eMedicine Specialties > Infectious Diseases > Bacterial Infections

Mycoplasma Infections

Ken B Waites, MD, Director of Clinical Microbiology, Professor, Department of Pathology, Division of Laboratory Medicine, University of Alabama at Birmingham

Updated: Nov 17, 2009

Introduction

Background

Mycoplasma species are the smallest free-living organisms. These organisms are unique among prokaryotes in that they lack a cell wall, a feature largely responsible for their biologic properties such as their lack of a reaction to Gram stain and their lack of susceptibility to many commonly prescribed antimicrobial agents, including beta-lactams. Mycoplasmal organisms are usually associated with mucosal surfaces, residing extracellularly in the respiratory and urogenital tracts. They rarely penetrate the submucosa, except in the case of immunosuppression or instrumentation, when they may invade the bloodstream and disseminate to different organs and tissues throughout the body.

Although scientists have isolated at least 17 species of Mycoplasma from humans, 4 types of organisms are responsible for most clinically significant infections that may come to the attention of practicing physicians. These species are Mycoplasma pneumoniae, Mycoplasma hominis, Mycoplasma genitalium, and Ureaplasma species. The focus of this article is infections caused by M pneumoniae; articles on Ureaplasma infections (eg, Ureaplasma Infection) and genital mycoplasmal infections contain discussions of infections caused by other mycoplasmal species.

Pathophysiology

M pneumoniae is perhaps best known as the cause of walking or atypical pneumonia, but the most frequent clinical syndrome caused by this organism is actually tracheobronchitis or bronchiolitis, often accompanied by upper respiratory tract manifestations. Pneumonia develops in only 5%-10% of persons who are infected. Acute pharyngitis and myringitis are less common.

After inhalation of respiratory aerosols, the organism attaches to host cells in the respiratory tract. The P1 adhesin and other accessory proteins mediate attachment, followed by induction of ciliostasis, local inflammation that consists primarily of perivascular and peribronchial infiltration of mononuclear leukocytes, and tissue destruction that may be mediated by liberation of peroxides. Recently, M pneumoniae has been shown to produce an exotoxin that is believed to play a role in the damage to the respiratory epithelium that occurs during acute infection.¹ The organism also has the ability to exist intracellularly.² Additionally, acute mycoplasmal respiratory tract infection may be associated with exacerbations of chronic bronchitis and asthma.³ More extensive information on the pathogenesis of mycoplasmal respiratory infections is available in a recent review article.⁴

Spread of infection throughout households is common, although person-to-person transmission is slower than for many other common bacterial respiratory tract infections; close contact appears necessary. Generally, the incubation period is 2-3 weeks. The organism may persist in the respiratory tract for several months, and sometimes for years in patients who are immunosuppressed, after initial infection.⁵

Frequency

United States

Researchers estimate that more than 2 million cases of M pneumoniae infections occur annually. M pneumoniae causes approximately 20% of community-acquired pneumonias that require hospitalization and probably an even greater proportion of those that do not require hospitalization. M pneumoniae may exist endemically in large urban areas. Epidemics occur every 3-7 years, with the incidence varying considerably from year to year. Disease tends to not be seasonal, except for a slight increase in late summer and early fall.²

International

M pneumoniae infections occur both endemically and in cyclic epidemics in Japan and several European countries, similar to what occurs in the United States. Less information is available for tropical or polar countries; however, based on seroprevalence studies, the disease also occurs in these regions, suggesting that climate and geography are not important determinants in the epidemiology of M pneumoniae infections.²

Mortality/Morbidity

• As the term walking pneumonia implies, the great majority of M pneumoniae respiratory tract infections are mild and self-limited, although administration of antimicrobials hastens clinical resolution. Hospitalization is sometimes necessary, but recovery is almost always complete and without sequelae. Studies have indicated that M pneumoniae is second only to Streptococcus pneumoniae as a cause of bacterial pneumonia that requires hospitalization in elderly adults.⁶ Subclinical infections may occur in 20% of adults infected with M pneumoniae, suggesting that some degree of immunity may contribute to the failure of clinical symptoms in some instances.
• Recent evidence suggests that M pneumoniae disease is sometimes much more severe than appreciated, even in otherwise healthy children and adults.³ Severe disease is more common in persons with underlying disease or immunosuppression. Children with sickle cell disease and functional asplenia may be at greater risk for severe respiratory tract disease due to M pneumoniae. While reports describe fatal cases of mycoplasmal pneumonia, the overall mortality rate is extremely low, probably less than 0.1%.

