Mycoplasma

Background

Mycoplasma is one of the tiniest free-living organisms known. It and its close cousin the Ureaplasma are the cause of a number of common diseases ranging from pneumonia to venereally associated urethritis. From a laboratory standpoint, Mycoplasma is often a contaminant of viral cultures. Thus it is important to establish whether a culture is a true pathogen.

OUTLINE

Epidemiology

Disease Associations

Pathogenesis

Laboratory/Radiologic/Other Diagnostic Testing

Gross Appearance and Clinical Variants

Histopathological Features and Variants

Special Stains/Immunohistochemistry/Electron Microscopy

Differential Diagnosis

Prognosis and Treatment

Commonly Used Terms

Internet Links

EPIDEMIOLOGY CHARACTERIZATION

SYNONYMS

INCIDENCE

Mycoplasma genitalium infections in asymptomatic men and men with urethritis attending a sexually transmitted diseases clinic in New Orleans.

Mena L, Wang X, Mroczkowski TF, Martin DH.

Louisiana State University Health Sciences Center and the Delgado Clinic, New Orleans Health Department, New Orleans, Louisiana 70112, USA.
Clin Infect Dis 2002 Nov 15;35(10):1167-73 Abstract quote
We report the results of a study of Mycoplasma genitalium (detected with a modified polymerase chain reaction [PCR] assay) in men with urethritis and in asymptomatic control subjects at a sexually transmitted diseases clinic in New Orleans.

Data for 97 men with urethritis and 184 asymptomatic men were available for analysis. M. genitalium infection rates in symptomatic and asymptomatic men who were negative for Chlamydia trachomatis and Neisseria gonorrhoeae were 25% and 7%, respectively (P=.006). M. genitalium coinfection rates among men with chlamydial and gonococcal urethritis were 35% and 14%, respectively. Men with M. genitalium urethritis resembled those with C. trachomatis in that both groups were younger and more likely to experience milder urethral symptoms.

Among men with urethritis, the sensitivities of PCR of urine and swab specimens for the detection of M. genitalium were 87% and 91%, respectively. M. genitalium is associated with nongonococcal urethritis in this population.

GEOGRAPHY

Prevalence of Mycoplasma pneumoniae in children in Diyarbakir, the south-east of Turkey.

Bosnak M, Dikici B, Bosnak V, Dogru O, Ozkan I, Ceylan A, Haspolat K.

Department of Pediatrics, Dicle University Medical School, Diyarbakir, Turkey.
Pediatr Int 2002 Oct;44(5):510-2 Abstract quote
BACKGROUND: Mycoplasma pneumoniae is a well known causative agent of infection in childhood but clinical presentation may be variable. History and physical examination may not be so helpful for the diagnosis. It is difficult to culture this infectious agent, with the culture technique for the multiplication of the organism for routine investigation hard to obtain. The determination of exposure and prevalence of the disease of any region should be helpful for clinical diagnosis. In this study, we aimed to determine the seroprevalence of M. pneumoniae in children aged 0-14 years in Diyarbakir and establish the distribution of infection prevalence of various age groups of children.

METHODS: Thirty streets were determined according to the cluster method for the 0-6 years age group. In this age group, a total of 180 blood samples were collected; so that there were 30 samples for each age. For children aged 7-14 years, elementary school children were selected. There were 70 elementary schools in the city and 14 schools were randomly selected according to the randomized numbers table with a 20% sample. Finally, 276 blood samples were collected. Mycoplasma pneumoniae was determined by using the enzyme immunoassay method. For this method MELOTEST Mycoplasma IgG reagent was used.

RESULTS: The highest seropositivity rate was encountered at 10 years of age (65%) and lowest was at 2 years of age (0%). The overall M. pneumoniae seropositivity was 27% when all ages were considered together. The first 2 years of age excluded this rate and was 31.9%. A sudden increase of seropositivity was observed at 7 years of age.

CONCLUSIONS: Increasing seroprevalence rates of M. pneumoniae after 2 years of age should alert clinicians to consider the organism in the differential diagnosis of infectious diseases in this age group. The low seroprevalence rates in the first 2 years of age was thought to be due to low risk of community-based spread of the organism in this age group. The most prominent increase in seroprevalence was at 10 years of age. This data indicated that M. pneumoniae should be kept in mind while making differential diagnosis of infections. The spreading of disease and community-based transmission is also important to consider. In our study, seroprevalence rates increased at 6 and 7 years of age, at the beginning of the school age as community-based transmission takes place most commonly in crowded circumstances. In conclusion, M. pneumoniae should be thought as an important infectious agent in childhood for all age groups.

DISEASE ASSOCIATIONS CHARACTERIZATION

ACUTE DISSEMINATED ENCEPHALOMYELITIS

Acute disseminated encephalomyelitis (ADEM) due to Mycoplasma pneumoniae infection in an adolescent.
Riedel K, Kempf VA, Bechtold A, Klimmer M.

Dept. of Medical Microbiology, Immunology and Hygiene, City Hospital Munich-Harlaching, Germany.
Infection 2001 Aug;29(4):240-2 Abstract quote
A 17-year-old boy presented with a severe form of an acute disseminated encephalomyelitis (ADEM) with hemiparesis and coma after initial symptoms of a flu-like febrile infection 1 week previously.

Titers against Mycoplasma pneumoniae were significantly increased in serum and cerebrospinal fluid (CSF). Detection of M. pneumoniae was achieved in the initial CSF sample using M. pneumoniae-specific PCR. The patient improved significantly on antimicrobial therapy with erythromycin and immunosupressive therapy with immunoglobulins and corticosteroids.

This case report demonstrates a well-documented course of a central nervous system (CNS) infection resulting in the ADEM syndrome.

ENDOMETRITIS

Association between Mycoplasma genitalium and acute endometritis.

Cohen CR, Manhart LE, Bukusi EA, Astete S, Brunham RC, Holmes KK, Sinei SK, Bwayo JJ, Totten PA.

Lancet 2002 Mar 2;359(9308):765-6 Abstract quote
Up to 70% of cases of pelvic inflammatory disease do not have a known cause. We recruited 115 women who had presented to a clinic for sexually transmitted diseases in Nairobi, Kenya with pelvic pain that had persisted for 14 days or less, to look for an association between Mycoplasma genitalium and endometritis.

