Clinical characteristics of patients
A total of 107 patients diagnosed with MPP, aged 81 days to 14 years, were enrolled in our study between December 1, 2016, and May 31, 2019. Of these, 55 patients were male. There was no significant difference in sex. Fifty-six patients were diagnosed with RMPP. The general characteristics of all 107 patients are shown in Table 1.
Table 1
General characteristics of the patients
Characteristic | No (%) |
Total | 107 |
Age (y) | 4.268 ± 3.294 |
Sex, No. (%) | |
Male | 55(51.40) |
Female | 52(48.60) |
Underlying diseases, No. (%) |
None | 98(91.59) |
Congenital heart disease | 5(4.67) |
Congenital biliary atresia | 2(1.87) |
Other diseases | 2(1.87) |
Symptoms and signs | |
Fever, No. (%) | 100(93.46) |
Duration of fever (d) | 7.690 ± 5.770 |
Cough, No. (%) | 107(100) |
Wheezing, No. (%) | 31(28.97) |
Duration of wheezing (d) | 0.00(0.00,5.00) |
RMPP, No. (%) | 56(52.34) |
Hypoxemia, No. (%) | 16(14.95) |
Mechanical ventilation, No. (%) | 7(6.54) |
Application of glucocorticoids, No. (%) | 60(56.07) |
Replacement of antibiotics, No. (%) | 19(17.76) |
7-day course of azithromycin, No. (%) | 42(39.25) |
Coinfection, No. (%) | 60(56.07) |
MP with A2063G mutation, No. (%) | 68(63.55) |
Prognosis after treatment, No. (%) |
Surviving | 105(98.13) |
Nonsurviving | 2(1.87) |
Data are No. (%) of patients, mean ± standard deviation (SD) or median (interquartile range). |
Distribution And Prevalence Of Pathogens
Among the 107 patients, 60 patient were coinfected with viruses, including human rhinovirus/enterovirus, ADV, RSV, parainfluenza virus type 1, parainfluenza virus type 3, parainfluenza virus type 4, coronavirus OC43, coronavirus 229E, FluA and FluB. The overall coinfection rate was 56.07%. ADV was the most prevalent organism, accounting for 22.43% (24/107), followed by parainfluenza virus (13.08%,14/107) and human rhinovirus/enterovirus (11.21%, 12/107). Two or more pathogens were detected in 11 patients, and the rate of infection with multiple viruses was 10.28%. Coinfections were more likely to be found in younger patients. Three years old may be an optimal cut-off value to distinguish viral coinfection from MP single infection using the machine learning-based method, the classification tree.
All patients enrolled in this study underwent A2063G and A2064G mutation gene tests with PCR. Sixty-eight (68/107, 63.55%) patients were confirmed to have a gene mutation, all of which were A2063G mutations, the most prevalent mutation in Asian countries. Among the 68 patients infected with drug-resistant MP, 40 (40/68, 58.82%) progressed to RMPP. However, only 16 (16/39, 41.03%) children infected by drug-sensitive MP were diagnosed with RMPP.
Clinical Characteristics Of General Mpp And Rmpp
Fifty-six (56/107, 52.34%) patients were diagnosed with RMPP during our research period. A2063G mutation and coinfection with ADV were more commonly detected in the RMPP group (P = 0.001; P = 0.019). More patients with RMPP continued having a fever after receiving macrolide antibiotic treatment for 48 hours (P < 0.001), leading to a significantly longer duration of fever (P < 0.001) and increasing the proportion of patients using glucocorticoids (P = 0.001). Although there were no significant differences in the leukocyte counts and CRP levels, the erythrocyte sedimentation rate (ESR) was higher in the RMPP group (P = 0.045). There were no remarkable differences in coinfection rates between the two groups, except for the patients with ADV coinfection (P = 0.019). ADV coinfection was more likely to be detected in patients with RMPP. With respect to the lung radiographs, more pulmonary consolidation was found in the patients with RMPP. In contrast, interstitial changes were likely to be discovered in general MPP (GMPP) (P = 0.02) (Table 2).