Race

• No racial predilection is apparent.

Sex

• Available studies indicate no sexual predilection for M pneumoniae disease.

Age

• M pneumoniae has long been associated with pneumonias in children aged 5-9 years, adolescents, and young adults. Infection is particularly common among college students and military recruits who are likely to live together in close proximity. M pneumoniae may be the most common agent causing bacterial pneumonia in such populations.
• In recent years, M pneumoniae infection has been common in persons older than 65 years, accounting for as much as 15% of community-acquired pneumonia cases in persons in this age group.
• The common misconception that M pneumoniae disease is rare among very young populations and among older adults has led to physician failure to consider the organism in the differential diagnoses of respiratory tract infections in persons in these age groups. Physicians should always consider M pneumoniae as a cause of pneumonia in persons of all ages, including children younger than 5 years. Although M pneumoniae disease in infants is somewhat uncommon, when it is present, it can be severe.⁷

Clinical

History

Typical symptoms can develop and persist over weeks to months and include flulike manifestations.

• Symptoms
  • Generalized aches and pains
  • Fever (usually £ 102°F)
  • Cough - Usually nonproductive
  • Sore throat (nonexudative pharyngitis)
  • Headache/myalgias
  • Chills but not rigors
  • Nasal congestion with coryza
  • Earache
  • General malaise
• In very young children, upper respiratory tract manifestations may predominate, whereas in older children and adults, lower respiratory tract symptoms are more likely.

Physical

Physical findings can be quite variable. Patients typically do not appear toxic or severely ill, but some abnormalities may be apparent in a significant proportion of cases.

• Physical findings include the following:
  • Oropharyngeal inflammation
  • Cervical adenopathy - Usually absent
  • Erythematous tympanic membranes
  • Conjunctivitis
  • Maculopapular or urticarial rash
• Chest auscultation in patients with pneumonia may demonstrate localized rhonchi and scattered moist rales, generally involving multiple lobes of the lung and sometimes accompanied by wheezes, with no signs of consolidation, egophony, or bronchial breathing.
• In many persons, chest auscultative and percussive abnormalities are minimal to absent.
• Extrapulmonary manifestations may occur in a minority of persons (see Complications).³

Causes

This is a bacterial infection caused by M pneumoniae.

Differential Diagnoses

Other Problems to Be Considered

Respiratory syncytial virus
Coxiella burnetii
Chlamydia pneumoniae
S pneumoniae
Legionella species
Mycobacterium species
Other miscellaneous bacterial species
Histoplasma capsulatum

Workup

Laboratory Studies

Consider the possibility of infection with M pneumoniae in patients of any age who present with respiratory tract infections. Laboratory investigation should focus on both the clinical illness (eg, tracheobronchitis vs pneumonia) and the many possible infectious etiologies that can cause clinically similar manifestations. The extent of laboratory investigation also should reflect the severity of the illness and whether the illness warrants hospitalization.

In as many as half of all cases of community-acquired pneumonias, the microbiological etiology is never determined, despite appropriate laboratory testing. The typical mild illness caused by M pneumoniae in otherwise healthy persons may not warrant a comprehensive microbiological investigation because empiric treatment with oral antimicrobials can cover M pneumoniae and most other bacterial agents that produce similar illnesses.

