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Abstract

Background

Mānuka honey 10+ is a  honey produced from the nectar of the mānuka tree, Leptospermum scoparium. It is collected by honeybees foraging on its tree, which grows in New Zeland and Australia. This honey is commonly sold as a supplement, or alternative medicine. While several components in mānuka honey are studied for their potential bactericidal properties vivo. Superantigens toxins produced by Staphylococcal aureus have caused the heart valves functioning and kills thousands American every year on bacterial complication Infective Endocarditis (IE). This endotoxin is causing extensive activation of inflammatory cells; patients may present nonspecifically with fever, weight loss but not limited to other immunological reactions and hemorrhagic reaction. Complications in the form of systemic emboli from vegetation fragments can damage blood vessels within various organs, including brain, eye, spleen, kidney, pulmonary, and heart. Honey has broad spectrum antimicrobial bacteria activity specifically for staph bacteria due to its high osmolarity and high concentration of hydrogen peroxide. There is a synergistic potential action in treating wounds by combine both oxacillin and manuka honey against MRSA (methicillin-resistant Staphylococcus aureus). Curcumin, the major constituent of Curcuma longa L. (Zingiberaceae family) is commonly called “turmeric”, has used widely for cooking in Asian cuisine. At relatively nontoxic dose, it is known to be effective against Staphylococcus aureus (S. aureus). In vivo, turmeric powder exerts even more potent effect when used in combination with various other IV antibiotic agents. Interestingly, paring of IV antibiotic regimen, manuka honey 10+ combine with turmeric powder might kill bacterial Staph Auerus Complicated Infective Endocarditis (IE) infection naturally.

Case presentation

We report two cases of complicated infective endocarditis (IE), were cured by using manuka honey 10+, and turmeric powder in addition to IV antibiotic; two of the cases were associated with a septic emboli, and one case was associated with a renal infarction, immunology reactions (Janeway lesions and Osler Node), and a Hemorrhagic Reaction (Roth spots). One case of a patient with mitral valve endocarditis was complicated by intracerebral septic emboli, non-tender erythematous lesions on palms and soles, and Osler node tender on the tip of the finger, pulmonary hypoxia. A second case also had a splenic infarction, mycotic aneurysm and abscess associated with infected cardiac thrombi.

Conclusions

Infection endocarditis (IE) caused by Staphyloccus aures is more often frequently associated with complications. Complications can be associated with cardiac, neurologic, renal, musculoskeletal, systemic complications related to infection, such as mycotic aneurysm, metastatic infection, and embolization. Due to mortality rate increases when complications develop, aggressive antibiotic therapy aren’t adequate, combined with Manuka Honey, Tumeric Powder are the best necessary regimen.

Keywords

Infective Endocarditis, Manuka Honey, Tumeric Powder,

Background:

Manuka honey 10+ has several antibacterial components, unlike other antibiotics; it does not induce resistance in bacteria. Its mechanism is altering the levels of protein synthesis components specifically at ribosomal protein location ⁽¹⁾⁽²⁾. Bacteria’s ability to reproduced and take over, were totally failed by using Manuka honey 10+; this experiment has done in the laboratory tests very successfully⁽³⁾⁽⁴⁾. In the past 60 years, Tumeric has shown potent antibacterial activity and other pharmacological actions ⁽⁵⁾. Currently, Curcumin has been developed markedly into an antibiotic against S. auerus and other bacteria strains ^(6)(7)(8). Globally, turmeric is marketed as a health supplement mainly for its antioxidant and anti-inflammatory properties. We report two cases of patients with complicated IE (Infective endocarditis)^{(9)(10)(11)(12)} included neurological, renal, musculoskeletal, and systemic complications related to mycotic aneurysm, embolization, and metastatic infection; both cases were cured by paring Manuka Honey, Tumeric Powder with IV Antibiotic, would create successful wound healing.

