Download Mycoplasma pneumoniae infection in children Authors: Dori F

Mycoplasma pneumoniae infection in children
Authors:
Dori F Zaleznik, MD
Jesus G Vallejo, MD
Section Editor:
Morven S Edwards, MD
Deputy Editor:
Mary M Torchia, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Nov 2016. | This topic last updated: May 13, 2016.
INTRODUCTION — Mycoplasma pneumoniae is one of three species of Mycoplasma that
frequently produce infection in humans. Mycoplasmas are ubiquitous and are the smallest
bacteria that can survive alone in nature. M. pneumoniae causes a wide variety of clinical
manifestations in children and adults, principally pneumonia.
The clinical features, diagnosis, and treatment of M. pneumoniae infection in children will be
reviewed here. M. pneumoniae infection in adults, M. hominis, M genitalium, and Ureaplasma
urealyticum infections are discussed separately. (See "Mycoplasma pneumoniae infection in
adults" and "Mycoplasma hominis and Ureaplasma urealyticum infections".)
MICROBIOLOGY — The term "mycoplasma" is widely used to refer to any organism within the
class Mollicutes, which is composed of five genera
(Mycoplasma, Ureaplasma, Acholeplasma, Anaeroplasma, andAsteroloplasma). More than 120
named Mycoplasma species exist, and 13 Mycoplasma species, twoAcholeplasma species, and
one Ureaplasma species have been isolated from humans. However, only four species are wellestablished human pathogens [1]:
●Mycoplasma pneumoniae
●Mycoplasma hominis
●Mycoplasma genitalium
●Ureaplasma urealyticum
A subsequently described species, M. amphoriforme, appears capable of causing relapsing
pneumonia through person-to-person spread in both immunocompetent and patients with
antibody deficiency [2-4].
M. pneumoniae grows under both aerobic and anaerobic conditions and can be isolated on
media supplemented with serum. The organism is fastidious, and isolation is not commonly
performed in clinical laboratories.
PATHOGENESIS — The mechanism by which mycoplasmas produce infection is becoming
better understood. Pathogenic organisms for humans and animals possess specialized tip
organelles that mediate their interactions with host cells [5]. This host-adapted survival is
achieved by surface parasitism of target cells, the acquisition of essential biosynthetic
precursors, and, in some cases, cell entry and intracellular survival. The organism most
commonly exists in a filamentous form and has adherence proteins that attach to epithelial
membranes with particular affinity for respiratory tract epithelium [6,7].
Once attached, M. pneumoniae produces hydrogen peroxide and superoxide, causing injury to
epithelial cells and their associated cilia. However, many of the pathogenic features of infection
with M. pneumoniae are believed to be immune-mediated rather than induced directly by the
bacteria [7,8]. An immune-mediated mechanism is supported by the finding that infants and
young children infrequently develop clinical findings of pneumonia despite evidence of M.
pneumoniae infection. In addition, the antibodies produced against the glycolipid antigens of M.
pneumoniae may act as autoantibodies because they crossreact with human red cells and brain
cells [9].
EPIDEMIOLOGY — M. pneumoniae is transmitted from person to person by infected
respiratory droplets during close contact. The incubation period after exposure averages three
weeks [10]. Infection occurs most frequently during the fall and winter but may develop yearround [9].
Although the frequency of pneumonia caused by all respiratory pathogens decreases in children
older than the age of five years, the relative importance of M. pneumoniae rises during the
school years. M. pneumoniaeaccounts for approximately 20 percent of acute pneumonias in
middle and high school students and up to 50 percent of cases in college students and military
recruits [11]. In 2015 population-based surveillance for community-acquired pneumonia
requiring hospitalization, M. pneumoniae was the sole pathogen detected (by polymerase chain
reaction [PCR]) in 8 percent of children (<18 years) [12]. M. pneumoniae accounted for an
increasing proportion of cases with increasing age (<2 years: 2 percent; 2 to 4 years: 5 percent;
5 to 9 years: 16 percent: 10 to 17 years: 23 percent). The cumulative attack rate in families
approaches 90 percent, and immunity is not long lasting [13].
CLINICAL FEATURES — Many infections caused by M. pneumoniae are asymptomatic [14].
When present, the signs and symptoms vary according to the stage of illness (figure 1). The
onset of the illness is gradual and usually is heralded by headache, malaise, and low-grade
fever [9,10]. Chills are frequent, but rigors are rare. Patient complaints usually exceed objective
findings because abnormalities on physical examination often are minimal.
Symptoms and signs caused by M. pneumoniae infection can be divided into those caused by
respiratory tract and those caused by extrapulmonary disease [10]. None of these
manifestations are unique to M. pneumoniae[15,16].
Respiratory tract disease — Many more patients with respiratory infection caused by M.
pneumoniae have a respiratory tract illness without pneumonia than have pneumonia. In one
review, for example, 75 to 100 percent of infected patients had an intractable, nonproductive
cough, while only 3 to 10 percent developed pneumonia [17].
The cough caused by M. pneumoniae infection ranges from nonproductive to mildly productive.
Wheezing and dyspnea also may occur, although dyspnea is not a common complaint. Chills
are common, but rigors are very rare.
Additional respiratory symptoms include pharyngitis (6 to 59 percent of patients), rhinorrhea (2
to 40 percent), and ear pain (2 to 35 percent). As many as 5 percent of patients have severe ear
pain resulting from hemorrhagic bullous myringitis [8], although one study using polymerase
chain reaction (PCR)-based testing failed to document M. pneumoniae in bullous or
hemorrhagic myringitis in children under the age of two years [18]. Clinically inapparent sinusitis
may coexist with pneumonia [8].
There may be no findings on chest auscultation even if pneumonia is present early in the course
of disease. However, scattered rales, wheezes, or both may develop later [10]. Other physical
findings related to the respiratory tract may include sinus tenderness, mild erythema of the
posterior pharynx, erythema, or occasionally bullae of the tympanic membrane, and
nonprominent cervical adenopathy.
Possible relation to asthma — M. pneumoniae infection may worsen asthma symptoms and
can produce wheezing in children who do not have asthma. A separate question, for which
there has been some experimental and clinical evidence, is whether M. pneumoniae might have
some pathogenic role in asthma [19,20].
This issue was addressed in a prospective study of children hospitalized for severe asthma [20].
