Logo American Journal of Case Reports

Call: 1.631.629.4328
Mon-Fri 10 am - 2 pm EST

Contact Us

Logo American Journal of Case Reports Logo American Journal of Case Reports Logo American Journal of Case Reports

20 November 2023: Articles  Saudi Arabia

Azithromycin Treatment for Acne Vulgaris: A Case Report on the Risk of Infection

Unknown etiology, Unusual or unexpected effect of treatment, Adverse events of drug therapy

Lina I. Alnajjar ORCID logo1ABDE, Shakir Bakkari ORCID logo2D, Reem Mohammed Alkahtani3EF, Malak A. Alasqah ORCID logo4EF, Ali I. Almuwinea ORCID logo5EF, Alaa A. Alhubaishi ORCID logo1AEF*

DOI: 10.12659/AJCR.941424

Am J Case Rep 2023; 24:e941424

0 Comments

Abstract

0:00

BACKGROUND: Clostridium difficile (C. difficile) is a gram-positive, anaerobic, spore-forming bacillus. It can lead to pseudomembranous colitis characterized by electrolyte disturbances, toxic megacolon, and septic shock. The risk of C. difficile infection is higher with use of certain classes of antibiotics, or when an antibiotic used for a long time. Azithromycin is a macrolide antibiotic known to be safe, with few adverse effects such as diarrhea, stomach pain, and constipation. Azithromycin is currently used for the treatment of acne, with different dosing regimens for patients who cannot receive traditional treatment based on practice guidelines.

CASE REPORT: A 41-year-old woman was treated with a course of azithromycin 500 mg by mouth 3 times weekly for 6 weeks for acne vulgaris. This was her second antibiotic course of acne treatment within 10 months. A few days after completion of the second azithromycin course, she presented to the clinic with worsening abdominal pain and frequent soft bloody stool. A complete blood count test, C. difficile toxin test, stool culture, and colonoscopy were ordered. She was diagnosed with C. difficile infection confirmed by C. difficile toxin and symptoms.

CONCLUSIONS: Despite the safety profile of azithromycin, our patient was predisposed to a non-severe case of C. difficile-associated diarrhea, most likely due to the repeated course of the azithromycin regimen that was used to treat her acne vulgaris. This report highlights the importance of managing patients with acne vulgaris according to current practice guidelines, and to report a link between the use of azithromycin as an acne treatment and the occurrence of C. difficile colitis.

Keywords: Abdominal Pain, acne vulgaris, Azithromycin, Clostridium Infections, diarrhea

Background

Clostridioides difficile (C. difficile) is a gram-positive, anaerobic, spore-forming bacillus [1]. It is the main cause of antibiotic-associated diarrhea, and it can lead to pseudomembranous colitis [1]. C. difficile infection is commonly reported with use of some classes of antibiotics: in descending order – clindamycin, cephalosporins, carbapenems, fluoroquinolones, and penicillin [2,3]. Longer duration of antibiotics use is associated with a higher risk of C. difficile infection [1].

Azithromycin is an antimicrobial medication classified as a macrolide antibiotic [4]. It is considered a broad-spectrum antibiotic and has activity against gram-negative, gram-positive, and anaerobic bacteria, including Propionibacterium acnes [4]. It works by inhibiting the microorganism’s protein synthesis through blocking the ribosomal subunit [5]. In addition to its antimicrobial effect, azithromycin demonstrates an affinity to inflammatory tissue by inhibiting the production of proinflammatory factors like tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), and nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase (NOx) [6]. It also has immunomodulatory effects by reducing the production of PGE2 and interleukin-8 (IL-8) cytokines [6]. Azithromycin is known to be a safe antibiotic with few adverse effects, which include diarrhea, stomach pain, and constipation [5].

Based on the American Academy of Dermatology guidelines, macrolides are not the first-line treatment for acne vulgaris, and they are only used when traditional antibiotics cannot be used [7]. However, macrolides such as azithromycin are currently used in clinical practice for acne treatment due to its antimicrobial and anti-inflammatory activity, in addition to its good safety profile [6]. Using azithromycin in the treatment of acne vulgaris can be in different dosing regimens, from 3 times a week to 4 days a month, with a duration of 2–3 months [7]. Many studies that compared azithromycin and doxycycline showed doxycycline was more effective, especially in patients older than 18 years, but showed a similar effect when administered with topical treatments like tretinoin and adapalene gel [6]. A meta-analysis of randomized controlled trials comparing the efficacy of azithromycin with doxycycline in acne treatment found that doxycycline causes more adverse effects than azithromycin [4]. The reported adverse effects include diarrhea, nausea, epigastric pain, photosensitivity, vaginitis, abnormal blood cell count, and vertigo [4].