Case presentation:

Patient 1

A 50-year-old manchief engineer worked for Boeing co. comes to the physician with malaise, anorexia, and fatiguefor the past 6 months. His medical history included hypertension. He has no cough, chest pain, arthralgia, or diarrhea. He underwent an uncomplicated dental root canal procedure 7 months ago. His temperature is 36.0 C (97 F), blood pressure is 135/76 mm Hg, pulse is 90/min, and respiration are 18/min. An early diastolic murmur is heardat the left sternal border. He appeared acutely ill and was dehydrated. The result of an initial chest X-ray was normal, and the patient’s electrocardiogram showed sinus tachycardia. CT chest, abdomen, pelvis with contrast was ordered; 1.5 Tesla magnet MRI brain with and without contrast also was ordered. CT scan result came back with no enhance masses are identified. There is no hydronephrosis, but there is a focal cortical scarring along lateral aspect of mild to lower left kidney. Suggestion from diagnostic radiologist there is a renal infarction or possible pylonephritis. MRI brain came result came back with several tiny foci of enhancement are identified, worrisome of embolic disease from unknown cause. A 2cmm focus of enhancement is detected in the left frontal white matter. A 3mm focus of enhancement is detected in the right frontal sulci. A 2mmm focus of enhancement is detected in the posterior left cerebellum. A 5mm focus of enhancement is detected the right posterior cerebellum. These lesions are associated with minimal edema, possibly due to their small size. A more subtle focus of peripheral enhancement in the inferior right cerebellum measures 3mm in size and is associated with susceptibility. This could reflect a cavernous angioma. There is a trace mucosal thickening in the paranasal sinuses. Several tiny foci of enhancement are detected in the bilateral brain (Figure 1a, 1b). Emergency physician prescribed Cipro 500mg twice daily for suspected of uncomplicated pylonephritis and renal infarction. ER doctor is about to discharge him home, however his brother requested for Doppler Echocardiogram, Tranesophageal Echo (TEE) and serial of blood culture to be done. While waiting for TEE and serial of Blood culture result, Transthoracic Doppler Echocardiogram (TTE) result back with Ejaction Fraction (EF) is 60%, Echogenic mass on the anterior leaflet of mitral leaflet (94x76mm) (Figure1c,1d). Echogenic mass on the anterior leaflet of mitral valve suspicious for vegetation. Transthoracic echocardiography (TTE) showed abnormal valve motion with evidence of vegetation but the patient’s mean diastolic pressure gradient was elevated at 10 mmHg. Transesophageal echocardiography (TEE) (Fig. 1e) and video showed hyperdynamic echogenic material attached to the MV. He was transferred to the Cardiac Care Unit (CCU), waiting for consultation from CT surgeon. On TEE, there is evidence of mitral valve vegetation with ecogenic mass up to 2.3cmx2.2cm on the anterior leaflet. CT surgeon and cardiologist decided to have open heart surgery to remove the vegetation ASAP. However, patient and his family member refused surgery plan, and decided to treat empiric with Ceftriaxone 2mg IV q24 and Daptomycin 8mg/kg IV q24 for 42 days through the PICC line. After completed 6 weeks of IVantibiotic through the PICC, cardiologist decided to reassess patient again by ordered TEE (Figure 1d). There is evidence of mitral valve vegetation with ecogenic mass up to 2.4cmx2.1cm on the anterior leaflet (Fig.1f). CT surgeon and cardiologist still insisted to have open heart surgery ASAP to prevent cardio-neurovascular events. Some family physician recommended to give Clopidogrel (Plavix) 75mg po daily, or give any fibrinolytic agent to dissolve the vegetation. Again, patient and family member rescinded all recommendations from both CT surgeon and cardiologist. Instead, patient decided to take two teaspoonful of Turmeric powder, two teaspoonful of Manuka Honey 10+ were bought from Trader Joe’s supermarket store, and taken as three times a day, and extend with Ceftriaxone 2mg IV q24, Daptomycin 8mg/kg IV q24 to two more weeks and re-assess again with TEE on week #8. TEE results come back with vegetation of 0.5cm (Fig1g), and result of culture is negative (Fig1h). Cardiologist, and infection disease physician decided to discontinue the current treatment plan, follow up patient bi-monthly outpatient visit. Patient is recommended to visit his primary care provider for annual routine visit.

Fig. 1a, 1b

Brain magnetic resonance imaging (a), (b) revealing tiny foci are detected in bilateral brain, and multiple different area of brain worrisome for embolic disease with history of endocarditis.

