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Antibiotic Resistance, Bacterial Overgrowth, Side Effects

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DrDelRosso.png
The above quote is by Dr. Del Rosso, Best Practices in Rosacea Treatment, An Educational Supplement to Dermatology Times, page 9

Introduction
"Dermatologists prescribe more oral antibiotic courses per clinician than any other specialty, and this use puts patients at risk of antibiotic-resistant infections and antibiotic-associated adverse events." [37] "Dermatologists, for example, prescribe five percent of antibiotics, but make up only one percent of all physicians." [38]

Rosacea has been treated by antibiotic therapy for over 50 years. [1] Tetracyclines (tetracycline hydrochloride and oxytetracycline) first became available in 1953, followed by doxycycline in 1967 and minocycline in 1972 and have become the most commonly prescribed first -line systemic antibiotic treatment for acne and rosacea. All tetracyclines are antimicrobials that exert a bacteriostatic effect by interfering with protein synthesis on the 30S ribosomal subunit. Additionally, these agents exert anti-inflammatory properties. [26]

No doubt this continued use of antibiotic therapy for rosacea is because of the success in reducing rosacea inflammation and controlling it which has been accepted as one of best methods in the treatment of rosacea. However, some of the long term effects of antibiotic treatment may possibly result in bacterial overgrowth, antibiotic resistance, candida albicans, and many side effects and riskes due to the long term use of this therapy which may lead to gram-negative folliculitis.

One report said that "Antimicrobial resistance poses a catastrophic threat." [28]

It is fairly well established that antibiotics mess with the gut. One study, published in the Proceedings of the National Academy of Sciences, supports the common wisdom that antibiotics can damage the 'good' germs living in the body. [2] A recent report said, "Antibiotic resistance is one of the most worrying problems during the treatment." [27]

Another report says, "Reports of serious adverse events and the increasing rates of bacterial resistance to tetracyclines at standard doses in patients undergoing long-term therapy have prompted interest in new therapeutic approaches for their use in acne and rosacea therapy." [3] Another report says similarly, "Improper use of oral antibiotics, including long-term use over months to years, has resulted in resistant bacteria that are posing a serious health threat..." [25]

"Antibiotics are widely prescribed in dermatology; therefore, judicious use of antibiotics in the treatment of noninfectious dermatological diseases (such as AV and rosacea) and increased education of dermatology patients have the potential for great impact in the stewardship of antibiotic therapies." [41]

If you haven't heard about minocycline induced lupus, you now have. 

Rosacea and Bacteria
Rosacea has been associated with at least five different types of bacteria:

Helicobacter Pylori [24]

Chlamydophila pneumoniae [4]

Propionibacterium [5]

Bacillus oleronius [6]

Staphylococcus epidermidis [7]

There is a growing list of bacteria associated with demodex mites and rosacea

Medical reports published at pubMed have associated rosacea with bacteria for some time time now and one theory on the cause of rosacea is that bacteria is involved and the use of antibiotics in treating rosacea has a long history. For years antibiotics were used as a secondary treatment, however, now antibiotics are used as a first line therapy for rosacea frequently. [8 ]

Long term use of antibiotics may lead to problems, i.e., bacterial overgrowth, antibiotic resistance, at least one fungus (candida) and a long list of side effects. 

AMR
A new acronym, AMR (antimicrobial resistance) has been coined for this and one article says, "AMR causes 700,000 deaths annually across the globe, a number projected to skyrocket to 10 million by 2050 without intervention." [36] "Estimates are that 700,000 to several million deaths result per year.  Each year in the United States, at least 2.8 million people become infected with bacteria that are resistant to antibiotics and at least 35,000 people die as a result." [42] AMR is a serious issue. 

Bacterial Overgrowth
An article by Cathy Wong [9] discusses how bacterial overgrowth in the small intestine can cause many health problems. One of the causes listed is taking antibiotics which most rosaceans have done. She discusses several natural methods on how to treat bacterial overgrowth. If you think that bacterial overgrowth may be a problem for you I suggest you read her article. How do you know if you have bacterial overgrowth? There are some tests to take to confirm it, for instance, taking bacterial cultures of small intestine fluid, or the lactulose hydrogen breath test.

