Mycoplasma Case File

Mycoplasma Case File

Eugene C.Toy, MD, Cynthia Debord, PHD, Audrey Wanger, PHD, Gilbert Castro, PHD, James D. Kettering, PHD, Donald Briscoe, MD

CASE 15

A 15-year-old teenager is brought to the office for evaluation of a cough and fever. His illness began several days ago with low-grade fever, headache, myalgias, and fatigue, and has slowly worsened. He now has a persistent cough. He has tried multiple over-the-counter cold and cough medications without relief. He has no significant medical or family history. No family members have been ill recently, but one of his good friends missed several days of school approximately 2 weeks ago with “walking pneumonia.” On examination he is coughing frequently but is not particularly ill-appearing. His temperature is 38.1°C (100.5°F), pulse is 90 beats per minute, and respiratory rate is 22 breaths per minute. His pharynx is injected (red and inflamed); otherwise, a head and neck exam is normal. His lung exam is notable only for some scattered rhonchi. The remainder of his examination is normal. A chest x-ray shows some patchy infiltration. A sputum Gram stain shows white blood cells but no organisms.

◆ What is the most likely etiology of this infection?

◆ What is the explanation for no organisms being seen on Gram stain?

◆ What rapid, although nonspecific, blood test can provide presumptive evidence of infection by this organism?

ANSWERS TO CASE 15: Mycoplasma

Summary: A 15-year-old adolescent presents with a persistent cough, patchy infiltrate on chest x-ray, and exposure to a friend with “walking pneumonia.”

◆ Most likely infectious agent: Mycoplasma pneumoniae

◆ Reasons no organisms are seen on Gram stain: Mycoplasma pneumoniae does not stain because it does not have a cell wall.

◆ Rapid blood test for presumptive evidence of M. pneumoniae: Cold agglutinins

CLINICAL CORRELATION

Mycoplasma pneumoniae is transmitted from person to person by aerosolized respiratory droplets and is most common in children and adolescents. Disease caused by M. pneumonia usually has an insidious onset and can progress to tracheobronchitis or pneumonia, which is often patchy or diffuse, as opposed to lobar. Because of the inability to diagnose this on microscopy, and the difficulty and length of time required for culture, serologic testing is often used to identify this organism.

APPROACH TO SUSPECTED Mycoplasma pneumoniae

PATIENT

Objectives

1. Know the structure and physiology of M. pneumoniae and other Mycoplasma organisms.
2. Know the clinical diseases associated with and tests for identification of M. pneumoniae.

Definitions

Tracheobronchitis: Inflammation of the trachea in addition to the bronchi; causing swelling & narrowing of the airways.

Rhonchi: A coarse rattling sound heard on auscultation of the lungs of a patient with partially obstructed airways.

Pruritus: Itching; can have many causes: food allergy, drug reation, kidney/ liver disease, aging or dry skin, cancers, infectious agents or other unknown causes.

DISCUSSION

Characteristics of Mycoplasma pneumoniae That Impact Transmission

Mycoplasma pneumoniae is a short, strictly aerobic rod. It has a trilamellar, sterol-containing cell membrane but no cell wall, therefore it is not identifiable with Gram or other stains. The lack of a cell wall also confers resistance against β-lactams and other antibiotics that act on the cell walls of bacteria. It is the smallest free-living bacterium, even during infection, it remains extracellular. It divides by binary fission and has a doubling time of approximately 6 hours, much slower than most bacteria. This contributes to the difficulty in isolating this organism by culture, as up to 6 weeks of incubation is required. Mycoplasma has the adherence protein Pl at one end, which is responsible for its attachment to a protein on target cells and may confer its preference for respiratory epithelium. When attached to ciliated respiratory epithelial cells, first the cilia and then the cell is destroyed. This interferes with normal mucociliary clearance and allows the lower airways to be irritated and contaminated with infectious agents.

Mycoplasma pneumoniae is transmitted from person to person by aerosolized respiratory droplets and secretions, and close association with an index case is usually required. No seasonal peak is observed. There is usually a 1–3 week incubation period before the onset of clinical disease. Although it can infect those of all ages, disease more commonly occurs in children and young adults. Mycoplasma pneumoniae is responsible for 15–20 percent of communityacquired pneumonias. Clinical presentation consists of a low-grade fever, headache, malaise, and later a nonproductive cough, with a slow resolution.

Diagnosis

Diagnosis is primarily made from clinical presentation. Because of the inability to diagnose the infection with microscopy and the difficulty and length of time required for culture, serologic testing is often used to confirm a clinical diagnosis. Antibody-directed enzyme immunoassays and immunofluorescence tests or complement fixation tests are used in diagnosis. Another useful test is to analyze the titer of cold agglutinins. Mycoplasma pneumoniae infection often results in the stimulation of an IgM antibody against the I-antigen on erythrocytes. This antigen-antibody complex binds at 4°C (39.2°F) causing the clumping of erythrocytes. Although this response can be triggered by other organisms, titers of these antibodies of 1:128 or greater, or a fourfold increase with the presence of an appropriated clinical presentation are considered presumptive evidence of M. pneumoniae disease.