With PCR, we detected M genitalium in the cervix, endometrium, or both in nine (16%) of 58 women with histologically confirmed endometritis and in one (2%) of 57 women without endometritis (p=0.02). Our results suggest that infection with M genitalium is strongly associated with acute endometritis in this population.

GUILLAIN-BARRE SYNDROME

Cross-reactive anti-galactocerebroside antibodies and Mycoplasma pneumoniae infections in Guillain-Barre syndrome.

Ang CW, Tio-Gillen AP, Groen J, Herbrink P, Jacobs BC, Van Koningsveld R, Osterhaus AD, Van der Meche FG, van Doorn PA.

Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Centre, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.
J Neuroimmunol 2002 Sep;130(1-2):179-83 Abstract quote
Anti-galactocerebroside (GalC) antibodies are reported to be present in GBS patients with preceding Mycoplasma pneumoniae (MP) infection.

We investigated the presence of anti-GalC reactivity in serum of a large group of GBS patients using ELISA and compared this with healthy controls and individuals with an uncomplicated MP infection. Anti-GalC antibody reactivity was present in 12% of the GBS patients. Furthermore, anti-GalC antibodies were associated with MP infections, a relatively mild form of the disease and demyelinating features. Anti-GalC antibodies cross-reacted with MP antigen.

In conclusion, anti-GalC antibodies in GBS patients may be induced by molecular mimicry with MP.

INFERTILITY

Serological investigation of Mycoplasma genitalium in infertile women.

Clausen HF, Fedder J, Drasbek M, Nielsen PK, Toft B, Ingerslev HJ, Birkelund S, Christiansen G.

Department of Medical Microbiology and Immunology, The Bartholin Building, University of Aarhus, DK-8000 Aarhus C, Denmark.
Hum Reprod 2001 Sep;16(9):1866-74 Abstract quote
BACKGROUND: The role of Mycoplasma genitalium in the pathogenesis of pelvic inflammatory disease has not been characterized.

METHODS: Sera from 308 infertile women were investigated for antibodies to M. genitalium by immunoblotting. Women with tubal factor infertility (TFI) made up 132 of the patients, 67 of the women had an infertile male partner and 109 were infertile for unknown reasons.

RESULTS: Of the TFI patients 29 (22.0%) were seropositive to the major adhesin, MgPa, of M. genitalium versus 11 (6.3%) in the group of women with normal tubes. No cross-reactions between MgPa and P1 of the related Mycoplasma pneumoniae were found. Besides, MgPa positive sera were confirmed by immunoblotting using a cloned fragment of the C-terminal part of MgPa specific to M. genitalium. Chlamydia trachomatis is known to be able to cause infertility as a result of salpingitis. Therefore, the sera were tested against C. trachomatis using a commercial ELISA test. Seventy-five (56.8%) of the TFI patients were seropositive to C. trachomatis. Eight (27.6%) TFI patients seropositive to MgPa were negative to C. trachomatis.

CONCLUSIONS: This study indicates that M. genitalium may be an independent risk factor in the development of an inflammatory process leading to scarring of the uterine tubes in women and thereby causing infertility.

INFLAMMATORY BOWEL DISEASE

High prevalence of Mycoplasma pneumoniae in intestinal mucosal biopsies from patients with inflammatory bowel disease and controls.

Chen W, Li D, Paulus B, Wilson I, Chadwick VS.

Wakefield Gastroenterology Centre and Research Institute, Wakefield Hospital, Newtown, New Zealand.
Dig Dis Sci 2001 Nov;46(11):2529-35 Abstract quote
Intestinal microflora are believed to play an important role in the pathogenesis of inflammatory bowel disease (IBD). Mycoplasma have been suggested previously as organisms of ubiquitous distribution with the potential to cause inflammatory diseases, including IBD in susceptible individuals.

The aim of this study was to determine the frequency of the presence of M. pneumoniae DNA in intestinal biopsies from patients with IBD and non-IBD controls using a microplate polymerase chain reaction-hybridization assay (PCR-ELISA). A total of 260 endoscopic biopsies (49 from 19 patients with Crohn's disease, 76 from 27 patients with ulcerative colitis, and 135 from 43 non-IBD controls) were used in this study.

Overall, M. pneumoniae-specific DNA was detected in 100 endoscopic biopsy samples (38.5%). Among them, the detection rate of M. pneumoniae DNA was significantly higher in biopsies from patients with CD (59.2%) than in those from patients with UC (26.3%) or non-IBD controls (37.7%) (chi2 = 13.65, P < or = 0.001). The high prevalence of M. pneumoniae in both IBD patients and controls suggest this organism is ubiquitous and may persist in the intestinal mucosa.

Epidemiological studies in IBD suggest acquisition of some agents early in life probably during epidemics in temperate latitudes. M. pneumoniae could be one of the ubiquitous agents implicated in the pathogenesis of IBD.

PATHOGENESIS CHARACTERIZATION

ANIMAL MODEL

Animal model of Mycoplasma pneumoniae infection using germfree mice.

Hayakawa M, Taguchi H, Kamiya S, Fujioka Y, Watanabe H, Kawai S, Kobayashi H.

Department of First Internal Medicine, Kyorin University School of Medicine, Tokyo 181-8611, Japan.
Clin Diagn Lab Immunol 2002 May;9(3):669-76 Abstract quote
We have attempted to establish a gnotobiotic mouse model monoassociated with Mycoplasma pneumoniae following single or repeated infection to examine the mechanism of pathogenesis following M. pneumoniae infection. M. pneumoniae inoculated into germfree mice colonized equally well at 10(5) CFU/lung in both single infection and repeated infection.

In histopathological observation, repeatedly infected mice showed pneumonia with mild infiltration of mononuclear cells and macrophages. Antibody titers against M. pneumoniae rose in the repeatedly infected mice but not in the singly infected mice. The percentage of CD4-positive, CD8-positive, and CD25-positive lymphocytes infiltrated in the lung was increased in the repeatedly infected mice. In contrast, the lymphocyte subset in the spleen was not significantly different among mock-, singly, and repeatedly infected mice.

