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Immune system as a new therapeutic target for antibiotics  [PDF]
Brygida Kwiatkowska, Maria Maslinska, Malgorzata Przygodzka, Joanna Dmowska-Chalaba, Justyna Dabrowska, Katarzyna Sikorska-Siudek
Advances in Bioscience and Biotechnology (ABB) , 2013, DOI: 10.4236/abb.2013.44A013

Since the discovery of penicillin by Fleming in 1928, the knowledge of the antibiotics’ spectrum and mechanism of action has been steadily increasing. Antibiotics became an effective tool in the fight against many pathogens, changing the prognosis of outcome for many serious diseases. It is already known that antibiotics not only have the antibacterial activity, but many of theme.g. macrolides, sulphonamides and tetracyclineshave immunomodulating effect, affecting functions of lymphocytes, macrophages and costimulatory molecules, macrophage migration and phagocytosis, as well as proinflammatory cytokine secretion. The expanding knowledge of the effects of antibiotics on the immune system has brought with it new applications of antibiotics in organ transplantation, invasive cardiology and treatment of autoimmune diseases such as rheumatoid arthritis or asthma.

Infection of the lymphatic system by Aureobasidium pullulans in a patient with erythema nodosum leprosum
Morais, Orlando Oliveira de;Porto, Cláudia;Coutinho, Anglya Samara Silva Leite;Reis, Carmélia Matos Santiago;Teixeira, Marcus de Melo;Gomes, Ciro Martins;
Brazilian Journal of Infectious Diseases , 2011, DOI: 10.1590/S1413-86702011000300019
Abstract: aureobasidium pullulans is a causal agent of phaeohyphomycosis, occasionally found in men and animals. as an agent of different opportunistic fungal processes, it may cause fungemia, systemic infections and abscesses in different viscera. this paper aims to report a case of a patient with infection of the lymphatic system by a. pullulans. a 23-year-old patient being treated for erythema nodosum leprosum presented a 60-day complaint of daily fever, hoarseness, odynophagia and weight loss. laboratory tests showed pancytopenia with severe neutropenia, cervical adenomegaly and solid contrast uptake lesion in the oropharyngeal region. due to neutropenia and sepsis the patient was initially treated with cefepime and vancomycin, but there was no clinical improvement. lymph node puncture-aspiration showed yeast-form fungus identified as a. pullulans by sequencing its region. the patient was treated with amphotericin b deoxycholate, leading to complete recovery of bone marrow function and regression of adenomegaly and the oropharyngeal lesion.
Impact of macrolide therapy on mortality of HIV-infected patients with community-acquired pneumonia in a tertiary teaching hospital
Mello, Claudia Figueiredo;Negra, Marinella Della;
Brazilian Journal of Infectious Diseases , 2011, DOI: 10.1590/S1413-86702011000300014
Abstract: background: bacterial pneumonia is one of the main causes of morbidity and mortality in patients infected by the human immunodeficiency virus (hiv). the main objective of this study was to evaluate the effect of macrolide therapy in combination with a beta-lactam based empiric regimen for inpatients with community-acquired pneumonia and hiv. methods: this is a retrospective cohort study of hospitalized patients. adult patients who had received treatment with ceftriaxone or ceftriaxone plus clarithromycin were included. results: 76 patients met the inclusion criteria. among baseline characteristics analyzed, only respiratory rate showed significant difference: patients who had received clarithromycin were more likely to have a respiratory rate > 30/min than patients who received only ceftriaxone (64% versus 36%, p = 0.03). icu admission was the only outcome that showed a significant difference, more frequent in the ceftriaxone plus clarithromycin group (45% versus 20%, p = 0.03). conclusions: this study does not support the addition of a macrolide to a beta-lactam based regimen in hiv-infected patients. this is probably related to the patients' immunodeficiency status, which impairs the immunomodulatory properties of the macrolides.
