Thiamphenicol Glycinate Acetylcysteinate Research Articles

Microbiological activity of thiamphenicol and thiamphenicol glycinate acetylcysteinate against clinically significant microorganisms and their biofilms

Objective. To determine the minimum inhibitory concentrations of thiamphenicol and thiamphenicol glycinate acetylcysteinate against clinically significant microorganisms and determine their efficacy against microbial biofilms. Materials and Methods. This study included 48 clinical strains isolated from the sputum of patients with respiratory tract infections (16 S. pneumoniae, K. pneumoniae and S. aureus strains). Antimicrobial susceptibility testing was performed using broth microdilution method. Biofilm formation culturing with antibiotics, N-acetylcysteine and their combinations was assessed in Mueller-Hinton broth and brain heart broth in 96-well plates. Biofilms are fixed with 2,5% glutaraldehyde solution, stained with 0,25% crystal violet solution, which is extracted by 33% acetic acid solution. Results. The MIC of thiamphenicol and thiamphenicol glycinate acetylcysteinate (in terms of thiamphenicol) were the same for 87,5% of strains. Thiamphenicol and thiamphenicol glycinate acetylcysteinate have been confirmed high antimicrobial activity against S. pneumoniae strains (MIC50 0,5 mg/l, MIC90 1-2 mg/l). Cultivation with chloramphenicol, thiamphenicol, thiamphenicol glycinate acetylcysteinate, combination of chloramphenicol and thiamphenicol with N-acetylcysteine contributed to significant reduction in the optical density of S. pneumoniae biofilms. Thiamphenicol increased biofilm formation in some resistant S. aureus and K. pneumoniae. Combination based on N-acetylcysteine neutralized this effect. Conclusions. Potentiation of antibacterial activity of thiamphenicol by N-acetylcysteine against S. pneumoniae biofilms has been shown.

Effectiveness of thiamphenicol glycinate acetilcysteinate in inhalation treatment of children with rhinosinusitis

The article evaluates the effectiveness of thiamphenicol glycinate acetylcysteinate for inhalation versus systemic antibiotic for oral administration in complex treatment of uncomplicated rhinosinusitis in the outpatient conditions.Characteristics of children and research methods. The prospective, single-center, randomized, pilot, open-label comparative study included 61 patients from 3 to 9 years old with acute rhinosinusitis meeting the inclusion criteria. Group 1: children were prescribed thiamphenicol glycinate acetylcysteinate (0.125 mg per inhalation twice a day), Group 2: patients received amoxicillin clavulanate at an age-specific dosage of 40-45 mg/kg orally 2 or 3 times a day. At each visit (Day 0 and Day 7–8) the scientists assessed such symptoms as nasal breathing and rhinoscopy findings (edema, hyperemia of the mucous membrane and nasal discharge) on a 10-point visual analogue scale. At the repeated examination (Day 7-8), they assessed the effectiveness of the treatment (recovery/improvement/cure), the duration of treatment (in days) and the number of drugs taken simultaneously, as well as the tolerability of treatment by the presence/absence of undesirable or side effects. The Python language (Python 3.8.) was used for statistical processing of the obtained data. They used the built-in functions from the Scipy module for calculation.Results. At the time of inclusion in the study (Day 0), the condition of the patients in both groups was comparable (p>0.05). When comparing condition of the patients on Day 0 and Day 7-8 there was a therapeutic effect in both groups for all studied symptoms (p<0.01) and for the duration of the treatment course (p=0.2302). Thiamphenicol glyceinate acetylcysteinate reduced the need for other drugs in the complex treatment of sinusitis (p<0.001). In most cases the result of treatment was assessed as recovery. None of the observed patients had undesirable side effects.Conclusion. Thiamphenicol glycinate acetylcysteinate (Fluimucil-antibiotic IT) in the form of inhalation is as effective as amoxicillin clavulanate for the treatment of children with acute uncomplicated rhinosinusitis. A decrease in the need to take additional drugs (p<0.001) can be considered as the advantage of thiamphenicol glycinate acetylcysteinate in complex treatment for uncomplicated rhinosinusitis.