In the study of cytokine productivity of spleen cells, production of interleukin (IL)-4 and IL-10 was significantly increased and that of gamma interferon was remarkably increased in the mice following repeated infection. These results indicate that a gnotobiotic mouse model monoassociated with M. pneumoniae was established and that immune mechanisms might be involved in the pathogenesis in pneumonia following M. pneumoniae infection.

LABORATORY/RADIOLOGIC/
OTHER TESTS
CHARACTERIZATION

RADIOLOGIC

LABORATORY MARKERS

EIA

Development of enzyme immunoassays to detect salivary sIgA to Chlamydia pneumoniae and Mycoplasma pneumoniae.

Tuuminen T, Vainionpaa R.

Thermo Labsystems, Helsinki, Finland.
Scand J Clin Lab Invest 2001;61(5):357-62 Abstract quote
Enzyme immunoassays (EIAs) for the detection of secretory IgA antibody (sIgA) to Chlamydia pneumoniae and Mycoplasma pneumoniae from saliva are described.

The presence of salivary sIgA in healthy laboratory personnel (mean age 40, range 25-62 years) was detected using conjugates of antibodies directed against secretory and alpha-chain domains. The EIA results for the detection of C pneumoniae sIgA antibodies were confirmed by a sensitive microimmunofluorescence method used as a reference.

Circulating IgA antibody levels in sera were also determined using commercial EIAs. Secretory IgA antibodies to both C pneumoniae and M. pneumoniae were detectable only from persons with positive or borderline circulating IgA antibodies. Moreover, C. pneumoniae sIgA was found in the saliva of a clinically healthy person whose serum IgA antibody levels had been constantly elevated during the past 7 years. In conclusion, because of their specificity the described methods could be used in further delineation of the role of anti-C pneumoniae and M. pneumoniae sIgA antibodies.

However, owing to the unexpected high frequency of these antibodies in saliva of clinically healthy persons, it seems unlikely that a single sIgA measurement from saliva is diagnostically more powerful than a single IgA measurement from serum to study and interpret the involvement of these pathogens in chronic respiratory diseases.

PCR

Longitudinal quantitative detection by real-time PCR of Mycoplasma genitalium in first-pass urine of men with recurrent nongonococcal urethritis.

Deguchi T, Yoshida T, Yokoi S, Ito M, Tamaki M, Ishiko H, Maeda S.

Department of Urology, Gifu University School of Medicine, 40 Tsukasa-Machi, Gifu City, Gifu 500-8705, Japan.
J Clin Microbiol 2002 Oct;40(10):3854-6 Related Articles, Links

Longitudinal quantitative detection by real-time PCR of Mycoplasma genitalium in first-pass urine of men with recurrent nongonococcal urethritis.

Deguchi T, Yoshida T, Yokoi S, Ito M, Tamaki M, Ishiko H, Maeda S.

Department of Urology, Gifu University School of Medicine, 40 Tsukasa-Machi, Gifu City, Gifu 500-8705, Japan. deguchit@cc.gifu-u.ac.jp

By using a TaqMan assay we monitored longitudinal changes in Mycoplasma genitalium loads in five men with recurrent M. genitalium-positive nongonococcal urethritis. We observed regrowth of M. genitalium persisting in hosts after treatment and a possible association of the increase in the M. genitalium load with emergence of symptoms and signs of nongonococcal urethritis in four of these patients.

GROSS APPEARANCE/
CLINICAL VARIANTS CHARACTERIZATION

GENERAL

VARIANTS

NEUROLOGICAL

Neurologic manifestations of Mycoplasma pneumoniae infections: diverse spectrum of diseases. A report of six cases and review of the literature.

Smith R, Eviatar L.

Division of Pediatric Neurology, Schneider Children's Hospital, Long Island Jewish Medical Center, New Hyde Park, New York 11040, USA.

Clin Pediatr (Phila) 2000 Apr;39(4):195-201 Abstract quote
Mycoplasma pneumoniae is a common cause of upper and lower respiratory tract infections of varying severity. It is also responsible for producing a wide spectrum of nonpulmonary manifestations including neurologic, hepatic, cardiac, and hematologic diseases. The neurologic manifestations are reported to be the most common nonpulmonary manifestations.

We describe six patients demonstrating the protean neurologic manifestations of Mycoplasma pneumoniae infections. Four patients presented with the central nervous system manifestations of pyramidal and extrapyramidal tract dysfunction, seizures, cognitive abnormalities, and cerebellar dysfunction. Two patients presented with transverse myelitis.

The outcome of this condition ranges from normal to severe residual deficits. Increased awareness of this disease entity may facilitate early diagnosis and thereby expedite starting appropriate therapy that may modify the outcome.

PHARYNGITIS

Emerging role of Mycoplasma pneumoniae in children with acute pharyngitis.

Esposito S, Cavagna R, Bosis S, Droghetti R, Faelli N, Principi N.

Pediatric Department I, University of Milan, Via Commenda 9, 20122 Milan, Italy.
Eur J Clin Microbiol Infect Dis 2002 Aug;21(8):607-10 Abstract quote
In order to define the role, the risk factors, and the clinical and laboratory characteristics of Mycoplasma pneumoniae infection in children with pharyngitis, 184 patients with acute non-streptococcal pharyngitis (102 males; median age, 5.33 years) were studied. Acute Mycoplasma pneumoniae infection was demonstrated in 44 (23.9%) patients.

A history of recurrent episodes of pharyngitis (defined as at least 3 acute episodes of pharyngitis in the 6 months preceding enrollment) appeared to be the more useful parameter for differentiating Mycoplasma pneumoniae pharyngitis from non-streptococcal non- Mycoplasma pneumoniae pharyngitis ( P<0.05 in multivariate analysis).

These data, which highlight the emerging role of Mycoplasma pneumoniae in acute pharyngitis, must be taken into account in the diagnosis and treatment of this clinical manifestation in children.

PNEUMONIA

Mycoplasma pneumoniae infections.

Hammerschlag MR.

Department of Pediatrics, SUNY Downstate Medical Center, Brooklyn, New York 11203-2098, USA.
Curr Opin Infect Dis 2001 Apr;14(2):181-6 Abstract quote
Mycoplasma pneumoniae is a frequent cause of community-acquired respiratory infections in children and adults. Although the organism is felt to be the most frequent 'atypical' pathogen responsible for community-acquired pneumonia in adults, the prevalence of M. pneumoniae varies greatly from study to study, depending on the population and the diagnostic methods used.