The following findings were noted:
●Among 119 children with previously diagnosed asthma, acute M. pneumoniae infection
was found in 20 percent and Chlamydia pneumoniae infection in 3.4 percent. The
diagnosis of acute infection was made serologically from either an immunoglobulin M (IgM)
response or at least a fourfold rise in immunoglobulin G (IgG) titers between the first and
second samples.
●Among 51 children with a first asthmatic attack, acute M. pneumoniae infection was found
in 50 percent and C. pneumoniae infection in 8.3 percent.
●Among 152 controls with stable asthma or rhinitis, M. pneumoniae infection was present
in 5.2 percent.
●At follow-up, the patients infected with M. pneumoniae or C. pneumoniae were more likely
to have recurrent asthma than those without these infections. Among infected patients,
recurrences tended to be rapid if the patient was not treated with a macrolide antibiotic.
Further data are needed before routine testing for atypical organisms can be recommended in
acute wheezing illnesses. (See "Approach to wheezing in infants and children" and "Wheezing
illnesses other than asthma in children".)
A prospective study suggested that the immune response to M. pneumoniae was altered in
children with asthma compared to controls without asthma [21]. In this study, fewer of the
asthmatic children had an IgG response to M. pneumoniae over the five-year period (3 of 82
versus 13 of 98 controls, p = 0.03). The number of patients positive for IgM antibody did not
differ between the groups. Cellular immune responses in mononuclear cells were greater in
those with measurable IgM than in children without IgM, whether or not they had asthma.
Extrapulmonary disease — Extrapulmonary abnormalities are an important part of
mycoplasma disease and may suggest the diagnosis. These manifestations include hemolysis,
skin rash, joint involvement, and symptoms and signs indicative of gastrointestinal tract, central
nervous system (CNS), and heart disease. Whether the pathogenesis of some or all of these
entities is caused by immune mechanisms or the direct action of the organisms is not clear.
Hemolysis — Antibodies (IgM) to the I antigen on erythrocyte membranes appear during the
course of infection and produce a cold agglutinin response in approximately 60 percent of
patients. Why mycoplasma infections promote the production of such antibodies and their
significance in pathogenesis is not known. Although hemolysis may be severe, usually it is not
clinically significant [9]. (See 'Cold agglutinins' below and"Pathogenesis of autoimmune
hemolytic anemia: Cold agglutinin disease".)
Mucocutaneous disease — Dermatologic manifestations may range from a mild erythematous
maculopapular or vesicular rash (which is most commonly seen accompanying respiratory tract
infections) to the Stevens-Johnson syndrome (SJS). M. pneumoniae is a common infectious
cause of SJS in children, which may occur in outbreaks [22]. M. pneumoniae also can cause
lesions limited to the mucous membranes (variably called "atypical SJS," "SJS without skin
lesions," and "M. pneumoniae-associated mucositis") [23-25]. Antibiotics may intensify the
dermatosensitive potential of M. pneumoniae [26]. (See "Stevens-Johnson syndrome and toxic
epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis", section on
'Etiology' and"Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical
manifestations, and diagnosis", section on 'Infection'.)
One report cites a case of papular purpuric gloves and socks syndrome ascribed to M.
pneumoniae infection in an adolescent [27]. Papular purpuric gloves and socks syndrome
usually is associated with parvovirus B19 infection. (See "Clinical manifestations and diagnosis
of parvovirus B19 infection", section on 'Erythema infectiosum'.)
CNS involvement — CNS manifestations occur in approximately 0.1 percent of all patients
with M. pneumoniae infections and in as many as 7 percent of patients requiring hospitalization
[28]. CNS involvement occurs most frequently in children and includes aseptic meningitis,
meningoencephalitis (which may be complicated by postencephalitic epilepsy), peripheral
neuropathy, transverse myelitis, cranial nerve palsies, and cerebellar ataxia [29-35]. In a
retrospective study of 365 children with M. pneumoniae detected in the cerebrospinal fluid
(CSF) or respiratory tract by PCR, 15.9 percent had acute neurologic symptoms [35]. In 11.5
percent of cases, CNS disease was attributable to M. pneumoniae. In these patients, two
distinct disease patterns were observed: one with a prodrome of ≥7 days, respiratory
manifestations, chest radiograph abnormalities, reactive IgM in acute serum, and detection
of M. pneumoniae in the respiratory tract, but not the CSF; and one with a prodrome of <7 days,
fewer respiratory manifestations, nonreactive IgM response, and detection of M. pneumoniae in
the CSF only. The pathogenesis of the CNS disease is uncertain. Possibilities include direct
infection and an immune-mediated reaction [28,35].
Although uncommon, CNS involvement is associated with significant morbidity and mortality.
One study evaluated 61 individuals with neurologic disease attributed to M. pneumoniae and
found that five (8 percent) patients died and 14 (23 percent) had severe sequelae [28]. Another
study reported adverse neurologic outcomes in 48.8 percent of children but no deaths were
reported [35].
Other — Gastrointestinal symptoms range from nonspecific (common) to those of pancreatitis
(rare); the latter disorder may be due in part to antibodies to M. pneumoniae [9].
Rheumatologic symptoms, including tender joints and muscles and a polyarthritis, can occur.
Although arthralgias are common, actual arthritis is rare. Arthritis is believed to result from
immune-mediated mechanisms; however, M. pneumoniae has been isolated from synovial fluid
in some patients with polyarthritis, suggesting a possible role for direct infection.
Cardiac and renal involvement is unusual [8]. Cardiac manifestations include rhythm
disturbances, heart failure, chest pain, and conduction abnormalities on the electrocardiogram.
Myocarditis rarely has been described in autopsy reports because the disease usually is not
fatal. Clinically significant glomerulonephritis is a rare complication that is presumed to be
secondary to immune complex deposition. In one case report, the glomerular disease correlated
with high titer cold agglutinins, and the patient developed chronic renal failure [36]. However, a
cause-and-effect relationship was not proven.
Radiographic features — The findings on chest radiography vary considerably in patients
with M. pneumoniae pneumonia and may be difficult to appreciate [37]. M.
pneumoniae involving the lung results in four frequently described chest radiograph patterns:
●Bronchopneumonia
●Plate-like atelectasis
●Nodular infiltration
●Hilar adenopathy
The most common radiographic finding is the peribronchial pneumonia pattern, which consists
of a thickened bronchial shadow, streaks of interstitial infiltration (image 1), and areas of
atelectasis; these changes have a predilection for the lower lobes. Hilar adenopathy was noted
in 34 percent of children in one study [38]. The finding of hilar adenopathy in children with
suspected M. pneumoniae infection should broaden the differential diagnosis to include
tuberculosis.
