrolides, Sulfonamides, Lipopeptides, Aminoglycosides and Carbapenems. While infectious disease specialists worry about continued efficacy in all categories, they are particularly concerned about Clostridium Difficile infections, carbapenem-resistant Enterobacteriaceae (CRE), and neisseria gonorrhoeae. Carbapenem resistance is particularly troubling as this class offers wide spectrum protection for moderate to extreme life-threatening infections, especially for those who have failed other treatment or become resistant to multiple other antibiotics.
Bacteria become drug resistant when their DNA or genes adjust to the antibiotic and send instructions to other bacteria to block the effectiveness of the drug. The challenges are to: Develop drugs that can overcome these genetic changes in bacteria; Diagnose and address outbreaks more readily; Develop novel treatment mechanisms; Improve reimbursement that encourages the costly research and development required to create innovative solutions to fight our creeping world-wide scourge.
Imagine the horror of taking your child to the doctor for strep throat only to discover that he has a drug-resistant bacterial infection for which no antibiotic is effective – or discovering that after a successful surgery, you have an infection which is resistant to the only drug available to treat it. That day is quickly approaching. According to FDA Commissioner Scott Gottlieb, M.D. and the Centers for Disease Control and Prevention, 2 million people in the USA are infected with bacteria resistant to antibiotics, and 23,000 die because of these infections.
Health Plans, health care providers and facilities all need to know that adverse responses to antibiotics are responsible for one in five emergency department (ED) visits, according to a CDC study, and constitute the most common cause for emergency room use, especially in children who are younger than 18. Nausea, vomiting, diarrhea, overdose, inappropriate access by young children and stomach pain are some antibiotic-related reasons for which people seek ED care. By far, allergic reactions are the most common reason, accounting for 78% of those seen in the ED. Most adverse rashes or anaphylactic reactions are caused by the penicillins and sulfonamides. The report continues, “more than one-half of the estimated 100 million antibiotic prescriptions written in the community each year for respiratory tract infections may be unnecessary.”
Common Drug Interactions
Ensuring members and patients read medication inserts is important in their understanding of the directions for taking antibiotics as well as potential interactions with food or other medications. Some of the most common adverse antibiotic interactions are as follows:
- Grapefruit juice may reduce absorption of penicillin and ampicillin.
- Minerals in dairy products may bind with tetracylines to prevent absorption and reduce their efficacy.
- Tetracyclines interact with anti-coagulants to alter their effect on blood clotting, which can be dangerous, especially when used with Warfarin.
- Erythromycin interacts with theophylline, an asthma drug, increasing levels of the asthma drug.
- Erythromycin interacts with statin drugs, designed to reduce cholesterol levels, resulting in a greater risk of muscle aches and soreness.
- Erythromycin interacts with carbamazepine, an anticonvulsant, thereby magnifying the effect of the seizure medication.
- Taking mineral supplements like calcium and magnesium with antibiotics like Cipro, a fluoroquinolone, reduces the effectiveness of the antibiotic.
Adverse Impact on “Good” Bacteria
More deadly consequences may occur since antibiotics erase normal flora along with the pathogens, paving the way for an invasion of fungal or other opportunistic infections like Clostridium difficile (C. Diff), a virulent bacteria causing severe diarrhea, that kills 14,000 Americans annually. While older and frail people are at the highest risk, even previously healthy individuals can get this infection when normal immunity is depleted by taking an antibiotic. When C-diff recurs and especially when it is resistant to currently available drugs, a fecal transplant may be needed to save lives and avoid devastating debility.
When individuals take an antibiotic for a virus or another unneeded application, they chance wiping out their normal immunity for no good reason, and increase the incidence of infections like C. Diff which destroy protective “good” bacteria for many months. C. Diff is spread by contact with infected surfaces or by healthcare workers who do not wash their hands properly. There is always the danger of developing resistance to the antibiotic, or even initially contracting a resistant form of C. Diff. Facilities need to be cognizant of C. Diff outbreaks, and contain them quickly so that they do not spread across the patient population of vulnerable people.
Fortunately, there are companies doing research into the microbiome, which involves studying the new frontier of how protective organisms in the gut work. A therapeutic agent is in late development, and a synthetic therapeutic is in early trials to address the serious problem of recurrent C. Diff.
Hospitals and other facilities have worked diligently to experiment with various sterilization and cleaning agents, and continue to change processes for managing central lines and catheters, while innovating to reduce infections arising from being treated in a healthcare facility. However, diligence in preventing infections and limiting their spread is an ongoing battle.
Health care providers are also admonished to advise their patients to take the entire prescription, so as to avoid partially treating a bacterial infection which may leave some resistant bacteria untreated or difficult to eradicate. Further, prescribing the narrowest spectrum antibiotic that will treat the infection is important, so the effectiveness of stronger, wider spectrum antibiotics can be reserved for the most serious bacterial infections.
