Macrolide Therapy Research Articles

The Effect of Erythromycin in Macrolide-Resistant Bordetella pertussis: Inhibitory Effect on Growth, Toxin Expression, and Virulence.

The macrolide-resistant Bordetella pertussis (MRBp) has appeared in Asia and has even been prevalent in China. Since the antibiotic sensitivity test is not carried out in the clinical setting, macrolide is still the first choice of antibiotic in MRBp infection. Further, the macrolide therapy for pertussis needs to be revised. Macrolide has always shown a positive effect on other macrolide-resistant bacterium infections in clinical applications. However, the mechanism of macrolide on MRBp remains unclear. The objective of this study was to investigate the effect of virulence of MRBp under the sub-MIC erythromycin. This study evaluated a representative isolate BP19147 (ptxP1/fhaB3-MRBp) under a series of sub-inhibitory concentrations of erythromycin. We measured the growth curve, biofilm formation, and autoaggregation assay under Stainer and Scholte (SS) broth. The relative gene expression was detected by RT-qPCR. The proteomics was detected by label-fee DIA. The growth ability and virulence factors of MR isolate BP19147 were inhibited by sub-MIC of erythromycin and had a concentration- dependent effect. From the proteomics results, the pertussis toxin, filamentous haemagglutinin, and pertactin did not show a statistical difference (p >0.05). Other virulence factors (including dermonecrotic toxin, Invasive Adenylate cyclase/haemolysin. etc) showed a statistical difference (p <0.05). In the KEGG enrichment, the BvgAS system, biofilm formation, and some adaptive systems were inhibited by erythromycin. The sub-MIC of erythromycin may reduce the virulence of MRBp, which will provide a theoretical basis for the rational use of erythromycin for MRBp infection and help the development of new antibiotics.

Impact of long-term macrolide therapy on the evaluation indicator of outpatient oral antimicrobial use according to the AWaRe classification

The WHO recently proposed a new indicator for judging the appropriateness of antimicrobial selection according to the AWaRe classification. Although macrolides are often administered for long-term macrolide therapy, the impact of this therapy on the indicator remains unclear. This study examined the impact of this therapy on the indicator for outpatient oral antimicrobial use. Using the JMDC claims database, outpatients who were prescribed an oral antimicrobial at least once between January and December 2022 (n = 2.66 million) were included in the study. The ratio of patient numbers and antimicrobial usage (AMU) were calculated based on age group (<15, 15–64, and ≥65 years) and prescription days (1–15, 16–30, 31–60, 61–90, and ≥91 days), and AMU of each drug was corrected for defined daily doses and classified according to the AWaRe. Patients with chronic airway disease for whom macrolides were prescribed for 91 days and more were defined as long-term macrolide therapy. Macrolides accounted for more than 30 % of total oral AMU in all age groups. In the elderly, 11.2 % of patients were prescribed macrolides for 91 days or more, accounting for 66.4 % of macrolide use. With regard to diseases that were associated with macrolide prescriptions, the percentage of patients prescribed for chronic airway diseases increased as the number of days of prescription increased. These results suggest that the impact of long-term macrolide therapy should be considered when assessing the appropriateness of outpatient oral AMU according to the AWaRe classification.

Model based on the automated AI-driven CT quantification is effective for the diagnosis of refractory Mycoplasma pneumoniae pneumonia