Inhaled antibiotics to improve efficacy and safety in the treatment of upper airway and lung inflammatory diseases

Inhaled antibacterial drugs have been used since the 1940s with greater or lesser effectiveness, due to the possibility of targeted delivery of drugs directly to the infection site at concentrations higher than MICs. High local concentrations of antibacterial agents expand the possibilities of treating infections caused by multiresistant strains and reduces antibiotic resistance in the population. The inhaled delivery method is characterized by a high level of safety due to the absence of systemic toxic effects, which reduces the risk of pseudomembranous colitis and other complications of antibiotic therapy. Thiamphenicol glycinate acetylcysteinate is a combined drug that includes thiamphenicol and N-acetylcysteine, which causes its antibacterial and mucolytic activity. The results of clinical studies have demonstrated the effectiveness of TGA in the treatment of acute and chronic bronchitis, chronic obstructive pulmonary disease, community-acquired pneumonia, laryngotracheitis, rhinosinusitis and other infections of the upper and lower respiratory tract. In pediatrics, the drug is used to treat bronchitis and pneumonia, especially those that cannot be treated with other antibacterial drugs, bronchiolitis, whooping cough, and cystic fibrosis. The article presents data on the effectiveness and safety of containing TGA. A wide spectrum of antibacterial actions, the ability to form high local concentrations of antibacterial and mucolytic components in the focus of infection, a low risk of serious side effects in both adults and children are noted. The topical use of the combination drug has proven to be effective not only in bringing about a pronounced clinical improvement, but also in reducing the frequency of use of systemic antibiotic therapy. The efficacy of thiamphenicol glycinate acetylcysteinate is not inferior to macrolide antibiotics.

A role of thiamphenicol glycinate acetylcysteinate for therapy of respiratory diseases (a review)

This article is a review of published studies on the clinical application of thiamphenicol glycinate acetylcysteinate (TGA) in the treatment of acute and chronic upper and lower respiratory tract diseases. Search for literature in Medline and eLibrary databases was performed. The special place that the drug holds in clinical practice, due to the specific properties of its components - mucolytic N-acetylcysteine (NAC) and antibiotic tiamphenicol. In addition to the usual mucolytic effects, NAC has antioxidant properties, which extends the range of its clinical effectiveness. The antibiotic thiamphenicol has antimicrobial activity against staphylococci, streptococci and gram-negative microorganisms. TGA can be administered by parenteral and inhalation routes. Inhalation route of drug injection is preferable in the treatment of acute and chronic bronchopulmonary diseases, because it allows to create a higher concentration of the drug in the respiratory tract, is associated with much less systemic effects and less often accompanied by the development of side effects. The results of TGA application in the treatment of both acute and chronic upper respiratory diseases (rhinosinusitis, otitis, pharyngotonsillitis) and bronchopulmonary diseases (chronic obstructive pulmonary disease, bronchoectasis) are considered in this review. It has been shown that the drug is quite effective in most patients and its effectiveness sometimes exceeds that of standard oral antibiotics. TGA also allows you to effectively combat biofilms, which have high antibacterial resistance. Thus, the published data allow us to speak about the high antibacterial effectiveness of TGA in acute and chronic infectious diseases of the upper and lower respiratory tract, including cases with the formation of biofilms.

