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Journal of Feline Medicine and Surgery Jul 2009Feline viral rhinotracheitis, caused by feline herpesvirus (FHV), is an upper respiratory tract disease that is often associated with feline calicivirus and bacteria. In... (Review)
Review
OVERVIEW
Feline viral rhinotracheitis, caused by feline herpesvirus (FHV), is an upper respiratory tract disease that is often associated with feline calicivirus and bacteria. In most cats, FHV remains latent after recovery, and they become lifelong virus carriers. Stress or corticosteroid treatment may lead to virus reactivation and shedding in oronasal and conjunctival secretions.
INFECTION
Sick cats shed FHV in oral, nasal and conjunctival secretions; shedding may last for 3 weeks. Infection requires direct contact with a shedding cat.
DISEASE SIGNS
Feline herpesvirus infections cause acute rhinitis and conjunctivitis, usually accompanied by fever, depression and anorexia. Affected cats may also develop typical ulcerative, dendritic keratitis.
DIAGNOSIS
Samples consist of conjunctival, corneal or oropharyngeal swabs, corneal scrapings or biopsies. It is not recommended that cats recently vaccinated with a modified-live virus vaccine are sampled. Positive PCR results should be interpreted with caution, as they may be produced by low-level shedding or viral latency.
DISEASE MANAGEMENT
'Tender loving care' from the owner, supportive therapy and good nursing are essential. Anorexic cats should be fed blended, highly palatable food - warmed up if required. Mucolytic drugs (eg, bromhexine) or nebulisation with saline may offer relief. Broad-spectrum antibiotics should be given to prevent secondary bacterial infections. Topical antiviral drugs may be used for the treatment of acute FHV ocular disease. The virus is labile and susceptible to most disinfectants, antiseptics and detergents.
VACCINATION RECOMMENDATIONS
Two injections, at 9 and 12 weeks of age, are recommended, with a first booster 1 year later. Boosters should be given annually to at-risk cats. For cats in low-risk situations (eg, indoor-only cats), 3-yearly intervals suffice. Cats that have recovered from FHV-associated disease are usually not protected for life against further disease episodes; vaccination of recovered cats is therefore recommended.
Topics: Animals; Antiviral Agents; Carrier State; Cat Diseases; Cats; Herpesviridae Infections; Herpesvirus Vaccines; Practice Guidelines as Topic; Societies; United States; Vaccination; Veterinary Medicine; Virus Latency; Virus Shedding
PubMed: 19481034
DOI: 10.1016/j.jfms.2009.05.003 -
BMJ Clinical Evidence Aug 2011Bronchiectasis is usually a complication of previous lower respiratory infection, and causes chronic cough and copious production of sputum, which is often purulent.... (Review)
Review
INTRODUCTION
Bronchiectasis is usually a complication of previous lower respiratory infection, and causes chronic cough and copious production of sputum, which is often purulent. Bronchiectasis may cause signs of chronic obstructive pulmonary disease. It can also be associated with cystic fibrosis and other congenital disorders, foreign body inhalation, and other causes of lung damage.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments in people with bronchiectasis but without cystic fibrosis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We performed a GRADE evaluation of the quality of evidence for interventions.
RESULTS
We found 19 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: anticholinergic therapy, beta(2) agonists, bronchopulmonary hygiene physical therapy, corticosteroids (inhaled, oral), exercise or physical training, hyperosmolar agents (inhaled), leukotriene receptor antagonists, methyl-xanthines (oral), mucolytics (bromhexine or deoxyribonuclease), prolonged-use antibiotics, and surgery.
Topics: Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Bronchiectasis; Cystic Fibrosis; Humans; Leukotriene Antagonists; Lung
PubMed: 21846412
DOI: No ID Found -
BMJ Clinical Evidence Jan 2008Bronchiectasis is usually a complication of previous lower respiratory infection, and causes chronic cough and copious production of sputum, which is often purulent.... (Review)
Review
INTRODUCTION
Bronchiectasis is usually a complication of previous lower respiratory infection, and causes chronic cough and copious production of sputum, which is often purulent. Bronchiectasis may cause signs of chronic obstructive pulmonary disease. It can also be associated with cystic fibrosis and other congenital disorders, foreign body inhalation, and other causes of lung damage.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments in people with bronchiectasis but without cystic fibrosis? We searched: Medline, Embase, The Cochrane Library and other important databases up to July 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We performed a GRADE evaluation of the quality of evidence for interventions.
