Study does not support low-dose azithromycin to treat chronic cough in IPF

ByErin T. Welsh, MA

Source/Disclosures

Source:

Guler SA, et al. Ann Am Thorac Soc. 2021;doi:10.1513/AnnalsATS.202103-266OC.

Disclosures:
Funke-Chambour reports receiving grants from Boehringer Ingelheim and Roche. Please see the study for all other authors’ relevant financial disclosures.

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Treatment with low-dose azithromycin for chronic cough in patients with idiopathic pulmonary fibrosis did not significantly improve cough-related quality of life, severity or frequency compared with placebo.

“Chronic cough is a common symptom in patients with idiopathic pulmonary fibrosis that impairs quality of life. This cough is often resistant to current drug approaches,” Manuela Funke-Chambour, MD, principal investigator in the department of pulmonary medicine at Bern University Hospital and with the Adult Pulmonary Research Group in the department of biomedical research at the University of Bern, Switzerland, told Healio. “Azithromycin is used in other chronic respiratory diseases associated with cough and has been speculated to reduce cough in idiopathic pulmonary fibrosis as well, but no randomized, placebo-controlled study has investigated this hypothesis before.”

Source: Adobe Stock.

The randomized, double-blind, controlled cross-over trial included 25 patients (mean age, 67 years; 23 men) with IPF. All patients underwent two 12-week intervention periods during which they were randomly assigned azithromycin 500 mg or placebo thrice weekly.

The primary outcome was change in cough-related quality of life, as measured by the Leicester cough questionnaire. Secondary outcomes were cough severity measured using the visual analog scale, health-related quality of life measured by the St. George’s Respiratory Questionnaire and objective cough frequency measured by audiovisual readings from 24-hour respiratory polygraphy.

Twenty patients completed the study.

Mean baseline cough-related quality of life score was 11.7 and the mean objective cough frequency score was 5.6 for those randomly assigned azithromycin and 11.3 and 5.8, respectively, for those assigned placebo. Researchers observed no significant change in cough-related quality of life (mean difference before and after treatment, 0.68; P = .29) or objective cough frequency (mean difference, 0.25; P = .7).

In addition, there was also no significant difference in change in polygraphy-measured cough frequency between the azithromycin and placebo groups.

“We hoped for an improvement of cough under the treatment with azithromycin. This is not the case,” Funke-Chambour said. “Azithromycin treatment in idiopathic pulmonary fibrosis for the indication of cough is thus not justified.”

No serious treatment-emergent adverse events were reported. Among those assigned azithromycin, gastrointestinal adverse events were more frequently reported than in the placebo group, and included diarrhea (43% vs. 5%), abdominal pain (19% vs. 0%) and nausea (19% vs. 5%). Respiratory infection was reported in four (19%) patients assigned azithromycin and three (14%) assigned placebo.

“The clinical problematic for the affected patients remains unresolved,” Funke-Chambour said. “Other drugs or approaches need to be tested to reduce cough in patients with idiopathic pulmonary fibrosis.”

For more information:

Manuela Funke-Chambour, MD, can be reached at [email protected].

Azithromycin User Reviews for Upper Respiratory Tract Infection

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Azithromycin in the treatment of bronchopulmonary infections | Konstantinova T.

D., Nonikov V.E., Makarova O.V., Vorobieva M.G.

The epidemiological situation in recent years is characterized [1,2,6] by the increased etiological significance of pathogens such as mycoplasma, legionella, chlamydia, widespread sensitization of the population to penicillin derivatives and sulfonamides, and a significant increase in the resistance of many microorganisms to the most commonly used antibiotics. To a large extent, the increase in resistance was the result of many years of template use in outpatient practice of co-trimoxazole and semi-synthetic tetracyclines. In recent years, fluoroquinolones have become more widely used in polyclinics – the result was the formation of strains resistant to these drugs.