Recent studies have found the prevalence of M. pneumoniae in adults with pneumonia to range from 1.9 to over 30%. M. pneumoniae is also a frequent cause of outbreaks of respiratory disease in institutional settings. However, the diagnosis of M. pneumoniae infection is hampered by the lack of standardized, rapid, specific methods. This problem was illustrated by the results of an investigation of an outbreak of M. pneumoniae infection in a federal training facility.

Accurate diagnosis required a combination of polymerase chain reaction and serology, as IgM antibodies were not present early in the course of the infection in many patients. Several papers evaluating various serological and polymerase chain reaction assays were published during the period of this review. An assessment of the actual performance of these tests was also hampered by the lack of standardized comparative methods. M. pneumoniae is susceptible in vitro to macrolides, tetracyclines and quinolone antibiotics; however, data are limited on the microbiological efficacy of these agents. Several pneumonia treatment studies were published during this period, practically all of them based the diagnosis of M. pneumoniae infection on serology; different methods and criteria were used in each study, and thus the microbiological efficacy could not be assessed.

The Infectious Disease Society of America recently stated in their revised Practice Guidelines for the Management of Community-Acquired Pneumonia in Adults that, as there were no diagnostic tests available that reliably and rapidly detect M. pneumoniae, therapy must usually be empirical.

HISTOLOGICAL TYPES CHARACTERIZATION

GENERAL

VARIANTS

LUNG

Severe bronchiolitis in acute Mycoplasma pneumoniae infection.

Ebnother M, Schoenenberger RA, Perruchoud AP, Soler M, Gudat F, Dalquen P.

Medizinische Klinik des Kantonsspitals, Universitat Basel, Switzerland.

Virchows Arch 2001 Dec;439(6):818-22 Abstract quote
We report on a 17-year-old patient with severe bronchiolitis due to Mycoplasma pneumoniae infection.

Despite an early 10-day course of clarithromycin, she developed progressive dyspnea, cough, fever, and severe obstructive ventilatory impairment. Sixteen days after onset of the disease a severe hemolytic anemia developed with only cold agglutinins positive at serologic screening.

Thoracoscopic lung biopsy revealed diffuse bronchiolitis with suppurative intrabronchiolar inflammation, lymphohistiocytic "cuffing" of the bronchioli, and foam cell aggregates within neighboring alveoli. The infiltrate consisted mainly of CD3+, CD8+ lymphocytes and CD68+ macrophages.

The diagnosis of Mycoplasma pneumoniae bronchiolitis was based on repeated complement fixation tests, which turned strongly positive only at day 74 after onset of the disease. Pulmonary function improved slowly under long-term prednisone treatment.

A study on intraalveolar exudates in acute mycoplasma pneumoniae infection.

Yoshinouchi T, Ohtsuki Y, Fujita J, Sugiura Y, Banno S, Sato S, Ueda R.

Department of Internal Medicine II, Nagoya City University, Medical School, Nagoya, Japan.

Acta Med Okayama 2002 Apr;56(2):111-6 Abstract quote
Pathologic features of Mycoplasma pneumoniae infection (M. pneumonia) are generally non-specific, and the literature regarding the pathologic features of M. pneumonia with intraalveolar exudates is limited. Clinical and histopathological studies were performed in 3 patients with M. pneumonia which did not respond to erythromycin and minocycline, but all rapidly recovered after corticosteroid therapy.

In pathologic findings, we observed intraalveolar exudates and focal organization in M. pneumonia, and its intraalveolar lesions were compared between M. pneumonia and bronchiolitis obliterans organizing pneumonia containing fibrin (BOOP). Immunohistochemical studies were performed using the streptavidin biotin peroxidase complex method with anti-alpha-smooth muscle actin antibody and anti-pancytokeratin AE1/AE3 antibody.

In pathologic findings, more fibrin deposits in intaalveolar lesions were observed in M. pneumonia than in BOOP. In intaalveolar lesions of M. pneumonia, a larger amount of nuclear debris, more neutrophils, and more erythrocytes were noted. Myofibroblasts were observed in the organization of BOOP, while in the intaalveolar lesions of M. pneumonia, myofibroblasts were not observed.

These results suggest that M. pneumonia with intraalveolar exudates responds well to corticosteroid and its intraalveolar lesions apparently differed from those in BOOP.

SPECIAL STAINS/IMMUNOPEROXIDASE/
OTHER CHARACTERIZATION

SPECIAL STAINS

IMMUNOPEROXIDASE

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES

PROGNOSIS AND TREATMENT CHARACTERIZATION

PROGNOSTIC FACTORS

TREATMENT

CLARITHROMYCIN

Mycoplasma pneumoniae and Chlamydia pneumoniae in asthma: effect of clarithromycin.

Kraft M, Cassell GH, Pak J, Martin RJ.

Department of Medicine, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver, CO 80206, USA.
Chest 2002 Jun;121(6):1782-8 Abstract quote
STUDY OBJECTIVES: To determine the effect of clarithromycin therapy in patients with asthma.

DESIGN: Randomized, double blind, placebo-controlled trial.

SETTING: A tertiary referral center.

PATIENTS OR PARTICIPANTS: Fifty-five subjects with chronic, stable asthma recruited from the general Denver, CO, community.

INTERVENTIONS: Patients underwent airway evaluation for Mycoplasma pneumoniae and Chlamydia pneumoniae by polymerase chain reaction (PCR) and culture, followed by treatment with clarithromycin, 500 bid, or placebo for 6 weeks.