Table 2
Clinical characteristics of GMPP and RMPP
Characteristics | GMPP (n = 51) | RMPP (n = 56) | P value |
Age (y) | 3.679 ± 3.193 | 4.805 ± 3.322 | 0.077 |
Sex (male/female) | 27/51 | 28/56 | 0.847 |
Clinical presentation |
Wheezing, No. (%) | 7(13.73) | 13(23.21) | 0.227 |
Hypoxemia, No. (%) | 4(7.84) | 12(21.43) | 0.060 |
Duration of fever (d) | 4.784 ± 2.831 | 10.339 ± 6.473 | < 0.001 |
Duration of wheezing (d) | 0.00(0.00,5.00) | 0.00(0.00,7.00) | 0.459 |
Extrapulmonary complications, No. (%) | 6(11.76) | 12(23.21) | 0.137 |
Imaging features, No. (%) | |
Consolidation, No. (%) | 22(43.14) | 37(66.07) | 0.02 |
Interstitial changes, No. (%) | 26(50.98) | 16(28.57) | 0.029 |
Laboratory detection | | |
White blood cell count (*109/L) | 9.583 ± 3.348 | 8.420 ± 3.530 | 0.084 |
Lymphocyte percentage (%) | 37.291 ± 14.817 | 32.352 ± 14.690 | 0.088 |
C-reactive protein (mg/l) | 12.00(8.00,25.00) | 11.00(5.00,25.75) | 0.664 |
ESR (mm/h) | 29.11 ± 19.935 | 37.88 ± 22.412 | 0.045 |
Coinfection, No. (%) | 28(54.90) | 32(57.14) | 0.847 |
Coinfection with adenovirus, No. (%) | 6(11.76) | 18(32.14) | 0.019 |
A2063G mutation, No. (%) | 20(39.22) | 40(71.43) | 0.001 |
Treatment | | | |
No fever within 48 hours after application of macrolides, No. (%) | 6(11.76) | 50(89.29) | < 0.001 |
Application of glucocorticoids, No. (%) | 24(47.06) | 44(78.57) | 0.001 |
Mechanical ventilation, No. (%) | 4(7.84) | 3(5.36) | 0.707 |
Data are No. (%) of patients, mean ± standard deviation (SD) or median (interquartile range). Abbreviation: General Mycoplasma pneumoniae pneumonia (GMPP); refractory Mycoplasma pneumoniae pneumonia (RMPP). |
Predictors Of Adenovirus Coinfection or Drug-resistant Mp Infection
As mentioned above, more children coinfected with ADV or infected with drug-resistant MP were found in the RMPP group than in the GMPP group. It is important to investigate the risk factors for ADV coinfection or macrolide-resistant MP infection. During the study period, 24 (24/107, 22.43%) patients were coinfected with ADV, which made the course of the disease more severe. Nine (9/24, 37.5%) patients who developed extrapulmonary complications were coinfected with ADV, whereas only 10 (10/83, 12.05%) children were diagnosed with extrapulmonary complications in the non-ADV group (P = 0.012). Wheezing and lung consolidation were more likely to occur in children with ADV coinfection than in those without (P = 0.002; P = 0.010). Furthermore, the duration of fever in ADV-coinfected patients was much longer than in the other patients (P = 0.007) (Table 3).
To identify drug-resistant MP infection, mutant gene detection was carried out. The total positive rate was 63.55%. The mutation rate was 71.43% in RMPP patients, which was significantly higher than that in the GMPP group (P = 0.001) (Table 2). More patients with prolonged fever duration after the appropriate administration of macrolides for 48 hours were in the group infected by drug-resistant MP than in the group not infected with drug-resistant MP (P = 0.002) (Table 4). In addition, a fever duration longer than 7 days had a strong relationship with drug-resistant MP infection according to multivariable logistic regression (OR = 3.500, 95% CI = 1.310–9.353, P = 0.012).