The prediction of refractory Mycoplasma pneumoniae pneumonia (RMPP) remains a clinically significant challenge. This study aimed to develop an early predictive model utilizing artificial intelligence (AI)-derived quantitative assessment of lung lesion extent on initial computed tomography (CT) scans and clinical indicators for RMPP in pediatric inpatients. A retrospective cohort study was conducted on patients with M. pneumoniae pneumonia (MP) admitted to the Children’s Hospital of Nanjing Medical University, China from January 2019 to December 2020. An early prediction model was developed by stratifying the patients with Mycoplasma pneumoniae pneumonia (MPP) into two cohorts according to the presence or absence of refractory pneumonia. A retrospective cohort of 126 children diagnosed with Mycoplasma pneumoniae pneumonia (MPP) was utilized as a training set, with 85 cases classified as RMPP. Subsequently, a prospective cohort comprising 54 MPP cases, including 37 instances of RMPP, was assembled as a validation set to assess the performance of the predictive model for RMPP from January to December 2021. We defined a constant Φ which can combine the volume and CT value of pulmonary lesions and be further used to calculate the logarithm of Φ to the base of 2 (Log2Φ). A clinical-imaging prediction model was then constructed utilizing Log2Φ and clinical characteristics. Performance was evaluated by the area under the receiver operating characteristic curve (AUC). The clinical model demonstrated AUC values of 0.810 and 0.782, while the imaging model showed AUC values of 0.764 and 0.769 in the training and test sets, respectively. The clinical-imaging model, incorporating Log2Φ, temperature(T), aspartate aminotransferase (AST), preadmission fever duration (PFD), and preadmission macrolides therapy duration (PMTD), achieved the highest AUC values of 0.897 and 0.895 in the training and test sets, respectively. A prognostic model developed through automated quantification of lung disease on CT scans, in conjunction with clinical data in MPP may be utilized for the early identification of RMPP.

Bronchiectasis management in adults: state of the art and future directions.

Formerly regarded as a rare disease, bronchiectasis is increasingly recognised. A renewed interest in this disease has led to significant progress in bronchiectasis research. Randomised clinical trials have demonstrated the benefits of airway clearance techniques, inhaled antibiotics and long-term macrolide therapy in bronchiectasis patients. However, the heterogeneity of bronchiectasis remains one of the most challenging aspects of management. Phenotypes and endotypes of bronchiectasis have been identified to help find "treatable traits" and partially overcome disease complexity. The goals of therapy for bronchiectasis are to reduce the symptom burden, improve quality of life, reduce exacerbations and prevent disease progression. We review the pharmacological and non-pharmacological treatments that can improve mucociliary clearance, reduce airway inflammation and tackle airway infection, the key pathophysiological features of bronchiectasis. There are also promising treatments in development for the management of bronchiectasis, including novel anti-inflammatory therapies. This review provides a critical update on the management of bronchiectasis focusing on treatable traits and recent randomised clinical trials.

Patients at risk of nontuberculous mycobacterial pulmonary disease who need testing evaluated using a modified Delphi process by European experts

BackgroundIdentifying patients at risk of nontuberculous mycobacterial pulmonary disease (NTM-PD) is challenging. Delays in NTM-PD identification and management are associated with declining lung function and increased morbidity and mortality.Study design and methodsEuropean NTM-PD experts (n=12) participated in a three-round modified Delphi process to score symptoms and comorbidities potentially associated with NTM-PD as reasons to test for nontuberculous mycobacteria.ResultsExperts reached a consensus on the symptoms and comorbidities that should and should not prompt testing for nontuberculous mycobacteria. Requirements for testing were scored as high (mean ≥7), medium (mean ≥4–&lt;7) or low (mean &lt;4). Nontuberculous mycobacteria testing should be undertaken when multiple suggestive symptoms are present simultaneously in all patients except those with cancer (7.3–8.8), or when radiology is indicative of NTM-PD (≥8.9). Symptoms of persistent sputum production, recurrent respiratory infection and haemoptysis should prompt testing for nontuberculous mycobacteria, particularly in those with underlying respiratory diseases. Symptomatic patients with bronchiectasis or previous tuberculosis/NTM-PD or those being prescribed or undergoing long-term macrolide therapy for a respiratory condition should also be tested. Testing is not warranted in patients without an underlying respiratory disorder or in those without a history of respiratory disorders unless presenting with multiple symptoms.ConclusionsAssessing patients’ risk of NTM-PD is challenging. This Delphi consensus process provides insight into symptoms and clinical characteristics that should prompt NTM-PD assessment. Timely testing and diagnosis would enable initiation of appropriate management.

