Clarithromycin as single agent for Patients With Suspected

or Confirmed COVID-19

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​

This is as simple as giving chloroquine alone or chloroquine  with azithromycin.

I think nobody thought about this yet. No one said any of this !!!

Only these 3 possibilities !!!

 

Everyone believes;  I think, that Azithromycin acts as an antibacterial agent for associated pneumonia.

The results of the Marcella people I believe, can be explained only in
three simple ways:

1) Azythromicin acts synergistically with OH-Chloroquine;
2) Azythromicin has an anti-viral effect independent of that of OH-Chloroquine.

3)   Both possibilities act in unison.

 

No one has come out to open the scene on this yet.

I attend many sick people in my office; many (until this came).
In winters for many years I have been using Clarithromycin (which Ihave seen is more effective than Azithromycin)when almost 90 percent of the consultations are feverish respiratorysymptoms; many of them only medicated with paracetamol for being considered viral by the Medical On Duty Rooms  and that in view of the aggravation or persistence of the picture consult me. The fever and the clinical picture improve miraculously 24 hours after giving Clarithromycin strikingly. I have seen this for years in hundreds or
thousands of patients. I always thought that the causative agents were mycoplasmas but slowly I began to convince myself that the action could also be antiviral.

Before this epidemic then and after the association they made with Hidoxychloroquine and Azithromycin, I quickly made the deduction :

 

“ more inclined to think from my experience that the action in this situation would be for macrolides eminently antiviral ”.

 

Azihromycin pharmacologically, could theoretically have better lung penetration. But according to my experience and that of the literature;
As an antiviral Clarithromycine would be much better.

 

That is why it would be essential to use Clarithromycin.

 

This (Clarithromycin as treatment or Prophylaxis As Single Agent) according to my perception could change the history of the pandemic and medicine. It would reduce the cost of the treatment and the potential adverse effects when associating other drugs like hydroxychloroquine.

It would be immediately available globally. It would immediately protect health workers. It would avoid the mortality associated with the disease. It would accelerate the inactivation of the viral load. I would avoid the economic debacle of the world. And if in an effort by all the governments of our planet it were given for a few days at the same time to all the inhabitants of the earth it would allow to eradicate the virus in 5 or 8 days

 

The Covid-19 Pandemic:

 

The greatest risk of spread worldwide of Covid-19 involves serious life-threatening problems against human security. Fever, cough, and shortness of breath are the main symptoms of the disease that can lead to pneumonia with a mortality rate of 1-5%. Currently, there are no approved medications for infectious coronavirus. Despite the fact that antiviral drugs such as protease inhibitors, integrase and / or polymerase enzymes are designed and are in advanced studies. Among these inhibitors, antiprotease inhibitors appear to work effectively in blocking virus replication and provide promising treatment for SARS and MERS disease but not yet advisable in a systematic way.

 

 

The Small French Study with Hydroxychloroquine and the Macrolide Azythromicyn:

 

The very small French study "showed a significant reduction in viral load" after six days of treatment and a "much shorter average viral load duration" compared to patients who received another treatment. Six patients in the trial were asymptomatic and 22 had symptoms of upper respiratory tract infection. Eight patients had lower respiratory tract infections. Twenty cases were treated in the study, with untreated patients acting as negative controls. Hydroxychloroquine treatment was found to significantly reduce viral load in patients with COVID-19, and had an improved effect when azithromycin was included in the treatment.

 

Interestingly, a patient who continued to test positive after being treated with hydroxychloroquine alone was given azithromycin starting on the eighth day and tested negative the following day.

 

This fact is of utmost importance since it would be inferred from said result that macrolide drugs could have an effect inherent in them as antivirals themselves. Especially Clarithromycin.

( PERSONAL )

 

 

Until now and according to the available scientific literature, no one in the world has done or proposed a controlled clinical trial to test the pure antiviral efficacy of a macrolide without any other drug associated with it, called azithromycin or clarithromycin.