RESULTS
We found 16 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: anticholinergic therapy, bronchopulmonary hygiene physical therapy, exercise or physical training, hyperosmolar agents (inhaled), leukotriene receptor antagonists, methyl-xanthines (oral), mucolytics (bromhexine or deoxyribonuclease), prolonged-use antibiotics, beta(2) agonists, steroids (inhaled, oral), and surgery.
Topics: Administration, Inhalation; Administration, Oral; Anti-Asthmatic Agents; Bronchiectasis; Cough; Humans; Leukotriene Antagonists; Lung; Sputum
PubMed: 19450337
DOI: No ID Found -
JAMA Neurology Apr 2020Mutations of the glucocerebrosidase gene, GBA1 (OMIM 606463), are the most important risk factor for Parkinson disease (PD). In vitro and in vivo studies have reported... (Clinical Trial)
Clinical Trial
IMPORTANCE
Mutations of the glucocerebrosidase gene, GBA1 (OMIM 606463), are the most important risk factor for Parkinson disease (PD). In vitro and in vivo studies have reported that ambroxol increases β-glucocerebrosidase (GCase) enzyme activity and reduces α-synuclein levels. These observations support a potential role for ambroxol therapy in modifying a relevant pathogenetic pathway in PD.
OBJECTIVE
To assess safety, tolerability, cerebrospinal fluid (CSF) penetration, and target engagement of ambroxol therapy with GCase in patients with PD with and without GBA1 mutations.
INTERVENTIONS
An escalating dose of oral ambroxol to 1.26 g per day.
DESIGN, SETTING, AND PARTICIPANTS
This single-center open-label noncontrolled clinical trial was conducted between January 11, 2017, and April 25, 2018, at the Leonard Wolfson Experimental Neuroscience Centre, a dedicated clinical research facility and part of the University College London Queen Square Institute of Neurology in London, United Kingdom. Participants were recruited from established databases at the Royal Free London Hospital and National Hospital for Neurology and Neurosurgery in London. Twenty-four patients with moderate PD were evaluated for eligibility, and 23 entered the study. Of those, 18 patients completed the study; 1 patient was excluded (failed lumbar puncture), and 4 patients withdrew (predominantly lumbar puncture-related complications). All data analyses were performed from November 1 to December 14, 2018.
MAIN OUTCOMES AND MEASURES
Primary outcomes at 186 days were the detection of ambroxol in the CSF and a change in CSF GCase activity.
RESULTS
Of the 18 participants (15 men [83.3%]; mean [SD] age, 60.2 [9.7] years) who completed the study, 17 (8 with GBA1 mutations and 9 without GBA1 mutations) were included in the primary analysis. Between days 0 and 186, a 156-ng/mL increase in the level of ambroxol in CSF (lower 95% confidence limit, 129 ng/mL; P < .001) was observed. The CSF GCase activity decreased by 19% (0.059 nmol/mL per hour; 95% CI, -0.115 to -0.002; P = .04). The ambroxol therapy was well tolerated, with no serious adverse events. An increase of 50 pg/mL (13%) in the CSF α-synuclein concentration (95% CI, 14-87; P = .01) and an increase of 88 ng/mol (35%) in the CSF GCase protein levels (95% CI, 40-137; P = .002) were observed. Mean (SD) scores on part 3 of the Movement Disorders Society Unified Parkinson Disease Rating Scale decreased (ie, improved) by 6.8 (7.1) points (95% CI, -10.4 to -3.1; P = .001). These changes were observed in patients with and without GBA1 mutations.
CONCLUSIONS AND RELEVANCE
The study results suggest that ambroxol therapy was safe and well tolerated; CSF penetration and target engagement of ambroxol were achieved, and CSF α-synuclein levels were increased. Placebo-controlled clinical trials are needed to examine whether ambroxol therapy is associated with changes in the natural progression of PD.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT02941822; EudraCT identifier: 2015-002571-24.