The first of the macrolides, erythromycin, was created in 1952, and drugs of this series were usually used as alternative drugs for penicillin allergy. The real rebirth of these antibiotics took place in the 80s of the twentieth century – after a dramatic outbreak of legionella pneumonia, accompanied by a 30% mortality rate. It was quickly established that macrolides are the optimal drugs for the treatment of infections caused by intracellular infectious agents: legionella, mycoplasma, chlamydia. This led to the widespread use of macrolides, tk. mycoplasmal pneumonias are very common (especially during the years of epidemiological trouble), and legionella pneumonias are characterized by high mortality. Research centers of the pharmaceutical industry have created a number of new drugs for oral and parenteral use, differing in terms of pharmacokinetics and pharmacodynamics.
The basis of the chemical structure of macrolides [5] is the macrocyclic lactone ring. Depending on the number of carbon atoms in the lactone ring, 14-membered (erythromycin, clarithromycin, roxithromycin), 15-membered (azithromycin) and 16-membered (josamycin, midecamycin, spiramycin) macrolides are isolated.
Azithromycin belongs to the azalide subclass because one carbon atom in its ring is replaced by a nitrogen atom. The structural features of individual drugs determine differences in pharmacokinetic characteristics, tolerability, the possibility of drug interactions, as well as some features of antimicrobial activity. Azithromycin is characterized by unique cellular kinetics, rapid and intense penetration into cells and interstitial tissues, high levels of antibiotic distribution in tissues and relatively low levels in the blood.
Azithromycin well suppresses (Table 1) gram-positive (pneumococci, streptococci, staphylococci) and gram-negative (moraxella, Haemophilus influenzae) microorganisms and intracellular agents (chlamydia, mycoplasma, legionella, ureaplasma). Other macrolides (except clarithromycin) are less active against Haemophilus influenzae [5,6]. If we take into account that in the etiological structure of community-acquired pneumonia, pneumococci, Haemophilus influenzae, Mycoplasma, Chlamydia take the leading positions, and exacerbations of chronic bronchitis (chronic obstructive pulmonary disease) are usually caused by pneumococci, Haemophilus influenzae, Moraxella (less often – Mycoplasma and Chlamydia), it is becoming clear that azithromycin is often the antibiotic of choice for the treatment of pulmonary patients.
In the countries of Western and Southern Europe, the widespread use of macrolides has led to an increase (up to 30%) of pneumococcal resistance to them. Corresponding indicators of resistance in our country [5], according to various estimates, do not exceed 4–8%. Features of azithromycin are determined not only by the spectrum of action, but also by the creation of high concentrations in the lung parenchyma and alveolar macrophages. Comparison of the concentrations created in various biological media shows that the concentrations of azithromycin in the lung parenchyma are 8–10 times higher, and in alveolar macrophages 800 times higher than in blood serum. Thus, this drug should be most effective in the treatment of pulmonary pathology.
Azithromycin remains in the site of infection for 4–5 or more days, depending on the dose and tissue structure. Due to the release of the antibiotic from phagocytes during their destruction, the concentration in the focus of infection rapidly increases [5]. High intracellular penetration and accumulation in cells and infected tissues determines the effectiveness of azithromycin, which exceeds the effect of other antibiotics, in infections caused by intracellular pathogens, including pathogens of dangerous infectious diseases (brucellosis, tularemia, etc.).
A feature of the pharmacodynamics of macrolides is a long-term post-antibiotic effect, due to which, when using an antibiotic in minimal inhibitory concentrations, the effect of the antibiotic continues after its withdrawal. With regard to azithromycin, a post-antibiotic effect lasting up to 90 hours is considered proven, and this allows to reduce the duration of antibacterial treatment.
Allergic sensitization to macrolides is relatively rare. Among the side effects, gastrointestinal manifestations predominate and, perhaps, some of them are due to the ability of macrolides to increase intestinal motility. Side effects are more frequent with erythromycin. Toxic and allergic side effects with the use of azithromycin are rare [5,6].