• Laboratory analysis
  • Twenty-five percent of patients develop leukocytosis; the rest have leukocyte counts within the reference range.
  • Thirty percent of patients have an elevated erythrocyte sedimentation rate.
  • Cellular response of sputum is mononuclear, with no bacteria visible with Gram staining.
  • About 75% of patients have a cold agglutinin titer of at least 1:32 by the second week of illness, disappearing by 6-8 weeks. This is not a specific test for M pneumoniae infection but the greater the cold agglutinin titer is (>1:64) in a patient with CAP, the more likely the cold agglutinins are due to M pneumoniae. No specific abnormalities of hepatic or renal function are likely to occur.
  • To confirm mycoplasmal respiratory tract infection, culture, molecular-based tests, and serological tests are necessary.
• Culture
  • Respiratory tract specimens suitable for culture include throat swabs, sputum, tracheal aspirates, bronchial lavage fluid, pleural fluid, or lung biopsy tissue, depending on the patient's clinical condition.
  • Mycoplasmal organisms have fastidious growth requirements and are often difficult to grow in a cell-free medium. Take care during specimen collection to inoculate into a suitable transport medium (eg, SP4 broth), at the bedside whenever possible, and to not allow desiccation. Clinicians advise freezing at -70°C if specimens cannot be transported to the diagnostic laboratory immediately after collection.
  • Growth in culture is slow, requiring 3 weeks in some cases, and the culture is not extremely sensitive for detecting M pneumoniae infection. The culture medium is often unavailable except from specialized reference laboratories. If culture is attempted, alternative procedures including serology and molecular-based nucleic acid amplification tests should also be performed.⁷
• Serological testing
  • Physicians use serology most frequently to confirm M pneumoniae infection.
  • Many clinicians prefer enzyme-linked immunosorbent assays to the older, less sensitive complement fixation assays and nonspecific cold agglutinin titers. These types of tests are widely available through commercial reference laboratories.
  • Because primary infection does not guarantee protective immunity against future infections and residual immunoglobulin G (IgG) may remain from earlier encounters with the organism, experts have launched a great impetus to develop sensitive and specific tests that can differentiate between acute and remote infection.
  • Definitive diagnosis requires seroconversion documented by paired specimens obtained 2-4 weeks apart. Although researchers purport that single-titer immunoglobulin M (IgM) or immunoglobulin A (IgA) assays reveal current infection, data regarding how long IgM persists after acute infection are not clear, and as many as 50% of adults may not mount a detectable IgM response. Conversely, some children may not mount a measurable IgG response, and the IgG response in adults may be delayed for several days. Therefore, relying on a single serological test can be clinically misleading, and experts recommend basing diagnosis of acute infection on seroconversion measured simultaneously in assays for both IgM and IgG. Use of serology for diagnosis of mycoplasmal infection is valid only if the patient has a satisfactory capacity of the humoral immune system to mount an antibody response.
• Rapid diagnostic enzyme-linked immunosorbent assays
  • One of the most significant advances in recent years for the diagnosis of M pneumoniae respiratory tract infections is the development of qualitative, rapid, single-specimen, membrane-based enzyme-linked immunosorbent assays that are readily adaptable to the primary care physician's office laboratory.⁸
  • The Remel IgG/IgM Antibody Test System (Remel Laboratories; Lenexa, Kan) measures both IgG and IgM simultaneously.
  • The Meridian ImmunoCard (Meridian Laboratories; Cincinnati, Ohio) measures only IgM.
  • Physicians can perform both tests without special expertise or equipment, and they can interpret the results in approximately 10 minutes, eliminating the need for collection of paired sera for later antibody measurement.
  • Both tests have a moderate complexity classification under the Clinical Laboratory Improvement Act (CLIA), allowing many physicians to offer serologic assays for M pneumoniae antibodies as a point-of-care test so that it can be used to direct patient management.
  • Such single-specimen assays have limitations as described above; perhaps the most practical use for the IgM ImmunoCard is when an acute infection with M pneumoniae is suspected in children and young adults.
• Molecular analysis
  • Researchers have developed molecular-based systems for detection of M pneumoniae using polymerase chain reaction (PCR); however, only limited information describing the application of this methodology in a clinical setting is available. Some reference laboratories offer PCR assays for detection of current mycoplasmal infection.
  • Carriage of mycoplasmas in the upper respiratory tract for variable periods following prior infection may confound the interpretation of a single positive polymerase chain reaction assay result. Furthermore, a PCR assay may reveal very small numbers of organisms that may not be of etiologic significance.
  • A specific threshold of quantity of mycoplasmas in the respiratory tract that can differentiate colonization from infection has not been established, so a highly sensitive detection method such as PCR performed in a nonquantitative manner may overestimate the clinical importance of M pneumoniae as a pathogen since it often cocirculates with other bacterial and viral respiratory pathogens. For these reasons, molecular-based assays should be accompanied by serological assays for maximum diagnostic accuracy unless testing a normally sterile body fluid in which the presence of any number of mycoplasmas would be considered evidence of disease.²