Reacciones adversas psiquiátricas asociadas a nuevos macrólidos: A propósito de tres casos
Sanz de Miguel,M.P.; Sancho Gracia,E.; Chapi Pe?a,B.; Campos Bernal,A.; Romero Gil,R.; García Vera,C.;
Pediatría Atención Primaria , 2010, DOI: 10.4321/S1139-76322010000300007
Abstract: macrolides represent the 10-15% of the world-wide market of oral antibiotics. they are one of the safer groups of antibiotics, being the severe adverse reactions very rare. they can produce gastrointestinal reactions, hepatotoxicity and ototoxicity. the psychiatric reactions are found sporadically among the adverse effects. cases reported to the fda showed that clarithromycin and ciprofloxacin are the most frequent antibiotics associated with the development of mania. the syndrome has been termed antibiomania. we present three clinical cases seen in a primary care office in the last year with similar pictures of hyperactivity and aggressiveness coinciding with the administration of antibiotics of the family of the macrolides.
Quimioprofilaxis en coqueluche: ?Sacar agua a canastos?
Cofré Guerra,José;
Revista chilena de infectología , 2006, DOI: 10.4067/S0716-10182006000100009
Abstract: pertussis chemoprophylaxis is indicated for contacts at risk of death or of severe complications if infected with bordetella pertussis; e.g. neonates and infants < 12 months of age, elderly individuals, individuals with cardiac and/or respiratory insufficiency, and pregnant women during their third trimester of pregnancy (in order to protect their offspring). available evidence indicates that pchp is effective and thus recommendable for high risk household contacts within a 21 day window after the beginning of symptoms of the index case, and if no secondary case has occurred, recommendation that may be extended to high risk individuals that co-habit with an index case at hospital, daycare centers or institutionalized elderly people. bordetella pertussis can be transmitted by respiratory droplets that can travel further than the critical distance of 1.5 meters. this long distance transmissibility is relevant when considering who should receive prophylaxis during a nosocomial outbreak. current evidence supports the use of macrolides and azalides for pertussis chemoprophylaxis; seven days of erythromycin or clarithromycin and five days of azythromycin are sufficient to eradicate b. pertussis
Genotypes and serotype distribution of macrolide resistant invasive and non- invasive Streptococcus pneumoniae isolates from Lebanon
Nedal Taha, George F Araj, Rima H Wakim, Souha S Kanj, Zeina A Kanafani, Ahmad Sabra, Marie-Therese Khairallah, Farah J Nassar, Marwa Shehab, Maysa Baroud, Ghassan Dbaibo, Ghassan M Matar
Annals of Clinical Microbiology and Antimicrobials , 2012, DOI: 10.1186/1476-0711-11-2
Abstract: Forty four macrolide resistant and 21 macrolide susceptible S. pneumoniae clinical isolates were tested for antimicrobial susceptibility according to CLSI guidelines (2008) and underwent molecular characterization. Serotyping of these isolates was performed by Multiplex PCR-based serotype deduction using CDC protocols. PCR amplification of macrolide resistant erm (encoding methylase) and mef (encoding macrolide efflux pump protein) genes was carried out.Among 44 isolates resistant to erythromycin, 35 were resistant to penicillin and 18 to ceftriaxone. Examination of 44 macrolide resistant isolates by PCR showed that 16 isolates harbored the erm(B) gene, 8 isolates harbored the mef gene, and 14 isolates harbored both the erm(B) and mef genes. There was no amplification by PCR of the erm(B) or mef genes in 6 isolates. Seven different capsular serotypes 2, 9V/9A,12F, 14,19A, 19F, and 23, were detected by multiplex PCR serotype deduction in 35 of 44 macrolide resistant isolates, with 19F being the most prevalent serotype. With the exception of serotype 2, all serotypes were invasive. Isolates belonging to the invasive serotypes 14 and 19F harbored both erm(B) and mef genes. Nine of the 44 macrolide resistant isolates were non-serotypable by our protocols.Macrolide resistance in S. pneumoniae in Lebanon is mainly through target site modification but is also