Place of topical antibacterial therapy for exacerbation of chronic bronchit

The questions not only about the optimal choice of antibacterial therapy in case of infection exacerbation of chronic bronchitis (CB), but also about the place of topical antibacterial drugs (TAD) are considered in this article. The aim of the study was to evaluate the clinical efficacy of combined inhalation TAD with mucolytic effect of thiamphenicol glycinate acetylcysteinate in patients with infectious exacerbation of CB. Methods . The study included patients (n = 99) with the CB, observed at the City Consulting and Diagnostic Pulmonology Center (Chelyabinsk). Two groups of patients were formed: 1 st group ( n = 44; mean age 46.3 ± 3.5 years) – subjects who received systemic ABD (amoxicillin/clavulanic acid 500/125 mg 2 times a day) and mucolytic drugs (acetylcysteine 600 mg 1 time per day); 2 nd group patients ( n = 45; mean age 45.9 ± 3.6 years) were administered Fluimucyl Antimicrobiotic IT at a dose of 500 mg per day by inhalation with nebulizer for 6 days. Results . According to the data of the conducted study the significant advantages of the use of inhalation ABD with mucolytic effect in the treatment of patients with acute CB in comparison with systemic ABD in combination with tableted acetylcysteine in the form of shortness of breath, cough, sputum excretion, improvement of patients quality of life in general are demonstrated. Conclusion . In most cases, when used in outpatient practice safe, with a good profile of sensitivity and resistance of inhalation ABD with mucolytic effect significantly improves the quality of management of patients with infectious CB exacerbation.

Role of combined mucolytic therapy in infectious and inflammatory diseases of the respiratory system in children

The use of combined medicines simultaneously influencing various pathogenetic mechanisms of inflammation and coughing becomes an essential direction of mucoactive therapy in childhood. One of these is thiamphenicol glycinate acetylcysteinate, which has both mucolytic and antibacterial effects, which significantly expands the possibilities of therapy in bacterial etiology of acute and exacerbation of chronic respiratory diseases, increases the effectiveness of therapeutic measures, improves compliance.

Topic inhaled antibiotic therapy in children with prolonged adenoiditis

Currently the issue of antibiotic resistance is urgent due to the unreasonable prescription of systemic antibiotics in the treatment of the upper respiratory tract infections. Frequent use of systemic antibiotic therapy in childhood leads to disruption of the microbiota and the development of secondary immunodeficiency. Alternative topical antibiotic therapy together with mucolytics allows the antibiotic to penetrate directly to the inflammation site and destroy biofilms. The article outlines the use of thiamphenicol glycinate acetylcysteinate in children with prolonged adenoiditis. In Russia this antibiotic is presented by Fluimucil® IT; it is manufactured in the form of a lyophilisate for both injectable solutions and solutions for inhalations and irrigation of mucous membranes. Thiamphenicol glycinate acetylcysteinate helps to improve the course of the disease, in some cases, to avoid invasive procedures and reduce the use of systemic antibiotics.

Approaches to the treatment of bacterial infections of the respiratory tract based on current data of the microbiome

Respiratory infections are mainly caused by viruses or bacteria that often interact. In the upper respiratory tract there is a wide range of commensals and potential pathogenic bacteria that, together with other bacteria, viruses and fungi, form complex ecological networks known collectively as “the microbiome”. It is assumed that this community is constantly exposed to synergistic and competitive interspecific interactions. The microbiome of the respiratory tract is a factor of respiratory health, which changes (respiratory viral infections, inappropriate use of antibiotics) can lead to bacterial complications and the spread of respiratory tract infections in. In the light of current guidelines for limiting the use of systemic antibiotics in case of uncomplicated acute respiratory tract infections, a real alternative is the use of topical antimicrobial agents, for example, thiamphenicol glycinate acetylcysteinate. The article presents the results of the use of the drug in respiratory infections of the upper and lower respiratory tract.

Topical issues of inhaled antibacterial therapy of respiratory diseases in children

Despite the fact that acute respiratory infections have viral etiology, the frequency of antibiotic prescriptions accounts for more than 70% in outpatient practice. However, the preventive administration of systemic antibiotics does not reduce the duration of the disease and the incidence of bacterial complications. In addition, the irrational use of antibiotic therapy can lead to the development of antibiotic resistance of infectious disease pathogens. The global problem of antibiotic resistance is seen as a serious threat to public health, and therefore the systemic antibiotic restriction policy is crucial, which helps to reduce the formation of antibiotic-resistant strains of infectious agents. The possibility of using local antibacterial drugs enables optimization of antibiotic therapy and reduces the risk of the development of antibiotic resistance. The article discusses the issues of use of thiamphenicol glycinate acetylcysteinate in various diseases in children.