Another Mycoplasma, M. hominis, causes pelvic inflammatory disease (PID), nongonococcal urethritis (NGU), pyelonephritis, and postpartum fever. Another cause of NGU and an organism that is detected with cold agglutinins is Ureaplasma urealyticum, a facultative anaerobic rod. Although this organism can also be a commensal, it can also lead to the sexually transmitted disease NGU and infertility. It is diagnosed via serology, by both cold agglutinins and specific serology with complement fixation and ELISA (enzymelinked immunosorbent assay) for IgM. Like Mycoplasma, culture is not reliable and takes many weeks. PCR probes are also used for diagnosis. The clinical picture of NGU consists of urethral discharge, pruritus, and dysuria. Typically, systemic symptoms are absent. The onset of symptoms in NGU can often be subacute. There are 3 million new cases of NGU (including M. hominis, U. urealyticum, Chlamydia trachomatis, and Trichomonas vaginalis) a year, and 10–40 percent of women suffer PID as a result, compared to only 1–2 percent of males, with morbidity from NGU because of stricture or stenosis. NGU occurs equally in men and women, though can be asymptomatic in 50 percent of women.

Treatment and Prevention

Mycoplasma pneumoniae-related pneumonia, as well as other Mycoplasma infections resulting in NGU, can be effectively treated with tetracycline and macrolides. Tetracyclines can be used to treat most mycoplasmas, as well as Chlamydia; whereas macrolides can be used to treat Ureaplasma infections, which are resistant to tetracycline. Mycoplasma pneumoniae infections are difficult to prevent because patients are infectious for extended periods of time, even during treatment. Several attempts have been made to produce inactivated and attenuated live vaccines without success.

COMPREHENSION QUESTIONS

[15.1] A 33-year-old woman is diagnosed with “walking pneumonia” caused by Mycoplasma. Which of the following best describes the characteristics of the etiologic organism?

A. Absence of a cell wall

B. Belonging to the class of Eukaryotes

C. Often evoke an IgM autoantibody response leading to human erythrocyte agglutination

D. Typically colonize the gastrointestinal tract

[15.2] Which of the following antibiotics is the best treatment for the above patient?

A. Ampicillin

B. Ceftriaxone

C. Erythromycin

D. Gentamicin

E. Vancomycin

[15.3] Mycoplasma organisms may also cause disease in nonpulmonary sites. Which of the following is the most commonly affected nonpulmonary site?

A. Meningitis

B. Prosthetic heart valve

C. Septic arthritis

D. Urethritis

[15.4] A 20-year-old man presents to the clinic with a history of fever and nonproductive cough. The patient’s chest x-ray shows consolidation of the right lower lobe. An infection with M. pneumoniae is considered as the cause of the patient’s pneumonia. Which of the following methods would confirm this diagnosis?

A. Culture of sputum specimen on solid medium

B. Detection of organism by microscopy

C. Complement fixation test of acute and convalescent sera

D. PCR amplification of patient’s sputum specimen

E. Enzyme immunoassay to detect cell wall antigens

Answers

[15.1] A. Mycoplasma are the smallest living organisms, and they do not have cell walls but rather have cell membranes. Thus, they are typically resistant to antibiotics that interfere with cell wall synthesis. Also, because of their absence of a cell wall, they are not usually detected on Gram stain. They have a propensity for attaching to respiratory, urethral, or genital tract epithelium.

[15.2] C. Erythromycin, clarithromycin, or azithromycin (macrolides) are effective against mycoplasma species.

[15.3] D. Mycoplasma and Ureaplasma species are commonly isolated from the lower genital tract. They are likely the most common cause of nonchlamydial nongonococcal urethritis.

[15.4] C. Diagnosis is primarily made from serologic testing (enzyme immunoassays, immunofluorescence, cold agglutinins) Answers A, B, D, and E are all incorrect: (A) culturing M. pneumoniae is difficult and slow and is not used for diagnosis; (B) Mycoplasmas lack a cell wall making microscopy inappropriate; (D) PCR amplification of a sputum specimen is not an appropriate method of diagnosis; (E) M. pneumoniae lacks a cell wall and thus, cell wall antigens.

MICROBIOLOGY PEARLS ❖ Mycoplasmas are small free-living microorganisms that lack a cell wall. ❖ Mycoplasma pneumoniae is a common cause of atypical pneumonia in children and adolescents. ❖ Symptoms include nonproductive cough, fever, headache, and “walking pneumonia.” ❖ Effective treatment is with erythromycin or tetracycline.

REFERENCES

Baseman JB, Tully JG. Mycoplasmas: sophisticated, reemerging, and burdened by their notoriety. Emerg Infect Dis 1997;3:21. www.cdc.gov/ncidod/EID/vol3no1/ baseman.htm. 

Murray PR, Rosenthal KS, Pfaller MA. Medical Microbiology, 5th ed. St. Louis, MO: Mosby, 2005:395–9. 

Loens K, Ursi D, Goossens H, et al. Molecular diagnosis of Mycoplasma pneumoniae respiratory tract infections. J Clin Microbiol 41:4915–23. 2003. 

Ryan JR, Ray CG. Sherris Medical Microbiology, 4th ed. New York: McGraw-Hill, 2004:409–11.

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