Some signs and symptoms of bacterial growth are:

abdominal bloating and gas after meals

pain

constipation

chronic loose stools or diarrhea -

(studies have found 48% to 67% of people with chronic diarrhea had bacterial overgrowth. soft, foul-smelling stools that stick to the bowl)

fatigue - megaloblastic anemia due to vitamin B12 malabsorption

depression

nutritional deficiency despite taking supplements

weight loss

abdominal pain

mucus in stools

bloating worse with carbs, fiber, and sugar

Some of the causes of bacterial overgrowth are:

Decreased motility in the small intestine - caused by excess dietary sugar, chronic stress, and conditions such as diabetes, hypothyroidism, and scleroderma. In the United States, up to 40% of chronic diarrhea in people with diabetes is associated with bacterial overgrowth.

Hypochlorhydria - as people get older, the amount of stomach acid they secrete decline. Because stomach acid is acidic and helps to kill bacteria in the small intestine, if there is less stomach acid, bacteria are more likely to proliferate. Another very common cause of hypochlorhydria is due to excessive use of antacids.

Structural abnormalities in the small intestine - gastric bypass surgery, small intestinal diverticula, blind loop, intestinal obstruction, and Crohn's disease fistula are some of the structural causes of bacterial overgrowth.

Other causes include immune deficiency, stress, certain medications such as steroids, antibiotics, and birth control pills, inadequate dietary fiber, and pancreatic enzyme deficiency.

Antibiotic Resistance
There is growing evidence that antibitoic resistance has been developing due to the widespread use of antibiotics in acne. One report concluded, "Long-term use of antibiotics in the treatment of acne vulgaris can lead to antimicrobial resistance with serious and intractable problems not limited to Propionibacterium acnes (P. acnes), the skin and acne vulgaris themselves, but also to other bacterial species, with systemic consequences." [11]

One reports says, "drug-resistant bacteria kill at least 23,000 people annually in America." [30]

The authors of one paper on this subject state, "Administration of antibiotics, often for prolonged periods, has become the de facto standard of care for acne (and rosacea). However, the world is now facing a health crisis relating to widespread antibiotic resistance. The authors provide current evidence to suggest that dermatologists should consider a radical departure from standard operating procedure by severely curtailing, if not outright discontinuing, the routine and regular use of antibiotics for acne." [31]

"Dermatologists are reducing their use of systemic antibiotics for rosacea and turning to therapies, such as azelaic acid, that do not have potential to induce bacterial resistance." [12]

The medical community has become increasingly aware of the problem of antibiotic resistance with long term use of oral antibiotics. “The risks of long-term topical and systemic antibiotic use include the emergence of antibiotic-resistant bacteria and the suppression of normal bacterial flora, leading to overgrowth of pathogenic organisms such as Candida species and Clostridium difficile." [13]

"Because widespread and long-term use of antibiotics has led to the emergence of resistant bacteria, dermatologists are now increasingly forced to seek alternate treatment strategies." [14]

According to this research patent application by Richard Gallo, "Oral and topical antibiotics are effective in treating rosacea yet resistance to the antimicrobial activity of commonly used antibiotics is high, approaching 80%." [15]

Candida albicans (a fungus or yeast) and rosacea have been linked in at least one research paper and may be related to what one person calls 'antibiotic syndrome.' [16]

One report concluded, "Attention should be paid to a possible future increase of strains with resistance to LVFX, as commonly prescribed ocular antibiotics bring emergence of resistant bacteria." [29]

"23,000 people die as a direct result of those infections or from conditions complicated by the antibiotic-resistant infection" [33]

"Antibiotic resistance occurs with both topical and systemic antibiotic use." [34]

"Prolonged antibiotic use associated with long term acne treatment regretably promotes multi-drug resistant strains of many common members of the skin microbiota. Many of the organisms involved are potential pathogens and represent additional risk with increases of antibiotic use in healthcare contexts (Miller et al., 1996; Levy, 2002; Dréno et al., 2004)." [35]

Side Effects of Long Term Use of Antibiotics
Some of the well known side effects of long term use of antibiotics are:

