Azithromycin

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Development of De Novo macrolide-resistance during treatment of Mycoplasma pneumoniae pneumonia: case report A 3-year-old girl developed De Novo macrolide-resistance during treatment with azithromycin for Mycoplasma pneumoniae pneumonia. The girl was diagnosed with high-risk pre-B-acute lymphoblastic keukemia in September 2017. In May 2018, she was admitted with few weeks history of fever and worsening cough in the setting continued treatment of acute lymphoblastic leukemia with doxorubicin and vincristine. She started receiving treatment with cefepime and continued to receive her home fluconazole for previously diagnosed Candida tropicalis osteomyelitis. Thereafter, she was diagnosed with M. pneumoniae pneumonia. The M. pneumoniae macrolide resistance real-time PCR assay showed lack of macrolide-resistance mutations in the 23S rRNA gene. The minimum inhibitory concentration (MIC) for erythromycin was 0.004 µg/mL, confirming macrolide susceptibility. Thus, she started receiving treatment with high-dose azithromycin 10 mg/kg/day for 3 days [route not stated]. Subsequently, her fever resolved, cough improved and she was discharged from the hospital. In October 2018, she was re-admitted for a febrile illness with worsening cough, which was present for 2 weeks prior to admission. Her family denied any sick contacts or family members with similar symptoms. On admission, she was neutropenic and her nasopharyngeal aspirate test was positive for rhinovirus and enterovirus [aetiologies unknown], but was negative for M. pneumoniae based on multiplexed PCR. Her lung examination was normal. Chest radiography revealed scattered interstitial infiltrates in both lungs. Over the next 7 days, she received cefepime and home fluconazole; however, her high-spiking fever continued and a subsequent decline in respiratory status indicated tachypnoea and hypoxaemia. Chest CT scan on day 8 of admission showed right upper lobe and right lower lobe pneumonia with right hilar and para-tracheal lymphadenopathy. A repeat nasopharyngeal multiplexed PCR assay was negative for previously recovered viruses and M. pneumoniae. The bronchoalveolar lavage (BAL) tested positive for M. pneumoniae on real-time PCR and culture. Azithromycin [route and dosage not stated] and vancomycin were added to her therapy due to persistent clinical worsening. The next day, a macrolide-resistance mutation in the 23S rRNA gene was identified in the isolate by M. pneumoniae macrolide resistance real-time PCR assay. Sequencing of the amplicon confirmed two different point mutations conferring macrolide resistance in a mixed population (A2063G or A2063T; Escherichia coli numbering 2058). BAL culture grew M. pneumoniae with an erythromycin MIC of 32 µg/mL, confirming development of macrolide [azithromycin] resistance. The girl was hypogammaglobulinaemic and received immune globulin. Also, her treatment with azithromycin was changed to levofloxacin, which eventually led to improvement of her fever, hypoxaemia and respiratory symptoms. Four days later, she was discharge