A few studies have linked macrolide use, including azithromycin, with C. difficile infection, but only in a low percentage of cases [8–11]. One study mentioned that azithromycin caused C. difficile infection with an odds ratio (OR) of 2.88 and confidence interval (CI) of 1.54–5.37, which was lower than with other antibiotics [9]. In addition, 2 meta-analyses have linked macrolide use with C. difficile infection, but only in a low percentage of cases and with no mention of a specific agent [10,11]. There are 2 published case reports of Moinuddin acne treatment with azithromycin [12,13]: the first used azithromycin 1 g/week for a patient with arthritis associated with acne [12], and the second report was of using azithromycin 500 mg/day for a patient with hidradenitis suppurativa (HS) [13].To the best of our knowledge, there are no reported cases that linked the use of azithromycin for the treatment of acne vulgaris with C. difficile-associated diarrhea.

Here, we report the case of a 41-year-old woman with acne vulgaris who developed C. difficile colitis following a second course of a 6-week course of azithromycin to treat her acne vulgaris.

Case Report

A 41-year-old woman presented to a dermatology clinic with a past medical history of severe acne vulgaris, hyperlipidemia, and migraine, with no past surgical history or prior hospitalization. She has been primarily treated with clindamycin 1% topical solution 2 times daily and azithromycin 250 mg by mouth 3 times weekly for 6 weeks based on her case and the dermatologist’s diagnosis. Eight months later, she had a dental implant in which she was prescribed amoxicillin/clavulanic acid 1 g by mouth for 10 days.

Ten months later, after completion of the first acne treatment regimen, the patient returned to the clinic with inflammatory acne vulgaris. The therapeutic plan was to reuse the previous regimen of azithromycin. Four days following her completion of the second course of azithromycin, she started to have mild abdominal pain, frequent soft stool (3 times a day) with abdominal gasses, and unusual stool odor. The pain was more frequent and kept worsening with softer bloody stool (around 5–6 times a day).

She presented to the gastroenterology clinic, and a complete blood count (CBC) test and C. difficile toxin A test were ordered, in addition to a colonoscopy. Her white blood count (WBC) as 9590 cells/µL (normal range: 4500–10 000 cells/µL) and the serum creatinine (SCr) was 0.6188 mg/dL (normal range: 0.59–1.04 mg/dL). The C. difficile toxin A test result came back positive. The colonoscopy revealed friable mucosa with white exudate extending from the rectum to the transverse colon, which is consistent with a C. difficile diagnosis (Figure 1). The 48-h stool culture revealed no growth of salmonella or shigella.

The patient was started on metronidazole 500 mg by mouth 3 times daily for 10 days. No improvement was noticed after completing the course. She still had mild abdominal pain and bloody diarrhea (3–4 times per day). As a result, the C. difficile toxin test was repeated, and the result came back positive. This time she was treated with vancomycin 125 mg by mouth 4 times daily for 10 days and her symptoms improved accordingly.

Discussion

We report the case of a woman diagnosed with C. difficile-associated diarrhea after recurrent use of azithromycin regimen for the treatment of severe acne vulgaris.

Acne vulgaris is a common cutaneous disorder characterized by inflammation of the pilosebaceous unit of a hair follicle and commonly caused by the anaerobic bacterium Propionibacterium acnes [14]. Many pharmacological options are very effective to reduce the inflammation of acne and improve the skin’s appearance, including topical oral and procedural therapies [7]. The selection is made based on the severity of acne vulgaris and patient preferences [7,15]. Based on the acne vulgaris treatment guideline, the first line of treatment for mild acne includes topical agents like benzoyl peroxide and retinoids, and topical antibiotics like clindamycin [7]. For moderate to severe cases, systemic agents can be used either alone or in combination with topical agents [7]. Systemic agents include isotretinoin and tetracyclines such as doxycycline. Macrolide can be used as an alternative treatment for those who cannot use doxycycline, such as pregnant women and children [7].

In our case, the patient was initially treated with clindamycin 1% topical solution 2 times daily and azithromycin 250 mg by mouth 3 times weekly for 6 weeks, which was not the first-line option in her case. Then, exactly the same course of azithromycin was repeated 10 months later, which might have increased her risk of C. difficile infection. In addition, between the 2 courses of azithromycin, she received another course of amoxicillin/clavulanic for her dental implant. As a result, after completing her second course of azithromycin, she was diagnosed with an initial episode of non-severe C. difficile infection based on her symptoms, colonoscopy, and laboratory data (WBC ≤15 000 cells/µL and SCr <1.5 mg/dl) [7]. The C. difficile infection was most likely due to the repeated course of the azithromycin regimen, since she had no risk factors such as history of colon disease or any gastrointestinal disease and she had not taken any laxatives for 48 h before her symptoms started.

Our patient was initially treated with metronidazole 500 mg by mouth 3 times daily for 10 days based on the hospital practice guidelines and had failed the treatment. Metronidazole treatment failure was unknown. However, she was re-treated successfully with vancomycin 125 mg by mouth 4 times daily for 10 days

Although azithromycin has a good safety profile and is rarely associated with reported cases of C. difficile, our case is a rare incidence that occurred after a repeated course of azithromycin to treat acne vulgaris. This case shows the importance of following the treatment guidelines carefully for managing acne vulgaris cases, and also highlights the role of infectious disease pharmacists in such decision-making for patient well-being and better health outcomes.