Imaging Studies

• Abnormalities on chest radiographs often appear more severe than predicted based on the clinical condition of the patient.
• Lobar consolidation is unusual.
• Diffuse or interstitial infiltrates that involve the lower lobes are the most common radiographic abnormalities.
• Small pleural effusions may develop in approximately 20% of cases.
• Lung involvement tends to be unilateral but can be bilateral.

Treatment

Medical Care

• Ambulatory care versus hospitalization
  • The choice of outpatient management versus hospitalization for persons with community-acquired pneumonia depends on the clinical syndrome and not the organism, largely because the microbiologic diagnosis is often unavailable when the physician must make these decisions.
  • Professional organizations of physicians and managed care organizations have developed management algorithms that include decision trees for diagnostic studies and management, including specifications of antimicrobial agents to be used. These guidelines vary somewhat, but, in general, the decision to hospitalize a patient depends on an assessment of the following:
    • The person's ability to tolerate and comply with oral medication
    • Whether the patient appears hypoxic or toxic to the extent that the physician suspects a bacteremic pneumonia
    • Whether the person is immunosuppressed
  • Relatively few patients with M pneumoniae pneumonia require hospitalization based on these criteria.
• Antimicrobials
  • Experts formerly believed that mycoplasmal respiratory tract infections were entirely self-limited and that antimicrobial treatment was not indicated.
  • Appropriate antimicrobial therapy shortens the symptomatic period and hastens radiological resolution of pneumonia and recovery, even though patients may shed organisms for several weeks.
  • When treating community-acquired pneumonia, physicians usually must provide empiric coverage for several different bacterial agents that may be responsible because the microbiologic diagnosis is seldom available at the initiation of treatment. Fortunately, many of the drugs of choice for treating M pneumoniae provide broad-spectrum coverage for other organisms.

Medication

M pneumoniae remains predictably susceptible to macrolides and tetracyclines; therefore, in vitro susceptibility testing to guide therapy is not indicated.

Oral erythromycin or one of the newer macrolides such as azithromycin or clarithromycin has long been the DOC for mycoplasmal respiratory tract infections. Tetracycline and its analogues are also active. Clindamycin is effective in vitro, but limited reports suggest it may not be active in vivo and thus is not considered a first-line treatment. Several of the newer fluoroquinolones exhibit bactericidal antimycoplasmal activity but are generally less potent in vitro than macrolides against M pneumoniae. Their advantage lies in the fact that they are active against all classes of bacteria that produce clinically similar respiratory tract infections, including macrolide-resistant S pneumoniae. As would be predicted by the lack of a cell wall, none of the beta-lactams is effective in vitro or in vivo against M pneumoniae, and neither are the sulfonamides or trimethoprim.²

Mycoplasma species are slow-growing organisms that have the capacity to reside intracellularly; thus, respiratory tract infections are expected to respond better to longer treatment courses than might be offered for other types of infections. Although physicians typically prescribe most treatment regimens (ie, both oral and parenteral) for 7-10 days, a 14- to 21-day course of oral therapy with most agents is also appropriate. A 5-day course of oral azithromycin is approved for the treatment of community-acquired M pneumoniae pneumonia. Clinical data indicate that this duration of treatment is of comparable efficacy to a 10-day course of erythromycin. Other drugs, including fluoroquinolones, have been approved for the treatment of mycoplasmal respiratory infections with shorter courses because of their favorable pharmacokinetics and tolerability.

