Chlamydia species and Mycoplasma pneumoniae

Chlamydia psittaci, Chlamydia pneumoniae, and Mycoplasma pneumoniae are a group of respiratory pathogens that have similar pulmonary and extrapulmonary manifestations. Recent studies suggest that C. pneumoniae and M. pneumoniae may play a role in the pathogenesis of asthma, but further studies are needed to delineate the importance of these organisms in this disease. The diagnosis of C. pneumoniae infection is hindered by the lack of a gold standard: Asymptomatic carriage of C. pneumoniae lowers the specificity of culture and polymerase chain reaction, and the current use of single high titers to identify infection also has specificity problems. Newer antibiotics simplify the management of infection with C. psittaci, C. pneumoniae, and M. pneumoniae and offer the potential for prophylaxis.     

Virus and Mycoplasma pneumoniae prevalence in a selected pediatric population with acute asthma exacerbation

Objective: To determine the prevalence of viral and atypical bacteria Mycoplasma pneumoniae infection in children experiencing asthma exacerbation and compare positive and negative subjects with regard to exacerbation severity, need for hospitalization, and treatment. Methods: One hundred sixty-nine asthmatic children aged 2–15 years old who were admitted to emergency rooms in Bogota, Colombia for acute asthma exacerbation were interviewed. Nasopharyngeal aspirates were taken for DNA and RNA extraction. M. pneumoniae and virus were detected by PCR using specific primers. Results: The prevalence of M. pneumoniae and viral infection in the study population was 12.4% and 83.7%, respectively. All subjects positive for M. pneumoniae were also positive for viral infection. Rhinovirus was the most frequently detected viral agent. No significant differences in severity of asthma exacerbations or in need for hospitalization between the virus or M. pneumoniae positive and negative groups were observed. A significantly lower percentage of M. pneumoniae positive subjects had used inhaled steroids over the six months prior to asthma exacerbation compared to M. pneumoniae negative subjects (38.1% vs. 68.2%), suggesting that inhaled corticosteroids may have a protective effect against M. pneumoniae infections. Conclusions: The M. pneumoniae and virus prevalence found in this study were similar to those described in the literature. The 100% co-infection rate observed suggests that viral infection can predispose patients to M. pneumoniae infection, and that this interaction may trigger asthmatic exacerbation. Further studies should be done to confirm the protective effect of inhaled corticosteroids on M. pneumoniae infection in patients with asthma exacerbations.     

Antibiotics in asthma

Asthma pathogenesis appears to be a result of a complex mixture of genetic and environmental influences. There is evidence that Mycoplasma pneumoniae and Chlamydia pneumoniae play a role in promoting airway inflammation that could contribute to the onset and clinical course of asthma. If antimicrobial therapy can eradicate these organisms, it might be possible to alter the course of the disease. Although antibiotics have no role in the routine management of acute exacerbations of asthma, certain macrolide antibiotics have been shown to have anti-inflammatory activity. Part of this effect is due to their known inhibition of steroid and theophylline metabolism, but through a myriad of mechanisms that are incompletely understood, macrolide antibiotics have additional broad anti-inflammatory properties that might prove useful in the management of asthma and other inflammatory diseases.     

Chlamydia pneumoniae,and mycoplasma pneumoniae: Are they related to severe asthma in childhood?