Utilizing Histopathology to Predict Success with Macrolide Therapy in CRS Patients.

There is currently interest regarding CRSsNP patients with refractory symptomatology following functional endoscopic sinus surgery, and which of these patients can derive benefit from low-dose macrolide therapy. In the present study, we analyze a cohort of over fifty CRSsNP patients on macrolide therapy; structured histopathological findings at the time of surgery were analyzed against the success of macrolide treatment. Independently, fibrosis, absence of squamous metaplasia, absence of eosinophilia, presence of neutrophilic infiltrate, and lymphoplasmocytic predominance were all associated with objective success of macrolide treatment; these findings may allow clinicians to more appropriately select patients for this therapy.

Ureaplasma urealyticum as a Cause of Ventriculitis in an Extremely Low Birth Weight Infant

Abstract Ureaplasma urealyticum (Uu) has rarely been described as a cause of ventriculitis in preterm infants. We report a preterm infant in whom Uu was detected in the tracheal secretion. Concurrent intraventricular hemorrhage III° with posthemorrhagic hydrocephalus occurred, necessitating the bilateral insertion of ventriculostomy access devices for treatment. Persisting high cerebrospinal fluid (CSF) protein and pleocytosis in the otherwise clinically unremarkable neonate subsequently led to the targeted detection of Uu in the CSF. Normalization of CSF parameters occurred only after prolonged intravenous and oral macrolide therapy.

Impact of Pharmacogenetic Markers on the Safety of Macrolide Therapy in Patients with Bacterial Complications of Influenza

Impact of Pharmacogenetic Markers on the Safety of Macrolide Therapy in Patients with Bacterial Complications of Influenza

The Effectiveness and Safety of Long-Term Macrolide Therapy for COPD in Stable Status: A Systematic Review and Meta-Analysis.

Background: Chronic obstructive pulmonary disease (COPD) is a prevalent condition with fewer treatments available as the severity increases. Previous systematic reviews have demonstrated the benefits of long-term macrolide use. However, the therapeutic differences between different macrolides and the optimal duration of use remain unclear. Methods: A systematic review and meta-analysis were conducted to assess the effectiveness of long-term macrolide use in reducing COPD exacerbations, compare the therapeutic differences among macrolides, and determine the appropriate treatment duration. Four databases (PubMed, Cochrane Library, Web of Science, and ICHU-SHI) were searched until 20 March 2023, and a random-effects model was used to calculate the pooled effect. Results: The meta-analysis included nine randomized controlled trials involving 1965 patients. The analysis revealed an odds ratio (OR) of 0.34 (95% confidence interval [CI] 0.19, 0.59, p < 0.001) for the reduction in exacerbation frequency. Notably, only azithromycin or erythromycin showed suppression of COPD exacerbations. The ORs for reducing exacerbation frequency per year and preventing hospitalizations were -0.50 (95% CI: -0.81, -0.19; p = 0.001) and 0.60 (95% CI: 0.3, 0.97; p = 0.04), respectively. Statistical analyses showed no significant differences between three- and six-month macrolide prescriptions. However, studies involving a twelve-month prescription showed an OR of 0.27 (95% CI: 0.11, 0.68; p = 0.005; I2 = 81%). Although a significant improvement in St George's Respiratory Questionnaire (SGRQ) total scores was observed with a mean difference of -4.42 (95% CI: -9.0, 0.16; p = 0.06; I2 = 94%), the minimal clinically important difference was not reached. While no adverse effects were observed between the two groups, several studies have reported an increase in bacterial resistance. Conclusions: Long-term use of azithromycin or erythromycin suppresses COPD exacerbations, and previous studies have supported the advantages of a 12-month macrolide prescription over a placebo.