Pleural effusions can be seen in as many as 20 percent of patients when lateral decubitus films
are performed [17]. Empyema is a rare complication of M. pneumoniae pneumonia.
(See "Epidemiology; clinical presentation; and evaluation of parapneumonic effusion and
empyema in children" and "Management and prognosis of parapneumonic effusion and
empyema in children".)
High-resolution computed tomography (HRCT) usually demonstrates abnormalities [37], but is
not routinely necessary for evaluating children with mycoplasma and should be used obtained
when results will affect management, given the risks of radiation exposure. (See "Radiationrelated risks of imaging studies", section on 'Pediatrics'.)
HRCT scan is more sensitive for demonstrating abnormalities than is chest radiography in
cases of M. pneumoniae pneumonia. In one study of 28 patients with documented M.
pneumoniae infection who underwent both studies, air-space opacification was visible on chest
radiography in 86 percent but was usually nonsegmental [37]. By contrast, nodules and
thickening of bronchovascular bundles were common HRCT findings (89 and 82 percent,
respectively) and significantly less frequent findings on chest radiograph (50 and 18 percent,
respectively).
Late structural abnormalities also can be identified on HRCT; a series of 38 children who had
been hospitalized with M. pneumoniae pneumonia were scanned one to two years later and
compared to 17 children who had not required hospitalization [39]. The hospitalized children had
more frequent abnormal scans (37 versus 12 percent), including bronchiectasis in 21 percent.
These findings were more common in younger children and those with higher antibody titers.
Laboratory features — Subclinical evidence of hemolytic anemia is present in most patients
with pneumonia, as suggested by a positive Coombs test and an elevated reticulocyte count.
Cold agglutinin titers are elevated in 50 percent of adult patients with mycoplasma disease, and
the titer usually exceeds 1:128 in patients with pneumonia [40]. Less well studied in children, the
accuracy of the cold agglutinin test in detecting upper respiratory infection caused by M.
pneumoniae is not known, and specificity is low if the titer is less than 1:64 because a variety of
other respiratory pathogens may induce an increase in cold agglutinins.
The peripheral white blood cell count (WBC) is normal or slightly elevated with neutrophilia.
Thrombocytosis can occur and probably represents an acute phase response. Reported
erythrocyte sedimentation rates range from 20 to more than 100 mm/hr, with higher rates
suggestive of more severe pulmonary disease [41].
In patients with neurologic involvement, the CSF typically reveals a lymphocytic pleocytosis,
elevated protein, and normal glucose. Isolation of M. pneumoniae in the CSF is possible but
rare [9,28].
DIAGNOSIS
Clinical suspicion — There are no distinguishing clinical or radiologic manifestations that allow
a secure diagnosis of mycoplasma pneumonia versus chlamydial or viral pneumonia [15].
Compared to those with pyogenic pneumonia, however, patients with mycoplasma pneumonia
tend to have a more gradual onset of symptoms, less respiratory distress, and usually a normal
white blood cell count. However, these findings are neither sufficiently sensitive nor specific to
exclude other etiologies. (See "Pneumonia in children: Epidemiology, pathogenesis, and
etiology", section on 'Etiologic agents' and "Community-acquired pneumonia in children: Clinical
features and diagnosis", section on 'Clues to etiology'.)
Approach to laboratory confirmation — Laboratory confirmation of M. pneumoniae is difficult
and should be pursued only if it will alter management. Laboratory testing is usually not
performed in outpatients with community-acquired pneumonia (CAP) because empiric treatment
is almost always successful, but laboratory testing may be warranted for children hospitalized
with CAP. (See "Community-acquired pneumonia in children: Clinical features and diagnosis",
section on 'Indications'.)
Unfortunately, there are no diagnostic tests that allow the reliable, rapid diagnosis of M.
pneumoniae [42,43]. The available tests are variable in sensitivity and specificity and do not
appear to differentiate between M. pneumoniae disease and asymptomatic colonization, so the
user must be cautious in the interpretation of results [14,43-45]. Given these shortcomings, a
high clinical suspicion is essential for early treatment of M. pneumoniae infection. The diagnosis
is usually confirmed in retrospect (eg, by clinical improvement with appropriate therapy).
The Infectious Diseases Society of America (IDSA) suggests serology or polymerase chain
reaction (PCR) tests for the laboratory diagnosis of M. pneumoniae [46]. When available, PCR
from a nasopharyngeal specimen can be done rapidly, has a high specificity, and is the
diagnostic test of choice. Serology using enzyme immunoassay of paired acute and
convalescent sera has traditionally been the mainstay of laboratory diagnosis and should be
performed when PCR is not available. (See 'Polymerase chain reaction' below
and'Serology' below.)
Most clinical laboratories do not attempt to culture M. pneumoniae because culture requires two
to three weeks and M. pneumoniae is fastidious. (See 'Gram stain and culture' below.)
Other tests, such as cold agglutinins, can occasionally be used to support a clinical diagnosis
when a rapid diagnosis must be made. (See 'Cold agglutinins' below.)
Polymerase chain reaction — Direct PCR detects genomic DNA and may be highly sensitive
and specific for M. pneumoniae in patients with respiratory tract infections [47-51]. However,
PCR may not reliably distinguish M. pneumoniae disease from asymptomatic carriage. In one
cross-sectional study, M. pneumoniaeDNA was detected with similar frequency in children with
and without symptoms of upper respiratory tract infection [14]. This small single-center study
should be validated at different sites and in different populations before concluding that PCR is
not useful for diagnosing active mycoplasma infection in children.
In 2012, a multiplex PCR assay was cleared by the US Food and Drug Administration (FDA) for
the diagnosis ofM. pneumoniae infection using nasopharyngeal samples [52,53]. This test
appears to have high sensitivity and specificity, but fewer than 10 positive samples were
available for analysis [54].
Although multiplex PCR has been FDA-cleared only for use on nasopharyngeal samples, PCR
can be performed on other respiratory specimens (eg, throat swabs, sputum samples,
bronchoalveolar lavage fluid) [55]. PCR can also be done on cerebrospinal fluid, but it has a low
diagnostic yield. (See "Molecular diagnosis of central nervous system infections", section on
'Bacteria'.)