In addition to the administration of antimicrobials for the management of M pneumoniae infections, other measures (eg, cough suppressants, antipyretics, analgesics) should be administered as needed to relieve headaches and other systemic symptoms. Because extrapulmonary manifestations are often diagnosed late in the course of disease, the benefit of early treatment is unknown.

In Japan over the past decade, there has been a worrisome emergence of macrolide resistance associated with a greater morbidity in persons with mycoplasmal pneumonias. Recent surveillance in China has shown that more than 80% of M pneumoniae isolates are highly resistant to macrolides.⁹ Reports from Europe and the United States have also documented resistance to macrolides and that it can have clinical implications.^10,11,12 This has led to development of real-time PCR-based assays to detect resistance genes directly in clinical specimens since cultures and conventional susceptibility tests require many more days.^12,10,11 In view of the increasing spread of macrolide resistance, clinicians are advised to monitor patient outcomes and to consider using alternative antimicrobial agents if an initial treatment with a macrolide is unsuccessful.¹³

Antibiotics

Therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting.

Erythromycin (E-Mycin, Ery-Tab, E.E.S.)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. For treatment of staphylococcal and streptococcal infections.
In children, age, weight, and severity of infection determine proper dosage. When bid dosing desired, half-total daily dose may be taken q12h. For more severe infections, double the dose.

Dosing

Adult

250-500 mg erythromycin stearate/base (or 400-800 mg ethylsuccinate) PO/IV q6h
Alternatively, 333 mg PO q8h; increase to 4 g/d depending on severity of infection

Pediatric

20-50 mg/kg/d PO divided in 3-4 doses; alternatively, 25-40 mg/kg/d IV divided qid

Interactions

Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis

Contraindications

Documented hypersensitivity; hepatic impairment

Precautions

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Caution in liver disease; estolate formulation may cause cholestatic jaundice; adverse GI effects are common (administer doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occurs

Clarithromycin (Biaxin, Biaxin XL)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Dosing

Adult

Immediate release: 250-500 mg PO q12h for 7-14 d
Extended release: 1 g PO q24h for 7 d

Pediatric

15 mg/kg PO divided bid

Interactions

Toxicity increases with coadministration of fluconazole, astemizole, and pimozide; effects decrease and adverse GI effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants, cyclosporine, tacrolimus, digoxin, omeprazole, carbamazepine, ergot alkaloids, triazolam, and HMG CoA-reductase inhibitors; serious cardiac arrhythmia may occur with coadministration of cisapride; plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmia and increase in QTc intervals occur with disopyramide; coadministration with omeprazole may increase plasma levels of both agents

Contraindications

Documented hypersensitivity; coadministration of pimozide, astemizole (recalled from US market), cisapride, or terfenadine (recalled from US market)

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Coadministration with ranitidine or bismuth citrate is not recommended with CrCl <25 mL/min; administer half dose or increase dosing interval if CrCl <30 mL/min; diarrhea may be sign of pseudomembranous colitis; superinfections may occur with prolonged or repeated antibiotic therapies

Azithromycin (Zithromax)

Semisynthetic antibiotic belonging to the macrolide subgroup of azalides and is similar in structure to erythromycin. Inhibits protein synthesis in bacterial cells by binding to the 50S subunit of bacterial ribosomes. Action generally is bacteriostatic but can be bactericidal in high concentrations or against susceptible organisms.