The Impact of Long-Term Macrolide Exposure on the Gut Microbiome and Its Implications for Metabolic Control.

Long-term low-dose macrolide therapy is now widely used in the treatment of chronic respiratory diseases for its immune-modulating effects, although the antimicrobial properties of macrolides can also have collateral impacts on the gut microbiome. We investigated whether such treatment altered intestinal commensal microbiology and whether any such changes affected systemic immune and metabolic regulation. In healthy adults exposed to 4 weeks of low-dose erythromycin or azithromycin, as used clinically, we observed consistent shifts in gut microbiome composition, with a reduction in microbial capacity related to carbohydrate metabolism and short-chain fatty acid biosynthesis. These changes were accompanied by alterations in systemic biomarkers relating to immune (interleukin 5 [IL-5], IL-10, monocyte chemoattractant protein 1 [MCP-1]) and metabolic (serotonin [5-HT], C-peptide) homeostasis. Transplantation of erythromycin-exposed murine microbiota into germ-free mice demonstrated that changes in metabolic homeostasis and gastrointestinal motility, but not systemic immune regulation, resulted from changes in intestinal microbiology caused by macrolide treatment. Our findings highlight the potential for long-term low-dose macrolide therapy to influence host physiology via alteration of the gut microbiome. IMPORTANCE Long-term macrolide therapy is widely used in chronic respiratory diseases although its antibacterial activity can also affect the gut microbiota, a key regulator of host physiology. Macrolide-associated studies on the gut microbiota have been limited to short antibiotic courses and have not examined its consequences for host immune and metabolic regulation. This study revealed that long-term macrolides depleted keystone bacteria and impacted host regulation, mediated directly by macrolide activity or indirectly by alterations to the gut microbiota. Understanding these macrolide-associated mechanisms will contribute to identifying the risk of long-term exposure and highlights the importance of targeted therapy for maintenance of the gut microbiota.

The Mechanism of Action and Clinical Efficacy of Low-Dose Long-Term Macrolide Therapy in Chronic Rhinosinusitis.

Various chronic inflammatory airway diseases can be treated with low-dose, long-term (LDLT) macrolide therapy. LDLT macrolides can be one of the therapeutic options for chronic rhinosinusitis (CRS) due to their immunomodulatory and anti-inflammatory actions. Currently, various immunomodulatory mechanisms of the LDLT macrolide treatment have been reported, as well as their antimicrobial properties. Several mechanisms have already been identified in CRS, including reduced cytokines such as interleukin (IL)-8, IL-6, IL-1β, tumor necrosis factor-α, transforming growth factor-β, inhibition of neutrophil recruitment, decreased mucus secretion, and increased mucociliary transport. Although some evidence of effectiveness for CRS has been published, the efficacy of this therapy has been inconsistent across clinical studies. LDLT macrolides are generally believed to act on the non-type 2 inflammatory endotype of CRS. However, the effectiveness of LDLT macrolide treatment in CRS is still controversial. Here, we reviewed the immunological mechanisms related to CRS in LDLT macrolide therapy and the treatment effects according to the clinical situation of CRS.

Exacerbation Prevention and Management of Bronchiectasis.

Bronchiectasis, which is characterized by irreversibly damaged and dilated bronchi, causes significant symptoms, poor quality of life, and increased economic burden and mortality rates. Despite its increasing prevalence and clinical significance, bronchiectasis was previously regarded as an orphan disease, and ideal treatment of this disease has been poorly understood. The European Respiratory Society and British Thoracic Society have recently published guidelines to assist physicians in the clinical field. Guidelines and reports suggest comprehensive management that includes both non-pharmacological and pharmacological treatment. Physiotherapy and pulmonary rehabilitation are two of the most important non-pharmacologic therapies in bronchiectasis patients; long-term inhaled antibiotics and macrolide therapy have gained significant evidence in reducing exacerbation risk in frequent exacerbators. In this review, we summarize recent updates on bronchiectasis treatment to prevent exacerbation and manage clinical deterioration.