Azithromycin is approved for clinical use in Russia for oral administration in tablets (500 mg) and capsules (250 mg), as well as in vials (500 mg) for intravenous administration.
A study of the practice of antibiotic therapy in a general hospital in 2004 showed that macrolides are in 4th place, behind b-lactam antibiotics, fluoroquinolones and aminoglycosides. In the treatment of pulmonological patients, macrolides are used much more widely and the frequency of their appointment is second only to b-lactam antibiotics. When prescribing macrolides in the Central Clinical Hospital, doctors most often (80%) preferred azithromycin.
Indications for the appointment of azithromycin are [4,5,6] infections of the upper respiratory tract (tonsillopharyngitis, acute otitis media, sinusitis), as well as bronchitis and community-acquired pneumonia. The so-called “atypical” pneumonias [1,3,4] are caused by intracellular agents – viruses, mycoplasma (50% of all cases), chlamydia, legionella, and azithromycin is the best antibiotic to treat most of them. Brief differences between atypical pneumonias [7] are shown in Table 2. The infection is often transmitted from person to person (in recent years, several family and work outbreaks of mycoplasma and chlamydial pneumonia have been observed). The disease usually begins with a prodrome in the form of acute respiratory viral infections of the type of laryngotracheitis, leukocytosis and a shift of the leukocyte formula to the left are usually not observed, the cough is usually dry or with scanty mucous sputum, sometimes whooping cough, bacteriological studies are uninformative. In X-ray examination, more often than usual with pneumonia, interstitial changes are noted, sometimes combined with mediastinal lymphadenopathy. Definitive diagnosis is possible by serotyping, which usually takes up to 2 weeks (paired sera). There is a rapid diagnosis of “legionnaires’ disease” by determining the legionella antigen in the urine, but in our country this study has not yet become widespread.
When establishing a diagnosis of pneumonia, the clinician must decide whether to prescribe antibiotic therapy, and the choice of first-line antibiotic is almost always empirical [2,4,6]. The knowledge, practical experience of the doctor and his assessment of clinical situations are important.
If community-acquired pneumonia has developed in a young patient, and the likely causative agents are pneumococci, mycoplasma and chlamydia, macrolides may be the drug of choice. Modern programs [6] for the treatment of mild pneumonia, both on an outpatient basis and in a hospital, provide for the possibility of oral administration of macrolides, and primarily azithromycin or clarithromycin.
Features of pharmacokinetics allow the use of azithromycin once a day. Naturally, drugs used once or twice a day have greater compliance and are readily used by patients. There are various regimens for oral administration of azithromycin. The most common dosage in the treatment of pulmonary diseases is 500 mg on the first day of treatment and 250 mg every 24 hours for the next 4 days. With this scheme, the duration of treatment for pneumonia is 5 days. The duration of treatment for pneumonia caused by mycoplasma and chlamydia is 14 days, and for legionella pneumonia – 21 days.
Treatment of pneumonia caused by common bacterial agents (pneumococci, streptococci, Haemophilus influenzae, etc.) can be reduced to three days if the daily dose is 500 mg.
Own experience in the use of azithromycin for 12 years is based on the treatment of more than 1400 patients with pneumonia with this antibiotic, and all the described oral therapy regimens, stepwise therapy, treatment with azithromycin in combination with b-lactam antibiotics were used with high efficiency. It is possible to confirm the effectiveness of a three-day therapy (course dose of 1500 mg) with azithromycin for mild pneumonia.
In addition to monotherapy with azithromycin, this antibiotic is often prescribed in combination with b-lactam drugs. If a patient is hospitalized for moderate or severe pneumonia, a de-escalation tactic is often practiced [2,6], which involves the use of a combination of antibiotics for initial therapy, and usually this is a combination of a b-lactam drug (aminopenicillins, cephalosporins, carbapenems) with a macrolide, which is prescribed based on the possibility of legionella or chlamydial infection. Subsequently, after the diagnosis is clarified, one of the drugs is canceled.