Topics: Aged; Ambroxol; Glucosylceramidase; Humans; Male; Middle Aged; Mutation; Parkinson Disease; Treatment Outcome
PubMed: 31930374
DOI: 10.1001/jamaneurol.2019.4611 -
The Cochrane Database of Systematic... May 2014Bronchiectasis is predominantly an acquired disease process that represents the end stage of a variety of unrelated pulmonary insults. It is defined as persistent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bronchiectasis is predominantly an acquired disease process that represents the end stage of a variety of unrelated pulmonary insults. It is defined as persistent irreversible dilatation and distortion of medium-sized bronchi. It has been suggested that with widespread use of high-resolution computed tomography, more bronchiectasis diagnoses are being made. Patients diagnosed with bronchiectasis frequently have difficulty expectorating sputum. Sputum therefore is retained in the lungs and may become infected, leading to further lung damage. Mucolytic agents target hypersecretion or changed physiochemical properties of sputum to make it easier to clear. One drug, recombinant human DNase, breaks down the DNA that is released at the site of infection by neutrophils.Mucus clearance along with antimicrobial therapy remains an integral part of bronchiectasis management. Chest physiotherapy along with mucolytic agents is commonly used in practice without clear supportive evidence.
OBJECTIVES
To determine whether ingested or inhaled mucolytics are effective in the treatment of patients with bronchiectasis.
SEARCH METHODS
We searched the Cochrane Airways Group Specialised Register and reference lists of relevant articles. We contacted experts in the field and drug companies. Searches were current as of June 2013.
SELECTION CRITERIA
Randomised trials of mucolytic treatment in people with bronchiectasis but not cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Data extraction was performed independently by two review authors. Study authors were contacted for confirmation.
MAIN RESULTS
Four trials (with a combined total of 528 adult participants) were included, but almost none of the data from these studies could be aggregated in a meta-analysis.One trial (with 88 participants) compared bromhexine versus placebo. Compared with placebo, high doses of bromhexine with antibiotics eased difficulty in expectoration (mean difference (MD) -0.53, 95% confidence interval (CI) -0.81 to -0.25 at 16 days); the quality of the evidence was rated as low. A reduction in sputum production was noted with bromhexine (MD -21.5%, 95% CI -38.9 to -4.1 at day 16); again the quality of the evidence was rated as low. No significant differences between bromhexine and placebo were observed with respect to reported adverse events (odds ratio (OR) 2.93; 95% CI 0.12 to 73.97), and again the quality of the evidence was rated as low.In a single small, blinded but not placebo-controlled trial of older (> 55 years) participants with stable bronchiectasis and mucus hypersecretion, erdosteine combined with physiotherapy over a 15-day period improved spirometry and sputum purulence more effectively compared with physiotherapy alone. The spirometric improvement was small (MD 200 mL in forced expiratory volume in one second (FEV1) and 300 mL in forced vital capacity (FVC)) and was apparent only at day 15, not at earlier time points.The remaining two studies (with a combined total of 410 participants) compared recombinant human DNase (RhDNase) versus placebo. These two studies were very different (one was a two-week study of 61 participants, and the other ran for 24 weeks and included 349 participants), and the opportunity for combining data from the two studies was very limited. Compared with placebo, recombinant human DNase showed no difference in FEV1 or FVC in the smaller study but showed a significant negative effect on FEV1 in the larger and longer study. For reported adverse events, no significant differences between recombinant human DNase and placebo were noted. In all of the above comparisons of recombinant human DNase versus placebo, the quality of the evidence was judged to be low.
AUTHORS' CONCLUSIONS
Given the harmful effects of recombinant human DNase in one trial and no evidence of benefit, this drug should be avoided in non-cystic fibrosis bronchiectasis, except in the context of clinical trials. Evidence is insufficient to permit evaluation of the routine use of other mucolytics for bronchiectasis. High doses of bromhexine coupled with antibiotics may help with sputum production and clearance, but long-term data and robust clinical outcomes are lacking. Similarly, erdosteine may be a useful adjunct to physiotherapy in stable patients with mucus hypersecretion, but robust longer-term trials are required.Generally, clinical trials in children on the use of various mucolytic agents are lacking. As the number of agents available on the market, such as RhDNase, acetylcysteine and bromhexine, is increasing, improvement of the evidence base is needed.