Effect of medical treatment on eradication of biofilms in chronic rhinosinusitis

Background: Long-term macrolides and intranasal corticosteroids have evidence-based recommendations. It has been reported that macrolide therapy caused objective and subjective improvements which correlated to the duration of therapy. Topical nasal steroids are the mainstay of treatment in CRS. It is proposed that intranasal steroid may increase the restoration of normal epithelium. Methods: Sample size of 24 in each group is sufficient to detect the difference between positivity rate with 80% power and 5% level of significance clinically diagnosed cases of CRS with nasal polyps in age group of 18-60 years were taken. Outcome was measured with multiple scoring systems like SNOT-20, CT scoring, endoscopic scoring system. Results: Significant improvement was seen in the SNOT-20 scores with p value of 0.011 and endoscopic scores with p value of 0.001 in group having macrolides along with steroids pre-operatively however the scores post-surgery didn’t show any significant change in both groups. The efficacy of macrolide with nasal steroidal spray or nasal spray alone showed no further benefit in the subjective outcome measures post operatively. Also, no statistically significant eradication of biofilms or decrease in density could be appreciated in both groups. Furthermore, there was no significant difference in recurrence rate. Conclusions: Our result demonstrated the subjective improvement in patients of macrolide group post treatment which could be attributed to its anti-inflammatory effect. Even though macrolides in combination with nasal spray reflected some improvement in the secondary outcomes but the primary outcome of eradication of biofilms couldn’t be achieved.

Usefulness of High-resolution Computed Tomography for Macrolide Therapy of Idiopathic Bronchiectasis.

High-resolution computed tomography (HRCT) correlates with clinical symptoms, respiratory function, and quality of life in bronchiectasis. We aimed to investigate the relationship between macrolide and acute exacerbation (AE) in idiopathic bronchiectasis classified by the Bronchiectasis Radiologically Indexed CT Score (BRICS). We retrospectively reviewed the medical records of patients diagnosed with idiopathic bronchiectasis between April 2014 and December 2020 at a single hospital. Overall, 115 patients with idiopathic bronchiectasis were selected and divided into three groups, according to the BRICS. Each group was divided into subgroups with and without macrolide therapy, and the number of patients with AE in each group was retrospectively compared. About 45, 48, and 22 patients were included in the mild, moderate, and severe groups, respectively. In the mild group, the subgroup with macrolide therapy had significantly fewer patients with single AE than those without macrolide ( P = 0.029). There was no significant difference in the moderate and severe groups ( P = 1.00 and 0.64, respectively). In the multiple AE, the subgroup with macrolide therapy had significantly fewer patients than those without macrolide therapy in the mild, moderate, and severe groups ( P = 0.024, 0.029, and 0.026, respectively). HRCT severity assessment might be useful in predicting treatment efficacy in patients with idiopathic bronchiectasis without previous AEs. Further large-scale clinical trials are required on the usefulness of HRCT in the future.

Prospects for macrolide therapy of asthma and COPD.

Macrolide compounds, many of which are derived from natural sources, all share a lactone ring structure, but of varying sizes. Their biological activities differ with structure and size but tend to overlap. Marketed macrolide drugs include immunosuppressives and antibiotics. Some of the latter have been shown to exert anti-inflammatory activities, due to direct effects on inflammatory cells and processes when used for respiratory infections. Consequently, azithromycin is included in clinical guidelines for COPD and asthma treatment, though it has the disadvantage, as an antibiotic, of increasing bacterial resistance. COPD and asthma, however, like several chronic inflammatory diseases involving other organs, are driven to a large extent by epithelial barrier dysfunction. Recently, azithromycin was shown to directly enhance epithelial barrier function and a new class of derivatives, barriolides, is under development with the lead indication COPD. It is thus likely that by circumventing antibiosis and acting on a crucial etiological disease process, this type of agent will open up a new, safer approach to COPD and asthma therapy with macrolides.

