SCCM Resource Library-Antibiotics, Enzymes, and Powders: Managing the Magic of Pharmacologic Agents Used in Complex Wounds

Video Transcription

Hi everybody, my name is Leslie Hamilton, I am an associate professor and pharmacist at the University of Tennessee Health Science Center College of Pharmacy, and I'm also a neurocritical care pharmacist.  Today I'll be talking about antibiotics, enzymes, and powders, managing the magic of pharmacologic agents that are used in complex wounds. I don't have any disclosures today.  And our objective for this presentation is to recognize how antibiotics, powders, and solutions may help or harm in the management of complex wounds.  So this data is taken from the CDC, and on their website they have a variety of different organisms and resistance mechanisms that are of concern.  And I just chose one of them, the carbapenem-resistant enterobacteriaceae.  And this is very scary to me because it's one of the most broad-spectrum classes that we have in terms of antimicrobials.  And in 2017 when this data was taken, about a thousand patients died from these types of infections, and it cost upwards of $130 million to treat these sorts of infections.  And over the past several years, as you can also see in the bar graph on the bottom, the incidence of these infections is continuing to rise.  So this is a continuing concern and something that is a call to all health care providers that we need to be judicious in the antimicrobials that we choose  and have good stewardship in our patients in the ICU and really limit courses in these sorts of patients.  So now we'll talk about some factors that contribute to antibiotic resistance and also hopefully some solutions that might help in patients with wound infections.  So diagnostic uncertainty, whether to get cultures and whether a patient's colonized or not.  Rapid diagnostic tests can help sometimes in these patients and giving us a faster answer than waiting sometimes for cultures that will take sometimes a day or two to come back.  And then also some biomarkers, even though some biomarkers are still very nonspecific, they can be used in this sort of patient population.  Another factor that can contribute is clinician inexperience, especially maybe providers who have not had patients with very severe wound infections before.  So we need to work on education and increased literature to help with this.  Clinician fear, maybe clinicians are scared that if they don't do broad spectrum antibiotics for a long period of time,  the patient won't get better or they potentially might get sued. So that's also something that we can help with education and also support.  And finally, sometimes patients demand antibiotics, as you all know, even if it's not indicated, maybe for a viral infection or something like that.  So it's also patient reinsurance and education in these sorts of situations. Now, depending on the type of condition that a patient has with a wound infection,  you really can think about what organisms that are most likely to grow and then that will help you pick your antimicrobials that you're using in these patients.  So some of the more difficult types of infections are burns where you have gram negatives like pseudomonas and then also have gram positives like strep and staph  and then can also have candida and aspergillus in these sorts of patients. So very broad spectrum, especially when it's a large total body surface area burn.  A cellulitis is typically strep or staph.  And so that can really help you narrow your antibiotics to gram positive coverage because these patients typically do not need gram negative coverage.  Now, chronic ulcers, they also can tend to be polymicrobial. So they can have staph and strep, pseudomonas, enterococcus, bacteroides, clostridium, those sorts of things.  And then as you move from gangrene and gas gangrene, you do have to think about the enterobacteriaceae group, also bacteroides and staph and strep.  Osteomyelitis, simple osteomyelitis. I'm not talking about other types of maybe surgical infections that may be associated and have some different bacteria.  Typically is staph, though other things, of course, can grow there. Then there's strep gangrene and neck fash, which often is a mixed infection.  And then finally, if a patient has toxic shock syndrome, it's often strep pyelogenes or staph aureus.  So as you're examining your patients, really think to yourself, is this wound infected?  So if you're trying to differentiate between active infection and something that's more chronic, is it red?  Is it warm to the touch? Is there swelling there? Is there secretions that are purulent and also pain?  And then does the patient, let's say it's in their arm, do they have loss of function in that in that limb, depending on how severe that wound may be?  Now, patients who have more of a chronic infection, there may be an odor associated with this infection,  abnormal and excess granulation tissue, kind of a bridging pocketing of purulent material.  Those sorts of things can hopefully help differentiate to you. Is this infected or is it more colonized and not actively infected?  So this is a great flow chart. And if you if you think about if the wound is clinically infected.  So is there an epidemiological reason to cure? And if there's not, don't culture the wound. It may have enterococcus there, but if there's no reason to epidemiologically,  like if you're worried about VRE or something like that, don't culture the wound because there is going to be some bacteria there.  Now, if there is an epidemiological reason to culture, then you can. And then then going through thinking about is there a reason to eradicate these colonizing organisms?  And if there's not, then antibiotic therapy is not indicated. If the wound is clinically infected, then get a appropriate biopsy tissue sample for culture.  Pick a appropriate antimicrobial regimen that is empirically based on what is most likely to grow.  Review culture and susceptibility results and then kind of go down the rest of this flow chart.  If it's negative, these culture results or colonizing organisms may be repeat culture once a patient's off antibiotics. And then if you have some presumed pathogens,  then you can help pick a more definitive regimen that you're really thinking about spectrum, route and also duration. So you want to have the narrowest spectrum possible.  We're going to talk a bit about topical, oral and parenteral antibiotics in a little bit. And then also duration and choosing the shortest duration possible for that patient.  So before we get into topical antibiotics, we are going to talk about collagenase or Santel, which is the most popular topical enzymatic agent.  And it's derived from a clostridium and it is used, as many of you know, for debridement. But the great thing about it is that it does not attack native collagen.  So it only is helping to breed the tissue that needs to be debrided. There are not that many large randomized trials with collagenase,  but a few that I want to present today is one was in a patient with a diabetic foot ulcers, about 100 patients, and they compared collagenase versus silver containing products.  And there is really no difference between them, that both products promoted reduction of ulceration. They also compare collagenase to medicinal honey.  And they did find that collagenase achieved faster granulation and epithelialization in patients who received it. And these were patients with pressure ulcers.  And there are about 500 or so wounds that were covered in this trial.  On the next few slides, we'll talk about topical antimicrobials and topical antiseptic agents. So this slide is going to cover our topical antimicrobials first.  So we are going to start with fucitic acid and it works by inhibiting protein synthesis. And its main use is in patients with staph aureus.  Maffinide is another option. But of note, remember that this is a sulfa based drug. So if a patient has a sulfa allergy, this drug should not be used in those patients.  It inhibits folic acid synthesis and it works for gram positives and gram negatives, including pseudomonas.  