Background: Mycoplasma pneumoniae and Chlamydia pneumoniae are frequent agents of acute respiratory diseases and they have been recognized as infectious triggers of asthma. Objective: To determine the frequency of these triggers and their relationship to severe asthma. Methods: 82 patients were enrolled in a prospective cross-sectional study from January 2007 to March 2013 and they were divided into three study groups: Group 1: 27 children with severe asthma, Group 2: 29 children with stable asthma and Group 3: 26 children which was the control group. Serological tests included IgG and IgM for both C. pneumoniae and M. pneumoniae. Results: Average age ± SD was 10.9 ± 2.5 for Group 1; 10.1 ± 2.9 for Group 2 and 9.9± 1.9 for Group 3 (p = 0.4). M. pneumoniae IgM was observed in 6/27 (22.2%) in Group 1, 2/29 (6.9%) in Group 2 and 0/26 in the Control Group (p = 0,01). C.pneumoniae IgM was present in 7/26 (26.9%) in Group 1, 2/29 (6.9%) in Group 2 and 0/26 in Group 3 (p = 0.005). No significant difference was observed between Group 2 and Group 3. M. pneumoniae IgG was observed in 7/27 (25.9%) in Group 1, 4/29 (13.7%) in Group 2 and 0/26 in the Control Group (p < 0,05). C.pneumoniae IgG was present in 8/26 (30.7%) in Group 1, 5/29 (17.2%) in Group 2 and 0/26 in Group 3 (p < 0,05). Conclusions: M. pneumoniae and C. pneumoniae may play a role in the development of severe asthma.     

Combination antibiotics as a treatment for chronic Chlamydia‐induced reactive arthritis: A double‐blind,placebo‐controlled,prospective trial

Objective

Chlamydia trachomatis and Chlamydophila (Chlamydia) pneumoniae are known triggers of reactive arthritis (ReA) and exist in a persistent metabolically active infection state in the synovium, suggesting that they may be susceptible to antimicrobial agents. The goal of this study was to investigate whether a 6‐month course of combination antibiotics is an effective treatment for patients with chronic Chlamydia‐induced ReA.

Methods

This study was a 9‐month, prospective, double‐blind, triple‐placebo trial assessing a 6‐month course of combination antibiotics as a treatment for Chlamydia‐induced ReA. Eligible patients had to be positive for C trachomatis or C pneumoniae by polymerase chain reaction (PCR). Groups received 1) doxycycline and rifampin plus placebo instead of azithromycin; 2) azithromycin and rifampin plus placebo instead of doxycycline; or 3) placebos instead of azithromycin, doxycycline, and rifampin. The primary end point was the number of patients who improved by 20% or more in at least 4 of 6 variables without worsening in any 1 variable in both combination antibiotic groups combined and in the placebo group at month 6 compared with baseline.

Results

The primary end point was achieved in 17 of 27 patients (63%) receiving combination antibiotics and in 3 of 15 patients (20%) receiving placebo. Secondary efficacy end points showed similar results. Six of 27 patients (22%) randomized to combination antibiotics believed that their disease went into complete remission during the trial, whereas no patient in the placebo arm achieved remission. Significantly more patients in the active treatment group became negative for C trachomatis or C pneumoniae by PCR at month 6. Adverse events were mild, with no significant differences between the groups.

Conclusion

These data suggest that a 6‐month course of combination antibiotics is an effective treatment for chronic Chlamydia‐induced ReA.

     

Azithromycin, clarithromycin and telithromycin inhibit MUC5AC induction by Chlamydophila pneumoniae in airway epithelial cells

BackgroundAirway mucus hypersecretion is an important problem in chronic respiratory diseases including bronchial asthma. Chlamydophila pneumoniae is recently confirmed to be a pathogen in bronchial asthma, but the relationship between C. pneumoniae and mucus hypersecretion is uncertain. In this study, we examined whether C. pneumoniae induces MUC5AC mucin in airway epithelial cells. We also examined the effects of macrolide and ketolide antibiotics on the C. pneumoniae-induced mucus production.MethodsMUC5AC production in bronchial epithelial cells after stimulation with C. pneumoniae was analyzed by ELISA and quantitative RT-PCR. NF-κB and phosphorylated ERK were also analyzed. For inhibition study, cells were pretreated with azithromycin, clarithromycin and telithromycin before stimulation.ResultsC. pneumoniae dose-dependently induced MUC5AC production and gene expression. The ERK-NF-κB pathway was involved in C. pneumoniae-induced MUC5AC production. Macrolides and ketolides dose-dependently reduced C. pneumoniae-induced MUC5AC production. However, azithromycin was apparently less effective than the other antibiotics. Clarithromycin and telithromycin, but not azithromycin, reduced NF-κB activation.ConclusionsClarithromycin and telithromycin were thought to interfere with the signal pathways between ERK and NF-κB. These results suggest that airway mucus hypersecretion is one of the mechanisms of C. pneumoniae-induced bronchial asthma, and that macrolide and ketolide antibiotics represent a novel therapeutic intervention in these patients.     

