Mycoplasma pneumoniae as a Cofactor in Severe Respiratory Infections

Cimolai, Nevio; Wensley, David; Seear, Michael; Thomas, E. T.

doi:10.1093/clinids/21.5.1182

Cited by 63 publications

(36 citation statements)

References 17 publications

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“…These findings are consistent with the results of the present study and suggest that the cytokines and chemokines affected by antimicrobial therapy have a role in orchestrating pulmonary inflammation and function after M. pneumoniae infection. Furthermore, evidence from human and animal studies also suggests that the more vigorous the immune response and cytokine stimulation in response to M. pneumoniae infection is, the more severe the pulmonary injury and clinical illness are (5,23,34,40).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of LBM415 (NVP PDF-713), a Novel Peptide Deformylase Inhibitor, for Treatment of Experimental Mycoplasma pneumoniae Pneumonia

Fonseca-Aten¹,

Salvatore²,

Mejías³

et al. 2005

Antimicrob Agents Chemother

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Mycoplasma pneumoniae is a major cause of community-acquired pneumonia. We evaluated the efficacy of LBM415, a novel peptide deformylase inhibitor antimicrobial agent, for the treatment of M. pneumoniae pneumonia in a mouse model. Eight-week-old BALB/c mice were intranasally inoculated once with 10 7 CFU of M. pneumoniae. Groups of mice were treated with LBM415 (50 mg/kg of body weight) or placebo subcutaneously daily for 13 days, starting 24 h after inoculation. Groups of mice were evaluated at the baseline; at days of treatment 1, 3, 6, and 13; and at 7 days after treatment. The MIC of LBM415 against M. pneumoniae was <0.005 g/ml. LBM415-treated mice had significantly lower bronchoalveolar lavage fluid M. pneumoniae concentrations than placebo-treated mice on days 6 and 13 of treatment. Compared with placebo treatment, therapy with LBM415 significantly decreased lung histopathology scores at days 3, 6, and 13 of treatment and at 7 days after treatment. Airway obstruction was significantly lower in LBM415-treated mice than in placebotreated mice on days 1, 3, and 6 of treatment and after 7 days of therapy, while airway hyperresponsiveness was significantly lower only on day 3 of therapy. The bronchoalveolar lavage fluid concentrations of tumor necrosis factor alpha, gamma interferon (IFN-␥), interleukin-6 (IL-6), IL-12, KC (functional IL-8), monocyte chemotactic protein 1, macrophage inflammatory protein 1␣, monokine induced by IFN-␥, and IFN-inducible protein 10 were significantly reduced in LBM415-treated mice compared with the levels in placebo-treated mice. There were no differences in the bronchoalveolar lavage fluid concentrations of granulocyte-macrophage colonystimulating factor, IL-1␤, IL-2, IL-4, IL-5, and IL-10 between the two groups of mice. LBM415 therapy had beneficial microbiologic, histologic, respiratory, and immunologic effects on acute murine M. pneumoniae pneumonia.Mycoplasma pneumoniae is an important cause of upper and lower respiratory tract infections in children and adults and is responsible for as many as 40% of cases of community-acquired pneumonia (7,15,28,33). Tetracyclines, macrolides, ketolides, and fluoroquinolones have in vitro activities against M. pneumoniae (43, 44). Most of these agents are primarily bacteriostatic for M. pneumoniae, and only the fluoroquinolones have been shown to be bactericidal (10, 42). While M. pneumoniae can be cultured from respiratory secretions for long periods after acute infection even after appropriate antimicrobial therapy, most antibiotics produce satisfactory clinical results, with a significant reduction in the duration of symptoms compared with no treatment (30,36). Macrolide and related antibiotics are generally considered the therapy of choice for M. pneumoniae infections in children and adults. Strains with acquired resistance to macrolides have rarely been described (29).LBM415 (previously known as NVP PDF-713) is a novel inhibitor of the bacterial enzyme peptide deformylase (PDF) and has been documented to have in vitro activity against...

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Section: Discussionmentioning

confidence: 99%

Evaluation of LBM415 (NVP PDF-713), a Novel Peptide Deformylase Inhibitor, for Treatment of Experimental Mycoplasma pneumoniae Pneumonia

Fonseca-Aten¹,

Salvatore²,

Mejías³

et al. 2005

Antimicrob Agents Chemother

View full text Add to dashboard Cite

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“…Current evidence from human and animal studies suggests that cytokine production and lymphocyte activation may either minimize disease through the enhancement of host defense mechanisms or exacerbate disease through immunological lesion development. Thus, the more vigorous the cell-mediated immune response and cytokine stimulation, the more severe the clinical illness and pulmonary injury (78,201,305,338,342,(404)(405)(406). This concept of immune-mediated lung disease provides a basis for consideration of immunomodulatory therapeutics in addition to conventional antimicrobial therapies in management of disease due to M. pneumoniae.…”