One study, for example, compared the sensitivity and specificity of PCR on throat swab
specimens with serology obtained from both hospitalized adults and children [48]. PCR had a
sensitivity of 92 percent and a specificity of 98 percent (using a combination of serology and
clinical data as the reference standard) and detected more cases of M. pneumoniae than did
serology. However, the sensitivity and specificity of PCR tests that are used by individual
institutions (which are not cleared by the FDA) are not generalizable [51].
Serology — Antibody titers begin to rise approximately seven to nine days after infection and
peak at three to four weeks. In general, a fourfold or greater increase in titer in paired sera
(separated by four weeks) is indicative of infection; a single titer is not definitive for diagnosis,
but convalescent titers are only necessary if they will change management [36,56-59].
Although antibody tests provide evidence of infection, definitive diagnosis is delayed by the
need to assay acute and convalescent serum. In addition, serologic tests do not appear to
distinguish M. pneumoniae disease from asymptomatic carriage. In a cross-sectional study of
children (3 months to 16 years), the prevalence of anti-M pneumoniae immunoglobulin M (IgM)
antibodies and age-adjusted anti-M. pneumoniae immunoglobulin G (IgG) antibodies was
similar among children with and without symptoms of upper respiratory tract infection [14]. This
small single-center study should be validated at different sites and in different populations
before concluding that serologic testing is not useful for diagnosing active mycoplasma infection
in children.
The complement fixation (CF) test, which measures "early" IgM (predominantly) and IgG
antibody (to a lesser extent) to M. pneumoniae, is highly sensitive for the detection of M.
pneumoniae infection [36]. A major disadvantage of the CF test is that false positive results may
occur, particularly during inflammatory reactions.
Enzyme immunoassay (EIA) techniques have largely replaced the complement fixation test
because EIA is more readily available. EIA is more sensitive in detecting acute infection than
culture and has sensitivity comparable to the polymerase chain reaction if there has been
sufficient time to develop an antibody response [57]. Agglutination antibody tests are also
available, but they appear less sensitive than EIA and complement fixation [60]. A number of
studies comparing commercially available antibody testing note a lack of comparability among
the tests and among different laboratories [59,61-63].
Antigen detection — Antigen detection can be performed by antigen capture-enzyme
immunoassay (Ag-EIA), which may detect 104cfu/mL (a level which should be present in the
majority of infections) [64]. One problem with Ag-EIA is that the ability to detect antigen may
vary with the time of sampling; the test is most often positive within seven days of onset.
Gram stain and culture — The isolation of M. pneumoniae on SP-4 medium is possible.
However, culture requires two to three weeks and M. pneumoniae is fastidious. As a result,
most clinical laboratories do not attempt to culture it [43].
A positive sputum Gram stain and culture can establish the diagnosis of bacterial pneumonia.
However, children younger than five years usually swallow sputum, so it is rarely available for
examination. (See "Community-acquired pneumonia in children: Clinical features and
diagnosis", section on 'Cultures'.)
Cold agglutinins — The formation of cold agglutinins is a nonspecific early IgM reaction
against the erythrocyte I antigen. We do not routinely suggest obtaining cold agglutinin antibody
titers in children because the accuracy of this test in detecting M. pneumoniae in children is not
known [43]. Nor do we recommend performing bedside cold agglutinins because bedside cold
agglutinins are neither sensitive nor specific for M. pneumoniae infection in children.
TREATMENT — The benefits of antimicrobial therapy for M. pneumoniae in children have not
been adequately studied [65]. Studies of efficacy are inconclusive.
Lower respiratory tract infections — Empiric treatment for M. pneumoniae pneumonia often
is initiated based on clinical suspicion given the difficulty with definitive diagnosis. We suggest
that suspected or documented M. pneumoniae lower respiratory tract infections in hospitalized
children be treated with a macrolide or tetracycline antibiotic. We also suggest that school-age
children and adolescents evaluated for community-acquired pneumonia (CAP) in the outpatient
setting who have findings compatible with atypical pathogens be treated with a macrolide
antibiotic. These suggestions are consistent with those in the 2011 Pediatric Infectious Diseases
Society (PIDS) and the Infectious Diseases Society of America (IDSA) guidelines [43]. Empiric
treatment of community-acquired pneumonia in children, including M. pneumoniae pneumonia,
is discussed separately. (See 'Diagnosis' above and "Community-acquired pneumonia in
children: Outpatient treatment", section on 'Empiric therapy' and "Pneumonia in children:
Inpatient treatment", section on 'Atypical pneumonia'.)
Recommended regimens include [51,66]:
●Azithromycin 10 mg/kg in one dose (maximum dose 500 mg) on the first day and
5 mg/kg in one dose (maximum dose 250 mg) for four days, or
●Clarithromycin 15 mg/kg per day in two divided doses (maximum daily dose 1 g) for 10
days, or
●Erythromycin 30 to 40 mg/kg per day in four divided doses (maximum daily dose 2 g) for
10 days
Azithromycin and clarithromycin have the advantages of less frequent dosing and fewer
gastrointestinal disturbances.
Additional options for children ≥8 years of age include:
●Doxycycline 2 to 4 mg/kg per day in one or two divided doses (maximum daily dose 200
mg) for 10 days, or
●Tetracycline 20 to 50 mg/kg per day in four divided doses (maximum daily dose 2 g) for
10 days
Studies supporting antibiotic treatment of documented M. pneumoniae lower respiratory tract
infections are limited [67]. Support is provided predominantly by in vitro studies and a
randomized trial in military recruits [68-70]. A 2014 systematic review of 17 studies (4294
patients) found insufficient evidence for efficacy of antimicrobial treatment of M.
pneumoniae lower respiratory tract infection, even in improving symptoms (eg, duration of fever)
[65]. The analysis was limited by publication bias; heterogeneity; and lack of blinding, consistent
diagnostic methods, reliable outcome measures, and information about duration of symptoms or
mixed infections in the included studies [65,71]. The authors concluded that there is a need for
prospective randomized trials, given the frequent use of macrolide antibiotics in children, often
for conditions that do not warrant antibiotics [72]. Pending more definitive studies it seems
reasonable to treat children with clinical and epidemiologic features compatible with M.
pneumoniae infection with antimicrobial regimens that include coverage for M.
pneumoniae, since documentation of M. pneumoniae infection frequently is lacking.