A few years ago, patient N., 44 years old, was hospitalized in our department with a diagnosis of severe multilobar (three lobes) pneumonia, complicated by respiratory failure and unstable hemodynamics. Initial antibiotic therapy was combined: meropenem 2.0 g intravenously every 12 hours and azithromycin 1.0 g/24 hours on the first day and 0.5 g/24 hours on the following days. On the background of the treatment, the patient’s condition improved rapidly. According to serotyping, pneumonia on the 4th day of treatment was deciphered as legionella. On the 5th day of treatment, meropenem was canceled and monotherapy with azithromycin continued. The outcome is recovery. It can reasonably be assumed that the outcome of the disease in the observed patient would be doubtful if the initial empirical antibiotic therapy was limited only to meropenem, and azithromycin was prescribed only after the legionella nature of pneumonia was established.
This observation prompted us to conduct de-escalation antibiotic therapy (b-lactam antibiotic + macrolide) in almost half of patients with pneumonia and in all cases of treatment of severe pneumonia.
In severe pneumonia, antibiotics are given intravenously. With intravenous use, azithromycin is dosed at 500 mg every 24 hours.
Consideration should be given to the costs of antibiotic therapy, which can be quite significant. In recent years, the so-called stepwise therapy has been successfully used [2,3,6]. When using azithromycin according to this technique, treatment begins with intravenous antibiotic 500 mg every 24 hours. Upon reaching the clinical effect (usually after 2–3 days), when antibiotic therapy provided an improvement in the patient’s condition, accompanied by a decrease or normalization of body temperature, a decrease in leukocytosis, it is possible to switch to oral administration of azithromycin (if good absorption is expected) at 0.25–0, 5/24 hours. With the high efficiency of such a technique, it is less expensive not only due to the difference in prices for parenteral and tablet preparations, but also due to a decrease in the consumption of syringes, droppers, and sterile solutions. Such therapy is more easily tolerated by patients and less often accompanied by side effects.
Intravenous and stepped azithromycin is commonly used in the treatment of severe pneumonia. In the treatment of other bronchopulmonary infections, as a rule, oral therapy can be limited.
Acute bronchitis is most commonly caused by influenza, parainfluenza, respiratory syncytial viruses, rhinoviruses and coronaviruses. Such bronchitis is usually treated symptomatically, since there are no universal antiviral drugs yet. The causative agents of acute bronchitis, amenable to antibiotic therapy, are mycoplasma, chlamydia, pneumococci, Haemophilus influenzae, Moraxella. For their treatment, doxycycline (not prescribed for persons under 17 years of age and pregnant women), macrolides (azithromycin and clarithromycin, which suppress Haemophilus influenzae and Moraxella), respiratory fluoroquinolones can be used.
The most common agents causing exacerbation of chronic obstructive pulmonary disease (COPD) are pneumococci, Haemophilus influenzae, Moraxella. Up to 10% of COPD exacerbations are caused by each of such intracellular agents as mycoplasma, chlamydia, viruses. Pathogenetically, COPD begins with chronic bronchitis [6], which explains the uniformity of trigger factors of the disease and microorganisms responsible for the development of infectious exacerbations. The cornerstones of the treatment of exacerbations of COPD are: the appointment of an antibiotic, an increase in the dosage of bronchodilators, the systemic use of glucocorticosteroids, oxygen therapy. Indications for the appointment of antibiotic therapy for exacerbations of COPD are the world-recognized criteria for antibiotic therapy of exacerbations of chronic bronchitis – an increase in the amount of sputum discharge and / or the appearance of purulent sputum and increased shortness of breath. In outpatient practice, an oral antibiotic that is most likely to suppress the infectious agent will be optimal. These may be b-lactam antibiotics, but their spectrum of activity does not extend to intracellular agents. Therefore, macrolides that suppress Haemophilus influenzae (azithromycin or clarithromycin) or respiratory fluoroquinolones are preferred.
The given data and own many years of experience indicate that currently azithromycin occupy one of the main positions in the treatment of bronchopulmonary infections.

