Just in time for “Get Smart about Antibiotics Week,” I had a refreshing experience recently, working in a different rural hospital. Over that week, I didn’t see one patient with “superbugs” other than the occasional MRSA. No one had the now scarier Gram negative bugs known as ESBLs (extended spectrum beta lactamases) or the even worse CREs (Carbapenem-resistent enterobacteraciae). I did my part to keep it that way, such as by teaching and modeling use of narrow spectrum, selective antibiotic use. I also have been thinking about the various hospitals I work at, wondering about the local practices that might lead to such vast differences in antibiotic resistance and prescribing patterns.
Multiple factors drive misuse of antibiotics. These are well-outlined in a very readable and (almost)* thorough review just published in The Lancet Infectious Diseases, “Antibiotic resistance—the need for global solutions,” including:
Spread of resistance
The magnitude of the spread is highlighted, particularly illustrated by the convergence of poverty and poor sanitation. For example, the highly resistant NDM-1 bacteria is now being found in 30% of seepage samples and 4% of drinking water samples in New Delhi. This poor hygiene and sanitation is compounded by “contaminated food, polluted water, overcrowding, and increased susceptibility to infection because of malnutrition or HIV.” With globalization, such organisms are spreading worldwide.
Resistant organisms are more difficult and more costly to treat, often requiring injectable, rather than oral antibiotics. Infections with resistant organisms are also far more deadly. This is especially true for newborns, in whom infections with resistant organisms more than doubles the death rate, to greater than 50%.
Resistant bacteria may also seriously inhibit the ability to do invasive procedures, such as transplants and even common orthopedic procedures like joint replacements, and may even prevent patients from receiving chemotherapy. A recent and frightening estimate is that 30-40% of patients undergoing hip replacements without effective antibiotics would develop an infections, and that 30% of these would be fatal.
Agricultural use: Shockingly, most of the 100,000-200,000 tons of antibiotics produced each year go to agricultural and veterinary use, according to the Lancet. Fortunately, the European Union has banned the use of antibiotics as growth promoters in animals. Unfortunately, the US has not yet followed suit.
Diagnostic testing: The Lancet commission authors rightly note that “Diagnostic uncertainty drives irrational use” of antibiotics. I agree that having rapid diagnostics that could distinguish between bacterial and viral infections (the latter, like “colds,” don’t respond to antibiotics) could be enormously helpful in reducing inappropriate antibiotic use. Current bacterial cultures generally take 2-4 days to provide usable information—in the meantime, patients are often given unnecessarily broad antibiotic coverage “just in case.”
The Lancet gives a good overview of the numerous technical difficulties in developing and performing rapid diagnostic assays, as well as the lack of consensus as to whether the tests should focus on genetics (resistance mechanisms) or antibiotic resistance and the difficulty of conducting clinical trials of diagnostic tests in real-world situations.
A View from the Trenches on Antibiotic Use
In addition to the excellent global perspective on antibiotics, my work in the "trenches" offers a few other insights as to problems that might more readily be tackled.
For example, there is a downside to hospitals’ increasing use of standard order sets and “quality assurance” efforts. Sometimes these efforts are misguided or have unintended consequences. One of the disturbing aspects about such “guidelines” is that they have a chilling effect on thinking. For example, a recent patient was put on extraordinarily broad spectrum antibiotics for pneumonia with a 3rd generation cephalosporin, a quinolone, and Clindamycin. I tried to walk through thinking with the house staff regarding what bacteria to expect in specific settings. I argued against Levaquin—it causes confusion, especially in the elderly, and promotes MRSA colonization, and resistance to quinolones is widespread, although they have only been in use for 30 years. Clindamycin is a terrific drug, but carries an increased risk of Clostridium difficile (“C. diff”) colitis. The patient was not at significant risk of highly resistant bacteria, based on her history. Yet I understood their fear of repercussions from not following a “guideline.” I agree with antibiotic stewardship guidelines, as long as they are suggestions and not absolute decrees. I—and the patient—won this round.
Similarly, one underappreciated driver of Vancomycin, Linezolid, and carbapenem antibiotic overuse is concern about patients who claim to be allergic to penicillins. It is imperative that health care workers learn to differentiate between true and serious allergies, such as anaphylaxis, vs. someone getting a minor rash or local injection site reaction, decades earlier, which would not preclude use of a penicillin or cephalosporin type of antibiotic. Physicians and nurses need also understand that cross-allergies between penicillins and cephalosporins are not that frequent. Patients, too, are often to blame as they list as allergies a drug that might have caused a minor upset stomach. They do not understand that intolerances are not the same as serious allergies. This faux “allergy” leads to a common error in ordering the antibiotics that should have more restricted use, saving them for when essential.
End of life
I’ve written before on how resistant organisms are spread in nursing homes, and then to hospitals, by inadequate isolation practices in many nursing homes. I’ve also written about futile care being an enormous and unaddressed factor driving antibiotic resistance.
I’m not sure what exactly the differences are between the most recent hospital I worked at and my usual ones, where resistant organisms such as ESBLs are widespread and now even CREs are seen, and the new hospital, where I saw no superbugs. Two obvious differences were apparent: the hospital without resistant Gram negative bacteria (CRE and ESBLs) is not associated with long-term acute care hospitals (LTACs), which are breeding grounds for superbugs. This hospital is also the only one I work at that has an active palliative care and hospice service. Both of these reduce the likelihood of futile care, thus lessening the chance of promoting antibiotic resistance. More antibiotics are restricted to Infectious Disease consultation or approval as well at this hospital. When I return, I look forward to exploring more differences.
Tackling antibiotic overuse
We’ve seen that there are many contributors to antibiotic overuse, including pressure from patients for prescriptions, inadequate and sometimes misleading education, limited timely diagnostic capabilities, and financial incentives for overprescription. One appealing suggestion is to use public funding to buy patents, with manufacturers then being “licensed to produce antibiotics on a scale appropriate for rational use.”
We need to emphasize education—for patients not to demand antibiotics, for practitioners to resist irrational demands (I know how difficult, frustrating, and time-consuming that route is!) and in proper antibiotic use. There are widespread differences in prescribing patterns even across the US, that cannot be accounted for by epidemiology or micro results.
I would like to see some antibiotics specifically restricted, and feel that antibiotics should be considered a national (and global) security issue.
Until these ideas of better education, changing the financial incentives for pharmaceutical companies, and improved diagnostics are implemented, we’ll need to continue with the public health messaging of “Get Smart about Antibiotics Week.”
Will effective antibiotics be there for you when you need them? Perhaps...but only if we start behaving as if they are the scarce and irreplaceable resource that many of us believe them to be.
*As Dr. Eli Perencevich astutely points out, infection control and prevention are not given appropriate attention in the Lancet report.
"Molecules to Medicine" banner Michele Banks
images all courtesy CDC