Macrolide resistance — M. pneumoniae resistant to macrolides has been reported in Asia,
France, Italy, Israel, and the United States [73-80]. In the United States, studies published in
2015 report macrolide resistance in 3.5 to 13.2 percent of M. pneumoniae [80,81].
The possibility of macrolide resistance should be considered in children with suspected M.
pneumoniaeinfection who do not respond as expected to macrolide therapy, particularly if the
child is severely ill. Prolonged fever (ie, ≥48 hours after the initiation of therapy) has been
reported in children with macrolide-resistant isolates were treated with macrolide antibiotics
[76,82].
Tetracyclines (eg, tetracycline, doxycycline) and fluoroquinolones (eg, levofloxacin) are
alternative treatments for macrolide-resistant strains of M. pneumoniae [68,78]. In pediatric
patients, fluoroquinolones are not routinely first-line therapy, but after assessment of risks and
benefits, may be a reasonable alternative for situations where no safe and effective substitute is
available [83,84]. (See "Fluoroquinolones", section on 'Use in children'.)
We suggest one of the following regimens [85,86]:
●Doxycycline 2 to 4 mg/kg per day in one or two divided doses (maximum daily dose 200
mg) for 10 days
●Levofloxacin
•≥6 months and <5 years – 10 mg/kg per dose every 12 hours for 10 days (maximum
daily dose 750 mg) for 10 days
•≥5 years – 10 mg/kg per dose once per day (maximum daily dose 500 mg) for 10
days
Upper respiratory tract infections — We do not suggest antibiotic therapy for M.
pneumoniae upper respiratory tract infections. The benefits of antimicrobial therapy for the
treatment of upper respiratory tract symptoms caused by M. pneumoniae have not been
adequately studied in children.
Central nervous system disease — Treatment of M. pneumoniae central nervous system
(CNS) disease is individualized according to the clinical syndrome and severity of illness.
Antibiotics are frequently administered given concern for long-term neurologic sequelae.
However, randomized trials evaluating antimicrobial and/oradjunctive therapies for M.
pneumoniae CNS disease are lacking. Consultation with an expert in pediatric infectious
diseases and/or pediatric neurology is suggested.
The pathogenesis of M. pneumoniae CNS disease is poorly understood [87]. Possible
mechanisms include direct invasion, immune mediation, and neurotoxicity. Antibiotics would not
be expected to have a major therapeutic role in immune mediated or neurotoxic disease. In
observational studies, glucocorticoids, antiinflammatory drugs, diuretics, and plasma exchange
have been used in addition to antibiotics without clear indication of benefit [7,30,35,88].
In a retrospective analysis of 42 children with definite, probable, or possible M.
pneumoniae CNS disease (eg, encephalitis, transverse myelitis, acute disseminated
encephalomyelitis, etc), 29 children received macrolide therapy, and 17 received glucocorticoids
[35]. Adverse neurologic outcome (eg, epilepsy, focal neurologic deficit) occurred in 15 of those
who received macrolides and 9 of those who received glucocorticoids.
Hemolytic anemia — The management of M. pneumoniae-related hemolytic anemia is
discussed separately. (See "Cold agglutinin disease", section on 'Treatment'.)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials,
"The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain
language, at the 5th to 6th grade reading level, and they answer the four or five key questions a
patient might have about a given condition. These articles are best for patients who want a
general overview and who prefer short, easy-to-read materials. Beyond the Basics patient
education pieces are longer, more sophisticated, and more detailed. These articles are written
at the 10th to 12th grade reading level and are best for patients who want in-depth information
and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print
or e-mail these topics to your patients. (You can also locate patient education articles on a
variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Pneumonia in children (The Basics)" and "Patient
education: Mycoplasma pneumonia in children (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Mycoplasma pneumoniae accounts for approximately 20 percent of acute pneumonias in
middle and high school students and up to 50 percent of cases in college students and
military recruits. (See 'Epidemiology'above.)
●The signs and symptoms of M. pneumoniae infection vary according to the stage of
illness (figure 1). Extrapulmonary manifestations may include hemolysis, rash,
musculoskeletal pain, and central nervous system, gastrointestinal, or cardiac involvement.
(See 'Clinical features' above.)
●Plain radiograph findings include bronchopneumonia, plate-like atelectasis, nodular
infiltration, hilar adenopathy, and pleural effusions. (See 'Radiographic features' above.)
●Laboratory features of M. pneumoniae infection may include positive Coombs test,
elevated reticulocyte count, elevated cold agglutinin titers, normal or slightly elevated white
blood cell count, thrombocytosis, and elevation of the erythrocyte sedimentation rate.
(See 'Laboratory features' above.)
●Compared to children with bacterial pneumonia, those with mycoplasma pneumonia tend
to have a more gradual onset of symptoms, less respiratory distress, and a normal white
blood cell count. However, these findings are neither sufficiently sensitive nor specific to
exclude other etiologies (eg, chlamydia or viral pneumonia). (See 'Diagnosis' above.)
●Specific diagnosis of M. pneumoniae relies upon nonculture techniques, including
serology and antigen detection. (See 'Diagnosis' above.)
●We suggest that suspected or documented M. pneumoniae lower respiratory tract
infection (figure 1) be treated with antimicrobial therapy (Grade 2B). We generally use a
macrolide or tetracycline antibiotic. Alternative regimens include (see 'Lower respiratory
tract infections' above):
•Azithromycin 10 mg/kg in one dose (maximum dose 500 mg) on the first day and
5 mg/kg in one dose (maximum dose 250 mg) for four days
•Clarithromycin 15 mg/kg per day in two divided doses (maximum daily dose 1 g) for
10 days
•Erythromycin 30 to 40 mg/kg per day in four divided doses (maximum daily dose 2 g)
for 10 days
•Doxycycline 2 to 4 mg/kg per day in one or two divided doses for 10 days (maximum
daily dose 200 mg) may be used in children ≥8 years of age
•Tetracycline 20 to 50 mg/kg per day in four divided doses for 10 days (maximum
daily dose 1 to 2 g) may be used in children ≥8 years of age
●Doxycycline or a fluoroquinolone (eg, levofloxacin) antibiotic should be used if macrolideresistance is suspected or documented, particularly if the child is severely ill.