Literature
1. Nonikov V.E. Atypical pneumonia: the rebirth of macrolides // New Medical Journal.–1995.–No. 1.–p.5–7
2. Nonikov V.E. Tactics of antibacterial chemotherapy of pneumonia //RMJ.–1997.–Vol. 5.–No. 24,– p.1568–1578
3. Nonikov V.E. Diagnosis and treatment of atypical pneumonia//Consilium medicum.–2001.–Vol. 3.– No. 3.–p.138–141
4. Nonikov V.E. Antibiotics–macrolides in pulmonological practice // Atmosphere: pulmonology and allergology.–2004.– No. 2 (13).– p.24–26
5. Strachunsky L.S., Kozlov S.R. Macrolides in modern clinical practice//1998.–Smolensk.–Rusich.–303 p.
6. Bartlett J. Management of Respiratory Tract Infections // Lippincott Williams & Wilkins. –2001.–277p.
7. Zackom H. Pulmonary Differential Diagnosis //W.B. Saunders.– 2000.– 885 p

Antibiotics for coughs: when should I take them?

Publication date: 06/18/2022
Updated: 06/18/2022

Contents:

Do I need antibiotics for cough?

Which antibiotic should adults take for a cough?

How to take antibiotics correctly?

Can a cough be cured without antibiotics?

Cough is not an independent disease, it is a symptom that may indicate the development of certain ailments. And the most common cause of cough is the so-called cold (acute respiratory viral infection).

SARS can be treated with a variety of medications, and many believe that antibiotics for coughs can help address the cause of the symptom. In the article, we will figure out whether this is so and when antibiotic therapy is indicated for coughing.

Treatment of cough with ARVI with antibiotics is completely inappropriate. First, antibacterial drugs cannot destroy viruses. And secondly, there is no specific treatment for ARVI, only symptomatic therapy is used. It consists in the use of antipyretics, drugs to facilitate the excretion of sputum, to relieve nasal congestion, etc.

Respiratory problems are often managed with herbal remedies such as Bronchipret®. It facilitates the excretion of sputum, reduces the frequency and intensity of coughing, and also helps to reduce inflammation.

Symptoms of a viral infection include a runny nose with profuse clear discharge, dry or wet cough, including a rather large amount of sputum. A bacterial infection can develop against a viral background or independently. Usually, the sputum is quite thick, has a yellowish or greenish color, contains impurities of pus, and has an unpleasant odor.

It is possible to suspect the addition of a bacterial infection by high body temperature, which persists for 3 days or more, a protracted course of the disease, lack of improvement, and shortness of breath.

It is important to understand that bacteria are very rarely the cause of primary infection, usually it all starts with a common cold or flu. This happens when the immune forces are weakened, for example, due to frequent SARS, allergic diseases, chronic inflammatory diseases, etc.

Adults need an antibiotic for coughing only when a bacterial or mixed infection occurs. All antibacterial drugs are effective only against coughs of bacterial origin. Indications for their use are the following diseases:0003

Antibacterial therapy should always be targeted and prescribed by a doctor strictly according to indications. Usually the need for the use of certain antibiotics is determined by several indicators:

• wheezing is heard;

• blood test results indicate active bacterial inflammation;

• The results of bacteriological examination of sputum confirmed the bacterium that causes inflammation.

It should also be noted that the prophylactic use of antibiotics is not advisable: it is not worth drinking them “just in case” against the background of a viral infection in order to prevent the development of a bacterial one.

If an antibiotic is indicated for a severe cough in adults, only a doctor should prescribe the drug. This is always an individual question. As a rule, the choice of antibiotic depends on the results of sputum analysis, which allows you to choose an effective drug for a particular bacterial infection.