The Change of Asthma-associated Immunological Parameters in Children with Mycoplasma pneumoniae Infection

Background. Mycoplasma pneumoniae (M. pneumoniae), an atypical pathogen, is increasingly recognized as a common and important pathogen. Previous studies showed that M. pneumoniae infection may play a role in asthmatic mechanisms based on evidence collected from peripheral blood or sputum of patients or animal models. However, evidence reported from the airways of patients has been rare. Objective. To estimate the role of M. pneumoniae infection in asthma by measuring the immunological parameters from peripheral blood and bronchoalveolar lavage fluid (BALF) in pediatric patients with mycoplasma pneumonia. Methods. A total of 30 patients with mycoplasma pneumonia and 37 patients without M. pneumoniae infection undergoing fiberoptic bronchoscopy were reviewed. The peripheral blood cell count, immunoglobulins (Ig), BALF cell count, and other clinical and laboratory data were reviewed and analyzed. Results. There were significantly more patients with raised basophil counts in the M. pneumoniae group than that in the control group (p = 0.033). Serum immunoglobulin (Ig) A, IgM, and IgG levels in the M. pneumoniae group were significantly higher than those in the control group (p = 0.008, p = 0.011, and p = 0.019, respectively). The percentage of eosinophils in BALF cells was in the range 0 to 10% in M. pneumoniae patients, while it ranged between 0 and 4% in the control group with a significant difference (p = 0.043). In the M. pneumoniae group, we found that the percentage of eosinophils in the BALF cells was positively correlated with age, the percentage of peripheral eosinophils, and BALF lymphocytes (r = 0.298, p = 0.030; r = 0.341, p = 0.014; r = 0.387, p = 0.006; respectively) and negatively correlated with total peripheral white blood cell (r = ?0.387, p = 0.005). Conclusion. These results suggest that M. pneumonia infection is associated with the asthma mechanism, especially in older children.     

The role of Chlamydia in upper respiratory tract infections

Although Chlamydia pneumoniae and Chlamydia psittaci are well-established causes of community-acquired pneumonia, little is known about the role of Chlamydia species in upper respiratory tract infections. C. pneumoniae may play a role in the pathogenesis of acute otitis media. Although C. pneumoniae has been isolated from the middle-ear fluid of children with otitis, children in whom the organism was isolated from middle-ear fluid improved despite being treated with antibiotics that are not active against C. pneumoniae. Although many patients with community-acquired pneumonia caused by C. pneumoniae have symptoms suggestive of sinusitis, there is only one report of isolation of the organism from the maxillary sinus of a patient with sinusitis. Studies of the association with pharyngitis are all based on serology, which often has a poor correlation with isolation of the organism by culture.     

Juvenile spondyloarthropathies associated with Mycoplasma pneumoniae infection

Background Reactive arthritis (ReA) has been sporadically reported as triggered by Mycoplasma pneumoniae. This study examined the potential relationship between the acute M. pneumoniae infection and juvenile spondyloarthropathy (jSpA) in children.Patients and methods Twelve patients with ReA secondary to acute M. pneumoniae were examined. M. pneumoniae-specific IgM, IgG and IgA antibodies were serologically confirmed by enzyme-linked immunosorbent assay (ELISA) tests (Savyon Diagnost., Israel). Due to the early appearance and relatively short life time of M. pneumoniae-specific IgM antibodies, their detection allowed the diagnosis of acute infection using single serum sample, confirmed by parallel serum in 7 of 12 patients. Specific IgM and IgG titers higher than 10 U/l were considered positive and those higher than 50 U/l as highly positive. Specific IgA antibodies were detected in only one patient.Results Four patients were female and eight were male. The mean age at onset was 9 years, and the mean duration of follow-up was 24.1 months (range 18–32). The mean number of involved joints was 2.8, and the knee joints were involved in 7 of 12 patients. The mean recovery time was 4.5 weeks (range 1–28) in eight reactive arthritis (ReA) cases; three patients developed enthesitis-related arthritis, and in one patient, genuine juvenile ankylosing spondylitis (jAS) was diagnosed. Two patients were HLA-B27-positive, and one patient was HLA-B7/B27-positive. Six patients had preceding respiratory symptoms, and five were treated with antibiotics.Conclusions Our findings provide clear evidence of ReA diagnosis following an acute M. pneumoniae infection that in four patients progressed to chronic jSpA. Our results suggest that detecting M. pneumoniae-specific antibodies in serological screening of jSpA patients might be useful. It is presently unclear whether antibiotic treatment would change the disease course in those patients.     