(See 'Macrolide resistance' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
REFERENCES
1.
Taylor-Robinson D. Infections due to species of Mycoplasma and Ureaplasma: an
update. Clin Infect Dis 1996; 23:671.
2.
Gillespie SH, Ling CL, Oravcova K, et al. Genomic Investigations unmask Mycoplasma
amphoriforme, a new respiratory pathogen. Clin Infect Dis 2015; 60:381.
3.
Pereyre S, Renaudin H, Touati A, et al. Detection and susceptibility testing of
Mycoplasma amphoriforme isolates from patients with respiratory tract infections. Clin Microbiol
Infect 2010; 16:1007.
4.
Ling CL, Oravcova K, Beattie TF, et al. Tools for detection of Mycoplasma
amphoriforme: a primary respiratory pathogen? J Clin Microbiol 2014; 52:1177.
5.
Baseman JB, Tully JG. Mycoplasmas: sophisticated, reemerging, and burdened by their
notoriety. Emerg Infect Dis 1997; 3:21.
6.
Feizi T, Loveless RW. Carbohydrate recognition by Mycoplasma pneumoniae and
pathologic consequences. Am J Respir Crit Care Med 1996; 154:S133.
7.
Baseman JB, Reddy SP, Dallo SF. Interplay between mycoplasma surface proteins,
airway cells, and the protean manifestations of mycoplasma-mediated human infections. Am J
Respir Crit Care Med 1996; 154:S137.
8.
Martin RE, Bates JH. Atypical pneumonia. Infect Dis Clin North Am 1991; 5:585.
9.
Luby JP. Pneumonia caused by Mycoplasma pneumoniae infection. Clin Chest Med
1991; 12:237.
10.
Clyde WA Jr. Clinical overview of typical Mycoplasma pneumoniae infections. Clin Infect
Dis 1993; 17 Suppl 1:S32.
11.
Mogabgab WJ. Mycoplasma pneumoniae and adenovirus respiratory illnesses in military
and university personnel, 1959-1966. Am Rev Respir Dis 1968; 97:345.
12.
Jain S, Williams DJ, Arnold SR, et al. Community-acquired pneumonia requiring
hospitalization among U.S. children. N Engl J Med 2015; 372:835.
13.
Foy HM, Kenny GE, Cooney MK, Allan ID. Long-term epidemiology of infections with
Mycoplasma pneumoniae. J Infect Dis 1979; 139:681.
14.
Spuesens EB, Fraaij PL, Visser EG, et al. Carriage of Mycoplasma pneumoniae in the
upper respiratory tract of symptomatic and asymptomatic children: an observational study. PLoS
Med 2013; 10:e1001444.
15.
Principi N, Esposito S. Emerging role of Mycoplasma pneumoniae and Chlamydia
pneumoniae in paediatric respiratory-tract infections. Lancet Infect Dis 2001; 1:334.
16.
Wang K, Gill P, Perera R, et al. Clinical symptoms and signs for the diagnosis of
Mycoplasma pneumoniae in children and adolescents with community-acquired pneumonia.
Cochrane Database Syst Rev 2012; 10:CD009175.
17.
Mansel JK, Rosenow EC 3rd, Smith TF, Martin JW Jr. Mycoplasma pneumoniae
pneumonia. Chest 1989; 95:639.
18.
Kotikoski MJ, Kleemola M, Palmu AA. No evidence of Mycoplasma pneumoniae in acute
myringitis. Pediatr Infect Dis J 2004; 23:465.
19.
Martin RJ, Chu HW, Honour JM, Harbeck RJ. Airway inflammation and bronchial
hyperresponsiveness after Mycoplasma pneumoniae infection in a murine model. Am J Respir
Cell Mol Biol 2001; 24:577.
20.
Biscardi S, Lorrot M, Marc E, et al. Mycoplasma pneumoniae and asthma in children.
Clin Infect Dis 2004; 38:1341.
21.
Atkinson TP, Duffy LB, Pendley D, et al. Deficient immune response to Mycoplasma
pneumoniae in childhood asthma. Allergy Asthma Proc 2009; 30:158.
22.
Olson D, Watkins LK, Demirjian A, et al. Outbreak of Mycoplasma pneumoniaeAssociated Stevens-Johnson Syndrome. Pediatrics 2015; 136:e386.
23.
Canavan TN, Mathes EF, Frieden I, Shinkai K. Mycoplasma pneumoniae-induced rash
and mucositis as a syndrome distinct from Stevens-Johnson syndrome and erythema
multiforme: a systematic review. J Am Acad Dermatol 2015; 72:239.
24.
Vujic I, Shroff A, Grzelka M, et al. Mycoplasma pneumoniae-associated mucositis--case
report and systematic review of literature. J Eur Acad Dermatol Venereol 2015; 29:595.
25.
Meyer Sauteur PM, Goetschel P, Lautenschlager S. Mycoplasma pneumoniae and
mucositis--part of the Stevens-Johnson syndrome spectrum. J Dtsch Dermatol Ges 2012;
10:740.
26.
Cherry JD. Anemia and mucocutaneous lesions due to Mycoplasma pneumoniae
infections. Clin Infect Dis 1993; 17 Suppl 1:S47.
27.
Pemira SM, Tolan RW Jr. Mycoplasma pneumoniae infection presenting as bullous
papular purpuric gloves and socks syndrome: novel association and review of the literature. Clin
Pediatr (Phila) 2011; 50:1140.
28.
Koskiniemi M. CNS manifestations associated with Mycoplasma pneumoniae infections:
summary of cases at the University of Helsinki and review. Clin Infect Dis 1993; 17 Suppl 1:S52.
29.
Smith R, Eviatar L. Neurologic manifestations of Mycoplasma pneumoniae infections:
diverse spectrum of diseases. A report of six cases and review of the literature. Clin Pediatr
(Phila) 2000; 39:195.
30.
Candler PM, Dale RC. Three cases of central nervous system complications associated
with Mycoplasma pneumoniae. Pediatr Neurol 2004; 31:133.
31.
Christie LJ, Honarmand S, Talkington DF, et al. Pediatric encephalitis: what is the role of
Mycoplasma pneumoniae? Pediatrics 2007; 120:305.
32.