Adverse drug reactions of macrolide therapy: analysis of spontaneous reports according to the Pharmacovigilance system

Adverse drug reactions of macrolide therapy: analysis of spontaneous reports according to the Pharmacovigilance system

Novel SPEF2 Variant in a Japanese Patient with Primary Ciliary Dyskinesia: A Case Report and Literature Review

Primary ciliary dyskinesia (PCD) is a genetic and congenital disease associated with an abnormal ciliary ultrastructure and function and is estimated to affect 1 in 15,000-20,000 individuals. A PCD diagnosis can be achieved by genotyping. Here, we performed whole-exome analysis for the diagnosis of PCD and described the detailed clinical characteristics of the case. A 39-year-old Japanese woman with sinusitis and bronchiectasis without situs inversus had had upper and lower respiratory symptoms since childhood and had received long-term macrolide therapy without an accurate diagnosis. A moderate deterioration of cilia function was observed by high-speed video microscopy analysis; additionally, the number of cells with moving cilia was fewer than that in patients without PCD. Electron microscopy revealed no apparent structural abnormalities. We performed whole-exome analysis and identified novel biallelic variants of SPEF2 in the homozygous state (c.1860_1861insCT). We confirmed the absence of SPEF2 protein expression in the cilia of the nasal mucosa using fluorescent immunostaining. Accordingly, she was diagnosed as having PCD with the SPEF2 variant. The present case suggests that the deterioration of cilia function is moderate, the number of respiratory cells with moving cilia might be reduced, and the respiratory condition could be severe in patients with PCD with the SPEF2 variant.

1325. Macrolide versus Non-macrolide in Combination with Steroids for the Treatment of Lobar or Segmental Mycoplasma Pneumoniae Pneumonia Unresponsive to Initial Macrolide Monotherapy

Abstract Background Mycoplasma pneumoniae (MP) is one of the most common causes of bacterial pneumonia in children. In the recent decade, macrolide-resistant MP (MRMP) has been increasing in proportion, leading to children unresponsive to initial macrolide therapy. The purpose of this study was to evaluate the outcomes of children with lobar or segmental MP pneumonia unresponsive to initial macrolide therapy, who received non-macrolide (NM), macrolide plus steroids (M+S), and non-macrolide plus steroids (NM+S) according to the 2019 guideline during the 2019-2020 Mycoplasma epidemic in South Korea. Methods This was a retrospective cohort study of children below 18 years old, admitted during the 2019-2020 MP outbreak for lobar or segmental MP pneumonia. The inclusion criteria were as follows: 1) sputum or nasopharyngeal swab MP PCR positive, 2) no history of pneumonia within one month of positive MP PCR, 3) lobar or segmental pneumonia on chest x-ray, and 4) initial treatment with macrolide monotherapy. Children that were unresponsive to the initial 3-5-day macrolide monotherapy were divided into 3 groups depending on the next regimen: NM, M+S, and NM+S group. Their outcomes were assessed. Results During May 2019 to March 2020 MP epidemic, a total 190 patients that fit all of the inclusion criteria were included as study participants. Of these, 16.8% (n=32/190) were responsive to initial macrolide monotherapy and 83.2% (158/190) were unresponsive. Of the 158 patients unresponsive during the initial 5-day macrolide therapy, 8.2% (n=13) were switched to a NM, 75.9% (n=120) were added steroids (M+S), and 15.8% (25/158) were switched to a non-macrolide plus steroids (NM+S). Treatment success rates were 46%, 81%, and 100% in the NM, M+S, and NM+S groups, respectively (P=0.001). Compared to patients in the NM+S group, those in the M+S group were 8.0 (Confidence interval [CI], 1.3-61.7; P=0.046) times more likely to have prolonged fever ≥4 days after the switch in treatment regimen compared to patients with NM+S, and 10.7 (CI, 1.5-108.7; P=0.046) times more likely in the NM group. Conclusion In patients with severe mycoplasma pneumonia with failure of response to initial macrolide therapy, a non-macrolide antibiotic plus steroid combination had the highest treatment success rate and shorter duration of fever. Disclosures All Authors: No reported disclosures.