Azithromycin is an antibiotic in the macrolide family widely used for bacterial infections. Side effects include stomach upset, diarrhea, nausea, vomiting, or abdominal pain. Less common but serious side effects include hearing damage or deafness, drooping eyelids and blurred vision, difficulty swallowing or speaking, muscle weakness, and liver damage. It is contraindicated for people allergic to azithromycin and other antibiotics, such as erythromycin, clarithromycin, and telithromycin. It is also contraindicated in people with liver and kidney disease.

Clarithromycin is another similar macrolide with perhaps similar pharmacological effect but with moderately superior efficacy and potentially also an antiviral effect ( see Bibliography ). Clarithromycin is also used in conjunction with other medications to treat stomach ulcers caused by Helicobacter pylori. It is usually administered as a 500 oral dose every 12 hours or as a long acting formulation once a day, both for 8 days.

 

PURPOSE OF THE PROTOCOL:

To Guarantee the detection and early diagnosis of a possible new case coronavirus (COVID-19)patient and even healthy carriers, in order to allow its inclusion in a research protocol with the exclusive use of Clarithromycin 500 long acting formulation that allows its administration once a day for 8 days and check if this treatment per se is able to reduce or make disappear the viral load of that new case or healthy carrier.

 

Triage:

Given the selection of the probable case and / or possible healthy carrier, and not having criteria of severity, after obtaining chest X-ray that does not indicate serious pulmonary compromise or dyspnea or other serious organic alteration, the oropharynx sample will be obtained and / or or nasopharynx and will be sent for PCR (to the Reference center) for Covid-19.

 

PRIMARY PROPHYLAXIS:

 

The main objective of epidemiological surveillance in the current situation is early detection of healthy cases or carriers, allowing the adequate care of patients and the implementation of research, prevention and control measures aimed at reducing the risk of spread of infection in the population.

 

Current evidence suggests that person-to-person spread is occurring, even among healthcare workers caring for patients suffering from COVID-19, which would be consistent with what is known about other similar pathogens. 

So far, no drugs or combinations have been recommended, nor are vaccines approved for the use of antiviral prophylaxis before or after exposure to COVID-19 available, since there is no evidence to support their use.

If clarithromycin reduced itself without the addition of any drugs plus the viral load of infected patients or carriers or positive contacts for the virus, the potential administration of only 8 days of global or global prophylaxis of Clarithromycin 500 UD could definitively end and in a few days with the pandemic.

It would also even be interesting to see its prophylactic effect on members of the health team directly involved in the care of patients of these characteristics.

Hence the urgent need for this trial.

TWO POSSIBLE VERY SIMPLE PROTOCOLS THAT SHOULD BE STARTED IMMEDIATELY AND SIMULTANEOUSLY:

 

1. TO DEMONSTRATE THE ANTIVIRAL AND THERAPEUTIC EFFECTIVENESS OF 500 MG OF ORAL CLARITHROMYCIN PROLONGED RELEASE FORMULATION AS A SOLE AGENT.

 

POSSIBILITY TO END THE PANDEMIC WITH ONLY ONE CYCLE OF THIS SCHEME IF OFFERED TO THE WHOLE WORLD POPULATION IN SIMULTANEOUS.

 

CASE RECRUITMENT PARAMETERS FOR OPTION 1

 

PATIENTS WITH INITIAL SIGNS AND SYMPTOMS (AT THE BEGINNING OF SYMPTOMS IN CLINICALLY UNCOMPLICATED SICKNESS NOT COMMITTED TO GRAVITY CLINICALLY)

RX THORAX APPARENTLY WITHOUT OR VERY LITTLE PULMONARY COMMITMENT

CT EVENTUALLY WITH MINIMUM SIGNS

GENERAL ANALYSIS WITHOUT SERIOUS FAILURES

GENERAL ANALYSIS:

HEMOGRAM ERS UREA GLYCEMIA CREATININ HEPATOGRAM LDH SPECIFIC ANALYSIS

RX

CT ( IT WOULD BE VERY USEFUL BUT I DON'T KNOW IF THE CENTERS WANT TO SPEND THAT MONEY IF THE RX LOOKS GOOD OR EVEN IF THE LUNG IS VERY COMMITTED IN RX THE URGENCY WILL NOT ALLOW TO DO MANY STUDIES BUT IF YOU CAN IT IS ADDED )