Antibacterial inhalation therapy with thiamphenicol glycinate acetylcysteinate in pulmonology

Thiamphenicol glycinate acetylcysteinate (TGA) is a combination of thiamphenicol, a broad-spectrum antibiotic, and mucolytic drug N-acetylcysteine. This article is a review of pharmacological, microbiological, and clinical effects of this combined drug. Inhaled TGA could be considered as a worthy alternative for oral mucolytics and oral antibiotics in treatment of upper and lower airway diseases, such as acute and chronic rhinosinusitis, otitis media, tonsillitis, acute bronchitis, and acute exacerbation of chronic bronchitis and chronic obstructive pulmonary disease, in children and adults.

Specific features of amphenicol determination in foodstuffs by HPLC/high resolution quadrupole time-of-flight mass spectrometry

simple method of sample preparation, identification, and determination of amphenicols in foodstuffs (chloramphenicol, chloramphenicol succinate, thiamphenicol, thiamphenicol glycinate acetylcysteinate, florfenicol, florfenicol amine) via high-performance liquid chromatography/high resolution quadrupole time-of-flight mass spectrometry by the exact masses of the ion that form in electrospray is proposed. The objects of analysis are meat (beef, pork, poultry), meat by-products, milk and dairy products, honey, and aquaculture products. Sample preparation consisted of extraction of the target components by acetonitrile and dilution of the extract twice with deionized water. Specific features in the determination of amphenicols and their derivatives associated with the emergence of various adducts in the electrospray device in the detection of both positive and negative ions were considered. A method of amphenicol determination by the addition method is proposed; it uses the summation of area signals of all registered adducts. The features and benefits of utilizing the method of standard additions are presented. The ranges of the defined contents are 0.1–10 ng/g for chloramphenicol and 1–100 ng/g for thiamphenicol and florfenicol. The relative standard deviation of the test results did not exceed 0.1; the duration of the analysis was 30–40 min.

Activity of aerosol thiamphenicol glycinate acetylcysteinate in a mouse model of S. pyogenes pneumonia.

Thiamphenicol glycinate acetylcysteinate (TGA, CAS 20192-91-0) is a water soluble ester of thiamphenicol (TAP) that allows a rapid utilization by the systemic route but also a direct local action when used as aerosol. To assess the efficacy of aerosolized TGA in the treatment of experimental pneumonia in mice, we compared its in vivo activity with that of thiamphenicol glycinate hydrochloride (TG), erythromycin (ERT) and amoxicillin (AMX), the last two compounds being more active in vitro than TAP. TGA, administered by aerosol route, showed better efficacy than the aerosolized TG, particularly as far as survival rate is concerned, and was significantly more potent than ERT and similar to AMX either administered by oral route. No significantly different therapeutic efficacy was observed when TGA was parenterally administered. The rapid release, at the site of infection, of TAP and N-acetylcysteine and the favourable pharmacokinetic properties of TGA accounted in large part for its high therapeutic efficacy against Streptococcus pyogenes pneumonia.

In vitro antibacterial activity of thiamphenicol glycinate acetylcysteinate against respiratory pathogens.

