a 7-year - old girl had been healthy until 7 days before she was admitted to niigata prefectural hospital , niigata , japan , on june 21 , 2010 , for cough and prolonged fever . on day 1 of her illness ,
the girl had visited her primary care physician and was prescribed azithromycin , a macrolide antimicrobial drug , for a lower respiratory tract infection . on day 7 of her illness ,
the girl s condition worsened acutely , with increased cough and fever , and she again visited her primary care physician .
a chest radiograph showed pulmonary infiltrates in the left upper lung , and the patient was referred to our hospital on day 8 of her illness .
the girl s history and family history were unremarkable . on hospital admission , the patient was alert and oriented .
her temperature was 38.9c , heart rate was 101 beats / min , and oxygen saturation was 97% .
the girl did not describe symptoms of myalgia , and physical examination did not show signs of erythema , hepatosplenomegaly , neurologic abnormalities , muscle weakness , or muscle atrophy .
results of the initial laboratory test were as follows : leukocyte count , 6.2  10 cells / l ( reference 3.08.6  10 cells / l ) ; hemoglobin , 1.95 mmol / l ( reference 1.672.31 mmol / l ) ; platelet count , 23.3  10/l ( reference 15.036.1  10/l ) ; c - reactive protein , 27 mg / l ( reference < 3.0 mg / l ) ; aspartate aminotransferase , 161 iu / l ( reference 1331 iu / l ) ; alanine aminotransferase , 83 iu / l ( reference 627 iu / l ) ; lactate dehydrogenase , 691 iu / l ( reference119229 iu / l ) ; blood urea nitrogen , 3.2 mmol urea / l ( reference 2.97.2 mmol urea /
l ) ; creatinine , 31.8 mol / l ( reference 44.270.6 mol / l ) ; sodium , 135 mmol / l ( reference 138146 mmol / l ) ; potassium , 4.1 mmol / l ( reference 3.64.9
mmol / l ) ; and chloride 96 mmol / l ( reference 99109 mmol / l ) . a venous blood gas determination on room air showed a ph of 7.464 ( reference 7.357.45kpa ) and carbon dioxide partial pressure of 4.9 kpa ( reference 4.76.0 kpa ) .
levels of serum glucose , albumin , calcium , amylase , and bilirubin were normal ( references 70109 mg / dl , 4.15.0 g / dl , 8.710.0 mg / dl , 39108 u / ml , and 0.30.9 mg / dl , respectively ) .
creatine phosphokinase was elevated to 12,159 ng / ml ( reference 45163 ng / ml ) .
urinalysis showed blood 3 + , but analysis of urine sediment by microscopy showed no erythrocytes .
the urine myoglobin level was 39,900 g / l ( reference < 10 g / l ) .
the serum concentration of cytokine interleukin ( il)-18 on admission was 612 pg / ml ( reference < 260 pg / ml ) , and the concentration of tumor necrosis factor ( tnf- ) was 3.48 pg / ml ( reference < 1.79 pg / ml ) .
the girl s fever did not respond to treatment with azithromycin , and she was given a tentative diagnosis of antimicrobial drug 
because the patient was < 8 years of age , she was started on treatment with tosufloxacin , a fluoroquinolone , granules for children ( 12 mg / kg / d ) and steroid therapy ( methylprednisolone , 1 mg / kg / d ) .
the patient s fever resolved the next day , and her urine output was maintained with intravenous hydration .
no signs or symptoms of muscle involvement developed during the patient s hospital stay . on day 16
after the patient was admitted to the hospital , results of laboratory testing showed improved values for creatine phosphokinase ( 1,855 ng / ml ) , aspartate aminotransferase ( 101 iu / l ) , alanine aminotransferase ( 162
pulmonary infiltrates seen on a chest radiograph had decreased substantially by day 16 , and the patient was discharged from the hospital . on day 8 after discharge , her abnormal test results returned to normal , and her illness showed no signs of relapse .
culture results for a respiratory sample obtained during hospitalization revealed normal bacterial flora , and the results for rapid diagnostic tests for influenza virus , adenovirus , and respiratory syncytial virus were negative at admission .
the m. pneumoniae antibody titer by the particle agglutination test was 1,280 at admission , and 2 days later , the antibody titer had increased to 10,240 . at hospital admission , with permission from the girl and her parents , a pharyngeal swab specimen was obtained to test for m. pneumoniae .
the sample was sent to the laboratory of the kanagawa prefectural institute of public health , chigasaki , japan , where pcr and restriction fragment length polymorphism analysis were performed as described ( 1 ) .
a macrolide - resistant m. pneumoniae strain with an ag transition at position 2063 of the 23s rrna gene ( designated a2063 g ) was detected .
laboratory test results from admission to 8 days after discharge are summarized in the table .
this case of rhabdomyolysis in a 7-year - old girl is an unusual extrapulmonary manifestation of antimicrobial drug  resistant m. pneumoniae infection .
rhabdomyolysis is characterized by rupture and necrosis of muscle fibers , resulting in the release of cell breakdown products into the bloodstream and extracellular space .
direct muscle injury is the most common cause of rhabdomyolysis , but a number of other causes are possible : hereditary enzyme disorders , drugs , toxins , endocrinopathies , malignant hyperthermia , neuroleptic malignant syndrome , heatstroke , hypothermia , electrolyte alterations , diabetic ketoacidosis and nonketotic hyperosmolar coma , severe hypothyroidism or hyperthyroidism , and bacterial or viral infections ( 2 ) .
bacterial and viral infections account for 5% of rhabdomyolysis cases in adults ( 3 ) . because pathomechanisms other than infection can cause rhabdomyolysis ( 4,5 )
, we can not say with certainty that m. pneumoniae infection caused this syndrome in the patient reported here .
one possible mechanism of rhabdomyolysis is induction of inflammatory cytokines , such as tnf- and il-1 .
these cytokines can cause acute proteolysis in a variety of organs , including skeletal muscles ( 6,7 ) , and m. pneumoniae can induce these cytokines ( 8) . our patient had high levels of tnf- and il-18 during the acute phase of m. pneumoniae infection , and it is highly possible that these m. pneumoniae 
no other apparent cause , such as trauma , endocrine disorder , or infection , other than m. pneumoniae , was found for the development of rhabdomyolysis in this patient .
a confounding factor in this case was that the extrapulmonary manifestation of m. pneumoniae infection was caused by an antimicrobial drug  resistant strain of m. pneumoniae .
approximately 15% of m. pneumoniae strains isolated from patients in japan are resistant to antimicrobial drugs ( 1,9,10 ) , which may explain why extrapulmonary manifestations of antimicrobial drug 
however , the proportion of antimicrobial drug  resistance in japan is increasing , so extrapulmonary manifestations of antimicrobial drug 
resistant m. pneumoniae infection might also increase . in conclusion , this case of rhabdomyolysis was associated with and , in the absence of any other apparent cause , appears to be attributable to infection with antimicrobial drug
the development of a system that can be used in routine clinical practice to rapidly identify antimicrobial drug  resistant m. pneumoniae would be highly beneficial in this era of increasing antimicrobial drug resistance .
 we describe a case of rhabdomyolysis in a patient infected with antimicrobial drug  resistant mycoplasma pneumoniae the patient s acute - phase serum levels of interleukin-18 and tumor necrosis factor were high , which suggests a pathogenic role for m. pneumoniae . in an era of increasing antimicrobial drug resistance , a system for rapidly identifying resistant m. pneumoniae would be beneficial . 
Case Report
Conclusions