Walter ND, Grant GB, Bandy U, et al. Community outbreak of Mycoplasma pneumoniae
infection: school-based cluster of neurologic disease associated with household transmission of
respiratory illness. J Infect Dis 2008; 198:1365.
33.
Weng WC, Peng SS, Wang SB, et al. Mycoplasma pneumoniae--associated transverse
myelitis and rhabdomyolysis. Pediatr Neurol 2009; 40:128.
34.
Lin JJ, Hsia SH, Wu CT, et al. Mycoplasma pneumoniae-related postencephalitic
epilepsy in children. Epilepsia 2011; 52:1979.
35.
Al-Zaidy SA, MacGregor D, Mahant S, et al. Neurological Complications of PCR-Proven
M. pneumoniae Infections in Children: Prodromal Illness Duration May Reflect Pathogenetic
Mechanism. Clin Infect Dis 2015; 61:1092.
36.
Kenny GE, Kaiser GG, Cooney MK, Foy HM. Diagnosis of Mycoplasma pneumoniae
pneumonia: sensitivities and specificities of serology with lipid antigen and isolation of the
organism on soy peptone medium for identification of infections. J Clin Microbiol 1990; 28:2087.
37.
Reittner P, Müller NL, Heyneman L, et al. Mycoplasma pneumoniae pneumonia:
radiographic and high-resolution CT features in 28 patients. AJR Am J Roentgenol 2000;
174:37.
38.
Niitu Y. M. pneumoniae respiratory diseases: clinical features--children. Yale J Biol Med
1983; 56:493.
39.
Kim CK, Chung CY, Kim JS, et al. Late abnormal findings on high-resolution computed
tomography after Mycoplasma pneumonia. Pediatrics 2000; 105:372.
40.
Tay YK, Huff JC, Weston WL. Mycoplasma pneumoniae infection is associated with
Stevens-Johnson syndrome, not erythema multiforme (von Hebra). J Am Acad Dermatol 1996;
35:757.
41.
Nagayama Y, Sakurai N, Yamamoto K. Clinical observations of children with
pleuropneumonia due to Mycoplasma pneumoniae. Pediatr Pulmonol 1990; 8:182.
42.
Thurman KA, Walter ND, Schwartz SB, et al. Comparison of laboratory diagnostic
procedures for detection of Mycoplasma pneumoniae in community outbreaks. Clin Infect Dis
2009; 48:1244.
43.
Bradley JS, Byington CL, Shah SS, et al. The management of community-acquired
pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the
Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin
Infect Dis 2011; 53:e25.
44.
Touati A, Benard A, Hassen AB, et al. Evaluation of five commercial real-time PCR
assays for detection of Mycoplasma pneumoniae in respiratory tract specimens. J Clin Microbiol
2009; 47:2269.
45.
Loens K, Goossens H, Ieven M. Acute respiratory infection due to Mycoplasma
pneumoniae: current status of diagnostic methods. Eur J Clin Microbiol Infect Dis 2010;
29:1055.
46.
Baron EJ, Miller JM, Weinstein MP, et al. A guide to utilization of the microbiology
laboratory for diagnosis of infectious diseases: 2013 recommendations by the Infectious
Diseases Society of America (IDSA) and the American Society for Microbiology (ASM)(a). Clin
Infect Dis 2013; 57:e22.
47.
Tjhie JH, van Kuppeveld FJ, Roosendaal R, et al. Direct PCR enables detection of
Mycoplasma pneumoniae in patients with respiratory tract infections. J Clin Microbiol 1994;
32:11.
48.
Blackmore TK, Reznikov M, Gordon DL. Clinical utility of the polymerase chain reaction
to diagnose Mycoplasma pneumoniae infection. Pathology 1995; 27:177.
49.
Ramirez JA, Ahkee S, Tolentino A, et al. Diagnosis of Legionella pneumophila,
Mycoplasma pneumoniae, or Chlamydia pneumoniae lower respiratory infection using the
polymerase chain reaction on a single throat swab specimen. Diagn Microbiol Infect Dis 1996;
24:7.
50.
Xu D, Li S, Chen Z, Du L. Detection of Mycoplasma pneumoniae in different respiratory
specimens. Eur J Pediatr 2011; 170:851.
51.
American Academy of Pediatrics. Mycoplasma pneumoniae and other Mycoplasma
species infections. In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th,
Kimberlin DW, Brady MT, Jackson MA, Long SS. (Eds), American Academy of Pediatrics, Elk
Grove Village, IL 2015. p.568.
52.
US Food and Drug Administration (FDA) News Release. FDA expands use for FilmArray
Respiratory Panel.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm304177.htm (Accessed
on June 11, 2012).
53.
Poritz MA, Blaschke AJ, Byington CL, et al. FilmArray, an automated nested multiplex
PCR system for multi-pathogen detection: development and application to respiratory tract
infection. PLoS One 2011; 6:e26047.
54.
Idaho Technology Inc. FilmArray Respiratory Panel - Information Sheet.
http://www.idahotech.com/pdfs/FilmArray/InfoSheet,%20FilmArray%20Respiratory%20Panel0229.pdf (Accessed on June 11, 2012).
55.
Baum SG. Mycoplasma pneumoniae and atypical pneumonia. In: Principles and Practice
of Infectious Diseases, 7th Ed, Mandell GL, Bennett JE, Dolin R. (Eds), Churchill Livingstone,
Philadelphia 2010. p.2481.
56.
Jacobs E. Serological diagnosis of Mycoplasma pneumoniae infections: a critical review
of current procedures. Clin Infect Dis 1993; 17 Suppl 1:S79.
57.
Waites KB, Talkington DF. Mycoplasma pneumoniae and its role as a human pathogen.
Clin Microbiol Rev 2004; 17:697.
58.
Daxboeck F, Krause R, Wenisch C. Laboratory diagnosis of Mycoplasma pneumoniae
infection. Clin Microbiol Infect 2003; 9:263.
59.
Nir-Paz R, Michael-Gayego A, Ron M, Block C. Evaluation of eight commercial tests for
Mycoplasma pneumoniae antibodies in the absence of acute infection. Clin Microbiol Infect
2006; 12:685.
60.
Thacker WL, Talkington DF. Comparison of two rapid commercial tests with complement
fixation for serologic diagnosis of Mycoplasma pneumoniae infections. J Clin Microbiol 1995;
33:1212.
61.