Fig. 1c, 1d

Transthoracic echocardiograms showing an elevated mean diastolic pressure gradient (a) of 10.3 mmHg and a hyperdynamic echogenic mass attached to the MV (b) (white arrows)

Fig. 1e, 1f, 1g (Waiting)

Fig 1h showed negative result after taken paring Manuka Honey 10+, Tumeric Powder and IV antibiotic regimen.

Additional file 1: TEE showed a hyper-dynamic echogenic mass attached to the mitral valve. (WMV 804 kb)

Patient 2

65-year-old Vietnamese women presented with generalized weakness and headache. Her medical history included diabetes mellitus and hypertension. Her physical examination revealed her blood pressure was 162/83 mmHg and her pulse rate was 90 beats/minute. The patient developed a fever (39.2 °C) after 4 weeks, without a definite source of infection. CMP lab test result came back with high creatinine level 2.0mg/dl, acute kidney injury has been diagnosed. Blood cultures revealed Staphylococcus aureus sensitive to Vancomycin. TEE revealed a globular, mobile, echogenic mass (2.3 × 1.0 cm) (Figure 2a). A peripherally inserted central catheter (PICC) was placed; consultant infection disease physician has ordered Ceftriaxone 2mg IV q24 and Daptomycin 8mg/kg IV q24 for 42 days through the PICC line. The patient’s fever subsided after treatment with antibiotics, but a vegetation and persistent septicemia were noted after 2 weeks of treatment. We performed coronary angiography prior to possible valve surgery and observed no significant coronary obstruction. CT surgeon and cardiologist recommended valve surgery but the patient’s husband refused. Patient’s husband refused all surgery because of the high morbidity and mortality risk. Patient’s husband decided to take Manuka Honey 10+, Tumeric powder in addition to current IV antibiotic regimen. After 3 weeks of using additional alternative medicine, TEE was ordered again; surprisingly, there is a non-mobile, echogenic mass (0.4×0.3cm) (Figure 2b), very insignificantly size, were attached to the tricuspid valve. Patient appeared as non-febrile, vital sign was normal; patient was discharged and followed up bi-monthly visit.

Fig 2a.

Fig 2a (L) and 2a (R) of Transesophageal Echocardiography revealing a globular, mobile, echogenic mass (2.3 × 1.0 cm; arrows) attached to the tricuspid valve.

Fig 2b (waiting)

DISCUSSION:

Manuka honey is sourced from nectar collected by honeybees foraging on the manuka tree, which grows in zealand.studybay.net/">New zealand.studybay.net/">Zealandand Australia⁽¹⁾. Many different types of honey have been used in medical remedies for thousands of years, both for antiseptic purposes and for the enhancement of chronic wound healing. Manuka honey has a very high level of dihydroxyacetone which produces methylglyoxal. Methylglyoxal is noted to not only have antibacterial properties, but also be bactericidal. This information was extracted from research that studied the effects of manuka honey on three different types of bacteria: Streptococcus pyogenes, Pseudomonas and Staphylococcus aureus (MRSA-15). The researchers were able to conclude that manuka honey does indeed affect the structure and activity of these three different types of bacteria. In the study of Streptococcus pyogenes, honey inhibited the growth of bacterial biofilm⁽⁴⁾. In the study of Pseudomonas, the use of manuka honey generated “significant changes” in the bacteria’s protein expression. Understanding that without adequate protein expression vital enzymatic activity is jeopardized. This could mean grave danger for the bacterium. When studying MRSA, it was observed that the bacteria seemed to have been susceptible to “relatively low” concentrations of manuka honey. Adding manuka honey to the IV antibiotic therapy seemed to have potentiated the efficacy of the drug. The minimum inhibitory concentration (MIC) or minimum bactericidal concentrations, was to used to measure this. Either test will measure the concentration of the drug that is needed to either kill the bacteria or retard its growth.For this reason manuka honey can be found in many patented wound care products, as it is regarded as a very significant component of topical ointments for superficial skin infections.