Dosing

Adult

500 mg PO qd for 1 d, then 250 mg PO qd for days 2-5 or 2 go PO given as a single dose
500 mg/d IV for 2 d, then 500 mg PO qd to complete a 7- to 10-d course

For prophylaxis, 500 mg PO loading dose, then 250 mg qd on days 2-5

Pediatric

IV formulation is not recommended for use in children
<6 months: Not established
>6 months: 10 mg/kg PO once on day 1; not to exceed 500 mg/d; 5 mg/kg PO qd on days 2-5; not to exceed 250 mg/d

Interactions

May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine

Contraindications

Documented hypersensitivity; hepatic impairment; do not administer with pimozide

Precautions

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Site reactions can occur with IV route; bacterial or fungal overgrowth may result with prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function, prolonged QT intervals, or pneumonia; caution in hospitalized, geriatric, or debilitated patients

Doxycycline (Vibramycin)

Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.

Dosing

Adult

200 mg PO/IV single loading dose, then 100 mg PO/IV q12h for 7-10 d

Pediatric

<8 years: Not recommended
>8 years: 4 mg/kg PO initially, then 2 mg/kg q12h for 7-10 d

Interactions

Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy; can increase hypoprothrombinemic effects of anticoagulants

Contraindications

Documented hypersensitivity; severe hepatic dysfunction

Precautions

Pregnancy

D - Unsafe in pregnancy

Precautions

Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last half of pregnancy through 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

Minocycline (Minocin)

Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.

Dosing

Adult

200 mg PO/IV single loading dose, then 100 mg PO/IV q12h for 7-10 d

Pediatric

<8 years: Not recommended
>8 years: 4 mg/kg PO initially, then 2 mg/kg q12h for 7-10 d

Interactions

Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy; can increase hypoprothrombinemic effects of anticoagulants

Contraindications

Documented hypersensitivity; severe hepatic dysfunction

Precautions

Pregnancy

D - Unsafe in pregnancy

Precautions

Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last half of pregnancy through 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

Levofloxacin (Levaquin)

Inhibits A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription.

Dosing

Adult

500 mg PO/IV qd for 7-14 d; alternatively, 750 mg PO/IV qd for 5 d

Pediatric

<18 years: Not recommended
>18 years: Administer as in adults

Interactions

Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; reduces therapeutic effects of phenytoin; probenecid may increase serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy

Moxifloxacin (Avelox)

Inhibits A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription.

Dosing

Adult

400 mg PO/IV qd for 7-14 d

Pediatric

<18 years: Not recommended
>18 years: Administer as in adults

Interactions

Antacids and electrolyte supplements reduce absorption; loop diuretics, probenecid, and cimetidine increase serum levels; NSAIDs enhance CNS stimulating effect; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)

Contraindications

Documented hypersensitivity; known QT prolongation; concurrent administration of drugs that cause QT prolongation

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy; induces seizures in CNS disorder

Gemifloxacin (Factive)

Inhibits DNA gyrase and topoisomerase IV, resulting in inhibition of bacterial DNA replication and transcription.

Dosing

Adult

CAP due to known or suspected S pneumoniae, H influenzae, M pneumoniae, or C pneumoniae: 320 mg PO qd for 5 d
CAP due to known or suspected Klebsiella pneumoniae, M catarrhalis, or multidrug-resistant S pneumoniae: 320 mg PO qd for 7 d

Pediatric

<18 years: Not recommended
>18 years: Administer as in adults

Interactions

Systemic availability reduced when aluminum- and magnesium-containing antacids, ferrous sulfate, vitamins containing zinc, and sucralfate are concomitantly administered; cimetidine and omeprazole may cause slight (clinically insignificant) increases in serum concentration; probenecid causes reduced clearance

Contraindications

Documented hypersensitivity; history of QT prolongation, patients with uncorrected electrolyte disorders, and patients receiving class IA or class III antiarrhythmic agents

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Self-limited maculopapular rash occurred in 2.8% of treated patients, usually after administration for 8-10 d; women <40 y and especially postmenopausal women taking hormone replacement therapy were most likely to develop rash; reduce dose in patients with CrCl <40 mg/d

Telithromycin (Ketek)

Blocks bacterial protein synthesis by binding to domains II and V of 23s rRNA of the 50S ribosomal subunit.