<Emphasis Type="Italic">Chlamydia pneumoniae</Emphasis> Infections in Asthma

Chlamydia pneumoniae is an intracellular pathogen that has been suggested to play a role in the pathology of asthma. However, so far none of the studies have provided clear evidence for a causative role of C. pneumoniae infections in asthma, although there is little doubt that chronic C. pneumoniae infection does aggravate asthma and should be treated.The diagnosis of C. pneumoniae infection is still a matter of concern for it is dependent on trained skilled personnel and can vary significantly between different diagnostic laboratories. This fact is also one of the major problems encountered when comparing epidemiological studies investigating the possible role of C. pneumoniae infections and their impact on the pathogenesis of other diseases.With regard to therapy, long-term treatment with macrolides is the best available method to eradicate C. pneumoniae. Successful therapy for C. pneumoniae, however, can also be complicated by the high possibility of de novo infection as epidemiological studies have shown that the prevalence of antibodies to C. pneumoniae increases with age in all populations studied. In the northern hemisphere the prevalence of C. pneumoniae is also affected by seasonal conditions. It is too early to draw any conclusions from the equatorial belt countries. The available data on C. pneumoniae in tropical countries indicate a much faster infection rate during early adulthood with 100% serological prevalence at an age greater than 25 years. This data, if confirmed, would argue against C. pneumoniae causing asthma since the asthma prevalence in those countries does not increase in a parallel pattern.An alternative interpretation of most studies could be that the increased rate of C. pneumoniae infections in patients with asthma results from a modified susceptibility towards the microorganism, due to yet unknown changes of the host cell’s physiology. It should be kept in mind that increased prevalence of C. pneumoniae infection is not restricted to asthma.Further studies are needed to understand the role of C. pneumoniae, especially of chronic infection, in the pathogenesis of inflammatory diseases with a specific focus on the effect that the microorganism triggers in the infected host cell. Only when we understand what C. pneumoniae does to its host cell will we be able to judge its impact on the overall status of an affected patient, and this knowledge will help us to develop a successful therapy.     

Higher incidence of persistent chronic infection of <Emphasis Type="Italic">Chlamydia pneumoniae</Emphasis> among coronary artery disease patients in India is a cause of concern

Background  

There is growing evidence that Chlamydia pneumoniae may be involved in the pathogenesis of atherosclerosis, as several studies have demonstrated the presence of the organism in atherosclerotic lesions. C. pneumoniae infections, which are especially persistent infections, have been difficult to diagnose either by serological methods or isolation of the organism from the tissue. Nucleic Acid Amplification tests (NAATs) has emerged as an important method for detecting C. pneumoniae. Inspite of high prevalence of C. pneumoniae specific antibodies in coronary heart disease patients, direct detection of C. pneumoniae in circulating blood of coronary artery disease (CAD) patients by sensitive nucleic acid amplification tests nested PCR (nPCR), multiplex PCR (mPCR) has not been carried out is required. Further correlation of the presence of C. pneumoniae in blood of CAD patients with C. pneumoniae specific IgA and IgG antibodies, which may indicative of the status of infection with the progression of atherosclerosis. This will help in order to prepare strategies for the antibiotic intervention to avoid the progression towards CAD.     