MEASUREMENTS AND RESULTS: Outcome variables were lung function, sinusitis as measured by CT, and the inflammatory mediators tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-4, IL-5, and IL-12 messenger RNA (mRNA) measured via in situ hybridization, in airway biopsies, and BAL. Mycoplasma or chlamydia were detected by PCR in 31 of 55 asthmatics. Treatment resulted in a significant improvement in the FEV(1), but only in the PCR-positive subjects (2.50 +/- 0.16 to 2.69 +/- 0.19 L, mean +/- SEM; p = 0.05). This was not appreciated in the PCR-negative subjects (2.59 +/- 0.24 to 2.54 +/- 0.18 L, p = 0.85) or the PCR-positive or PCR-negative subjects who received placebo. Sinus CTs revealed no change in sinusitis with clarithromycin treatment. In situ hybridization revealed no significant difference in baseline airway tissue or BAL-mediator expression between the PCR-positive and PCR-negative subjects. However, the PCR-positive subjects who received clarithromycin demonstrated a reduction in TNF-alpha (p = 0.006), IL-5 (p = 0.007), and IL-12 (p = 0.004) mRNA in BAL and TNF-alpha mRNA in airway tissue (p = 0.0009). The PCR-negative subjects who received clarithromycin only demonstrated a reduction in TNF-alpha (p = 0.01) and IL-12 (p = 0.002) mRNA in BAL and TNF-alpha mRNA in airway tissue (p = 0.004). There were no significant differences in cytokine expression in those subjects who received placebo.

CONCLUSIONS: These observations support the hypothesis that clarithromycin therapy improves lung function, but only in those subjects with positive PCR findings for M pneumoniae or C pneumoniae.

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Eight Edition. Mosby 1996.
Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.
Weedon D. Weedon's Skin Pathology. Second Edition. Churchill Livingstone. 2002.
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Robbins Pathologic Basis of Disease. Sixth Edition. WB Saunders 1999.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.

Commonly Used Terms

Commonly Used Terms

Nongonococcal urethritis-Ureaplasma is the most common cause of this descriptive category. It is often overlooked in routine cultures.

Internet Links

Pathologists Who Make A Difference

Last Updated 11/28/2002

DISEASE ASSOCIATIONS	CHARACTERIZATION
ACUTE DISSEMINATED ENCEPHALOMYELITIS
Acute disseminated encephalomyelitis (ADEM) due to Mycoplasma pneumoniae infection in an adolescent. Riedel K, Kempf VA, Bechtold A, Klimmer M. Dept. of Medical Microbiology, Immunology and Hygiene, City Hospital Munich-Harlaching, Germany.	Infection 2001 Aug;29(4):240-2 Abstract quote A 17-year-old boy presented with a severe form of an acute disseminated encephalomyelitis (ADEM) with hemiparesis and coma after initial symptoms of a flu-like febrile infection 1 week previously. Titers against Mycoplasma pneumoniae were significantly increased in serum and cerebrospinal fluid (CSF). Detection of M. pneumoniae was achieved in the initial CSF sample using M. pneumoniae-specific PCR. The patient improved significantly on antimicrobial therapy with erythromycin and immunosupressive therapy with immunoglobulins and corticosteroids. This case report demonstrates a well-documented course of a central nervous system (CNS) infection resulting in the ADEM syndrome.
ENDOMETRITIS
Association between Mycoplasma genitalium and acute endometritis. Cohen CR, Manhart LE, Bukusi EA, Astete S, Brunham RC, Holmes KK, Sinei SK, Bwayo JJ, Totten PA.	Lancet 2002 Mar 2;359(9308):765-6 Abstract quote Up to 70% of cases of pelvic inflammatory disease do not have a known cause. We recruited 115 women who had presented to a clinic for sexually transmitted diseases in Nairobi, Kenya with pelvic pain that had persisted for 14 days or less, to look for an association between Mycoplasma genitalium and endometritis. With PCR, we detected M genitalium in the cervix, endometrium, or both in nine (16%) of 58 women with histologically confirmed endometritis and in one (2%) of 57 women without endometritis (p=0.02). Our results suggest that infection with M genitalium is strongly associated with acute endometritis in this population.
GUILLAIN-BARRE SYNDROME
Cross-reactive anti-galactocerebroside antibodies and Mycoplasma pneumoniae infections in Guillain-Barre syndrome. Ang CW, Tio-Gillen AP, Groen J, Herbrink P, Jacobs BC, Van Koningsveld R, Osterhaus AD, Van der Meche FG, van Doorn PA. Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Centre, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.	J Neuroimmunol 2002 Sep;130(1-2):179-83 Abstract quote Anti-galactocerebroside (GalC) antibodies are reported to be present in GBS patients with preceding Mycoplasma pneumoniae (MP) infection. We investigated the presence of anti-GalC reactivity in serum of a large group of GBS patients using ELISA and compared this with healthy controls and individuals with an uncomplicated MP infection. Anti-GalC antibody reactivity was present in 12% of the GBS patients. Furthermore, anti-GalC antibodies were associated with MP infections, a relatively mild form of the disease and demyelinating features. Anti-GalC antibodies cross-reacted with MP antigen. In conclusion, anti-GalC antibodies in GBS patients may be induced by molecular mimicry with MP.
INFERTILITY
Serological investigation of Mycoplasma genitalium in infertile women. Clausen HF, Fedder J, Drasbek M, Nielsen PK, Toft B, Ingerslev HJ, Birkelund S, Christiansen G. Department of Medical Microbiology and Immunology, The Bartholin Building, University of Aarhus, DK-8000 Aarhus C, Denmark.	Hum Reprod 2001 Sep;16(9):1866-74 Abstract quote BACKGROUND: The role of Mycoplasma genitalium in the pathogenesis of pelvic inflammatory disease has not been characterized. METHODS: Sera from 308 infertile women were investigated for antibodies to M. genitalium by immunoblotting. Women with tubal factor infertility (TFI) made up 132 of the patients, 67 of the women had an infertile male partner and 109 were infertile for unknown reasons. RESULTS: Of the TFI patients 29 (22.0%) were seropositive to the major adhesin, MgPa, of M. genitalium versus 11 (6.3%) in the group of women with normal tubes. No cross-reactions between MgPa and P1 of the related Mycoplasma pneumoniae were found. Besides, MgPa positive sera were confirmed by immunoblotting using a cloned fragment of the C-terminal part of MgPa specific to M. genitalium. Chlamydia trachomatis is known to be able to cause infertility as a result of salpingitis. Therefore, the sera were tested against C. trachomatis using a commercial ELISA test. Seventy-five (56.8%) of the TFI patients were seropositive to C. trachomatis. Eight (27.6%) TFI patients seropositive to MgPa were negative to C. trachomatis. CONCLUSIONS: This study indicates that M. genitalium may be an independent risk factor in the development of an inflammatory process leading to scarring of the uterine tubes in women and thereby causing infertility.
INFLAMMATORY BOWEL DISEASE
High prevalence of Mycoplasma pneumoniae in intestinal mucosal biopsies from patients with inflammatory bowel disease and controls. Chen W, Li D, Paulus B, Wilson I, Chadwick VS. Wakefield Gastroenterology Centre and Research Institute, Wakefield Hospital, Newtown, New Zealand.	Dig Dis Sci 2001 Nov;46(11):2529-35 Abstract quote Intestinal microflora are believed to play an important role in the pathogenesis of inflammatory bowel disease (IBD). Mycoplasma have been suggested previously as organisms of ubiquitous distribution with the potential to cause inflammatory diseases, including IBD in susceptible individuals. The aim of this study was to determine the frequency of the presence of M. pneumoniae DNA in intestinal biopsies from patients with IBD and non-IBD controls using a microplate polymerase chain reaction-hybridization assay (PCR-ELISA). A total of 260 endoscopic biopsies (49 from 19 patients with Crohn's disease, 76 from 27 patients with ulcerative colitis, and 135 from 43 non-IBD controls) were used in this study. Overall, M. pneumoniae-specific DNA was detected in 100 endoscopic biopsy samples (38.5%). Among them, the detection rate of M. pneumoniae DNA was significantly higher in biopsies from patients with CD (59.2%) than in those from patients with UC (26.3%) or non-IBD controls (37.7%) (chi2 = 13.65, P < or = 0.001). The high prevalence of M. pneumoniae in both IBD patients and controls suggest this organism is ubiquitous and may persist in the intestinal mucosa. Epidemiological studies in IBD suggest acquisition of some agents early in life probably during epidemics in temperate latitudes. M. pneumoniae could be one of the ubiquitous agents implicated in the pathogenesis of IBD.

