Guidelines for Antibiotic Decision-making

Key points: Antibiotics serve as a potent therapy that enable clinicians to protect patients from infections (surgical prophylaxis, use in cancer chemotherapy) and contribute to life-saving measures for patients who are ill with an infection. The following measures provide a framework for decision-making related to antibiotic selection and duration.

Alexander Fleming at his lab

The first report of penicillin use on Anne Miller on March 14, 1942 (HIPAA waived) for “blood poisoning” left an indelible impression on the practice of medicine. With an otherwise untreated infection after a miscarriage the month before, she was given an injection of teaspoon equivalent dose of penicillin every 4 hours. After 24 hours, her fever had abated and after one approximately one month of therapy, she was cured. She was able to live a full life to the age of 90 and died in 1999. (Eric Lax, The Mold in Dr. Florey’s Coat). Unfortunately not long after penicillin’s mainstream use did reports of bacterial resistance come. It followed a common theme observed in nature before the discovery of antibiotics and thereafter – an antibiotic selection pressure leads to the growth of resistant bacteria. Are we approaching a post-antibiotic era, where patients will succumb to infections, or can a more judicious use of antibiotics delay further resistance?

Example of testing for resistance — the discs are antibiotic-impregnated. A solution of bacteria is smeared onto the entire plate. Where there is clearance, this is a sign of no growth of bacteria. When there is growth adjacent to the disk, this would mean resistance.

Below are six general guidelines that every patient should know:

  1. Antibiotics are best used in patients with infection.

This seemingly obvious statement is not always so in medicine. Sometimes a patient isn’t able to sense the source or reason for an infection, because of the nature of the infection or problems with their immune system. An examining physician may not have enough findings or clues to discern between an infection versus another condition. Initially, if a patient is showing signs of instability, even if it remains unclear after evaluation, a “shoot first, ask questions later” approach is necessary and possibly life-saving. Both infectious and non-infectious processes can sometimes present with instability. It is incumbent on the physician to advance the workup, looking for potential sources of infection, weighing in and out likelihoods and risks and narrowing in on the diagnosis. Other times, when a patient is clinically stable, a work-up toward a cause with a “watch and wait” approach is reasonable. If a patient is not found to have any obvious infection, a patient may be observed off of antibiotics while advancing toward a more definite answer. Blindly administering antibiotics without recognizing the source or differential diagnosis is fraught with dilemma and subjects a person to potentially stopping a work-up for causes or unnecessary exposure to antibiotics. An abating fever may just be coincidental to starting antibiotics, such as with a viral infection.

2. For most infections, antibiotics just buy time.

In most infections, the antibiotics can help reduce pathogen burden until the host immune system can overtake and neutralize the infection. It is not unusual that supportive measures alone can improve a patient, even if the firstline antibiotic given is insufficient. For example, a patient presents with a kidney infection (pyelonephritis), a more serious ascending urinary tract infection, and is found to have a positive blood and urine culture for a multi-drug resistant E. coli which was resistant to the original antibiotic administered intravenously in the emergency department and the prescription. She was feeling better after they hydrated her and two days later, she is called to come back to ER to discuss results and possibly admit her for intravenous antibiotics. She is feeling better and there is an oral antibiotic option. Clearly, the infection had improved regardless of the antibiotics. Often for more severe infections, the initial days of the antibiotic are the most important, after which time healing and reduction of inflammation occurs and the body strengthens its immune response. The art of treating infectious diseases is to determine the “sweet spot” of treatment, the point where the infection is treated and not able to relapse.

3. Antibiotic treatments are best used for short periods of time in appropriate doses.

Most antibiotic durations are not evidence-based and are consensus-driven, meaning guided by a panel of experts. The optimal duration of antibiotics has become an area of increasing research given increase awareness of bacterial resistance and complications of longer-courses of antibiotics. Historically, antibiotics were used until the patient improved clinically by a reduction of fever, inflammation, erythema (redness at site) or other symptoms. In the last few decades, more rigid and longer antibiotic durations have been employed, often without regards to the specifics of the individual case. Duration of therapy can vary from a few days in the setting of a urinary tract infection (UTI) to approximately four or more weeks in the setting of a heart valve or bone infection. For some infections, recent studies have compared shorter courses with longer courses and have found these to be equal, with a risk reduction of antibiotic-associated complications. However, source control* is paramount in infection control and is enough to reduce the duration of antibiotics.

Examples of durations of antibiotics:

UTI (uncomplicated): 3 days UTI (complicated* with bloodstream): 7 days Community acquired pneumonia: 5-7 days Endocarditis (heart valve): 4-6 weeks Osteomyelitis (bone infection), contiguous 5-21 days (prior 6 weeks) Abdominal abscesses*: 5-7 days

4. Antibiotics are chemotherapy that come with risks.

The term “chemotherapy” was used originally in the early 1900s by Paul Ehrlich to refer to any chemical used to treat disease. Most people are familiar with the term in the treatment of cancer, but it was also used for antibiotics. Perhaps the term conveys more greatly its risks. Patients may develop any number of reactions from antibiotics, including immune responses to the foreign substance, toxicities associated with the chemical, as it relates to liver and kidney metabolism of the substance or its affects on the bone marrow, after effects of the medication or complications from its administration. A physician should weight risks and benefits accordingly when selecting an antibiotic, administration route and duration.

5. Antibiotic use can shift bacterial flora of the host and environment.

This relates to the concept that “nature abhors a vacuum”. In and on the patient, there is increased colonization with resistant bacteria (e.g. MRSA or C. diff) or yeast after exposure to antibiotics. I have noted this particularly with quinolones and cephalosporins. The antibiotics can become a risk factor for future infections, for example Clostridium difficile diarrhea which can become a severe, life threatening colitis in some. On a micro-scale, patients that are exposed to antibiotics develop more resistant bacteria from an antibiotic selection pressure. On a population and epidemiologic scale, antibiotics used haphazardly in nature (for example to promote better livestock growth – a whopping 70% of total antibiotic use in the U.S.) or prescribed in clinics can lead to the development of resistant bacteria. Diseases such as tuberculosis, which is believed to infect about a third of the world’s population (mostly latent TB infection), are emerging with extensive drug resistance (XDR-TB).

6. Antibiotics used judiciously produce immediate and long-term benefits.

Simply shifting from a 14 day course of treatment for pneumonia to a 5-7 day course leads to similar outcomes but can reduce bacterial resistance rates in a hospital and risks of antibiotic-related complications, such as an adverse reaction, C. difficile and gut microbiome disruption. On a larger scale, with less antibiotic selection pressure, bacteria often shift to more favorably growing wild-type forms.

Please Share this information. Thanks from Your Health Forum. Dr. Cirino