QUICK TEST FOR COVID 19 PCR FOR COVID 19 EVENTUALLY

PHARINGED ISOPATE FOR INFLUENZA VIRUSES AND OTHER NON-COVID RESPIRATORIES (THIS IS NOT ESSENTIAL)

 

IF THERE IS NO CONTRAINDICATION

 

BEGINS WITH CLARITHROMYCIN 500 LONG ACTING FORMULATION ONE PER DAY ORAL

 

 IF THE QUICK TEST GIVES NEGATIVE CONTINUES CLARITHROMYCIN

 

IF IGM POSITIVE IT CONTINUES ON RECEIVING THE DRUG

IF THE PCR POSITIVE  AND HAVE NOT WORSEN AT 48-72 HOURS OR BETTER CONTINUE DRUG FOR 8 DAYS.

 

 IF PCR POSITIVE AND HAS GOT WORST, ADD HYDROXYCHLOROKINE AND ENTER IF IT IS POSSIBLE TO THE HOSPTITAL.

 

IF PCR POSITIVE POSITIVE AND HAS NOT WORSEN ON THE 3RD DAY, THE RX IS REPEATED AND IT IS REPEATED PCR FOR COVID 19 AND CONTINUES THE 8 DAYS IN THE SAME WAY OF NEGATIVE OR POSITIVE.

 

 IF THE PATIENT DOES NOT WORSEN ON THE 8TH DAY, CLARITHROMYCIN IS STOP AND IN DAY 9 WILL DO RX AND PCR AGAIN.

 

THE PATIENT IS FOLLOWED FOR ANOTHER WEEK AND IF IT DOES NOT WORSEN REPEAT THE QUICK TEST IF POSSIBLE.

IF THE PATIENT GETS WORST AT ANY TIME, HE GOES INTO THE HOSPITAL IF POSSIBLE AND RECEIVES HIDOXICLOROQUIN WITH THE CLARITHROMYCIN.

 

OPTION 2

 

( IT CAN / SHOULD BE DONE IN SIMULTANEOUS WITH OPTION 1)

 

HEALTH PERSONNEL STRONGLY EXPOSED AND WITH A SIMILAR DEGREE OF EXPOSURE TO COVID 19.

 

(IN FULL EPIDEMIC THEY SHOULD BE THE MOST EXPOSED IN ADMISSION ROOMS) WHILE THE STUDY LASTS.

 

TWO GROUPS OF 20 DOCTORS / NURSES ARE SELECTED EACH OF BOTH GROUPS DO:

COVID 19 QUICK TEST (IgM-IgG) AND COVID 19 PCR IF IT IS POSSIBLE.

 

OR  PCR ALONE.

 

CLINICALLY THEY SIGN THAT THEY FEEL HEALTHY

THEY DON'T TAKE ANY OTHER MEDICATION DURING THE COURSE OF THE STUDY

THEY DO RX IF NOT BEING PREGNANT IF A WOMAN.

THEY ALL SHOULD NOT HAVE SIGNS OF PULMONARY INVOLVEMENT.

 

GROUP 1

 

IF NO CONTRAINDICATION ON DAY 1 OF RECRUITMENT BEGINS: CLARITHROMYCIN 500 LONG ACTING FORMULATION 1 X DAY FOR 15 DAYS

 

GROUP 2 NOTHING

 

POSITIVES AT THE BEGINNING OF EITHER OF THE TWO GROUPS BEGIN

CLARITHROMICINA 500 LONG ACTING FORMULATION ONCE A DAY AND ARE FOLLOWED ACCORDING TO OPTION 1 OF THESE PROTOCOLS IN DOMESTIC INSULATION WHILE THEY DO NOT WORSE.

 

ALL PEOPLE IS FOLLOWED FOR 15 DAYS

 

THOSE WHO WORSE DESPITE BEING WITH CLARITHROMYCIN IN GROUP 1 ARE CARRIED OUT AND HYDROXYCHLOROQUINE IS STARTED IN THE HOSPITAL IF POSSIBLE.

