This article discusses the potential uses of the Bismuth subsalicylate (BSS) and NAC combination against infections.
Bismuth subsalicylate is the active ingredient in Pepto Bismol® and is an effective antimicrobial. BSS is part of the treatment protocol for Peptic Ulcer disease.
Bismuth’s antimicrobial and antisecretory properties make it ideal for preventing Traveler’s diarrhea.
For systemic use, bismuth has to be absorbed well in the intestines. However, less than one percent of B.SS is absorbed when taken by mouth. Therefore, if higher doses are needed, large amounts are needed to be taken.
In a study by Yacyshyn et al. for COVID-19, their subjects had to take 48 bismuth tablets in three days. The high volume of tablets decreased patient compliance, and many of them did not continue the study. The authors had to cut down the dose in half.
Despite the lower dose, the BSS eradicated salivary SARS-CoV-2 and improved the patients’ COVID-19 symptoms.
NAC and Bismuth combination
In December 2021, a rodent study from Hong Kong by Wang and colleagues showed that oral bismuth, together with N-acetyl cysteine (NAC), increased the absorption of bismuth and led to a decrease in the number of SARS-CoV-2 in the lungs, liver, spleen, and kidneys and resolved the COVID-19 symptoms.
The increased bismuth absorption opens a new door in using BSS as an antimicrobial. Many scientists from previous years are already aware of the antimicrobial properties of BSS and have devised ways to increase its absorption to treat several infections. However, most depend on industrial manufacturing.
NAC is the most affordable and easiest way to increase oral absorption of BSS since both are over the counter. In this article, I list the organisms eradicated by bismuth compounds and their significance.
N-acetyl cysteine is an FDA-approved drug for treating acetaminophen (Tylenol) poisoning. It is sold over the counter for its many health uses.
I must stress that using BSS+NAC in the following organisms still requires definitive studies. I don’t recommend combining them without physician supervision.
Bacteria and fungi susceptible to BSS
1. Clostridium Difficile
C Diff. diarrhea can happen after or during a course of antibiotics. It is treated with antibiotics like metronidazole and vancomycin. Ironically, they can cause C. Diff too.
C. diff diarrhea can be frustrating to patients and doctors since they tend to recur in 20% of the cases and can lead to sepsis and death.
Mahony et al. reported that synthetic bismuth compounds could enter the C. diff bacteria to exert their antimicrobial activity.[1]
The increased bismuth absorption with the addition of NAC may be useful for recurrent or systemic C Diff. infection.
One other positive thing about the use of bismuth is that, unlike antibiotics, it does not alter the normal flora of the stomach.[4] Therefore, it can stop the vicious cycle of antibiotic treatment leading to more C diff.
2. Enterobacteria producing metallo-βeta-lactamases
Enterobacters are bacteria of the intestinal tract. When exposed to antibiotics, they can produce Metallo-β-lactamases (MBLs) enzymes that give them drug resistance, a growing concern.
These MBLs are difficult to treat. An MBL example is the New Delhi Metallo-β-lactamase 1 (NDM-1). NDM-1-related resistance is highly transferable to other common human pathogens, including Enterobacteriaceae, Pseudomonas, and Acinetobacter, and makes them antibiotic resistant too.
Bacteria with NDM-1 also have genes that encode other resistance determinants. Those genes can transfer antibiotic resistance to almost all classes of antibiotics available. Patients infected with drug-resistant bacteria have a 50% mortality.[2]
In a study by Wang et al., they demonstrated that a combination of bismuth compounds and a β-lactam antibiotic restored the antibiotic activity in NDM-1-positive Escherichia coli (E. coli).[2]
The concept is similar to Augmentin’s Amoxicillin and clavulanic acid combination, where an antibiotic is combined with a beta-lactamase inhibitor to prevent certain bacteria from becoming resistant to amoxicillin.
3. Staphylococcus aureus and Candida albicans
S. Aureus is a common bacteria in the skin and nose. Sometimes they can cause severe infections like bacteremia, sepsis, endocarditis, bone infections, and pneumonia in susceptible people.
Candida Albicans is a fungus that can cause skin and internal infections. Topical antifungals are used for candidal skin infections and are relatively easy to treat. However, invasive Candidiasis can happen in hospitalized patients who have been treated with several courses of antibiotics.
Vasquez-Munoz et al. formulated a bismuth nanoparticle compound that was effective against S. aureus and C. Albicans in free-flowing and biofilm stages.[3]
Antibiotics cannot reach pathogens within biofilms which is one reason for antibiotic failure. Biofilms can be present in Foley catheters and intravenous lines.
4. Methicillin-Resistant Staphylococcus Aureus
When S. Aureus develop antibiotic resistance to penicillin-type drugs, they are called Methicillin-resistant S. Aureus (MRSA).