Conclusions

The acne vulgaris regimen of azithromycin of 250 mg 3 times weekly has been increasingly used in dermatology clinics for the treatment of acne vulgaris, despite being considered an alternative treatment based on the American Academy of Dermatology guidelines. A thorough assessment of the patient’s history, including the previous antibiotic regimen used and patient eligibility, needs to be considered before prescribing azithromycin for acne vulgaris. This report highlights the importance of managing patients with acne vulgaris according to current practice guidelines, and to report a link between the use of azithromycin as an acne regimen and the risk of C. difficile colitis occurrence.

References:

1.. Mounsey A, Lacy Smith K, Reddy VC, Nickolich S: Am Fam Physician, 2020; 101(3); 168-175

2.. Brown KA, Fisman DN, Moineddin R, Daneman N: PLoS One, 2014; 9(8); e105454

3.. Brown KA, Khanafer N, Daneman N, Fisman DN: Antimicrob Agents Chemother, 2013; 57(5); 2326-32

4.. Kim JE, Park AY, Lee SY, Comparison of the efficacy of azithromycin versus doxycycline in acne vulgaris: A meta-analysis of randomized controlled trials: Ann Dermatol, 2018; 30(4); 417-26

5.. Sandman Z, Iqbal OA, Azithromycin. [Updated 2023 Jan 15]: StatPearls [Internet], 2023, Treasure Island (FL), StatPearls Publishing Available from: https://www.ncbi.nlm.nih.gov/books/NBK557766/

6.. Kardeh S, Saki N, Jowkar F, Efficacy of azithromycin in treatment of acne vulgaris: A mini review: World J Plast Surg, 2019; 8(2); 127-34

7.. Zaenglein AL, Pathy AL, Schlosser BJ, Guidelines of care for the management of acne vulgaris: J Am Acad Dermatol, 2016; 74(5); 945-73 e33

8.. Gorenek L, Dizer U, Besirbellioglu B: Hepatogastroenterology, 1999; 46(25); 343-48

9.. Teng C, Reveles KR, Obodozie-Ofoegbu OO, Frei CR: Int J Med Sci, 2019; 16(5); 630-35

10.. Brown KA, Khanafer N, Daneman N, Fisman DN: Antimicrob Agents Chemother, 2013; 57(5); 2326-32

11.. Slimings C, Riley TV: J Antimicrob Chemother, 2014; 69(4); 881-91

12.. Schaeverbeke T, Lequen L, de Barbeyrac B, Propionibacterium acnes isolated from synovial tissue and fluid in a patient with oligoarthritis associated with acne and pustulosis: Arthritis Rheum, 1998; 41(10); 1889-93

13.. Revuz J, Disseminate recurrent folliculitis as the presenting picture of hidradenitis suppurativa: Ann Dermatol Venereol, 2017; 144(11); 715-18

14.. McLaughlin J, Watterson S, Layton AM, Propionibacterium acnes and acne vulgaris: New insights from the integration of population genetic, multi-omic, biochemical and host-microbe studies: Microorganisms, 2019; 7(5); 128

15.. Eichenfield DZ, Sprague J, Eichenfield LF, Management of acne vulgaris: A review: JAMA, 2021; 326(20); 2055-67

In Press

09 Jan 2024 : Case report  China (mainland)

Challenges of Post-Venipuncture Jugular Venous Thrombosis in Patients with Secondary Hyperparathyroidism: A...

Am J Case Rep In Press; DOI: 10.12659/AJCR.943270  

0:00

09 Jan 2024 : Case report  Saudi Arabia

Neurotrophic Keratopathy in Marfan Syndrome Patient After Micropulse Transscleral Cyclophotocoagulation: A ...

Am J Case Rep In Press; DOI: 10.12659/AJCR.942538  

0:00

03 Feb 2024 : Case report  USA

Definitive Closure Using an Ovine Reinforced Tissue Matrix in Contaminated Penetrating Abdominal Trauma

Am J Case Rep In Press; DOI: 10.12659/AJCR.943188  

10 Jan 2024 : Case report  China (mainland)

Herpes Simplex Keratitis as a Complication of Pterygium Surgery

Am J Case Rep In Press; DOI: 10.12659/AJCR.942401  

Most Viewed Current Articles

10 Jan 2022 : Case report  Germany

A Report on the First 7 Sequential Patients Treated Within the C-Reactive Protein Apheresis in COVID (CACOV...

DOI :10.12659/AJCR.935263

Am J Case Rep 2022; 23:e935263

19 Jul 2022 : Case report  Saudi Arabia

Atlantoaxial Subluxation Secondary to SARS-CoV-2 Infection: A Rare Orthopedic Complication from COVID-19

DOI :10.12659/AJCR.936128

Am J Case Rep 2022; 23:e936128

05 Mar 2022 : Case report  Brazil

Acute Limb Ischemia After Self-Injection of Crushed Morphine Tablets into the Radial Artery: Role of Infrar...

DOI :10.12659/AJCR.935336

Am J Case Rep 2022; 23:e935336

02 Apr 2022 : Case report  Saudi Arabia

Infective Endocarditis Caused by Pseudomonas luteola in a Pediatric Patient. A Case Report and Review of Li...

DOI :10.12659/AJCR.935743

Am J Case Rep 2022; 23:e935743

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923