After 30 years of therapeutic use, thiamphenicol glycinate acetylcysteinate (CAS 20192-91-0) is still widely employed in the treatment of upper and lower respiratory tract infections. This is due to its particular characteristic to exert at pulmonary level, either the antibacterial activity of thiamphenicol (CAS 15318-45-3) and the mucolytic activity of N-acetylcysteine (CAS 616-91-1). The aim of this study was to evaluate the present pattern of susceptibility of several clinical isolates to thiamphenicol and the interference of N-acetylcysteine on this parameter. The studies have been performed in vitro. Equimolar concentrations of N-acetylcysteine and even higher concentrations did not interfere with the antibacterial activity of thiamphenicol against Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae. The spectrum of activity of thiamphenicol was similar to that observed in the past and was superior to that of erythromycin and amoxicillin. The activity of thiamphenicol was greater than that of erythromycin against H. influenzae and streptococci and equivalent versus Branhamella catarrhalis. In comparison with amoxicillin the activity of thiamphenicol was higher against H. influenzae and B. catarrhalis and slightly lower against streptococci. The results demonstrate that thiamphenicol maintains its therapeutic value confirming the importance of thiamphenicol glycinate acetylcysteinate in the treatment of respiratory tract infections.

Aerosol Antibiotic Therapy in Children with Chronic Upper Airway Infections: A Potential Alternative to Surgery

Tonsillectomy and adenoidectomy remain the first choice treatment of chronic or recurrent acute infections of the upper respiratory tract in children. The aim of this study is to investigate the efficacy of the combination of thiamphenicol glycinate acetylcysteinate plus beclomethasone, administered as aerosol, in children awaiting tonsillectomy and/or adenoidectomy. The study comprised 204 children, aged 1 to 12 years, with chronic adenotonsillitis who had been listed for surgery due to obstructive symptoms and recurrent acute infections. Patients were randomized to treatment with thiamphenicol glycinate acetylcysteinate, dosage 250 mg/day in 2 administrations plus beclomethasone with a dosage of 400 microg/day in 2 administrations, or no treatment, control group, unless required. The drugs were administered by aerosol for 10 days/month over a period of 6 months. Clinical visits were at 4, 7 and 12 months after the start of treatment. The primary efficacy outcome was the reduction in the number of patients requiring surgery. Secondary efficacy measures were the reduction of nasal obstruction, the decrease in the number of infectious episodes and the tolerability of the treatment. Aerosol treatment with thiamphenicol glycinate acetylcysteinate plus beclomethasone resulted in a significantly lower proportion of patients requiring surgery (29 of 101; 29 percent) compared to patients in the control group (100 of 103; 97 percent) (p < 0.0001). Treatment was also associated with a reduction of nasal obstruction and a decrease in the number of infectious episodes. No treatment-related adverse events were reported and the aerosol therapy proved easy to administer to children. The aerosol therapy with the combination of thiamphenicol glycinate acetylcysteinate plus beclomethasone was able to prevent or postpone surgery in a substantial percentage of patients, without adverse events. These preliminary results suggest that this novel approach could play a role in the antibiotic prophylaxis of chronic infectious diseases of the upper airways.

A Therapeutic Approach in the Treatment of Infections of the Upper Airways: Thiamphenicol Glycinate Acetylcysteinate in Sequential Treatment (Systemic-Inhalatory Route)

Eight hundred and seventeen patients with upper respiratory tract infections were treated with thiamphenicol glycinate acetylcisteinate (TGA) or other standard antibiotics for 6-10 days in a randomised trial. In 419 out of 817 patients, the symptomatology was severe and they were treated with TGA in sequential therapy (TGA 500 mg- as thiamphenicol- b.i.d. intramuscularly on the first day and TGA 500 mg b.i.d by aerosol during the following days) (n=151), or with antibiotics of comparison (n=268) given intramuscularly. In this group the disappearance of the symptomatology with TGA ranged from 90 percent of the patients with otitis media to 94 percent in pharyngotonsillitis and rhinosinusitis; in this latter group TGA was significantly better than cefazolin. In 398 patients with mild symptomatology TGA (250 mg as thiamphenicol- b.i.d.) was given by aerosol (n=149) and the antibiotics of comparison by oral route (n=249). In TGA patients, the disappearance of symptoms was achieved in 87 percent of those with rhinosinusitis, in 88 percent of those with pharyngotonsillitis and in 91 percent of those with otitis media. S. pyogenes, S. pneumoniae and H. influenzae were the most frequently isolated pathogens, and none of the isolated bacteria proved to be resistant to TGA. Microbiological eradication was obtained in TGA groups in a percentage of patients ranging from 90.2 to 96.0 percent in those with severe forms, and from 86.2 to 91.6 percent in those with a mild clinical picture. Investigators rated the TGA efficacy as excellent in 96-100 percent of the patients with severe forms and in 85.5-100 percent of the patients with mild forms, whereas in the group of patients with rhinosinusitis the comparison of TGA versus other treatment was significantly in favour of TGA. The Investigator rating of treatment tolerability significantly favoured TGA in sequential treatments in comparison to the other antibiotics. No patient dropped out from the trial because of adverse events.