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
VARIANTS
NEUROLOGICAL
Neurologic manifestations of Mycoplasma pneumoniae infections: diverse spectrum of diseases. A report of six cases and review of the literature. Smith R, Eviatar L. Division of Pediatric Neurology, Schneider Children's Hospital, Long Island Jewish Medical Center, New Hyde Park, New York 11040, USA.	Clin Pediatr (Phila) 2000 Apr;39(4):195-201 Abstract quote Mycoplasma pneumoniae is a common cause of upper and lower respiratory tract infections of varying severity. It is also responsible for producing a wide spectrum of nonpulmonary manifestations including neurologic, hepatic, cardiac, and hematologic diseases. The neurologic manifestations are reported to be the most common nonpulmonary manifestations. We describe six patients demonstrating the protean neurologic manifestations of Mycoplasma pneumoniae infections. Four patients presented with the central nervous system manifestations of pyramidal and extrapyramidal tract dysfunction, seizures, cognitive abnormalities, and cerebellar dysfunction. Two patients presented with transverse myelitis. The outcome of this condition ranges from normal to severe residual deficits. Increased awareness of this disease entity may facilitate early diagnosis and thereby expedite starting appropriate therapy that may modify the outcome.
PHARYNGITIS
Emerging role of Mycoplasma pneumoniae in children with acute pharyngitis. Esposito S, Cavagna R, Bosis S, Droghetti R, Faelli N, Principi N. Pediatric Department I, University of Milan, Via Commenda 9, 20122 Milan, Italy.	Eur J Clin Microbiol Infect Dis 2002 Aug;21(8):607-10 Abstract quote In order to define the role, the risk factors, and the clinical and laboratory characteristics of Mycoplasma pneumoniae infection in children with pharyngitis, 184 patients with acute non-streptococcal pharyngitis (102 males; median age, 5.33 years) were studied. Acute Mycoplasma pneumoniae infection was demonstrated in 44 (23.9%) patients. A history of recurrent episodes of pharyngitis (defined as at least 3 acute episodes of pharyngitis in the 6 months preceding enrollment) appeared to be the more useful parameter for differentiating Mycoplasma pneumoniae pharyngitis from non-streptococcal non- Mycoplasma pneumoniae pharyngitis ( P<0.05 in multivariate analysis). These data, which highlight the emerging role of Mycoplasma pneumoniae in acute pharyngitis, must be taken into account in the diagnosis and treatment of this clinical manifestation in children.
PNEUMONIA
Mycoplasma pneumoniae infections. Hammerschlag MR. Department of Pediatrics, SUNY Downstate Medical Center, Brooklyn, New York 11203-2098, USA.	Curr Opin Infect Dis 2001 Apr;14(2):181-6 Abstract quote Mycoplasma pneumoniae is a frequent cause of community-acquired respiratory infections in children and adults. Although the organism is felt to be the most frequent 'atypical' pathogen responsible for community-acquired pneumonia in adults, the prevalence of M. pneumoniae varies greatly from study to study, depending on the population and the diagnostic methods used. Recent studies have found the prevalence of M. pneumoniae in adults with pneumonia to range from 1.9 to over 30%. M. pneumoniae is also a frequent cause of outbreaks of respiratory disease in institutional settings. However, the diagnosis of M. pneumoniae infection is hampered by the lack of standardized, rapid, specific methods. This problem was illustrated by the results of an investigation of an outbreak of M. pneumoniae infection in a federal training facility. Accurate diagnosis required a combination of polymerase chain reaction and serology, as IgM antibodies were not present early in the course of the infection in many patients. Several papers evaluating various serological and polymerase chain reaction assays were published during the period of this review. An assessment of the actual performance of these tests was also hampered by the lack of standardized comparative methods. M. pneumoniae is susceptible in vitro to macrolides, tetracyclines and quinolone antibiotics; however, data are limited on the microbiological efficacy of these agents. Several pneumonia treatment studies were published during this period, practically all of them based the diagnosis of M. pneumoniae infection on serology; different methods and criteria were used in each study, and thus the microbiological efficacy could not be assessed. The Infectious Disease Society of America recently stated in their revised Practice Guidelines for the Management of Community-Acquired Pneumonia in Adults that, as there were no diagnostic tests available that reliably and rapidly detect M. pneumoniae, therapy must usually be empirical.