Dosing

Adult

800 mg PO qd for 7-10 d

Pediatric

Not established

Interactions

CYP 3A4 inhibitor and substrate; coadministration with other CYP 3A4 inhibitors (eg, itraconazole, ketoconazole) decreases elimination and increases Cmax and AUC; CYP 3A4 inducers (eg, rifampin) decrease telithromycin Cmax and AUC by 79% and 86%, respectively; increases Cmax and AUC of other CYP 3A4 substrates (eg, cisapride, pimozide, simvastatin, lovastatin, atorvastatin, midazolam, triazolam); HMG-CoA reductase inhibitors (eg, simvastatin, atorvastatin, lovastatin) should be temporarily discontinued because of increased myopathy risk when coadministered; increases digoxin and theophylline serum levels; decreases sotalol Cmax and AUC secondary to decreased absorption; caution with other drugs that increase QTc interval (eg, quinidine, procainamide, dofetilide)

Contraindications

Documented hypersensitivity; concomitant administration with cisapride or pimozide; myasthenia gravis; prolonged QT interval; uncorrected electrolyte abnormalities; clinically significant bradycardia; concomitant administration with class IA or class III antiarrhythmic agents; history of hepatitis and/or jaundice with use of macrolides

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Caution in severe renal impairment (limited data exist); consider the diagnosis of pseudomembranous colitis if diarrhea occurs following antibiotic treatment; may prolong QTc interval (caution with heart conduction abnormalities); common adverse effects include diarrhea and nausea; visual disturbances related to slowing ability of accommodation and release of accommodation, resulting in blurred vision, difficulty focusing, and diplopia, sometimes occur; acute hepatic failure and severe liver injury (fatal in some cases) have been reported (if clinical hepatitis or liver enzyme elevations combined with other systemic symptoms occur, permanently discontinue)

Follow-up

Further Outpatient Care

• With appropriate treatment, uncomplicated episodes of M pneumoniae infection can be expected to resolve clinically within 7-10 days after onset.
• Additional laboratory tests or radiographs are not usually necessary unless the illness does not respond to therapy, which would raise questions about the accuracy of the microbiological diagnosis.
• The presence of extrapulmonary manifestations may warrant further workup and follow-up, depending on their nature and severity.
• Improvement of pneumonia on chest radiographs may lag behind clinical improvement.

Deterrence/Prevention

• Antimicrobial prophylaxis
  • As with other bacterial infections, researchers have studied the value of antimicrobial prophylaxis for those in contact with persons with M pneumoniae infection.
  • Klausner et al (1998) reported that the administration of oral azithromycin plus standard epidemic control measures significantly reduced secondary attack rates following an outbreak of M pneumoniae pneumonia in a long-term care facility for mentally and developmentally disabled persons.¹⁴
  • Previous studies using tetracyclines also demonstrated the efficacy of chemoprophylaxis in reducing transmission of M pneumoniae pneumonia.
• Vaccines
  • Researchers have studied vaccines for many years, but they have not produced a vaccine for general use.
  • The fact that natural infection does not confer complete protective immunity against future infections makes this approach less promising.
• Because of the endemicity of infection with M pneumoniae in susceptible populations, isolating patients is seldom practical and generally is not recommended.

Complications

• Extrapulmonary complications
  • Extrapulmonary complications may occur simultaneously with the onset of respiratory manifestations or as long as several days later. These complications may predominate to the extent that physicians may overlook a primary respiratory tract infection. Less than 10% of cases of M pneumoniae infections are associated with nonrespiratory illnesses, with the exception of various skin rashes, nausea, vomiting, and diarrhea, which may occur more often.⁸
  • When extrapulmonary manifestations occur, however, they clearly can complicate the diagnosis and the recovery; they also make hospitalization more likely. Thus, a careful history and physical examination are essential, and follow-up is indicated.
  • Researchers believe that an autoimmune response plays a role in some extrapulmonary complications, but, because M pneumoniae has been isolated directly from cerebrospinal, pericardial, and synovial fluids and from other extrapulmonary sites, always consider direct invasion by this organism.
  • Extrapulmonary manifestations may include the following:
    • Meningoencephalitis
    • Ascending (ie, Guillain-Barré) paralysis
    • Transverse myelitis
    • Myopericarditis
    • Cardiac arrhythmia
    • Raynaud phenomenon
    • Hemolytic anemia
    • Disseminated intravascular coagulation
    • Renal failure
    • Arthritis
    • Erythema multiforme (ie, Stevens-Johnson syndrome)
    • Erythema nodosum
    • Urticaria
    • Ulcerative stomatitis
    • Nausea
    • Vomiting
    • Diarrhea