Despite the fact that the algorithm of actions in case of a suspected bacterial infection is simple, there are situations when a person’s condition is rapidly deteriorating. There is simply no time to wait for answers from bacteriological studies, and in this case, the doctor will prescribe broad-spectrum antibiotics, and after the start of therapy, he will wait for the results and observe the dynamics.

Sometimes it is necessary to try several treatment options before finding an effective one.

Antibiotics for dry cough

Antibiotics for dry cough in adults are not usually prescribed. The absence of sputum is a possible indication that thick and viscous mucus is difficult to cough up and you need to help the body to remove it. For this, mucolytics are used – drugs that help thin the sputum and stimulate its excretion.

In some cases, a non-productive cough is neurogenic in nature – it occurs due to stimulation of the cough center in the brain, and not due to the entry of polluted air into the lungs or the formation of sputum. In this case, antibiotics will also often be useless. You will need to find out the causes of dry cough, you may need antitussive drugs, etc.

Antibiotics for severe cough

A severe cough can indicate both a large amount of sputum and difficulty in expectorating it. Sometimes frequent coughing spells indicate a specific infection, such as whooping cough.

When a severe cough is caused by acute inflammation of the lower respiratory tract, antibiotics may be appropriate. They will be prescribed by a doctor.

Antibiotics for coughs with sputum

Antibiotics for coughs with large amounts of sputum may not be needed. If the cough is of an infectious and inflammatory nature, the following types of drugs are prescribed:

Inhalations are also prescribed, both with saline solution and with the use of drugs, if possible.

Antibiotics for persistent coughs

Coughs that persist after illness should be treated with mucolytics, anti-inflammatory drugs, and other agents. In some cases, an additional examination is required to find out the cause of a prolonged cough. Antibiotics may be prescribed if a bacterial pathogen is identified.

Adults who cough with phlegm should take antibiotics at the same time. This helps to create and maintain the concentration of active substances necessary for the destruction of pathogenic bacteria. Otherwise, microorganisms will begin to form resistance to the substance, which will make treatment difficult.

Antibiotic regimen depends on the type of antibiotic:

• macrolide antibiotics are usually taken once a day;

• penicillins are taken up to 3 times a day;

• Your doctor may prescribe

  cephalosporins intravenously or intramuscularly.

As a rule, the course of treatment is not less than five and not more than ten days. On average, if the antibiotic is chosen correctly, relief occurs within 72 hours. If there is no improvement, the doctor will probably change the drug.

Do not increase the dosage on your own. This can cause complications, but will not speed up recovery. It is impossible to interrupt the course of treatment if relief has come: the pathogenic bacteria remaining in the body may develop resistance, and as a result, they will no longer be able to cope with antibiotics.

Antibacterial drugs have another feature that affects the speed of recovery. With a cough of bacterial origin, it is very important not only to influence the cause of the disease, but also to help the airways clear sputum.

Antibiotics alone may not be enough if the respiratory organs are not taken care of. It is important to take measures to thin the sputum and facilitate its removal, even with the correct selection of antibiotic therapy.

The course of treatment of cough due to viruses involves the use of drugs that thin the sputum and facilitate its excretion, increase the lumen of the bronchi, if spasm occurs. Therefore, antibiotics for cough and runny nose are usually not prescribed – symptomatic treatment is quite enough.

As a rule, therapy involves the use of antipyretic and anti-inflammatory drugs, drugs to facilitate nasal breathing.

In general, recovery can be accelerated by humidifying and purifying the air in the room. To do this, you can use a humidifier, regularly carry out wet cleaning, drink enough liquid. It is better to avoid irritants in the form of dusty and dry air, tobacco smoke. If you feel like you’re about to cough, try to sit up straight to make it easier to clear your throat.

The use of herbal preparations is an alternative to the use of antibiotics, if there are no contraindications, that is, with a viral origin of the cough. They have mucolytic and anti-inflammatory effects. One such cough medicine is Bronchipret®.

It reduces the intensity and frequency of coughing fits, helps to reduce inflammation and facilitates the elimination of sputum.