And it has uses in burns. So this can be a very good broad spectrum topical antimicrobial.  Mupiricin does inhibit protein synthesis like fucitic acid, but it only works on gram positives, mainly staph aureus.  But it does not work against enterococcus. So a triple antibiotic ointment like polymyxin,  baxitracin and neomycin has three different mechanisms of action working as a cellular detergent, inhibiting cell wall synthesis and also interfering with protein synthesis.  And depending on which antibiotic you're talking about in this combo, polymyxin is mainly for gram negatives.  Baxitracin is for staph aureus and the neomycin works for multiple gram positives and negatives, but it does not cover pseudomonas.  And then you'll also see the polymyxin has some holes in its coverage as well for some of the gram negatives.  And then finally, silver sulfadiazine, it disrupts your cell wall and it has most of its use in burns, gram positive, gram negatives, and it also does cover yeast.  Moving on to the topical antiseptics, we have chlorhexidine, which will be denoted by CHG through the rest of the presentation.  It disrupts cell wall and it has both gram positive and gram negative coverage, but it covers gram positives more than the gram negatives.  Povidone iodine, it oxidizes proteins, nucleotides and fatty acids. And this one and also sodium hypochlorite or Dakin's solution, as you'll see, are both very, very broad spectrum.  So they cover gram positive, gram negative, fungi, protozoa, viruses. So they really are working against most everything.  But you also have to think, too, that you're killing off your normal microorganisms that are on your body when, if you have regular use of these sorts of solutions.  So that's something to consider and how broad spectrum they both are. So when you're thinking about a topical agent versus a perineural agent or in addition to a perineural agent,  here's some some things to kind of think about. Do you have a clean wound in your patient and you want to use it as these agents as prophylaxis?  From several trials that this use is really discouraged. There's no benefit of these agents in these sorts of patients with a clean wound.  How about a patient who has a recurrent infection and you want this to be as a prophylaxis in these patients?  There have been some trials about bleach baths done for at least 15 minutes a certain number of times a week.  And in patients with recurrent MRSA infections that there may be some role of these bleach baths in these patients. So what about prophylaxis and operative wounds?  There is literature, especially in the cardiothoracic surgery population, about staph aureus decolonization. So nasal mupiricin can be used, same as topical chlorhexidine.  And then if there's a shortage or patient is not able to receive chlorhexidine, they can get povidone iodine.  A note that is important, though, is that be careful if people have severe thyroid disease because of the iodine content in povidone iodine.  Also topical antisepsis with chlorhexidine.  However, take note that there's a certain drying time of chlorhexidine due to the risk of surgical fires of the alcohol content that's in chlorhexidine.  In ICU patients, there is some literature about chlorhexidine baths in these patients.  However, there have been some increased concerns about resistance and if it helps breed resistant microorganisms in these patients. That is a concern.  I know some institutions also will use the nose and nasal applicators as well for decontamination. So there is pretty sparse literature, but those are just some considerations.  So in consideration of when to use systemic antibiotics, there are several principles to think about. Does this patient have increased bio burdens?  There are a large amount of microorganisms in the wound. Is there a cellulitis that accompanies this wound infection? Does the patient have osteo? Are they immunocompromised?  Do they have HIV? Do they have cancer and undergoing chemotherapy? Those sorts of things that might compromise host defense. Do they have bacteremia or have sepsis or septic shock?  These are all things that should make you think, okay, systemic antibiotics are indicated in this situation.  Now, taking all of this into account, some questions to consider as we move on to the literature in the next few slides is,  when should IV antibiotics maybe be used preferentially over PO? Or is there an opportunity to use oral antibiotics instead of IV antibiotics in certain situations?  And also, some of our literature for osteomyelitis and the duration of treatment is changing a bit. And there's been some recent literature that we'll cover on the next few slides.  So also ask yourself, what's the optimal duration for your patient if they do have osteomyelitis? So the OVIVA trial was published in New England Journal of Medicine in 2019,  and they compared oral versus IV antibiotics for bone and joint infections. These patients had to be enrolled within seven days of surgery.  But if they were having more conservative treatment and they did not have surgery, it was just within seven days of the antibiotic therapy being initiated.  They were randomized to either IV or antibiotics to complete six weeks of therapy, and there were about 527 patients in both groups.  And treatment failure was seen in 14.6 percent of the IV group patients and 13.2 percent of the oral patients.  In the intention to treat analysis, there was no difference in the risk of definitive treatment failure. And comparing PO to IV, and you'll see the confidence interval down below.  And there was also no difference in serious adverse events.  But as you would expect, there were more catheter complications like phlebitis and those sorts of things in the patients who received IV therapy,  9.4 percent versus 1 percent in the PO group. In another trial in clinical infectious diseases published just last year,  they compared three weeks versus six weeks of antibiotics for diabetic foot osteomyelitis.  So these patients all had surgical debridement and they were randomized to either three or six weeks of antibiotics.  And there were about somewhere between 40 and 50 patients in each group.  Now, they did exclude patients with implants, patients who had other reasons that they had to get antibiotics greater than three weeks.  If they had a full amputation and if there's also complete bone destruction. Now, interestingly enough, they had very strict criteria on the antibiotics the patients could receive.  Levofloxacin, Augmentin, Clindamycin, Linazolid, Metronidazole, Estreunium, and also Zosyn, IV and PO options for these patients.  So looking at the results, there was a remission that was achieved in 84 percent of patients in the three week arm and in 73 percent of patients.  In the six week arm in their intention to treat analysis. So the P value was 0.21. So it was not statistically significant.  And also there were no differences found in adverse events or remission in the protocol population.  So these two trials, even though it's just two trials, has given us some more literature that maybe we could use oral antibiotics instead of IV antibiotics in patients to treat these wound infections.  And also, even though most of us have been taught that osteomyelitis always needs six weeks of antimicrobial therapy,  there might be certain situations that three weeks of therapy may be just as appropriate as six weeks of therapy.  So in conclusion, antimicrobial stewardship is very important and it's important for all of us in all professions in preventing drug resistance and also preserving available treatment options.  Unfortunately, it there are not a lot of antimicrobials that are in the pipeline for our resistant infection.  So we need to preserve what we have. If possible, we should all work to limit treatment courses of antibiotics as long as it's appropriate in those patients.  And then finally, in some patients, topical therapies may be appropriate and they especially can get good coverage in their areas and can get good concentrations locally in those areas.  So when appropriate, please do consider those those agents in these patients. I appreciate your time and thank you so much for listening today.

