Management of Macrolide-resistant Mycoplasma pneumoniae Infection

Abstract

To the Editors: In April 2012, Yamada et al1 reported an increasing trend of macrolide resistance in Mycoplasma pneumoniae strains in the United States. In Europe, reports of macrolide resistance in M. pneumoniae are still uncommon. This is the first Belgian case report describing the course and management of an infection with a proven macrolide-resistant M. pneumoniae strain. An 8-year-old girl presented with high fever, cough, mild tachypnea and left basal crepitations on lung auscultation. The white blood cell count was 5800/µL with 45% neutrophils and the C-reactive protein was 14.4 mg/L. Chest radiograph showed alveolar consolidation in the lingula and right middle lobe. Oral amoxicillin was started. The following day, she was admitted to hospital with persisting fever (up to 40.1°C) and dehydration. Testing by polymerase chain reaction (PCR) for M. pneumoniae on an upper airway swab specimen was positive, and azithromycin (200 mg daily for 5 days, ie, 10 mg/kg) was prescribed. She was discharged from hospital when she had been afebrile for 48 hours. One week later, she presented because of persistent severe cough and recurrence of high fever. Clinical examination revealed crepitations mainly in the right chest. The white blood cell count was 9600/µL with 59% neutrophils, and the C-reactive protein was 2 mg/L. Erythrocyte sedimentation rate was 40 mm/h. An upper airway swab specimen was negative for influenza virus A and B, parainfluenza virus type 1–4, respiratory syncytial virus, human metapneumovirus and adenovirus. M. pneumoniae PCR was still positive. Chest roentgenogram showed an alveolar consolidation in the right upper and left lower lobes and in the lingula. Azithromycin was restarted but without clinical improvement during the next 3 days. Antibiotic therapy was changed to ciprofloxacin (20 mg/kg/d in 3 doses) because a macrolide-resistant M. pneumoniae strain was suspected. The girl became afebrile after 24 hours. Ciprofloxacin was continued for 14 days. Lung auscultation and chest radiograph slowly normalized. A few days after discontinuation of ciprofloxacin, a new cough developed. A control throat swab still showed M. pneumoniae by PCR testing. The cough cleared spontaneously. Extensive investigations to exclude underlying humoral or cellular immunodeficiency were performed after resolution of the Mycoplasma infection but were all negative. To confirm the macrolide resistance of the M. pneumoniae strain, DNA extracts from the respiratory samples were taken before starting antibiotics, 4 days after the 5-day course of azithromycin, 3 days after changing to ciprofloxacin and 3 weeks after stopping ciprofloxacin therapy. All samples were analyzed for mutations in the 23S ribosomal RNA of M. pneumoniae associated with macrolide resistance.2 Sequencing showed that the strain in the first sample was macrolide-susceptible whereas the sequences obtained from later samples showed a mutation at position 2063 (A–G) of 23S ribosomal RNA representing the most common cause of macrolide resistance in M. pneumoniae. Because the strain initially had the macrolide-susceptible genotype, the mutation could have occurred de novo during therapy.3 Otherwise, the patient might have been infected by different genotypes of M. pneumoniae. However, all strains in the 4 samples belonged to the same genotype: variant 2b (P1-type) and VNTR-type 5/3/6/6/2 indicating the persistence of an identical strain.4 Out of concern for development of fluoroquinolone resistance of the strain obtained after ciprofloxacin therapy, nested PCRs were performed that revealed no differences in the partly sequenced gyrA, gyrB, parB and parC genes. The cause of the cough after ciprofloxacin treatment remains unclear. This case confirms the development of macrolide resistance during adequate therapy for M. pneumoniae pneumonia. We recommend molecular characterization of strains in infections not responding to treatment with macrolides. Veroniek Saegeman, MD, PhD Department of Laboratory Medicine UZ Leuven Marijke Proesmans, MD, PhD Department of Paediatrics UZ Leuven Leuven, Belgium Roger Dumke, PhD Dresden University of Technology Institute of Medical Microbiology and Hygiene Dresden, Germany