In Vitro Susceptibility and Eradication of Chlamydia Pneumoniae Cardiovascular Strains from Coronary Artery Endothelium and Smooth Muscle Cells

Recovery of viable Chlamydia pneumoniae from atheromas of coronary heart diseases patients has initiated pilot studies to eradicate C. pneumoniae from vascular tissue by antibiotic treatment. To provide data for the selection of effective antibiotics, we investigated the in vitro activity of anti-chlamydial antibiotics to eliminate vascular strains of C. pneumoniae from coronary endothelial and smooth muscle cells, celltypes that are involved in the pathogenesis of atherosclerosis. Methods. The susceptibility of the obligate intracellular chlamydiae was studied in primary coronary endothelial cells, smooth muscle cells and immortalized epithelial cells. Minimal inhibitory concentrations (MICs) were determined for ofloxacin, levofloxacin, trovafloxacin, moxifloxacin, erythromycin, azithromycin, roxithromycin, rifapentin and rifampin. Results. In vitro, rifampin was the most effective drug overall. Moxifloxacin and trovafloxacin were as effective as the macrolides of which roxithromycin was the most active one. Conclusions. Actively replicating C. pneumoniae can be eliminated in vitro from cell types, involved in the pathogenesis of atherosclerosis by various antibiotics. These data provide an experimental background for the selection of antibiotics in clinical eradication studies and will help to assess the potential success of prevention and eradication therapies.     

Physiopathologie et diagnostic des infections à Mycoplasma pneumoniae

Mycoplasma pneumoniae is the only mycoplasma clearly involved in respiratory tract infections in man. Implicated most often in tracheobronchitis, it is the second most frequent agent responsible for community-wide bacterial pneumonia, and in addition it probably causes asthma exacerbations. M. pneumoniae infection occurs endemically, with epidemic peaks every 4–7 years, mostly in children above five years of age. The laboratory diagnosis of these infections, mainly by serology, is made only in severe cases because of the fastidious growth of this microorganism. M. pneumoniae can, however, be detected easily by molecular amplification techniques. Macrolides and related antibiotics are considered the treatment of choice for M. pneumoniae infection in both adults and children. Antibiotic sensitivity testing of M. pneumoniae is not done routinely because resistant isolates have only rarely been described, the results are delayed, and they have no immediate therapeutic consequence.     

Mycoplasma pneumoniae et infections respiratoires aiguës

Mycoplasma pneumoniae infection can be entirely asymptomatic but it can also lead to bronchitis or pneumonis. M. pneumoniae is the first cause of community-acquired pneumonia in children older than five years of age. Clinical symptoms are often mild but treatment is required because of the risk of sequelae, mainly a decrease of gas diffusion. In children at risk for asthma, M. pneumoniae infection can cause acute attacks. In a study performed on children with an attack of severe asthma with hypoxemia hospitalized at the St-Vincent-de-Paul hospital, 26% of those having an exacerbation of their pre-existing asthma had a mycoplasma infection. Furthermore, when hospitalized for their first asthma attack, 50% of those children who were at risk for asthma had a mycoplasma infection.     

Ribosomal resistance: Emerging problems and potential solutions

Many systemic antibiotics use ribosomal inhibition to suppress the replication of bacteria. Current research suggests that resistance to macrolide, lincosamide, and streptogramin B (MLS_B) antibiotics is emerging among clinical isolates of Streptococcus pyogenes and Streptococcus pneumoniae. Erythromycin methylases, encoded by erm genes, modify an essential adenine residue in 23S rRNA and confer cross-resistance to MLS_B antibiotics. More recently, macrolide efflux (mef) genes were identified in isolates of S. pyogenes and S. pneumoniae that show resistance to 14- and 15-membered macrolides (M phenotype). Resistance to MLSB has been associated with the increased use of erythromycin, and the recent emergence of the M phenotype has coincided with the marketing of newer macrolides. However, despite increasing macrolide resistance among clinical isolates of S. pneumoniae, convincing data on treatment failures directly attributable to MLSB or M phenotypes are limited. Possible solutions to emerging MLS_B and M phenotype resistance include the introduction of alternative antibiotics, the more prudent use of antibiotics, combination therapy, molecular diagnostics, enhanced understanding of pharmacodynamic variables, and redefined resistance breakpoints.     