Topics: Anti-Bacterial Agents; Bromhexine; Bronchiectasis; Deoxyribonucleases; Drug Therapy, Combination; Expectorants; Humans; Randomized Controlled Trials as Topic; Recombinant Proteins; Thioglycolates; Thiophenes
PubMed: 24789119
DOI: 10.1002/14651858.CD001289.pub2 -
BMC Neurology Feb 2019Currently there are no disease-modifying treatments for Parkinson's disease dementia (PDD), a condition linked to aggregation of the protein α-synuclein in subcortical... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Currently there are no disease-modifying treatments for Parkinson's disease dementia (PDD), a condition linked to aggregation of the protein α-synuclein in subcortical and cortical brain areas. One of the leading genetic risk factors for Parkinson's disease is being a carrier in the gene for β-Glucocerebrosidase (GCase; gene name GBA1). Studies in cell culture and animal models have shown that raising the levels of GCase can decrease levels of α-synuclein. Ambroxol is a pharmacological chaperone for GCase and is able to raise the levels of GCase and could therefore be a disease-modifying treatment for PDD. The aims of this trial are to determine if Ambroxol is safe and well-tolerated by individuals with PDD and if Ambroxol affects cognitive, biochemical, and neuroimaging measures.
METHODS
This is a phase II, single-centre, double-blind, randomized placebo-controlled trial involving 75 individuals with mild to moderate PDD. Participants will be randomized into Ambroxol high-dose (1050 mg/day), low-dose (525 mg/day), or placebo treatment arms. Assessments will be undertaken at baseline, 6-months, and 12-months follow up times. Primary outcome measures will be the Alzheimer's disease Assessment Scale-cognitive subscale (ADAS-Cog) and the ADCS Clinician's Global Impression of Change (CGIC). Secondary measures will include the Parkinson's disease Cognitive Rating Scale, Clinical Dementia Rating, Trail Making Test, Stroop Test, Unified Parkinson's disease Rating Scale, Purdue Pegboard, Timed Up and Go, and gait kinematics. Markers of neurodegeneration will include MRI and CSF measures. Pharmacokinetics and pharmacodynamics of Ambroxol will be examined through plasma levels during dose titration phase and evaluation of GCase activity in lymphocytes.
DISCUSSION
If found effective and safe, Ambroxol will be one of the first disease-modifying treatments for PDD.
TRIAL REGISTRATION
ClinicalTrials.gov NCT02914366, 26 Sep 2016/retrospectively registered.
Topics: Aged; Ambroxol; Brain; Dementia; Double-Blind Method; Female; Humans; Male; Middle Aged; Parkinson Disease; Research Design
PubMed: 30738426
DOI: 10.1186/s12883-019-1252-3 -
Turkish Journal of Medical Sciences Dec 2021Currently there is not an effective antiviral treatment for COVID-19, but a large number of drugs have been evaluated since the beginning of the pandemic, and many of... (Review)
Review
BACKGROUND/AIM
Currently there is not an effective antiviral treatment for COVID-19, but a large number of drugs have been evaluated since the beginning of the pandemic, and many of them have been used for the treatment of COVID-19 despite the preliminary or conflicting results of the clinical trials. We aimed to review and summarize all of the current knowledge on the antivirals for COVID-19
RESULTS
There are 2 main drug groups for SARS-CoV-2: agents that target proteins or RNA of the virus or interfere with proteins or biological processes in the host that support the virus. The main drug groups include inhibitors of viral entry into the human cell (convalescent plasma, monoclonal antibodies, nanobodies, mini proteins, human soluble ACE-2, camostat, dutasteride, proxalutamide, bromhexin, hydroxychloroquine, umifenovir nitazoxanid, niclosamide, lactoferrin), inhibitors of viral proteases (lopinavir/ritonavir, PF-07321332, PF-07304814, GC376), inhibitors of viral RNA (remdesivir, favipiravir, molnupiravir, AT-527, merimepodib, PTC299), inhibitors of host proteins supporting virus (plitidepsin, fluvoxamine, ivermectin), and agents supporting host natural immunity (Interferons).