mediated through efflux pumps, with serotype 19F having dual resistance and being the most prevalent and invasive.Streptococcus pneumoniae continues to be a major cause of morbidity and mortality in humans. It is one of the most significant bacterial pathogens causing community acquired infections, most notably pneumonia, otitis media, bacteremia, and meningitis [1,2]. Treatment of pneumococcal infections is becoming difficult due to the high prevalence of penicillin-resistant strains and to the rapid development of resistance to other antimicrobials including macrolides. These drugs are extensively used for the treat
Efeito anti-inflamatório dos macrolídeos em doen?as pulmonares da infancia
Luisi, Fernanda;Gandolfi, Thays Dornelles;Daudt, Arthur Dondonis;Sanvitto, Jo?o Pedro Zelmanowicz;Pitrez, Paulo Márcio;Pinto, Leonardo Araujo;
Jornal Brasileiro de Pneumologia , 2012, DOI: 10.1590/S1806-37132012000600016
Abstract: macrolides are drugs that have antimicrobial effects, especially against intracellular pathogens. various studies have shown that macrolides might also have anti-inflammatory effects. macrolides inhibit the production of interleukins and can reduce pulmonary neutrophilic inflammation. clinical trials have demonstrated beneficial effects of macrolides in various chronic lung diseases. the objective of this study was to review recent data in the medical literature on the anti-inflammatory effects of macrolides in childhood lung diseases by searching the medline (pubmed) database. we used the following search terms: "macrolide and cystic fibrosis"; "macrolide and asthma"; "macrolide and bronchiolitis obliterans"; and "macrolide and acute bronchiolitis". we selected articles published in international scientific journals between 2001 and 2012. clinical studies and in vitro evidence have confirmed the anti-inflammatory effect of macrolides in respiratory diseases. some clinical trials have shown the benefits of the administration of macrolides in patients with cystic fibrosis, although the risk of bacterial resistance should be considered in the analysis of those benefits. such benefits are controversial in other respiratory diseases, and the routine use of macrolides is not recommended. further controlled clinical trials are required in order to assess the efficacy of macrolides as anti-inflammatory drugs, so that the benefits in the treatment of each specific clinical condition can be better established.
Distribution of erm genes and low prevalence of inducible resistance to clindamycin among staphylococci isolates
Coutinho, Vivian de Lima Spode;Paiva, Rodrigo Minuto;Reiter, Keli Cristine;de-Paris, Fernanda;Barth, Afonso Luis;Machado, Alice Beatriz Mombach Pinheiro;
Brazilian Journal of Infectious Diseases , 2010, DOI: 10.1590/S1413-86702010000600004
Abstract: introduction: resistance to macrolides, lincosamides and streptogramins b (mlsb antibiotics) in staphylococci may be due to modification in ribosomal target methylase encoded by erm genes. the expression of mlsb resistance lead to three phenotypes, namely constitutive resistance (cmlsb), inducible resistance (imlsb), and resistance only to macrolides and streptogramins b (msb). the imlsb resistance is the most difficult to detect in the clinical laboratory. objective: this study investigated the expression of mlsb resistance and the prevalence of the erm genes among 152 clinical isolates of staphylococcus aureus and coagulase-negative staphylococcus (cns) from hospital de clínicas de porto alegre. methods: primary mlsb resistance was detected by the disk diffusion method. isolates with imlsb phenotype were tested by double-disk induction method. all isolates were tested by a genotypic assay, pcr with specific primers. results: a total of 46.7% of staphylococci were positive for cmlsb; 3.3% for imlsb and 3.3% for msb. one or more erm genes were present in 50.1% of isolates. the gene erma was detected in 49 isolates, ermc in 29 and ermb in 3. conclusion: the prevalence of the erma, ermb and ermc genes were 29.6%, 17.1% and 0.66% respectively, and constitutive resistance was the most frequent as compared to the other two phenotypes.