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/Immunohistochemistry/Electron Microscopy
Differential Diagnosis
Prognosis and Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY	CHARACTERIZATION
SYNONYMS
INCIDENCE
Mycoplasma genitalium infections in asymptomatic men and men with urethritis attending a sexually transmitted diseases clinic in New Orleans. Mena L, Wang X, Mroczkowski TF, Martin DH. Louisiana State University Health Sciences Center and the Delgado Clinic, New Orleans Health Department, New Orleans, Louisiana 70112, USA.	Clin Infect Dis 2002 Nov 15;35(10):1167-73 Abstract quote We report the results of a study of Mycoplasma genitalium (detected with a modified polymerase chain reaction [PCR] assay) in men with urethritis and in asymptomatic control subjects at a sexually transmitted diseases clinic in New Orleans. Data for 97 men with urethritis and 184 asymptomatic men were available for analysis. M. genitalium infection rates in symptomatic and asymptomatic men who were negative for Chlamydia trachomatis and Neisseria gonorrhoeae were 25% and 7%, respectively (P=.006). M. genitalium coinfection rates among men with chlamydial and gonococcal urethritis were 35% and 14%, respectively. Men with M. genitalium urethritis resembled those with C. trachomatis in that both groups were younger and more likely to experience milder urethral symptoms. Among men with urethritis, the sensitivities of PCR of urine and swab specimens for the detection of M. genitalium were 87% and 91%, respectively. M. genitalium is associated with nongonococcal urethritis in this population.
GEOGRAPHY
Prevalence of Mycoplasma pneumoniae in children in Diyarbakir, the south-east of Turkey. Bosnak M, Dikici B, Bosnak V, Dogru O, Ozkan I, Ceylan A, Haspolat K. Department of Pediatrics, Dicle University Medical School, Diyarbakir, Turkey.	Pediatr Int 2002 Oct;44(5):510-2 Abstract quote BACKGROUND: Mycoplasma pneumoniae is a well known causative agent of infection in childhood but clinical presentation may be variable. History and physical examination may not be so helpful for the diagnosis. It is difficult to culture this infectious agent, with the culture technique for the multiplication of the organism for routine investigation hard to obtain. The determination of exposure and prevalence of the disease of any region should be helpful for clinical diagnosis. In this study, we aimed to determine the seroprevalence of M. pneumoniae in children aged 0-14 years in Diyarbakir and establish the distribution of infection prevalence of various age groups of children. METHODS: Thirty streets were determined according to the cluster method for the 0-6 years age group. In this age group, a total of 180 blood samples were collected; so that there were 30 samples for each age. For children aged 7-14 years, elementary school children were selected. There were 70 elementary schools in the city and 14 schools were randomly selected according to the randomized numbers table with a 20% sample. Finally, 276 blood samples were collected. Mycoplasma pneumoniae was determined by using the enzyme immunoassay method. For this method MELOTEST Mycoplasma IgG reagent was used. RESULTS: The highest seropositivity rate was encountered at 10 years of age (65%) and lowest was at 2 years of age (0%). The overall M. pneumoniae seropositivity was 27% when all ages were considered together. The first 2 years of age excluded this rate and was 31.9%. A sudden increase of seropositivity was observed at 7 years of age. CONCLUSIONS: Increasing seroprevalence rates of M. pneumoniae after 2 years of age should alert clinicians to consider the organism in the differential diagnosis of infectious diseases in this age group. The low seroprevalence rates in the first 2 years of age was thought to be due to low risk of community-based spread of the organism in this age group. The most prominent increase in seroprevalence was at 10 years of age. This data indicated that M. pneumoniae should be kept in mind while making differential diagnosis of infections. The spreading of disease and community-based transmission is also important to consider. In our study, seroprevalence rates increased at 6 and 7 years of age, at the beginning of the school age as community-based transmission takes place most commonly in crowded circumstances. In conclusion, M. pneumoniae should be thought as an important infectious agent in childhood for all age groups.

LABORATORY/RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
RADIOLOGIC
LABORATORY MARKERS
EIA
Development of enzyme immunoassays to detect salivary sIgA to Chlamydia pneumoniae and Mycoplasma pneumoniae. Tuuminen T, Vainionpaa R. Thermo Labsystems, Helsinki, Finland.	Scand J Clin Lab Invest 2001;61(5):357-62 Abstract quote Enzyme immunoassays (EIAs) for the detection of secretory IgA antibody (sIgA) to Chlamydia pneumoniae and Mycoplasma pneumoniae from saliva are described. The presence of salivary sIgA in healthy laboratory personnel (mean age 40, range 25-62 years) was detected using conjugates of antibodies directed against secretory and alpha-chain domains. The EIA results for the detection of C pneumoniae sIgA antibodies were confirmed by a sensitive microimmunofluorescence method used as a reference. Circulating IgA antibody levels in sera were also determined using commercial EIAs. Secretory IgA antibodies to both C pneumoniae and M. pneumoniae were detectable only from persons with positive or borderline circulating IgA antibodies. Moreover, C. pneumoniae sIgA was found in the saliva of a clinically healthy person whose serum IgA antibody levels had been constantly elevated during the past 7 years. In conclusion, because of their specificity the described methods could be used in further delineation of the role of anti-C pneumoniae and M. pneumoniae sIgA antibodies. However, owing to the unexpected high frequency of these antibodies in saliva of clinically healthy persons, it seems unlikely that a single sIgA measurement from saliva is diagnostically more powerful than a single IgA measurement from serum to study and interpret the involvement of these pathogens in chronic respiratory diseases.
PCR
Longitudinal quantitative detection by real-time PCR of Mycoplasma genitalium in first-pass urine of men with recurrent nongonococcal urethritis. Deguchi T, Yoshida T, Yokoi S, Ito M, Tamaki M, Ishiko H, Maeda S. Department of Urology, Gifu University School of Medicine, 40 Tsukasa-Machi, Gifu City, Gifu 500-8705, Japan.	J Clin Microbiol 2002 Oct;40(10):3854-6 Related Articles, Links Longitudinal quantitative detection by real-time PCR of Mycoplasma genitalium in first-pass urine of men with recurrent nongonococcal urethritis. Deguchi T, Yoshida T, Yokoi S, Ito M, Tamaki M, Ishiko H, Maeda S. Department of Urology, Gifu University School of Medicine, 40 Tsukasa-Machi, Gifu City, Gifu 500-8705, Japan. deguchit@cc.gifu-u.ac.jp By using a TaqMan assay we monitored longitudinal changes in Mycoplasma genitalium loads in five men with recurrent M. genitalium-positive nongonococcal urethritis. We observed regrowth of M. genitalium persisting in hosts after treatment and a possible association of the increase in the M. genitalium load with emergence of symptoms and signs of nongonococcal urethritis in four of these patients.

