Reducing Antibiotic Resistance in Chronic Skin Conditions
Treatment for hidradenitis suppurativa often involves antibiotics for first-line management, but little is known about whether this strategy induces bacterial resistance. To explore this possibility, Ginette Okoye, MD, and colleagues, conducted an analysis of 239 patients with hidradenitis suppurativa. Dr. Okoye spoke with Consultant360 to share the details of what she learned and to offer her perspective on how the study’s findings might change treatment choices for hidradenitis suppurativa. Dr. Okoye is an Associate Professor of Dermatology at the Johns Hopkins School of Medicine in Baltimore, Maryland.
What led you to pursue research on antimicrobial resistance in hidradenitis suppurativa?
I take care of many patients with hidradenitis suppurativa, and I prescribe more antibiotics than almost any other drug. I began to wonder if the sheer volume of antibiotics we give to those patients could be a problem.
Out of curiosity, I started to culture the purulent material that patients have in their lesions. I was especially concerned with patients whose lesions were not responding to therapy, or patients who had hidradenitis suppurativa as well as evidence of infection around their lesions (ie, cellulitis).
When I cultured the material from the lesions, I started to see antibiotic resistance, particularly clindamycin resistance. This is concerning because we frequently prescribe both topical and oral clindamycin to patients with hidradenitis suppurativa.
Shocked, I wondered if the prescriptions we give for clindamycin and other antibiotics were driving the bacterial milieu to be resistant. Once we looked at the data, we saw that the patients who used topical clindamycin at any point prior to their bacterial culture were more likely to have clindamycin resistance.
Although clindamycin resistance is concerning, there is a solution. When we use clindamycin alone topically, even in acne, it is more likely to cause bacterial resistance. However, when we combine clindamycin with benzoyl peroxide, the chance of resistance decreases significantly. As a result, if I give someone topical clindamycin, I either ask that patient to use a benzoyl peroxide wash in the same area as the clindamycin, or I give the patient a compounded topical preparation containing both benzoyl peroxide and clindamycin.
Are there any downsides to prescribing the combination?
One downside is that the compound preparation can be more expensive than clindamycin alone. The benzoyl peroxide wash can also be drying and irritating to some patients. However, the wash comes in many different strengths, anywhere from 2.5% to 10%, and it can be titrated according to the patient’s comfort.
Additionally, benzoyl peroxide bleaches clothing, and this can be a problem for patients. Both the wash and the compounded cream may bleach towels, underwear, bras, and the underarms of shirts.
Do you have any tips for explaining the combination prescription for patients?
I tell patients that I would like to add an extra medication so that the clindamycin will continue to work well for them. For some patients, I’ll go into the whole bacterial resistance issue because many patients have heard of it in the news. With other patients, I’ll explain it by saying, “There’s a chance the clindamycin will eventually stop working for you and that the bacteria on your body will get used to it. Adding the benzoyl peroxide tends to make the medications work better and for longer.”
The compounded cream is usually covered by insurance, but if it is not, then I will still prescribe the clindamycin and provide the patient with a list of over-the-counter benzoyl peroxide washes.
For almost all patients, I recommend bleach baths 2 to 3 times per week. The patients should fill a full tub of water; add a quarter cup of plain, unscented bleach; and then sit in the tub for 5 to 10 minutes.
An advantage of bleach baths is that we know that there is little, if any, bacterial resistance to bleach. Bleach kills bacteria by punching holes in the cells, and bacteria are incapable of becoming resistant to that, whereas antibiotics kill bacteria in a biochemical manner that bacteria can eventually fight.
In your study, was there resistance to tetracyclines in addition to clindamycin?
There was actually a lack of resistance to tetracyclines, which was interesting and shocking to me. Tetracyclines are the most common antibiotic used in hidradenitis suppurativa, but we did not find resistance. We are not sure why. The lack of resistance might be a result of the pharmacologic properties of tetracyclines, but we do not yet know.
How have you changed your practice based on what you learned in your study? (continued on next page)
Based on what we know, I’ve made adjustments to the way I teach residents. There is currently no evidence suggesting we should avoid treating patients with tetracyclines. As a result, I still give patients long-term tetracyclines for 2 to 3 months of treatment, with doxycycline or minocycline. If the patient has refractory disease, or if the patient has evidence of superinfection of their hidradenitis suppurativa lesions, then I would use a 2- to 4-week course of a non-tetracycline antibiotic such as oral clindamycin with or without rifampin, TMP-SMX, or a fluoroquinolone. But I would not use those antibiotics for long-term treatment at baseline.
I also changed my approach to culturing in my practice. If a patient is not responding, or if their purulent drainage changes, including becoming malodorous or a different color, then I will culture the discharge.
Culturing allows you to make an informed decision about which antibiotic to choose. The culture may grow a different type of bacteria than you were expecting, or a type of bacteria that is showing resistance to a particular medication. As a clinician, you want to avoid prescribing a medication that is driving the patient’s bacterial flora in the wrong direction.
Is culturing currently a common practice? Is there any pushback to the approach you described?