CONCLUSION
When taking into account the results of all the available laboratory and clinical trials on the subject, monoclonal antibodies seem to be the most effective treatment for COVID-19 at the moment, and high-titer convalescent plasma also could be effective when administered during the early phase of the disease. As lopinavir/ritonavir, hydroxychloroquine, merimepodib, and umifenovir were found to be ineffective in RCTs, they should not be used. Additional studies are needed to define the role of remdesivir, favipiravir, interferons, ivermectin, dutasteride, proxulutamide, fluvoxamine, bromhexine, nitazoxanide, and niclosamid in the treatment of COVID-19. Finally, the results of phase trials are waited to learn whether or not the newer agents such as molnupiravir, PF-07321332, PF-07304814, plitidepsin and AT-527 are effective in the treatment of COVID-19.
Topics: Antiviral Agents; COVID-19; Humans; Immunization, Passive; Pandemics; SARS-CoV-2; COVID-19 Serotherapy; COVID-19 Drug Treatment
PubMed: 34391321
DOI: 10.3906/sag-2106-250 -
JAMA Network Open Jun 2023Ambroxol was identified as an enhancer of stability and residual activity of several misfolded glucocerebrosidase variants in 2009.
IMPORTANCE
Ambroxol was identified as an enhancer of stability and residual activity of several misfolded glucocerebrosidase variants in 2009.
OBJECTIVES
To assess hematologic and visceral outcomes, biomarker changes, and safety of ambroxol therapy for patients with Gaucher disease (GD) without disease-specific treatment.
DESIGN, SETTING, AND PARTICIPANTS
Patients with GD who could not afford enzyme replacement therapy were enrolled and received oral ambroxol from May 6, 2015, to November 9, 2022, at Xinhua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China. Thirty-two patients with GD (29 with GD type 1, 2 with GD type 3, and 1 with GD intermediate types 2-3) were enrolled. Of those, 28 patients were followed up for longer than 6 months; 4 were excluded due to loss of follow-up. Data analyses were performed from May 2015 to November 2022.
INTERVENTION
An escalating dose of oral ambroxol (mean [SD] dose, 12.7 [3.9] mg/kg/d).
MAIN OUTCOMES AND MEASURES
Patients with GD receiving ambroxol were followed up in a genetic metabolism center. Biomarkers of chitotriosidase activity and glucosylsphingosine level, liver and spleen volumes, and hematologic parameters were measured at baseline and various time points throughout the ambroxol treatment.
RESULTS
A total of 28 patients (mean [SD] age, 16.9 [15.3] years; 15 male patients [53.6%]) received ambroxol for a mean (SD) duration of 2.6 (1.7) years. Two patients with severe symptoms at baseline experienced deterioration of hematologic parameters and biomarkers and were deemed nonresponders; clinical response was observed in the other 26 patients. After 2.6 years of ambroxol treatment, the mean (SD) hemoglobin concentration improved from 10.4 (1.7) to 11.9 (1.7) g/dL (mean [SD], 1.6 [1.7] g/dL; 95% CI, 0.8-2.3 g/dL; P < .001), and the mean (SD) platelet count improved from 69 (25) to 78 (30) × 103/µL (mean [SD], 9 [22] × 103/µL; 95% CI, -2 to 19 × 103/µL; P = .09). The mean (SD) spleen volume decreased from 17.47 (7.18) to 12.31 (4.71) multiples of normal (MN) (mean [SD], -5.16 [5.44] MN; 95% CI, -10.19 to -0.13; P = .04), and the mean (SD) liver volume decreased from 1.90 (0.44) to 1.50 (0.53) MN (mean [SD], -0.39 [0.42] MN; 95% CI, -0.75 to -0.04; P = .03). Biomarker median percentage changes from baseline were -43.1% for chitotriosidase activity (from 14 598 [range, 3849-29 628] to 8312 [range, 1831-16 842] nmol/mL/h; z = -3.413; P = .001) and -34.1% for glucosylsphingosine level (from 251.3 [range, 73.6-944.2] to 165.7 [range, 21.3-764.8] ng/mL; z = -2.756; P = .006). Patients were divided into subgroups according to age when initiating treatment; those who received treatment at a younger age (mean [SD] age, 6.3 [2.7] years) experienced more rapid improvements: hemoglobin concentration increased by 16.5% (from 10.3 [1.5] to 12.0 [1.5] g/dL; mean [SD] change, 1.6 [1.6] g/dL; 95% CI, 0.7-2.5 g/dL; P = .002), and platelet count increased by 12.0% (from 75 [24] to 84 [33] × 103/µL; mean [SD] change, 9 [26] × 103/µL; 95% CI, -5 to 24 × 103/µL; P = .17); whereas chitotriosidase activity decreased by 64.0% (from 15 710 [range, 4092-28 422] to 5658 [range, 1146-16 843] nmol/mL/h; z = -2.803; P = .005), and glucosylsphingosine level decreased by 47.3% (from 248.5 [range, 122.8-674.9] to 131.0 [range, 41.1-448.5] ng/mL; z = -2.385; P = .02). Three of the 28 patients experienced mild and transient adverse events.