Beersma MF, Dirven K, van Dam AP, et al. Evaluation of 12 commercial tests and the
complement fixation test for Mycoplasma pneumoniae-specific immunoglobulin G (IgG) and IgM
antibodies, with PCR used as the "gold standard". J Clin Microbiol 2005; 43:2277.
62.
Talkington DF, Shott S, Fallon MT, et al. Analysis of eight commercial enzyme
immunoassay tests for detection of antibodies to Mycoplasma pneumoniae in human serum.
Clin Diagn Lab Immunol 2004; 11:862.
63.
Busson L, Van den Wijngaert S, Dahma H, et al. Evaluation of 10 serological assays for
diagnosing Mycoplasma pneumoniae infection. Diagn Microbiol Infect Dis 2013; 76:133.
64.
Marmion BP, Williamson J, Worswick DA, et al. Experience with newer techniques for
the laboratory detection of Mycoplasma pneumoniae infection: Adelaide, 1978-1992. Clin Infect
Dis 1993; 17 Suppl 1:S90.
65.
Biondi E, McCulloh R, Alverson B, et al. Treatment of mycoplasma pneumonia: a
systematic review. Pediatrics 2014; 133:1081.
66.
Block S, Hedrick J, Hammerschlag MR, et al. Mycoplasma pneumoniae and Chlamydia
pneumoniae in pediatric community-acquired pneumonia: comparative efficacy and safety of
clarithromycin vs. erythromycin ethylsuccinate. Pediatr Infect Dis J 1995; 14:471.
67.
Gardiner SJ, Gavranich JB, Chang AB. Antibiotics for community-acquired lower
respiratory tract infections secondary to Mycoplasma pneumoniae in children. Cochrane
Database Syst Rev 2015; 1:CD004875.
68.
Bébéar C, Pereyre S, Peuchant O. Mycoplasma pneumoniae: susceptibility and
resistance to antibiotics. Future Microbiol 2011; 6:423.
69.
Critchley IA, Jones ME, Heinze PD, et al. In vitro activity of levofloxacin against
contemporary clinical isolates of Legionella pneumophila, Mycoplasma pneumoniae and
Chlamydia pneumoniae from North America and Europe. Clin Microbiol Infect 2002; 8:214.
70.
KINGSTON JR, CHANOCK RM, MUFSON MA, et al. Eaton agent pneumonia. JAMA
1961; 176:118.
71.
Colin AA, Yousef S, Forno E, Korppi M. Treatment of Mycoplasma pneumoniae in
pediatric lower respiratory infection. Pediatrics 2014; 133:1124.
72.
Hersh AL, Shapiro DJ, Pavia AT, Shah SS. Antibiotic prescribing in ambulatory
pediatrics in the United States. Pediatrics 2011; 128:1053.
73.
Peuchant O, Ménard A, Renaudin H, et al. Increased macrolide resistance of
Mycoplasma pneumoniae in France directly detected in clinical specimens by real-time PCR
and melting curve analysis. J Antimicrob Chemother 2009; 64:52.
74.
Averbuch D, Hidalgo-Grass C, Moses AE, et al. Macrolide resistance in Mycoplasma
pneumoniae, Israel, 2010. Emerg Infect Dis 2011; 17:1079.
75.
Yamada M, Buller R, Bledsoe S, Storch GA. Rising rates of macrolide-resistant
Mycoplasma pneumoniae in the central United States. Pediatr Infect Dis J 2012; 31:409.
76.
Kawai Y, Miyashita N, Yamaguchi T, et al. Clinical efficacy of macrolide antibiotics
against genetically determined macrolide-resistant Mycoplasma pneumoniae pneumonia in
paediatric patients. Respirology 2012; 17:354.
77.
Chironna M, Sallustio A, Esposito S, et al. Emergence of macrolide-resistant strains
during an outbreak of Mycoplasma pneumoniae infections in children. J Antimicrob Chemother
2011; 66:734.
78.
Okada T, Morozumi M, Tajima T, et al. Rapid effectiveness of minocycline or
doxycycline against macrolide-resistant Mycoplasma pneumoniae infection in a 2011 outbreak
among Japanese children. Clin Infect Dis 2012; 55:1642.
79.
Kawai Y, Miyashita N, Kubo M, et al. Nationwide surveillance of macrolide-resistant
Mycoplasma pneumoniae infection in pediatric patients. Antimicrob Agents Chemother 2013;
57:4046.
80.
Zheng X, Lee S, Selvarangan R, et al. Macrolide-Resistant Mycoplasma pneumoniae,
United States. Emerg Infect Dis 2015; 21:1470.
81.
Diaz MH, Benitez AJ, Cross KE, et al. Molecular Detection and Characterization of
Mycoplasma pneumoniae Among Patients Hospitalized With Community-Acquired Pneumonia
in the United States. Open Forum Infect Dis 2015; 2:ofv106.
82.
Yoo SJ, Kim HB, Choi SH, et al. Differences in the frequency of 23S rRNA gene
mutations in Mycoplasma pneumoniae between children and adults with community-acquired
pneumonia: clinical impact of mutations conferring macrolide resistance. Antimicrob Agents
Chemother 2012; 56:6393.
83.
Bradley JS, Jackson MA, Committee on Infectious Diseases, American Academy of
Pediatrics. The use of systemic and topical fluoroquinolones. Pediatrics 2011; 128:e1034.
84.
US Food and Drug Administration. FDA Safety Communication: FDA advises restricting
fluoroquinolone antibiotic use for certain uncomplicated infections; warns about disabling side
effects that can occur together. http://www.fda.gov/Drugs/DrugSafety/ucm500143.htm
(Accessed on May 13, 2016).
85.
Chien S, Wells TG, Blumer JL, et al. Levofloxacin pharmacokinetics in children. J Clin
Pharmacol 2005; 45:153.
86.
American Academy of Pediatrics. Tables of antibacterial drug dosages. In: Red Book:
2015 Report of the Committee on Infectious Diseases, 30th, Kimberlin DW, Brady MT, Jackson
MA, Long SS. (Eds), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.881.
87.
Yiş U, Kurul SH, Cakmakçi H, Dirik E. Mycoplasma pneumoniae: nervous system
complications in childhood and review of the literature. Eur J Pediatr 2008; 167:973.
88.
Daxboeck F. Mycoplasma pneumoniae central nervous system infections. Curr Opin
Neurol 2006; 19:374.