MRSA infections can be hospital-acquired where they are associated with invasive procedures or devices, such as surgeries, intravenous tubing, or artificial joints.
MRSA can also be community-acquired and manifest as rapidly spreading cellulitis, and skin boils.
A study by Ma et al. combined Bismuth nanospheres with three classes of ineffective antibiotics against (MRSA).[5] The antibiotics are:
- βeta-lactams – cefuroxime, cefotaxime and piperacillin
- Quinolone – ciprofloxacin
- Aminoglycoside – gentamicin
Their result showed that only the gentamycin and Bismuth nanoparticle combination could stop MRSA growth. This study shows that not all antibiotics combined with bismuth will work against MRSA.[5]
5. Periodontitis
Porphyromonas gingivalis is considered to be the “keystone” bacteria in periodontitis. Periodontitis is an inflammation of the gums. It is the major cause of severe tooth loss and edentulism in adults globally.
Periodontitis is related to metabolic syndrome, and they make each other worse. A study from the University of Hong Kong showed that metronidazole and colloidal bismuth citrate eradicated P. gingivalis without damaging human gum cells.[6]
NAC and bismuth subsalicylate were effective not only in SARS-CoV-2, the cause of COVID-19, but also in the Alpha variant, the SARS virus, the MERS coronavirus, and the seasonal human coronavirus 229E.
You can read my article on how Colloidal bismuth and NAC inhibit SARS-CoV-2 replication
After reading this article, it is tempting to try NAC and bismuth subsalicylate with other antibiotics, but precautions should be taken.
Warning
N.A.C. can interact with nitroglycerin, chloroquine, anti-hypertensives, and blood thinners.
Medline Plus says that if you are taking tetracycline antibiotics such as demeclocycline (Declomycin), doxycycline (Doryx, Vibramycin), minocycline (Dynacin, Minocin), and tetracycline (Sumycin), take them at least 1 hour before or 3 hours after taking bismuth subsalicylate.
As mentioned earlier, the active ingredient in the brand and generic forms of Pepto-Bismol is bismuth subsalicylate.
Bismuth is non-toxic for humans (Lethal Intake > 5-20 g/day/Kg, for years)[4]. However, the subsalicylate becomes salicylate which is like aspirin. Although quite rare, bismuth toxicity can occur in patients.
Bismuth subsalicylate toxicity primarily occurs in patients who overdose or take it for extended periods. Toxicity is generally seen in patients who ingest more than 150 mg/kg of salicylates (or >6.5 g of aspirin equivalent).[4]
Concluding thoughts
While new antibiotics are being approved this year, they will be expensive and not affordable to those without insurance, and even with insurance, they will have a higher co-pay.
Increased bismuth absorption with NAC and antibiotics can be a game changer in this world where antibiotic resistance is becoming a big problem and will extend the usefulness of current antibiotics.
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References:
- Mahony DE, Lim-Morrison S, Bryden L, Faulkner G, Hoffman PS, Agocs L, Briand GG, Burford N, Maguire H. Antimicrobial activities of synthetic bismuth compounds against Clostridium difficile. Antimicrob Agents Chemother. 1999 Mar;43(3):582-8. doi: 10.1128/AAC.43.3.582. PMID: 10049270; PMCID: PMC89163.
- Wang R, Lai TP, Gao P, Zhang H, Ho PL, Woo PC, Ma G, Kao RY, Li H, Sun H. Bismuth antimicrobial drugs serve as broad-spectrum metallo-β-lactamase inhibitors. Nat Commun. 2018 Jan 30;9(1):439. doi: 10.1038/s41467-018-02828-6. PMID: 29382822; PMCID: PMC5789847.
- Vazquez-Munoz, R., Arellano-Jimenez, M.J. & Lopez-Ribot, J.L. Bismuth nanoparticles obtained by a facile synthesis method exhibit antimicrobial activity against Staphylococcus aureus and Candida albicans. BMC BioMed eng 2, 11 (2020). https://doi.org/10.1186/s42490-020-00044-2
- Budisak P, Abbas M. Bismuth Subsalicylate. [Updated 2022 Jun 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.
- Ma et al. Synergistic antibacterial effect of Bi2S3 nanospheres combined with ineffective antibiotic gentamicin against methicillin-resistant Staphylococcus aureus. Journal of Inorganic Biochemistry. Volume 168, March 2017, Pages 38-45
- Wang, Chuan & Li, Xuan & Cheng, Tianfan & Sun, Hongzhe & Jin, Lijian. (2021). Eradication of Porphyromonas gingivalis Persisters Through Colloidal Bismuth Subcitrate Synergistically Combined With Metronidazole. Frontiers in Microbiology. 12. 748121. 10.3389/fmicb.2021.748121.
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