CONCLUSIONS AND RELEVANCE
In this case series of ambroxol repurposing among patients with GD, long-term treatment with ambroxol was safe and associated with patient improvement. Improvements in hematologic parameters, visceral volumes, and plasma biomarkers were larger among patients with relatively mild symptoms of GD and patients who received initial treatment at younger ages.
Topics: Humans; Male; Adolescent; Child; Child, Preschool; Gaucher Disease; Ambroxol; China; Biomarkers; Hemoglobins
PubMed: 37342037
DOI: 10.1001/jamanetworkopen.2023.19364 -
Multidisciplinary Respiratory Medicine 2017Since its introduction to the market in 1963, bromhexine, an over-the-counter drug, has been investigated for its activity in animal models and in humans with diverse... (Review)
Review
Since its introduction to the market in 1963, bromhexine, an over-the-counter drug, has been investigated for its activity in animal models and in humans with diverse respiratory conditions. Bromhexine is a derivate of the plant used in some countries for the treatment of various respiratory diseases. Bromhexine has been found to enhance the secretion of various mucus components by modifying the physicochemical characteristics of mucus. These changes, in turn, increase mucociliary clearance and reduce cough. Principal clinical research studies were primarily developed in an era when stringent methodological approaches and good clinical practices were not developed yet. Clinical studies were conducted mainly in patients with chronic bronchitis and in patients with various respiratory diseases, and demonstrated the efficacy of bromhexine in improving respiratory symptoms. Furthermore, the co-administration of antibiotics with bromhexine amplified the actions of the antibiotic. Although the clinical evidence shows only modest but positive results, bromhexine is indicated for its mucoactive activity. Larger trials with adequate methodology are required to identify when treatment with bromhexine can improve clinical outcomes.
PubMed: 28331610
DOI: 10.1186/s40248-017-0088-1 -
Expert Opinion on Drug Metabolism &... Mar 2019Major unmet needs remain for improved antibiotic treatment in lung infections. While development of new antibiotics is needed to overcome resistance, other approaches to... (Review)
Review
Major unmet needs remain for improved antibiotic treatment in lung infections. While development of new antibiotics is needed to overcome resistance, other approaches to optimize therapy using existing agents are also attractive. Ambroxol induces lung autophagy at human-relevant doses and improves lung levels of several approved antibiotics. Areas covered: This review discusses preclinical and clinical studies of the effects of ambroxol (and its prodrug precursor bromhexine) co-treatment upon levels of antibiotics in lung tissue, sputum, and bronchoalveolar lavage fluid. Expert opinion: Ambroxol co-treatment is associated with significant increases in lung tissue and airway surface fluid levels of a range of antibiotics including beta lactams, glycopeptides, macrolides, nitrofurans, and rifamycins. In most cases, the increased levels are only modest and are insufficient to overcome high-level resistance against that same antibiotic class, and so co-treatment with ambroxol is unlikely to alter clinical outcomes. Additionally, for most antibiotics there is no evidence that outcomes in non-resistant disease are improved by higher drug levels, and there is limited efficacy of co-treatment of antibiotics with ambroxol for most pathogens. The two cases where ambroxol may improve therapy are rifampin-sensitive tuberculosis and non-tuberculous mycobacterial infection, and vancomycin sensitive methicillin resistant Staphylococcus aureus pneumonia.
Topics: Ambroxol; Animals; Anti-Bacterial Agents; Bacterial Infections; Bromhexine; Drug Resistance, Bacterial; Expectorants; Humans; Lung; Lung Diseases; Tissue Distribution
PubMed: 30721101
DOI: 10.1080/17425255.2019.1578748