Teratogenic effects

Tooth discoloration and alteration of bone growth if used by patients 12 years of age

Photosensitivity

Gastrointestinal distress

Uncommon and minocycline-specific

Vertigo

Hyperpigmentation

Lupus-like syndrome/autoimmune hepatitis

Changes in bacterial microflora

Gram-negative folliculitis

Vaginal candidiasis

Antibiotic resistance

Can reduce future treatment options

Can induce cross-resistance

Can be transferred from commensal to pathogenic microorganisms

"For moderate to severe and inflammatory acne vulgaris, oral antibacterials are standard care components, with tetracyclines and macrolides usually preferred. However, these agents have certain limitations, among which are photosensitivity (tetracyclines), adverse vestibular effects (minocycline), gastrointestinal disturbances (particularly with macrolides and doxycycline), dysbiosis and microbial resistance concerns." [39]

Weight Gain [40]

SIBO
Small Intestinal Bacterial Growth has been associated with rosacea. [17]

Oracea™
You might want to consider taking Oracea™ (10 mg of timed released doxycycline and 30 mg of immediate release doxycycline) which is claimed reduces the antibiotic resistance which has been seen in using high dose doxycycline and other antibiotics. [18] One report on this said, "Therapy with subantimicrobial dosing and with topical treatments can modulate the inflammation of rosacea without exerting antibiotic pressure responsible for the emergence of antibiotic resistance." [32]

Doxycycline

It has been noted by one report that "resistance to doxycycline can occur in a few days, with resistant bacteria in abundance after just seven days of treatment with 100 mg doxycyline daily," though this report wasn't about Oracea (or low dose timed released doxycycline) but instead about high dose doxycycline. [19]

Rifaximin
It has been reported that a short term treatment of Rifaximin may be an alternative to long term Oracea or Doxycycline treatment or other antibiotic. [20]

Topical Taurine Bromamine (TauBr)
You might consider using Topical Taurine Bromamine for rosacea if you are suffering from antibiotic resistance. [21]

Gram Negative Folliculitis
Usually people who had Gram-negative folliculitis are those who had complications with acne vulgaris or rosacea that develops in patients who have received systemic antibiotics for prolonged periods. [22]

Cooling Inflammation might prove a helpful treatment for long term antibiotic use. [23]

H Pylori as a Factor in Rosacea
A controversial theory keeps coming up about H Pylori's role in rosacea. [24]

Treatments for bacterial overgrowth
Probiotics

Diet - Low carbohydrate diet (like the Rosacea Diet [10])

Eradicate unfriendly bacteria in the small intestine using herbs such as peppermint oil.

Replace - Bacterial overgrowth impairs friendly bacteria ("probiotics") and digestive enzymes.

Betaine Hydrochloride

Herbs such as:

enteric coated peppermint oil

Grapefruit seed extract -

(for people who don't like taking capsules, grapefruit seed extract can be found in liquid form. Add a few drops to a glass of water and drink in between meals)

Oregano oil capsules

Garlic

Flaxseed Oil

Berberine - goldenseal, oregon grape

Olive leaf extract

Pau d'arco

Endnotes

[1] Rosacea 101: Includes the Rosacea Diet
Brady Barrows, Appendix M, Antibiotics, page 201
iUniverse 2007

[2] Do You Have A Gut Feeling?

[3] Subantimicrobial Dose Doxycycline for Acne and Rosacea: Conclusions
Joseph B. Bikowski, MD, Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA

[4] Rosacea 101: Includes the Rosacea Diet, Appendix D, Theory 6, Bacteria, page 169

[5] Rosacea 101: Includes the Rosacea Diet, Appendix R, page 215
See also end note 3

[6] Mite-related bacterial antigens stimulate inflammatory cells in rosacea.
Lacey N, Delaney S, Kavanagh K, Powell FC.
Br J Dermatol. 2007 Sep;157(3):474-81. Epub 2007 Jun 26

[7] Staphylococcus epidermidis: A possible role in the pustules of rosacea.
J Am Acad Dermatol. 2010 Oct 11;
Authors: Whitfeld M, Gunasingam N, Leow LJ, Shirato K, Preda V
J Am Acad Dermatol. 2010 Oct 11.