Severe<Emphasis Type="Italic"> Chlamydia pneumoniae</Emphasis> infection in a patient with mild neutropenia during treatment of Hodgkin’s disease

Chlamydia pneumoniae is known to cause acute respiratory tract infections in the non-immunocompromised population. So far, no data about the incidence of chlamydial infections in neutropenic patients are available. Macrolide antibiotics are not considered to be first-line treatment options in neutropenic patients. We report the case of a patient with Hodgkins disease who developed C. pneumoniae pneumonia during mild neutropenia. C. pneumoniae should be considered as a causative agent of pneumonia in neutropenic patients.     

Colonization of paediatric lower respiratory tract with genital Mycoplasma species

Background and objective: Recently, much attention has been given to the possible role played by pathogens that colonize neonatal or paediatric airway and their potential involvement in chronic respiratory disease. The goal of the current study was to evaluate the prevalence of Mycoplasma organisms in the BAL fluid of paediatric patients suffering from a variety of chronic respiratory diseases to determine if there was any clear disease association with bacterial presence. Methods: We examined 319 paediatric BAL samples for the presence of M. genitalium, M. hominis, U. urealyticum, U. parvum and M. pneumoniae DNA with species‐specific PCR. Results: Mycoplasma DNA was found in 32.6% (104/319) of patient samples; 10% (32/319) for M. pneumoniae, 8.8% for U. parvum, 2.8% for U. urealyticum; 4.7% for M. hominis and 9.1% for M. genitalium. There were no significant clinical and laboratory differences except serum IgE in asthmatics according to Mycoplasma colonization or not. Elevated levels of IgE were found more often in Mycoplasma DNA‐negative patients than patients with bacterial DNA, 85/109 versus 24/109 respectively (P < 0.0001). There was no difference in the frequency of Mycoplasmas between the asthmatics and the non‐asthmatics; 30.6% (69/225) versus 37.2% (35/94) for Mycoplasma 16S DNA, and 8% versus 14.9% for M. pneumoniae, respectively. Conclusions: Our data indicate that in addition to M. pneumoniae, urogenital Mycoplasma species may colonize the airway of patients with chronic respiratory diseases. There was, however, no association between chronic asthma diagnosis and Mycoplasma colonization in this study.     

Once-Daily Ciclesonide In Children: Efficacy and Safety in Asthma

Chlamydia pneumoniae infection might play a role in the pathology of asthma, but its role in infantile asthma remains obscure. The presence of Chlamydia pneumoniae was serologically determined in wheezing infants who were then re-examined 1-year later to determine whether or not asthma is associated with this type of infection. Wheezing infants progressed to asthma more frequently after infection with Chlamydia pneumoniae than those who were not infected. These findings suggested that Chlamydia pneumoniae infection triggers asthma in wheezy infants.     

Chlamydia pneumoniae and atherosclerosis

Chlamydia pneumoniae (C. pneumoniae) is a common respiratory pathogen. Many reports have documented the presence of C. pneumoniae in atheromatous coronary arteries, aorta, carotid arteries, and peripheral arteries using a variety of techniques. There is clear experimental evidence that C. pneumoniae can infect macrophages, endothelial cells, smooth muscle cells, and induce the formation of foam cells. Evidence from basic research and epidemiologic studies suggest that C. pneumoniae can induce macrophage foam cell formation by dysregulating native LDL uptake or metabolism (or both). Relatively small, secondary prevention studies, have suggested that antibiotic therapy might reduce monocyte activation and C. pneumoniae antibody titers, reduce inflammatory markers and possibly reduce adverse cardiovascular events. It is possible that C. pneumoniae enhances atherogenesis by causing inflammation and eliciting immune responses and may be one of the factors contributing to this multifactorial disease process.