Efficacy of N-Acetyl-Cysteine in Combination with Thiamphenicol in Sequential (Intramuscular/Aerosol) Therapy of Upper Respiratory Tract Infections Even When Sustained by Bacterial Biofilms

A total of 102 patients with recurrent upper respiratory tract infections underwent microbiological exploration with appropriate sampling and direct biopsies of the infected sites. Therapy was then started and on day 1 each patient received two intramuscular injections of thiamphenicol glycinate acetylcysteinate (TGA). From day 2 to 10 sequential therapy with the same drug was continued employing TGA administered by aerosol.All putative etiologic agents recovered were susceptible to thiamphenicol and only 24 demonstrated the ability to produce in vitro biofilms. The organisms comprised 10 Staphylococcus aureus, 6 Streptococcus pyogenes, 4 Streptococcus pneumoniae and 3 Haemophilus influenzae.Of the 24 subjects in whom biofilms were demonstrated to be present in vivoby Scanning Electron Microscopy, clinical and bacteriological cure was obtained in 21 cases (87.5%) following sequential therapy with TGA. Failures were considered to be persistent signs and symptoms at day 15 after initiation of treatment and lack of eradication of 3 S. aureus strains, despite their in vitro susceptibility to thiamphenicol.Very few adverse events attributable to TGA were reported in this cohort of patients. In no case was discontinuation of treatment deemed necessary by the attending physician.

Influence of thiamphenicol on the primary functions of human polymorphonuclear leucocytes against Streptococcus pyogenes

Current antibiotic therapy encourages the use of antibiotics that may potentiate the host’s immune defences. We therefore investigated the effect of thiamphenicol (TAP), the active principle of thiamphenicol glycinate acetylcysteinate (TGA), on human granulocyte functions, mainly phagocytosis and intracellular killing of Streptococcus pyogenes. Our findings support the use of thiamphenicol in the treatment of respiratory tract infections caused by S. pyogenes as it acts directly against the pathogen as well as in cooperation with PMNs by eliciting their intracellular killing.

Recent Clinical Evidence of the Efficacy and Safety of Thiamphenicol Glycinate Acetylcysteinate and Thiamphenicol Glycinate

Thiamphenicol is a broad-spectrum antimicrobial agent active against penicillin-resistant Streptococcus pneumoniae, Staphylococcus aureus VISA strains, most methicillin-resistant isolates and atypical pathogens such as Mycoplasma pneumoniae and Chlamydia pneumoniae). Thiamphenicol is present as glycinate hydrochloride (TG) and glycinate acetylcysteinate (TGA) esters in the parenteral and aerosol dosage form. This multicenter, double-blind, randomized clinical trial aimed to evaluate the efficacy and tolerability of aerosol administration of TGA, compared to TG, in the treatment of acute and/or exacerbated infections of the respiratory tract. Results showed that both treatments ameliorated the symptoms (frequency and severity of cough, difficulty in expectoration) associated with the evaluated pathologies, i.e. tra-cheobronchitis, acute and exacerbated chronic bronchitis. The investigators rated both treatments Good or Very Good in 90% of patients at the end of treatment, with «Very Good» for patients treated with TGA (37%) compared to 28% of patients treated with TG. Both treatments were well tolerated with fewer than 5% of patients experiencing an adverse event.