Efforts to Impact the Prevention and Treatment of Bacterial Infections
In August, 2017, the FDA Center for Drug Evaluation and Research (CDER) published “Antibacterial Therapies for Patients with an Unmet Medical Need for the Treatment of Serious Bacterial Diseases Guidance for the Industry”. This FDA position paper was released shortly after the 21st Century Cures Act (Public Law 114-255) was enacted. Section 3042 of this law established a limited population pathway for specified antibacterial and anti-fungal drugs (LPAD) intended for use in treating individuals with serious or life-threatening infections where limited or no other drugs are available. Although the FDA plans to streamline the development and approval process, safety and efficacy will remain a major consideration. Physicians and limited population users have to evaluate the risk versus the reward of taking fast-tracked drugs that may not have the usual degree of vetting, because severe debility and / or death may be the alternative for these individuals.
In June, 2018, The FDA issued Draft Guidance for the implementation of section 506(h) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), added by section 3042 of the 21st Century Cures Act, 2 20 21 which established the limited population pathway for antibacterial and antifungal drugs (LPAD pathway). 3 22 23 24 Section 506(h)(5) of the FD&C Act requires FDA to issue guidance for limiting the use to individuals impacted by serious and life-threatening bacterial infections for which there are limited or no medications available, while demonstrating the safety, effectiveness and risk vs. reward of taking these newly approved, fast-tracked drugs. The public comment period is now occurring.
In groundbreaking research at Purdue University, a new compound, termed F6, was found to be as effective as antibiotics with FDA approval for the treatment of gram positive organisms such as, methicillin-resistance staphylococcus and vancomycin-resistant staphylococcus. So far, the researchers have been unable to a create drug resistant version of F6 despite conducting several experiments to do so. These Purdue University researchers just published their findings in the European Journal of Medicinal Chemistry in mid-June, 2018.
Appropriate Antibiotic Use and Infection Prevention
In addition to the FDA and CDC, there is a global watchdog known as the Alliance for the Prudent Use of Antibiotics (APUA). With chapters in 66 countries, APUA aims to ensure access to effective treatment while encouraging appropriate antibiotic use to slow drug resistance. Known for its research, input into influence on policies, surveillance, databases, biodefense and public education, APUA is an example of a multifaceted global initiative that contributes on many levels to ensuring that the world will continue to have access to essential powerful drugs to treat infection.
Infections can be prevented or limited by optimizing health and immunity, keeping immunizations up to date, avoiding unneeded antibiotic use, using antibiotics as directed, handwashing, and safe food preparation. Avoiding people with communicable diseases and covering one’s mouth when coughing or sneezing are critical.
Nearly half of the antibiotics used in animals and prescribed for people are unnecessary, so their use should be more diligently managed. It is prudent to read food labels to be knowledgeable about the use of antibiotics in food, as well as where the food is sourced. Checking dates for recommended use and avoiding packages that look old or withered / discolored is also recommended. Additional best practices are washing raw food before use, keeping hands and work surfaces clean, avoiding undercooked food – especially meats, poultry, fish and eggs – and storing foods at the proper temperature.
International travel precautions are essential in avoiding microbial infections. When ill from foreign travel, it is important to mention the country to the infectious disease specialist so that someone who is experienced in diseases from that specific locality can be consulted. For example, tropical medicine is a discrete specialty for which many American physicians have little or no experience.
Immune-suppressed persons need to take special precautions and avoid large crowds, children with communicable diseases, and even fresh fruit and vegetables in extreme cases. This group includes, but is not limited to, individuals with immune disorders, cancer, kidney disease, transplants, and those who are depleted from extended illnesses.
Identification Through Analytics
Advanced Plan for Health’s Poindexter analytics platform has a sophisticated database with predictive modeling capabilities designed to identify high risk members along with their diagnostic and drug utilization history over several years. Our clinical leadership team is constantly researching areas such as this, and determining how our clients may best identify them within Poindexter.
To find microorganisms that are drug resistant, look at active disease processes under ICD-10-CM codes such as – A49.02-Infection, A41.02-Sepsis, or J15.212-Pneumonia. The list will include Methicillin Resistant Staphylococcus aureus (MRSA), as well as many others.
In addition, there are ICD-10-CM code sets which include a group of codes beginning with Z16 that may be used to identify the general resistance of microorganisms or their non-responsiveness to specific antimicrobial drugs. The set includes specific antibiotic resistance, such as vancomycin resistance (Z16.21), and general groupings, such as antiviral drugs (Z16.33).
The APH Poindexter analytics data warehouse includes an easy-to-use advanced search tool to enable users to enter the codes for antibiotic resistant microorganisms in order to identify the individual members who fit the search parameters. Poindexter also provides users with the ability to dive into the medical and pharmacologic history, biometrics and clinical notes with the advantage of seeing care gaps and predictive modeling risks to determine compliance with the Plan of Care, future costs, admissions, and various disease states like the probability of having a stroke or myocardial infarct.
For more information on how Advanced Plan for Health’s team is working with clients in critical areas such as these, please contact us here.