Potential role of Demodex mites and bacteria in the induction of rosacea.

[8] Rosacea 101: Includes the Rosacea Diet, Chapter 5, Treatment, page 22

[9] Natural Remedies for Bacterial Overgrowth, Your Guide to Alternative Medicine.
Cathy Wong

[10] Rosacea 101: Includes the Rosacea Diet

[11] The development of antimicrobial resistance due to the antibiotic treatment of acne vulgaris: a review.
Patel M, Bowe WP, Heughebaert C, Shalita AR.
J Drugs Dermatol. 2010 Jun;9(6):655-64.

[12] Changes in rosacea comorbidities and treatment utilization over time.
Yentzer BA, Fleischer AB Jr.
J Drugs Dermatol. 2010 Nov;9(11):1402-6.

[13] Antibiotic Treatment of Acne May Be Associated With Upper Respiratory Tract Infections
Margolis DJ, Bowe WP, Hoffstad O, Berlin
JA Archives of Dermatology, 2005;141(9):1132-1136

[14] Common and Alternate Oral Antibiotic Therapies for Acne Vulgaris: A Review
Journal of Drugs in Dermatology, September 2007, Vol. 6, Issue 9;
Kathani Amin MD, Christy C. Riddle MD, Daniel J Aires MD, Eric S. Schweiger MD
Division of Dermatology, Department of Internal Medician, KUMC, Kansas City, KSV

[15] Patent application title: METHODS AND COMPOSITIONS FOR THE TREATMENT OF SKIN DISEASES AND DISORDERS
Inventors: Richard L. Gallo Jurgen Schauber Kenshi Yamasaki
Agents: Joseph R. Baker, APC;Gavrilovich, Dodd & Lindsey LLP
Assignees: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Origin: SAN DIEGO, CA US
IPC8 Class: AA61K4800FI
USPC Class: 514 44 A
Patent application number: 20090318534

[16] Autosomal Dominant Familial Chronic Mucocutaneous Candidiasis Associated with Acne Rosacea
HL Ee, HH Tan, SK Ng; Ann Acad Med Singapore 2005; 34:571-4 • Full Article

[17] SIBO and Rosacea

[18] Oracea

[19] SDEF: Treatments for Rosacea Contribute to Growth of Antibiotic Resistance
By Peggy Peck, Executive Editor, MedPage Today, Published: February 17, 2009
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco .
Primary source: Skin Disease Education Foundation Hawaii Dermatology Seminar
Source reference:
Baldwin HE "Everything's coming up rosey" SDEF 2009.

[20] Rifaximin treatment for SIBO has resulted in improvement with rosacea is some patients. See SIBO and Rosacea

[21] Topical Taurine Bromamine (TauBr)

[22] "Gram-negative folliculitis occurs in patients who have had moderately inflammatory acne for long periods and have been treated with long-term antibiotics, mainly tetracyclines, a disease in which cultures of lesions usually reveals a species of Klebsiella, Escherichia coli, Enterobacter, or, from the deep cystic lesions, Proteus." Wikipedia

[23] Cooling Inflammation

[24] Rosacea 101: Includes the Rosacea Diet, Appendix C, page 167

See also this post:

H Pylori

[25] Threat of Bacterial Resistance Can Be Minimized in Rosacea, Rosacea Review Fall 2010

[26] see end note 14

[27] Antibiotic therapy in skin diseases
Owczarek W, Wydrzyńska A, Paluchowska E., Pol Merkur Lekarski.
2011 May;30(179):367-72.

[28] Medical News Today
Antimicrobial Resistance Poses Grave Threat, 11 Mar 2013
Kelly Fitzgerald

[29] Clin Ophthalmol. 2013;7:695-702. doi: 10.2147/OPTH.S43323. Epub 2013 Apr 9.
Prevalence of drug resistance and culture-positive rate among microorganisms isolated from patients with ocular infections over a 4-year period.
Shimizu Y, Toshida H, Honda R, Matsui A, Ohta T, Asada Y, Murakami A.
Department of Ophthalmology, Juntendo University Shizuoka Hospital, Shizuoka, Japan.