Non-typeable Haemophilus influenzae airways infection: the next treatable trait in asthma?

Asthma is a complex, heterogeneous condition that affects over 350 million people globally. It is characterised by bronchial hyperreactivity and airways inflammation. A subset display marked airway neutrophilia, associated with worse lung function, higher morbidity and poor response to treatment. In these individuals, recent metagenomic studies have identified persistent bacterial infection, particularly with non-encapsulated strains of the Gram-negative bacterium Haemophilus influenzae. Here we review knowledge of non-typeable H. influenzae (NTHi) in the microbiology of asthma, the immune consequences of mucosal NTHi infection, various immune evasion mechanisms, and the clinical implications of NTHi infection for phenotyping and targeted therapies in neutrophilic asthma. Airway neutrophilia is associated with production of neutrophil chemokines and proinflammatory cytokines in the airways, including interleukin (IL)-1β, IL-6, IL-8, IL-12, IL-17A and tumour necrosis factor. NTHi adheres to and invades the lower respiratory tract epithelium, inducing the NLR family pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammasomes. NTHi reduces expression of tight-junction proteins, impairing epithelial integrity, and can persist intracellularly. NTHi interacts with rhinoviruses synergistically via upregulation of intracellular cell adhesion molecule 1 and promotion of a neutrophilic environment, to which NTHi is adapted. We highlight the clinical relevance of this emerging pathogen and its relevance for the efficacy of long-term macrolide therapy in airways diseases, we identify important unanswered questions and we propose future directions for research.

Macrolide versus Non-Macrolide in Combination with Steroids for the Treatment of Lobar or Segmental Mycoplasma pneumoniae Pneumonia Unresponsive to Initial Macrolide Monotherapy.

In the last few decades, macrolide-resistant Mycoplasma pneumoniae (MRMP) has been increasing in proportion. This study aimed to evaluate the treatment outcomes of children with lobar or segmental MP pneumonia unresponsive to the initial 3–5-day macrolide therapy, who then switched to either a non-macrolide, macrolide + steroid, or a non-macrolide + steroid regimen, according to the 2019 KSPID and KAPARD guideline during the 2019–2020 Mycoplasma epidemic in South Korea. A total of 190 patients <18 years old were admitted during the study period for MP lobar or segmental pneumonia, and 16.8% (n = 32/190) were responsive to the initial macrolide monotherapy, whereas 83.2% (158/190) were refractory. The median age of the patients was 7 (interquartile range [IQR], 5–9) years old and 46.2% (n = 73/158) were male. The overall treatment success rates of non-macrolide, macrolide + steroid, and non-macrolide + steroid groups were 46.2%, 80.8%, and 100.0%, respectively. Patients in the non-macrolide + steroid group had the shortest fever duration after a regimen change of 1 (IQR, 0–3) day compared with patients in the non-macrolide group and macrolide + steroid group; 2 (IQR, 1–4) days and 2 (IQR, 1–3.3) days (p = 0.004), respectively. Follow-up CRP (ß, 0.169; CI, 0.050–0.287; p = 0.006), macrolide + steroid therapy (ß, −1.694; CI, −2.463–−0.925; p < 0.001), and non-macrolide+ steroid therapy (ß, −2.224; CI, −3.321–−1.127; p < 0.001) were shown to be significantly associated with the duration of fever after admission. To conclude, in patients with severe MP pneumonia that failed to respond to the initial macrolide therapy, a non-macrolide + steroid had the highest treatment success rate and a shorter duration of fever.