Culturing only takes an extra few minutes. However, I don’t think that culturing should be part of a general visit for hidradenitis suppurativa because many patients have purulence but do not have infection. On the other hand, culturing may be appropriate in certain circumstances, such as when a patient’s disease behavior starts to change and the color or odor of the purulence starts to change. Culturing may also be appropriate if a patient starts having more pain, redness, or fevers.
Should trimethoprim/sulfamethoxazole (TMP-SMX) and ciprofloxacin ever be used in absence of secondary infection?
Although those antibiotics are in our limited armamentarium for treating the disease, we need to remember that the majority of bacteria that grow in hidradenitis suppurativa are staphylococcus and streptococcus, which are gram-positive bacteria that should respond to tetracyclines or oral clindamycin.
I typically would use ciprofloxacin for more severe cases in which the patient does not respond to the first-line treatment. Clinicians certainly can use ciprofloxacin, but it should not be a first-line treatment. Instead, I would prefer that clinicians use ciprofloxacin based on culture data. If the patient is not doing well and the clinician does a culture that grows a gram-negative bacteria, then it is worth going after that bacteria with ciprofloxacin. Thus, ciprofloxacin (and other fluoroquinolones) should be used for short courses of directed therapy against specific bacteria, and it should not be a first-line treatment or for long courses of therapy.
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Have you seen any cases where tetracyclines and ciprofloxacin were cultured as resistant? What do you do in those cases?
In those cases I would stop using antibiotics. I would recommend bleach baths and then move on to adjunctive non-antibiotic therapies. This type of culture data suggests that antibiotic therapy will likely be ineffective, and suggests that our antibiotic therapies are breeding resistant bacteria.
One of the interesting findings from our study is that the patients who were on TMP-SMX were more likely to grow a specific gram-negative bacteria called Proteus mirabilis. The same scenario occurred with Escherichia coli and ciprofloxacin. It is possible that the use of certain antibiotics, such as TMP-SMX and ciprofloxacin may be a marker for patients with more severe disease, or for patients with long-standing disease who have exhausted baseline therapies.
Are you pursuing future research on this topic?
Yes, we submitted a few grants this year. It would be good to do a prospective study of patients who are relatively antibiotic naïve, and then start them on antibiotics and see how their flora changes.
What are some other areas in hidradenitis suppurativa to further explore in future research?
I find the lifestyle modification aspect of hidradenitis suppurativa management interesting because I think it is an effective strategy, possibly more effective than many medical therapies. Lifestyle modifications include weight loss, smoking cessation, and low carbohydrate/low glycemic index diets.
Have you seen patients make those changes and have good results?
Yes, absolutely. The disease does not go away, but the severity of it changes. For example, if a patient loses 10 pounds, the severity of the disease will change a fair amount, but if the patient loses 20 pounds, we will typically see a significant decrease in the severity of the disease. I have also had a few patients undergo bariatric surgery, and after the subsequent massive weight loss, the activity of their hidradenitis suppurativa decreased tremendously. Results from lifestyle modifications are encouraging, but the modifications are often difficult for patients.
What are some diagnostic challenges associated with hidradenitis suppurativa?
Many patients with hidradenitis suppurativa are treated by non-dermatologists for a long time, including the emergency department, primary care, and obstetrics and gynecology. The lesions in hidradenitis suppurativa resemble bacterial abscesses, so some patients are treated incorrectly for a long time. However, the correct diagnosis is usually made once patients see a dermatologist.
What would you like practitioners who are unfamiliar with hidradenitis suppurativa to keep in mind when evaluating abscesses?
Consider hidradenitis suppurativa:
- If a patient is getting recurrent abscesses under the arm, in the groin, or the buttocks
- If these abscesses are not accompanied by fever, chills, and the usual signs of infection
- If the patient has scars in the underarms, groin, or buttocks from previous lesions.
One abscess does mean hidradenitis suppurativa, but recurrence of abscesses in specific areas of the body does point to the diagnosis. In addition, remember that smoking, obesity, and female gender are risk factors for hidradenitis suppurativa.
Are there any other aspects of hidradenitis suppurativa management that you would like to highlight?
I think that surgical management of hidradenitis suppurativa does not receive the attention it deserves. Many clinicians have seen surgeries go poorly, but, in experienced hands, surgery can be a useful adjunctive therapy. This is because patients with hidradenitis suppurativa have abscesses in addition to chronic lesions called sinus tracts. The sinus tracts are basically full of purulent material, and they do not improve with medical treatment. Thus, a patient could be on antibiotics or other medical therapies, but those sinus tracts will remain. The only way to get rid of them is to surgically remove them. This surgery involves a long healing period, but the procedure can significantly improve patents’ quality of life by eliminating chronically draining sinus tracts.
In my experience, the more radical the surgery, the more likely the patient will do well. The surgeon has to be experienced enough to remove all of the affected tissue. It is a difficult surgery and a tough recovery, but the results are worth it for some patients.
References
Fischer AH, Haskin A, Okoye GA. Patterns of antimicrobial resistance in lesions of hidradenitis suppurativa. J Am Acad Dermatol. 2017;76(2):309-313.