[30] The Antibiotic Crisis, by Francis Weaver, November 16, 2013, The Week

[31] Skin Therapy Lett. 2013 Aug;18(5):1-4.
A controversial proposal: no more antibiotics for acne!
Muhammad M, Rosen T.

[32] J Drugs Dermatol. 2012 Jun;11(6):725-30.
Diagnosis and treatment of rosacea: state of the art.
Baldwin HE.
 
[33] This article by Salon dated December 30, 2013 mentions the death rate due to antibiotic resistance:
 
[34] J Clin Aesthet Dermatol. 2016 Apr; 9(4): 18–24.
Published online 2016 Apr 1.
PMCID: PMC4898580
Status Report from the Scientific Panel on Antibiotic Use in Dermatology of the American Acne and Rosacea Society
Part 1: Antibiotic Prescribing Patterns, Sources of Antibiotic Exposure, Antibiotic Consumption and Emergence of Antibiotic Resistance, Impact of Alterations in Antibiotic Prescribing, and Clinical Sequelae of Antibiotic Use
James Q. Del Rosso, DO,corresponding author Guy F. Webster, MD, Ted Rosen, MD, Diane Thiboutot, MD, James J. Leyden, MD, Richard Gallo, MD, PhD, Clay Walker, PhD, George Zhanel, PhD, and Lawrence Eichenfield, MD
 
[35] Front. Microbiol., 25 July 2017 | https://doi.org/10.3389/fmicb.2017.01381
Non-antibiotic Isotretinoin Treatment Differentially Controls Propionibacterium acnes on Skin of Acne Patients
Angela E. Ryan-Kewley, David R. Williams, Neill Hepburn and Ronald A. Dixon
 
 
[37] JAMA Dermatol. 2019 Jan 16;:
Trends in Oral Antibiotic Prescription in Dermatology, 2008 to 2016.
Barbieri JS, Bhate K, Hartnett KP, Fleming-Dutra KE, Margolis DJ
 
[38] Scroll down in this thread you are currently reading to post dated June 1, 2016
 
[39] Drugs. 2019; 79(3): 325–329.
Sarecycline: First Global Approval
Emma D. Deeks
 
[40] "Chronic use of antibiotics during adulthood may have long-lasting impacts on BMI. Associations may differ by antibiotic class, and confounding by indication may be important for some antibiotic classes."
PLoS One. 2019; 14(5): e0216959.
Chronic antibiotic use during adulthood and weight change in the Sister Study
Melissa Furlong, Sandra Deming-Halverson, Dale P. Sandler
 
[41] J Clin Aesthet Dermatol. 2019 Jun; 12(6): 30–41.
Patient Awareness of Antimicrobial Resistance and Antibiotic Use in Acne Vulgaris
James Q. Del Rosso, DO, Theodore Rosen, MD, Dimitry Palceski, DO, and Maria Jose Rueda, MD
 
[42] Antimicrobial resistance, Wikipedia

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An article published by The Conversation reports, that "two million people are infected with antibiotic-resistant bacteria in the United States each year, and 23,000 people die as a result of these infections."  This report also points out, "Dermatologists, for example, prescribe five percent of antibiotics, but make up only one percent of all physicians."

Antibiotic resistance is a very serious matter. The same article quotes Tom Frieden, the director of the Centers for Disease Control and Prevention, who said in a press conference on May 26, 2016, "The medicine cabinet is empty for some patients. It is the end of the road for antibiotics unless we act urgently."

Perspectives on antibiotic resistance: how we got here, where we’re headed, The Conversation

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"Healing my gut has been a long journey and is still not completely healed. Both of my naturopath doctors are convinced that my overuse of antibiotic (in particular two years of Oracea) cause me serious gut issues. I understand this will be controversial here, but I would strongly advise against anyone considering Oracea or any antibiotic long-term. Even this low dose can cause serious imbalance in your gut that can surface years later and the results are not fun." Matt [MP1985 4th June 2019 02:59 AM Post no 19] Rosacea Forum

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