 

THEY LEAVE THE GROUP IN THESE CASES AND ARE NOT REPLACED.

 

AT DAY 8 PCR IS REPEATED ON EVERYONE AND RX THORAX ALSO

 

ON THE 15TH DAY PCR AND RX THORAX ARE REPEATED

 

IF AVAILABLE RAPID TESTS ( IgM-IgG are also done at the same times ).

 

THE RESULTS ARE STATISTICALLY ANALYZED AND COMMUNICATED / PUBLISHED

 

IF ENCOURAGING THESE RESULTS:

 

IT WILL BE PROPOSE TO THE GOVERNMENTS OF THE WORLD AND QUICKLY:

TO MANAGE ALL THE WORLD POPULATION THAT DOES NOT HAVE A CONTRAINDICATION AND SIMULTANEOUSLY AROUND THE WORLD ONE CYCLE OF CLARITHROMYCIN 500 LONG ACTING FORMULATION 1 X DAY FOR 8 DAYS ORAL.

 

AND THE VIRUS THEN DISAPPEARS FROM THE FACE OF THE EARTH.

 

 

BIBLIOGRAPHY (CLARITHROMYCYN, MACROLIDES AND RESPIRATORY VIRAL DISEAS )  PLEASE SEE WITH DETAIL.

 

Immunomodulator Clarithromycin Enhances Mucosal and Systemic Immune Responses and Reduces Re-Infection Rate in Pediatric Patients with Influenza Treated with Antiviral Neuraminidase Inhibitors:

A Retrospective Analysis

Wakako Shinahara1, Etsuhisa Takahashi1, Takako Sawabuchi1, Masaru Arai2, Nobuo Hirotsu3, Yoshio Takasaki4, Shizuo Shindo5, Kyoko Shibao6, Takashi Yokoyama7, Kiyoshi Nishikawa8, Masahiro Mino9, Minako Iwaya10, Yuji Yamashita11, Satoshi Suzuki12, Dai Mizuno1, Hiroshi Kido1*

 

Kudoh S, Uetake T, Hagiwara K, Hirayama M, Hus LH, et al. (1987)

Clinical effects of low-dose long-term erythromycin chemotherapy on diffuse pan- bronchiolitis. Nihon Kyobu Shikkan Gakkai Zasshi 25:632–642.

 

Labro MT. (2001)

Anti-inflammatory activity of macrolides: a new therapeutic potential? Antimicrob Agents Chemother 45:44–47.

 

Suzuki T, Yamada M, Sekizawa K, Hosoda M, Yamada N, et al. (2002) Erythromycin inhibits rhinovirus infection in cultured human tracheal epithelial cells. Am J Respir Crit Care Med 165:1113–1118.

 

Tahan F, Ozcan A, Koc N. (2007)

Clarithromycin in the treatment of RSV bronchitis: a double-blind, randomized placebo-controlled trial. Eur Respir J 29:91–97.

 

Sato K, Suga M, Akaike T, Fujii S, Muranaka H, et al. (1998)

Therapeutic effect of erythromycin of influenza virus-induced lung injury in mice. Am J Respir Crit Care Med 157:853–857.

 

Maeda S, Yamada Y, Nakamura H, Maeda T. (1999)

Efficacy of antibiotics against influenza-like illness in an influenza epidemic. Pediatr Int 41:274–276.

 

Tsurita M, Kurokawa M, Imakita M, Fukuda Y, Watanabe Y, et al. (2001) Early augmentation of interleukin (IL)-12 level in the airway of mice administrated orally with clarithromycin or intranasally with IL-12 results in alleviation of influenza infection. J Pharmacol Exp Ther 298:362–368.

Sawabuchi T, Suzuki S, Iwase K, Ito C, Mizuno D, et al. (2009)

Boost of mucosal secretory immunoglobulin A response by clarithromycin in paediatric influenza. Respirology 14:1173–1179.

