Mycoplasma infection in Malaysian children : laboratory investigation and antimicrobial therapy

Introduction Mycoplasma is the smallest and simplest self limiting bacteria. It is the commonest cause of primary atypical pneumonia resistant to ?-lactam antibiotics in older children and young adults. Clinical diagnosis of Mycoplasma pneumoniae pneumonia is difficult as viral and other pneumonias show similar clinical features. Numerous studies were undertaken that provided new insights into the various clinical presentations associated with M. pneumoniae infection.1,2 Few reports showed that it could also cause severe disease not limited to the respiratory tract but involving extra-pulmonary manifestations.3 The most common clinical findings of these patients were cough and fever where most of them had benign course and survived. The white blood cell count was often normal. However, extensive pneu-


Introduction
Mycoplasma is the smallest and simplest self limiting bacteria.It is the commonest cause of primary atypical pneumonia resistant to ?-lactam antibiotics in older children and young adults.Clinical diagnosis of Mycoplasma pneumoniae pneumonia is difficult as viral and other pneumonias show similar clinical features.Numerous studies were undertaken that provided new insights into the various clinical pre-sentations associated with M. pneumoniae infection.1,2 Few reports showed that it could also cause severe disease not limited to the respiratory tract but involving extra-pulmonary manifestations.3 The most common clinical findings of these patients were cough and fever where most of them had benign course and survived.The white blood cell count was often normal.However, extensive pneu-monia can produce a profound leukocytosis.1 In a clinical setting where M. pneumoniae infection is suspected, serology is often used in diagnosis.Previous studies compared the clinical features of patients with M. pneumoniae pneumonia to other pathogens and these studies were predominantly adult case series rather than involving children. 2 A study done in Singapore and Finland showed that the majority of M. pneumoniae infections were in school-aged children. 4 The increasing seroprevalence rates of M. pneumoniae after 2 years of age should alert clinicians to consider the organism in the differential diagnosis of infectious diseases in this age group.5 Hence, the above prompted us to conduct a study on clinical features, laboratory investigation and antimicrobial therapy of children infected with M. pneumoniae in the paediatric ward of our tertiary hospital, Universiti Kebangsaan Malaysia Medical Centre.

Study population:
A retrospective cross-sectional study was conducted on 111 paediatric patients at Universiti Kebangsaan Malaysia Medical Centre (UKMMC) from January 2010 to December 2012.Patients who admitted to the paediatric ward and suspected to M. pneumoniae infection were included in the study.However, the patients those had underlying lung disease, obtained insufficient sera samples were excluded from the study.Demographics: The patients' list was obtained from Medical Microbiology Department and the medical records were traced via the record office of UKMMC.They were categorised into two distinct groups based on the results of serological tests.Clinical manifestations': Clinical information was obtained tracing the medical report of record file of UKMMC.All the manifestations were tabulated from the patients under study.Diagnostic test: Enzyme-linked immunosorbent assay (ELISA) was used to detect IgM antibody of the suspected children of M. pneumoniae infection.The test was performed as per the manu-facturer's recommendation ( Mycoplasma pneumoniae IgM-ELISA Kit , Nova Tec Immunodiagnostica GmbH, Waldstr.23 A6 D-63128 Dietzenbach, Germany).The children were classified as seropositive and seronegative based on the results.Statistical analysis: Results were analysed using IBM SPSS Statistics 21.P< 0.05 was considered to be statistically significant.

Results:
Demographics: A total of 111 children admitted during the study period were analysed.Forty-five (40.5%) children had serological evidence of M. pneumoniae infection.Children with positive M. pneumoniae serology were more likely to be older (median age 5.0 [interquartile range 2-7] years, p < 0.001).

Clinical manifestations:
The predominant symptoms were fever and cough which occurred in 99 (89.2%) and 84 patients (75.7%) respectively.Among those having fever, 49 (44.1%) had fever for more than six days.Table 1 compares the clinical parameters between the two groups.There was significant association between cough and serology response whereby patients with cough were more likely to be seronegative (55, 65.5%; p = 0.023).There was no association found with other clinical manifestations.Crackles were the commonest physical sign where 49 (44.1%)patients had crackles during auscultation.Tachypnoea was recorded in 47 patients (42.3%) and bronchial breathing in 9 (8.1%) patients.10 9 /L), were in the normal range.When comparing between the two groups, there were no significant difference in the full blood count parameters.

Clinical response after antimicrobial therapy:
During admission, antibiotics were prescribed for 100 (90.1%) children.The patients were treated with a wide range of antimicrobial regimens where they were generally classified into ß-lactams monotherapy, macrolides monotherapy and the combination of a ß-lactam plus macrolide.
Sixty four patients received ß-lactam monotherapy and 49 (76.6%) of them were cured ( From the analysis, there was no association between duration of fever longer than six days and the serology result.However, previous study reported that the duration of fever in children with M. pneumoniae infection were likely to be longer as compared to those without infection.9 This is probably due to the fact that 53.3% of our seropositive children are less than five years old.
The clinical signs studied in this research including tachypnoea, bronchial breathing and crackles were not found to have a significant association with serology results.Although another author 9 demonstrated that crackles were more likely in M. pneumoniae infection; there were no other studies that supported this.
Study by Chen et al. 10 showed significant association between M. pneumoniae infection with neutropaenia and thrombocytopaenia where it was thought due to formation of antiplatelet and antineutrophil autoantibodies that caused the cytopaenias.On the other hand, an Australian study showed that patients with M. pneumoniae were more likely to develop thrombocytosis.11 Our findings showed that laboratory findings are rarely diagnostic for M. pneumoniae and are not useful in therapeutic decision making.
In the present study sixty four patients received ßlactam monotherapy and 49 (76.6%) of them were cured.On the other hand, only 18 patients received macrolide monotherapy with 100% cured.Previous studies suggested that the use of macrolide should be considered for children admitted with community acquired pneumonia when M. pneumoniae was suspected .12 However, ?-lactam antibiotic was commonly started empirically when it was difficult to

Table : 2: Full blood count parameters on admission in the study population
Sulong A, Murugaan T, Balakrishnan A/L, En NL, Zain NM, Mohd Sabri FL, Satariah Ali UK, Othman SN, Rahman MM

Table - 3: Clinical outcomes and antimicrobial therapy diagnose
M. pneumoniae based on initial clinical and laboratory findings before performing further diagnostic test for M. pneumoniae.The study showed treatment will reduce the morbidity of pneumonia and also reduce the duration of symptoms.These effects are seen more significantly with macrolide as compared to penicillin.Therefore, macrolide is still the antibiotic of choice as empirical treatment for children with CAP aged more than five years old when M. pneumoniae is highly suspected.In conclusion, our results reemphasise that M. pneumoniae should be kept in mind as a cause of commu-nity-acquired pneumonia of children in Malaysia.Although clinical parameters and laboratory findings have limited use of predicting M. pneumoniae infection, certain factors like age group and absence of cough may aid in deciding if the use of macrolide is needed.Acknowledgement:Authors are thankful to Dean of the Faculty of Medicine, Head of the Department of Medical Microbiology & Immunology and laboratory staffs, Universiti Kebangsaan Malaysia for their cooperation and assistance.