Prognosis

• Most persons who are free of underlying conditions that may adversely affect the outcome of a respiratory tract infection can expect an excellent prognosis and a full return of pulmonary function.
• For the minority of patients who have severe disease, diminished lung function may persist for weeks to months.
• For the few persons who experience disseminated extrapulmonary symptoms, particularly neurologic manifestations, recovery can require weeks to months. While most recover fully and uneventfully, some persons with neurologic manifestations may experience long-term paralysis and reports describe cases of permanent neurologic deficits.

Miscellaneous

Medicolegal Pitfalls

• No medicolegal pitfalls are described.

References

1. Kannan TR, Provenzano D, Wright JR, Baseman JB. Identification and characterization of human surfactant protein A binding protein of Mycoplasma pneumoniae. Infect Immun. May 2005;73(5):2828-34. [Medline].

2. Waites KB, Talkington DF. Mycoplasma pneumoniae and its role as a human pathogen. Clin Microbiol Rev. Oct 2004;17(4):697-728, table of contents. [Medline].

3. Talkington DF, Waites KB, Schwartz S, Besser RE. Emerging from obscurity: Understanding pulmonary and extrapulmonary syndromes, pathogenesis, and epidemiology of human Mycoplasma pneumoniae infections. In: Scheld WM, Craig WA, Hughes JM, eds. Emerging Infections. Vol 5. Washington, DC: ASM Press; 2001:57-84.

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Keywords

mycoplasmata, mycoplasmal infection, walking pneumonia, atypical pneumonia, tracheobronchitis, bronchiolitis, upper respiratory tract infection, community-acquired pneumonia, CAP, bacterial pneumonia

Contributor Information and Disclosures

Author

Ken B Waites, MD, Director of Clinical Microbiology, Professor, Department of Pathology, Division of Laboratory Medicine, University of Alabama at Birmingham
Ken B Waites, MD is a member of the following medical societies: American Society for Microbiology and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Medical Editor

Maria D Mileno, MD, Assistant Professor, Department of Internal Medicine, Division of Infectious Diseases, Brown University
Maria D Mileno, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, International Society of Travel Medicine, and Sigma Xi
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Charles V Sanders, MD, Edgar Hull Professor and Chairman, Department of Internal Medicine, Professor of Microbiology, Immunology and Parasitology, Louisiana State University School of Medicine at New Orleans; Medical Director, Medicine Hospital Center, Charity Hospital and Medical Center of Louisiana at New Orleans; Consulting Staff, Ochsner Medical Center
Charles V Sanders, MD is a member of the following medical societies: Alliance for the Prudent Use of Antibiotics, Alpha Omega Alpha, American Association for the Advancement of Science, American Association of University Professors, American Clinical and Climatological Association, American College of Physician Executives, American College of Physicians, American Federation for Medical Research, American Foundation for AIDS Research, American Geriatrics Society, American Lung Association, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Association for Professionals in Infection Control and Epidemiology, Association of American Medical Colleges, Association of American Physicians, Association of Professors of Medicine, Infectious Disease Society for Obstetrics and Gynecology, Infectious Diseases Society of America, Louisiana State Medical Society, Orleans Parish Medical Society, Royal Society of Medicine, Sigma Xi, Society of General Internal Medicine, Southeastern Clinical Club, Southern Medical Association, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

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