HISTOLOGICAL TYPES	CHARACTERIZATION
GENERAL
VARIANTS
LUNG
Severe bronchiolitis in acute Mycoplasma pneumoniae infection. Ebnother M, Schoenenberger RA, Perruchoud AP, Soler M, Gudat F, Dalquen P. Medizinische Klinik des Kantonsspitals, Universitat Basel, Switzerland.	Virchows Arch 2001 Dec;439(6):818-22 Abstract quote We report on a 17-year-old patient with severe bronchiolitis due to Mycoplasma pneumoniae infection. Despite an early 10-day course of clarithromycin, she developed progressive dyspnea, cough, fever, and severe obstructive ventilatory impairment. Sixteen days after onset of the disease a severe hemolytic anemia developed with only cold agglutinins positive at serologic screening. Thoracoscopic lung biopsy revealed diffuse bronchiolitis with suppurative intrabronchiolar inflammation, lymphohistiocytic "cuffing" of the bronchioli, and foam cell aggregates within neighboring alveoli. The infiltrate consisted mainly of CD3+, CD8+ lymphocytes and CD68+ macrophages. The diagnosis of Mycoplasma pneumoniae bronchiolitis was based on repeated complement fixation tests, which turned strongly positive only at day 74 after onset of the disease. Pulmonary function improved slowly under long-term prednisone treatment.
A study on intraalveolar exudates in acute mycoplasma pneumoniae infection. Yoshinouchi T, Ohtsuki Y, Fujita J, Sugiura Y, Banno S, Sato S, Ueda R. Department of Internal Medicine II, Nagoya City University, Medical School, Nagoya, Japan.	Acta Med Okayama 2002 Apr;56(2):111-6 Abstract quote Pathologic features of Mycoplasma pneumoniae infection (M. pneumonia) are generally non-specific, and the literature regarding the pathologic features of M. pneumonia with intraalveolar exudates is limited. Clinical and histopathological studies were performed in 3 patients with M. pneumonia which did not respond to erythromycin and minocycline, but all rapidly recovered after corticosteroid therapy. In pathologic findings, we observed intraalveolar exudates and focal organization in M. pneumonia, and its intraalveolar lesions were compared between M. pneumonia and bronchiolitis obliterans organizing pneumonia containing fibrin (BOOP). Immunohistochemical studies were performed using the streptavidin biotin peroxidase complex method with anti-alpha-smooth muscle actin antibody and anti-pancytokeratin AE1/AE3 antibody. In pathologic findings, more fibrin deposits in intaalveolar lesions were observed in M. pneumonia than in BOOP. In intaalveolar lesions of M. pneumonia, a larger amount of nuclear debris, more neutrophils, and more erythrocytes were noted. Myofibroblasts were observed in the organization of BOOP, while in the intaalveolar lesions of M. pneumonia, myofibroblasts were not observed. These results suggest that M. pneumonia with intraalveolar exudates responds well to corticosteroid and its intraalveolar lesions apparently differed from those in BOOP.

SPECIAL STAINS/IMMUNOPEROXIDASE/ OTHER	CHARACTERIZATION
SPECIAL STAINS
IMMUNOPEROXIDASE

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSTIC FACTORS
TREATMENT
CLARITHROMYCIN
Mycoplasma pneumoniae and Chlamydia pneumoniae in asthma: effect of clarithromycin. Kraft M, Cassell GH, Pak J, Martin RJ. Department of Medicine, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver, CO 80206, USA.	Chest 2002 Jun;121(6):1782-8 Abstract quote STUDY OBJECTIVES: To determine the effect of clarithromycin therapy in patients with asthma. DESIGN: Randomized, double blind, placebo-controlled trial. SETTING: A tertiary referral center. PATIENTS OR PARTICIPANTS: Fifty-five subjects with chronic, stable asthma recruited from the general Denver, CO, community. INTERVENTIONS: Patients underwent airway evaluation for Mycoplasma pneumoniae and Chlamydia pneumoniae by polymerase chain reaction (PCR) and culture, followed by treatment with clarithromycin, 500 bid, or placebo for 6 weeks. MEASUREMENTS AND RESULTS: Outcome variables were lung function, sinusitis as measured by CT, and the inflammatory mediators tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-4, IL-5, and IL-12 messenger RNA (mRNA) measured via in situ hybridization, in airway biopsies, and BAL. Mycoplasma or chlamydia were detected by PCR in 31 of 55 asthmatics. Treatment resulted in a significant improvement in the FEV(1), but only in the PCR-positive subjects (2.50 +/- 0.16 to 2.69 +/- 0.19 L, mean +/- SEM; p = 0.05). This was not appreciated in the PCR-negative subjects (2.59 +/- 0.24 to 2.54 +/- 0.18 L, p = 0.85) or the PCR-positive or PCR-negative subjects who received placebo. Sinus CTs revealed no change in sinusitis with clarithromycin treatment. In situ hybridization revealed no significant difference in baseline airway tissue or BAL-mediator expression between the PCR-positive and PCR-negative subjects. However, the PCR-positive subjects who received clarithromycin demonstrated a reduction in TNF-alpha (p = 0.006), IL-5 (p = 0.007), and IL-12 (p = 0.004) mRNA in BAL and TNF-alpha mRNA in airway tissue (p = 0.0009). The PCR-negative subjects who received clarithromycin only demonstrated a reduction in TNF-alpha (p = 0.01) and IL-12 (p = 0.002) mRNA in BAL and TNF-alpha mRNA in airway tissue (p = 0.004). There were no significant differences in cytokine expression in those subjects who received placebo. CONCLUSIONS: These observations support the hypothesis that clarithromycin therapy improves lung function, but only in those subjects with positive PCR findings for M pneumoniae or C pneumoniae.