 

Takahashi E, Kataoka K, Indalao IL, Konoha K, Fujii K, et al. (2012)

Oral clarithromycin enhances airway immunoglobulin A (IgA) immunity through induction of IgA class switching recombination and B-cell-activating factor of the tumor necrosis factor family molecule on mucosal dendritic cells in mice infected with influenza A virus. J Virol 86:10924–10934.

 

J Pharmacol Exp Ther. 2010 Apr;333(1):81-90. 2009 Dec 29.

Clarithromycin inhibits type a seasonal influenza virus infection in human airway epithelial cells.

Yamaya M1, Shinya K, Hatachi Y, Kubo H, Asada M, Yasuda H, Nishimura H, Nagatomi R.

 

Mediators Inflamm. 2012; 2012: 649570. 

Published online 2012 Jun 6. 

Macrolide Therapy in Respiratory Viral Infections

Jin-Young Min and  Yong Ju Jang *

 

Kanoh S, Rubin BK.

Mechanisms of action and clinical application of macrolides as immunomodulatory medications. 

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Clarithromycin inhibits progeny virus production from human influenza virus-infected host cells. 

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Effect of clarithromycin on experimental rhinovirus-16 colds: a randomized, double-blind, controlled trial.

 American Journal of Medicine. 2000;108(6):453–459. 

 

 Suzuki T, Yamaya M, Sekizawa K, et al.

Erythromycin inhibits rhinovirus infection in cultured human tracheal epithelial cells. 

American Journal of Respiratory and Critical Care Medicine. 2002;165(8):1113–1118. 

 

 Jang YJ, Kwon HJ, Lee BJ.

Effect of clarithromycin on rhinovirus-16 infection in A549 cells. 

European Respiratory Journal. 2006;27(1):12–19. 

 

 Inoue D, Kubo H, Sasaki T, et al.

Erythromycin attenuates MUC5AC synthesis and secretion in cultured human tracheal cells infected with RV14. 

Respirology. 2008;13(2):215–220. 

Wang JH, Lee SH, Kwon HJ, Jang YJ.

Clarithromycin inhibits rhinovirus-induced bacterial adhesions to nasal epithelial cells. Laryngoscope. 2010;120(1):193–199. 

 

Gielen V, Johnston SL, Edwards MR.

Azithromycin induces anti-viral responses in bronchial epithelial cells. 

European Respiratory Journal. 2010;36(3):646–654. 

 

Tahan F, Ozcan A, Koc N.

Clarithromycin in the treatment of RSV bronchiolitis: a double-blind, randomised, placebo-controlled trial. 

European Respiratory Journal. 2007;29(1):91–97.

 

Kneyber MCJ, Van Woensel JBM, Uijtendaal E, Uiterwaal CSPM, Kimpen JLL. Azithromycin does not improve disease course in hospitalized infants with respiratory syncytial virus (RSV) lower respiratory tract disease: a randomized equivalence trial. 

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Asada M, Yoshida M, Suzuki T, et al.

Macrolide antibiotics inhibit respiratory syncytial virus infection in human airway epithelial cells. Antiviral Research. 2009;83(2):191–200. 

 

Sato K, Suga M, Akaike T, et al. Therapeutic effect of erythromycin on influenza virus-induced lung injury in mice. American Journal of Respiratory and Critical Care Medicine. 1998;157(3):853–857

 

Tsurita M, Kurokawa M, Imakita M, Fukuda Y, Watanabe Y, Shiraki K.

Early augmentation of interleukin (IL)-12 level in the airway of mice administered orally with clarithromycin or intranasally with IL-12 results in alleviation of influenza infection. 

Journal of Pharmacology and Experimental Therapeutics. 2001;298(1):362–368. 

 

Sawabuchi T, Suzuki S, Iwase K, et al.

Boost of mucosal secretory immunoglobulin A response by clarithromycin in paediatric influenza. 

 

Yamaya M, Shinya K, Hatachi Y, et al.

Clarithromycin inhibits type A seasonal influenza virus infection in human airway epithelial cells. 

Journal of Pharmacology and Experimental Therapeutics. 2010;333(1):81–90. 

 

Parnham MJ.

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