Table 3
Risk factors for MPP with adenovirus coinfection
Characteristics | With adenovirus coinfection (n = 24) | Without adenovirus coinfection (n = 83) | P value |
Age (y) | 3.362 ± 2.590 | 4.531 ± 3.440 | 0.078 |
Sex (male/female) | 13/11 | 42/41 | 0.819 |
Clinical presentation |
Wheezing, No. (%) | 10(41.67) | 10(12.05) | 0.002 |
Hypoxemia, No. (%) | 6(25.00) | 10(12.05) | 0.189 |
Extrapulmonary complications, No. (%) | 9(37.50) | 10(12.05) | 0.012 |
Duration of fever (d) | 12.083 ± 9.343 | 6.422 ± 3.357 | 0.007 |
Duration of wheezing (d) | 0.00(0.00,8.00) | 0.00(0.00,5.00) | 0.570 |
Fever longer than 7 days, No. (%) | 20(83.33) | 36(43.37) | 0.001 |
Imaging features | |
Consolidation, No. (%) | 19(79.17) | 40(48.19) | 0.010 |
Interstitial changes, No. (%) | 5(20.83) | 37(44.58) | 0.056 |
Laboratory tests | | |
White blood cell count (*109/L) | 9.003 ± 3.487 | 8.966 ± 3.496 | 0.964 |
Lymphocyte percentage (%) | 36.488 ± 14.274 | 34.153 ± 15.106 | 0.491 |
C-reactive protein (mg/l) | 10.00(4.00,25.00) | 12.00(7.25,25.00) | 0.997 |
A2063G mutation, No. (%) | 9(37.50) | 51(61.45) | 0.060 |
Treatment | | |
No fever within 48 hours after application of macrolides, No. (%) | 5(20.83) | 26(31.33) | 0.445 |
Application of glucocorticoids, No. (%) | 17(70.83) | 51(61.45) | 0.476 |
Mechanical ventilation, No. (%) | 1(4.17) | 6(7.23) | 1 |
Data are No. (%) of patients, mean ± standard deviation (SD) or median (interquartile range). |
Table 4
Risk factors for MPP with A2063G mutation
Characteristics | Without A2063G mutation (n = 39) | With A2063G mutation (n = 68) | P value |
Age (y) | 3.792 ± 3.537 | 4.642 ± 3.069 | 0.187 |
Sex (male/female) | 23(58.97) | 32(47.06) | 0.699 |
Clinical presentation |
Wheezing, No. (%) | 10(25.64) | 10(14.70) | 0.621 |
Hypoxemia, No. (%) | 8(20.51) | 8(11.76) | 0.599 |
Extrapulmonary complications, No. (%) | 9(23.08) | 10(14.70) | 0.802 |
Duration of fever (d) | 7.234 ± 6.356 | 8.050 ± 5.293 | 0.470 |
Duration of wheezing (d) | 0.00(0.00,6.50) | 0.00(0.00,5.00) | 0.499 |
Fever longer than 7 days, No. (%) | 16(41.03) | 35(51.47) | 0.019 |
Imaging features, No. (%) | |
Consolidation, No. (%) | 30(76.92) | (42,65) | 0.122 |
Interstitial changes, No. (%) | 16(41.03) | 26(38.24) | 0.425 |
Laboratory tests, No. (%) | | |
White blood cell count (*109/L) | 9.274 ± 3.179 | 8.740 ± 3.701 | 0.433 |
Lymphocyte percentage (%) | 35.023 ± 15.922 | 34.410 ± 14.142 | 0.834 |
C-reactive protein (mg/l) | 13.00(8.00,29.00) | 11.00(4.50,22.00) | 0.107 |
ESR (mm/h) | 29.950 ± 21.995 | 36.620 ± 21.102 | 0.136 |
Treatment | | |
No fever within 48 hours after application of macrolides, No. (%) | 21(53.85) | 10(14.70) | 0.002 |
Application of glucocorticoids, No. (%) | 24(61.54) | 44(64.71) | 0.026 |
Mechanical ventilation, No. (%) | 4(10.26) | 3(4.35) | 0.697 |
Data are No. (%) of patients, mean ± standard deviation (SD) or median (interquartile range). |
Multivariable logistic regression was further carried out to verify the associations between the variables and ADV coinfection. Patients with symptoms of wheezing (X1) (OR = 5.559, 95% CI = 1.726–17.901, P = 0.004), consolidation on chest X-ray (X2) (OR = 4.290, 95% CI = 1.305–14.106, P = 0.016) and extrapulmonary complications (X3) (OR = 4.225, 95% CI = 1.331–13.603, P = 0.015) all had a higher risk of ADV coinfection than their counterparts (Table 5). Therefore, based on logistic regression, a prediction model including wheezing, lung consolidation and extrapulmonary complications was established: Logit(P) = (-2.931) + 1.715X1 + 1.456X2 + 1.488X3. The predictive values of the individual risk factors and the prediction model were assessed by ROC curve analysis, which showed that the model had a high level of diagnostic accuracy, with an AUC of 0.795 (95% CI 0.679–0.893, P < 0.001). Additionally, wheezing, lung consolidation and extrapulmonary complications had some predictive value separately (Fig. 1).
Table 5
Analysis of risk factors related to adenovirus coinfection
Variables | OR (95%) | P value |
Wheezing | 5.559(1.726–17.901) | 0.004 |
Lung consolidation | 4.290(1.305–14.106) | 0.016 |
Extrapulmonary complications | 4.225(1.331–13.603) | 0.015 |