In addition to Staphylococcus aureus’s susceptibility to manuka honey, it is also vulnerable to Curcumin. Curcumin, like manuka honey, also exhibits potent activity against a highly resistant strain of Staphylococcus aureus, MRSA, both alone and when combined with antibiotics⁽⁶⁾. Mun’s study was conducted to show that when combined with curcumin, the antibacterial agents Triton X-100 and Tris were effective at inhibiting MRSA growth to 59% and 63%, respectively. Both agents are instrumental in increasing the permeability of a bacteria’s cell wall, thereby causing them to lyse or rupture. This is a very effective dynamic feature of many bactericidal products and curcumin seems to potentiate it. Nonetheless, S. aureus is the culprit in many different infections from pediatrics to adult medicine. Not only is it normally found on our skin, but it is also indicated in such major infections as infective endocarditis (IE), osteomyelitis and sepsis. Like many other microbials, S. aureus has mutated and evolved to be able to thrive in otherwise inhospitable environments, but also to resist modern day chemical therapy.

Pairing manuka honey 10+, turmeric powder and current IV antibiotic⁽⁸⁾, this concoction will create a very strong antibiotic effect that may be capable of fighting off the complication of IE (Infective endocarditis)^{(9)(10)(11)(12)}. Similar to other natural remedies, this recipe does not have adverse effects on those using it, and turmeric can even be taken in supplemental form. However, may it be noted that it is discouraged in use for treatment of gallbladder ailments, as it increases the contractions of the gallbladder muscles. It is also worth noting that combining turmeric with antiglycemic medications may not be good in patients with bouts of hypoglycemia because turmeric is known to assist these medications in lowering blood sugar even more. Likewise in patients with hypotension, or low blood pressure. Turmeric is also known to lower the blood pressure even more. Therefore, patients with the above issues may need to consult their physician before using turmeric, as it may exacerbate their underlying health concerns and lead to more serious problems.

Conclusions:

IE is associated with cardiac, neurologic, renal, musculoskeletal, and systemic complications related to the infection. Predisposing factors include the infecting pathogen, duration of illness, prior therapy, and underlying comorbidities. Complications can occur before, during, and after completion of therapy. IE caused by S. aureus is associated with complications more frequently. Because the mortality rate increases with complications, aggressive antibiotic therapy combined with alternative medicine such as Manuka Honey 10+, Tumeric Powder will speed up the healing process and decrease inflammation reaction phase. Honey contains a protein known as defensing-1 which is produced by the bees. The protein is important in fighting against antibiotic-resistant microorganisms. So, when the two ingredients are combined with antibiotic, they form a highly potent and fast-acting antibiotic, which leads to healing.

Abbreviations:

CT: Computed tomography

EVD: External ventricular drain

IE: Infective endocarditis

MA: Mycotic aneurysm

MVR: Mitral valve replacement

PICC: Peripherally inserted central catheter

TEE: Transesophageal echocardiography

TTE: Transthoracic echocardiography

Declaration Statement:

*All authors have no corporate/commercial relationship with any pharmaceutical companies (this includes any stock ownerships, gift, free or reimbursed travel/vacations). These cases reports are only for educational purpose, not related to commercial purpose. We don’t have any conflict of interest before and after submission of this manuscript.

*Ethical approval: All procedures performed in our studies involving human participants were in accordance with the international ethical standards of our institution. Informed consents were obtained from all individual participants included in the study.

*There is no funding or grant involved for this manuscript

Each author listed below has seen and approved the submissionof this version of the manuscript and takes full responsibility for the manuscript.

* Each author contributed equally into these cases reports.

There are no prior publications or submissions with any overlapping information, including studies and patients from these case reports to any journal around the world.

Acknowledge:

We are grateful to all CT surgeon, cardiologist, infection disease physician at Orange Coast Memorial Community, Orange, California for all the patient data. Grateful thank to Department of Biological Chemistry and Pharmacology, Department of Family Medicine at The Ohio State University, College of Medicine, Columbus, OH, USA; Chair of Preventative Medicine Department at CDU/UCLA School of Medicine, Los Angeles, CA, USA; Department of Internal Medicine of Sentana Medical Center, Virginia, USA Grateful thank to all staff members of Internal Medicine and Psychiatry House staff physician at Bronx-Lebanon Hospital, NY, USA; all physician staff at Nephrology Division of Internal Medicine Department at Albany University Medical Center, Albany, New York, USA; all cardiology staff physician of Department of Cardiology at Pham Ngoc Thach University of Medicine, HCM City, Vietnam; Staff Cardiology physician at Phuong Chau International Hospital, Can Tho City, Vietnam; Cardiology Staff Physician at Valle D’ltria Hospital, Martina Franca, Italy.

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