Section: Cytotoxicity and Inflammationmentioning

confidence: 99%

“…M. pneumoniae may also be present in the respiratory tract concomitantly with other pathogens (47,109,137,180,182,252,446), and there is some evidence from humans and animal models indicating that infection with M. pneumoniae may precede and somehow intensify subsequent infections with various respiratory viruses and bacteria, including S. pyogenes and Neisseria meningitidis (78). Potential explanations for such a synergistic effect include immunosuppression or alteration in respiratory tract flora due to the presence of M. pneumoniae (78,255,269,358). Children with functional asplenia and immune system impairment due to sickle cell disease, other conditions such as Down syndrome, and various immunosuppressive states are at risk of developing more fulminant pneumonia due to M. pneumoniae (38,137,151,192,273,378,403).…”

Section: Vol 17 2004 M Pneumoniae As a Human Pathogen 707mentioning

confidence: 99%

Mycoplasma pneumoniaeand Its Role as a Human Pathogen

2004

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Mycoplasma pneumoniae is a unique bacterium that does not always receive the attention it merits considering the number of illnesses it causes and the degree of morbidity associated with it in both children and adults. Serious infections requiring hospitalization, while rare, occur in both adults and children and may involve multiple organ systems. The severity of disease appears to be related to the degree to which the host immune response reacts to the infection. Extrapulmonary complications involving all of the major organ systems can occur in association with M. pneumoniae infection as a result of direct invasion and/or autoimmune response. The extrapulmonary manifestations are sometimes of greater severity and clinical importance than the primary respiratory infection. Evidence for this organism's contributory role in chronic lung conditions such as asthma is accumulating. Effective management of M. pneumoniae infections can usually be achieved with macrolides, tetracyclines, or fluoroquinolones. As more is learned about the pathogenesis and immune response elicited by M. pneumoniae, improvement in methods for diagnosis and prevention of disease due to this organism may occur

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“…MP may precede and intensify subsequent infections with various respiratory viruses and bacteria. 5 Such data raise the question of how statements on efficacy of therapies for MP can be made when there is not even the knowledge of which organisms are being targeted.…”

mentioning

confidence: 99%

Treatment of Mycoplasma pneumoniae in Pediatric Lower Respiratory Infection

et al. 2014

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In this issue of Pediatrics, Biondi et al 1 present a rigorous systematic review and meta-analysis of the literature on the use of antibiotics to treat community-acquired (CA) lower respiratory infections (LRIs) secondary to Mycoplasma pneumoniae (MP). Consistent with previous studies, but on a larger scale, the evidence is deemed insufficient to support or refute such treatments for MP.The following comments, although largely addressed in the article, are intended to highlight the caution that is required on the part of the reader when attempting to implement these conclusions to everyday practice. In particular, we must point out that lack of evidence of efficacy is not evidence of inefficacy when addressing current treatment paradigms. The problems of this and previous studies lie in the lack of uniformity of diagnostic methods, complicated by the fact that mixed infections with other microorganisms often go undiagnosed and contaminate any analysis of treatment efficacy. The small number of studies and their heterogeneity add to our inability to conclude either way, and therefore statements about results of MP-oriented antibiotic treatment are difficult to substantiate, particularly when applied to individual cases.MP is a common cause of CA LRI, particularly in school-aged children and adolescents. It is responsible for at least 40% of cases of CA pneumonia (CAP) and as many as 18% of cases requiring hospitalization in children. 2The diagnosis of MP infection is difficult and nonuniform, and serology and nucleic acid amplification (polymerase chain reaction) are mostly used. Few commercial serologic assays have been shown to have appropriate sensitivity and specificity.3 Conversely, polymerase chain reaction may overestimate the incidence of MP and cost considerations limit its use. These factors frequently limit or delay diagnosis and introduce arbitrariness to therapeutic decisions.Even when the diagnosis is made, there is evidence that MP infections are often mixed; Korppi et al 4 reported .50% of MP CAP to be mixed infections, with Streptococcus pneumoniae identified in two-thirds of cases. MP may precede and intensify subsequent infections with various respiratory viruses and bacteria.5 Such data raise the question of how statements on efficacy of therapies for MP can be made when there is not even the knowledge of which organisms are being targeted.Patients with MP infections mostly recover spontaneously, and it is difficult to assess how intervention and the timing thereof within the course of the infection can be factored in when studying the results of therapies. In human studies, antibiotics have been shown to shorten the clinical course of MP infection, 6 but at the same time carriage of organisms in the upper respiratory tract may not be eliminated.7 It is therefore difficult to assess the effect of medication when organism eradication is not achieved, and thus the response of MP, unlike bacterial infections, is inherently more subtle and variable. Biondi

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Mycoplasma pneumoniae as a Cofactor in Severe Respiratory Infections

Cited by 63 publications

References 17 publications

Evaluation of LBM415 (NVP PDF-713), a Novel Peptide Deformylase Inhibitor, for Treatment of Experimental Mycoplasma pneumoniae Pneumonia

Evaluation of LBM415 (NVP PDF-713), a Novel Peptide Deformylase Inhibitor, for Treatment of Experimental Mycoplasma pneumoniae Pneumonia

Mycoplasma pneumoniaeand Its Role as a Human Pathogen

Treatment of Mycoplasma pneumoniae in Pediatric Lower Respiratory Infection

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