Video Summary

In this video, Leslie Hamilton, an associate professor and pharmacist, discusses the use of antibiotics, enzymes, and powders in managing complex wounds. She highlights the increasing concern of antibiotic resistance and the need for judicious use of antimicrobials. Factors that contribute to antibiotic resistance include diagnostic uncertainty, clinician inexperience, clinician fear, and patient demand for antibiotics. Hamilton emphasizes the importance of considering the type of infection and the organisms likely to grow when selecting antimicrobials. She provides a flowchart for determining whether a wound is infected and when to use systemic antibiotics. Hamilton also discusses the use of topical antibiotics, such as fucidic acid and mupirocin, and topical antiseptics, such as chlorhexidine and povidone iodine. She presents data from studies comparing oral versus IV antibiotics for bone and joint infections and the duration of antibiotics for diabetic foot osteomyelitis. Overall, Hamilton emphasizes the need for antimicrobial stewardship to prevent drug resistance and preserve treatment options.

Asset Subtitle

Integument, Quality and Patient Safety, 2022

Asset Caption

With the increased acuity and aging of the critical care population and the multiple comorbidities associated with specialty conditions, the incidence of catastrophic wounds has significantly increased. Many of these wounds may be preventable and managed earlier. This session will highlight the unique situations in which these wounds develop—whether they are caused by pressure ulcers, unique infectious diseases, pharmaceutical reactions, or oncologic conditions—how critical care professionals can identify their causes, and ways to identify and manage them to successful outcomes.

Meta Tag

Content Type Presentation

Knowledge Area Integument

Knowledge Area Quality and Patient Safety

Knowledge Level Intermediate

Knowledge Level Advanced

Membership Level Select

Tag Wound Healing

Tag Evidence Based Medicine

Year 2022

Keywords

antibiotic resistance

antimicrobials

topical antibiotics

systemic antibiotics

antimicrobial stewardship

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