To be completely honest, antibiotics confuse the hell out of me, and I noticed recently that I subconsciously avoid the topic if possible. I blame this on the fact that generally we aren’t starting antibiotics in the field, and if we are transporting them, they rarely require much titration. I would even argue that these infusions can even at times be pushed down the line of importance in the three channel pump world that some organizations operate within. I am going to take the next few blogs and attempt to break down the essentials of antibiotic therapy. What do we need to know? On the morning of Friday, September 28, 1928 a Scottish scientist named Alexander Fleming recalls walking into his laboratory in the basement of the St.Mary’s Hospital located in London. He noticed a Petri dish containing the bacteria staphylococcus had been left open and exposed to the elements of an open window. The open window had caused mold to form amongst the staphylococcus within the dish and created a small halo of inhibited bacteria growth. This eureka moment caused him to suspect that the mold had actually regressed the growth of the bacteria. We now fast forward 90 years and have more antibiotics than we could have ever imagined. However these were all formed based off the Penicillin experiment in 1928. The goal when trying to suppress a bacterial growth is to combat it with specific coverage. If we give something that has a wide spectrum, we kill good bacteria as a casualty. So how do we determine what breed of invader we are dealing with? The Usual Suspects! A blood culture is drawn and examined under a microscope for bacteria growth. The bacteria can be simplified into a few different shapes under microscopic view. Circles (Coccus)
Rods (Bacillus)
Squiggles (Spirochete)
Gram Staining A gram stain is a differential stain in the initial identification of two large groups of bacteria. Gram Positive and Gram Negative bacteria will be recognized by their peptidoglycan layers. Gram Positive has a thick, impermeable cell wall that remains crystal violet (purple) throughout the staining sequence. Gram Negative does not possess the same thickness of the Gram positive wall and thus is able to be decolorized and retains the safranin (pink). Reasonably we could conclude these distinguishable layers would rank the importance of the cell, however, you may be surprised to find out that Gram Negative bacteria are the typical human pathogen. They are antibiotic resistant not due to their peptidoglycan layer but because of their two outer membrane walls rich in lipids and proteins. Only one outer membrane wall is found in the Gram Positive cell. The staining process will bring out some basic information about the cell shape, size, and arrangement. So now we can discern the two bacterias and start selecting the proper agent to lyse the bacteria membrane and inhibit growth. Lab Time! Let’s pretend you are observing cultures of a patient and under the microscope you see the following organism.
We can identify groups of cocci clumped together. This is called staphylococcus. Whereas a line of single cocci would be called streptococcus. It is noted that during the gram stain test, the bacteria remains purple. We can see that staphylococcus is a gram positive bacteria (thicker cellular membrane). So notwlet’s see how our culture responds to several different antibiotics in the Petri dish.
The slightly noticeable halo around penicillin, shows that the staphylococcus was resistant to our first generation broad spectrum antibiotic. This means it would not be very efficient to place this patient on penicillin to kill the infection. Penicillin saved many lives and seemed to be a miracle discovery. However, it soon became apparent that infections once treated by penicillin, had reduced the peripheral halo size in the petri dish and grown resistant.
There needed to be something stronger for cases such as these. In 1959 Methicillin was discovered. This was going to replace penicillin in cases of bacteria that had grown resistant. As you can probably assume the staphylococcus strand of bacteria once more evolved into the widely known methicillin resistant staphylococcus aureus (MRSA). What’s interesting to me is that in 1953, Vancomycin's was created as an antibiotic for staphylococcal resistant to penicillin. So why wasn’t Vancomycin's as popular? 1.It wasn’t stable in the oral administration route (Intravenous preference). 2.Early trials used impure forms of the drug ("Mississippi mud"), which were found to be toxic to the inner ear, and the kidneys. These findings led to Vancomycin's being relegated to the position of a drug of last resort.
Why is this important for transport medicine?
We would hardly feel comfortable transporting a patient on a medication that we knew absolutely nothing about, however these infusions are often moved down the line of importance. This may or may not be an issue depending on the time of discontinuation and kill pattern of the agent being used.
Three Ways To KILL!
1.Concentration Dependent
These agents depend on the maximum concentration (CMAX) to effectively kill bacteria. Usually given as a single bolus.
2.Time Dependent (The one we probably shouldn't just DC for transport)
A certain amount of time is needed to effectively kill bacteria. This time above the minimum inhibitory concentration (MIC) can be interrupted by EMS discontinuing the antibiotic prematurely for transport.
3.Area Under Concentration (AUC) Time Curve.
The AUC is the concentration of drug above the MIC that is in the plasma after a certain amount of time. Each agent will have a certain concentration it needs over a predetermined time to be effective. These are typically given at a certain time over a few therapy sessions. Brief interruptions should not affect accumulative concentration is restarted at receiving facility.
In part two we will discuss what antibiotics/patients need careful dosing regiments and consideration for transport. Stay tuned!
References:
https://openi.nlm.nih.gov/detailedresult.php?img=PMC3940399_coidi-27-165-g003&req=4
https://lifeinthefastlane.com/ccc/antimicrobial-kill-characteristics/
https://lifeinthefastlane.com/ccc/minimum-inhibitory-concentration-mic/