Experimental pleurodesis induced by antibiotics (macrolides or quinolones)
Teixeira, Lisete R.;Vargas, Francisco S.;Acencio, Milena M. P.;Bumlai, Renan U. M.;Antonangelo, Leila;Marchi, Evaldo;
Clinics , 2006, DOI: 10.1590/S1807-59322006000600012
Abstract: purpose: chemical pleurodesis is a therapeutic tool for the treatment of recurrent pleural effusions, mainly those of neoplastic etiology. in the past, tetracycline was the sclerosant agent of choice in clinical practice, but presently, there is no consensus about an ideal agent. the aim of this study was to evaluate the effectiveness of macrolides (azithromycin and clarithromycin) or quinolones (levofloxacin and gatifloxacin) in inducing experimental pleurodesis in rabbits. method: forty new zealand rabbits randomized into groups of 10 received (at a total volume of 2 ml for each animal) 1 of the 4 drugs by intrapleural injection. after 28 days, the animals were euthanized and the pleural cavity was evaluated macroscopically and microscopically. results: the intensity of the macroscopic adhesions was mild in all groups. on microscopic analysis, minimal pleural fibrosis and inflammation were observed in all animals. conclusion: the macrolides (azithromycin or clarithromycin) and the quinolones (levofloxacin or gatifloxacin) when injected into the normal pleural space of rabbits are not effective in promoting pleurodesis. additional research is required to identify sclerosing agents capable of inducing pleurodesis.
Utility of adjunctive macrolide therapy in treatment of children with asthma: a systematic review and meta-analysis
Mikailov A, Kane I, Aronoff SC, Luck R, DelVecchio MT
Journal of Asthma and Allergy , 2013, DOI: http://dx.doi.org/10.2147/JAA.S38652
Abstract: ility of adjunctive macrolide therapy in treatment of children with asthma: a systematic review and meta-analysis Review (1533) Total Article Views Authors: Mikailov A, Kane I, Aronoff SC, Luck R, DelVecchio MT Published Date January 2013 Volume 2013:6 Pages 23 - 29 DOI: http://dx.doi.org/10.2147/JAA.S38652 Received: 29 September 2012 Accepted: 06 November 2012 Published: 16 January 2013 Anar Mikailov,1 Ilona Kane,2 Stephen C Aronoff,3 Raemma Luck,3, Michael T DelVecchio3 1Beth Israel Deaconess Medical Center, Boston, MA, 2St Christopher's Hospital for Children, Philadelphia, PA, 3Department of Pediatrics, Temple University School of Medicine, Philadelphia, PA, USA Raemma Luck is now deceased Background: The purpose of this study was to investigate macrolides as an adjunct to an asthma controller regimen in children with asthma. Methods: Prospective clinical trials of macrolide therapy in children with asthma using outcome measures of change in forced expiratory volume in one second (FEV1) and/or oral corticosteroid requirement were searched for in PubMed up to December 2009. The reference lists of studies were also included in the analysis, as well as those listed in published meta-analyses. Results: The literature search yielded 116 studies, six of which were included in this meta-analysis. The change in FEV1 from baseline with adjunctive use of macrolide therapy in all children was not significant (0.25% predicted; 95% confidence interval [CI] 0.37, 0.86 predicted, P = 0.43); however, the change in FEV1 among children receiving daily oral corticosteroids was significant (3.89% predicted; 95% CI 0.01, 7.79, P = 0.05). Addition of macrolide therapy to the treatment of children with oral corticosteroid-dependent asthma resulted in a statistically significant decrease in daily corticosteroid dosage ( 3.45 mg/day; 95% CI 5.79, 1.09 mg/day, P = 0.004). This reduction in daily corticosteroid dosage was directly proportional to the duration of macrolide therapy ( 0.17 mg methylprednisolone per week of macrolide therapy; 95% CI 0.33, 0.021, P = 0.025). Conclusion: Addition of macrolides to the treatment regimen of children with oral corticosteroid-dependent asthma improves FEV1 and decreases the daily dosage of corticosteroids required for control in these children. The degree of dose reduction is directly related to the duration of macrolide therapy. Additional large, randomized, placebo-controlled trials of adjunctive macrolide use in children with oral corticosteroid-dependent asthma are required to verify this observation.
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