Abstract
Objective
Mycoplasma pneumoniae is a major pathogen of community-acquired bacterial pneumonia (CABP). Macrolide-resistant Mycoplasma pneumoniae (MRMP) harboring the 23S rRNA A2063G mutation poses a global therapeutic challenge. Omadacycline, a novel aminomethylcycline approved for CABP, exhibits activity against MRMP. However, real-world data on omadacycline for A2063G-mutated MRMP pneumonia remain limited. In this study, we present our clinical experience with intravenous omadacycline in patients with genetically confirmed A2063G-mutated MRMP pneumonia.
Methods
We retrospectively analyzed the clinical data of eight patients with MRMP pneumonia confirmed by metagenomic next-generation sequencing (mNGS). All patients had failed prior macrolide or fluoroquinolone therapy and received a 7-day course of intravenous omadacycline. Clinical symptoms, inflammatory parameters, chest CT findings, and safety were evaluated.
Results
Eight patients were included. Significant reductions in inflammatory markers were observed after treatment: the neutrophil count decreased from (6.92 ± 2.13)×109/L to (4.67 ± 1.03)×109/L (P = 0.02), C-reactive protein decreased from (68.17 ± 50.35) mg/L to (14.77 ± 19.34) mg/L (P = 0.01), and serum amyloid A decreased from (497.28 ± 319.79) mg/L to (28.35 ± 32.28) mg/L (P < 0.01). Chest CT showed marked resolution of pulmonary lesions in seven patients. No treatment-related adverse events requiring discontinuation were reported.
Conclusion
Omadacycline demonstrates promising clinical efficacy and a favorable safety profile for the treatment of pneumonia caused by A2063G-mutated MRMP, promoting both clinical and radiological recovery. Larger prospective controlled studies are warranted to confirm these findings.
Keywords: omadacycline; Mycoplasma pneumoniae; macrolide-resistant; efficacy, safety
Introduction
Mycoplasma pneumoniae is a prominent etiological agent of CABP, particularly among young adults and children. Macrolides have long functioned as the first-line therapy for this infection. Nevertheless, the global prevalence of MRMP has escalated alarmingly, with resistance rates exceeding 90% in certain Asian countries.1 The primary resistance mechanism involves a point mutation in the 23S rRNA gene, most frequently A2063G, which confers high-level resistance to macrolides.2,3 The emergence of MRMP leads to prolonged fever, exacerbated respiratory symptoms, and radiological progression despite macrolide therapy, thereby complicating clinical management. The fluoroquinolones and tetracyclines are recommended as alternatives.4 Fluoroquinolones are utilized cautiously in the pediatric population owing to their potential adverse effects on cartilage development.4
First-generation tetracyclines (eg., oxytetracycline, chlortetracycline) are microbial metabolites; their unstable chemical structure readily leads to drug resistance. Second-generation tetracyclines (eg., doxycycline, minocycline) are semi-synthetic modifications that improve stability and lipophilicity, resulting in better cellular uptake.5 Nevertheless, although tetracycline resistance remains infrequent, it has been documented that conventional tetracyclines are often compromised by efflux pumps and ribosomal protection mechanisms that reduce antimicrobial activity.1 Third-generation tetracyclines (eg., tigecycline, omadacycline, eravacycline) feature structural modifications at the C7 and C9 positions, which enable them to circumvent the major resistance mechanisms.5 Omadacycline, a novel aminomethylcycline antibiotic, is approved for the treatment of adults with CABP. Designed to overcome canonical tetracycline resistance mechanisms, omadacycline maintains potent activity against strains resistant to traditional tetracyclines via efflux pumps or ribosomal protection mechanisms, with favorable pharmacokinetic properties, high lung tissue penetration, and a low propensity for inducing resistance. In vitro studies have demonstrated that it exhibits broad-spectrum activity against Gram-positive, Gram-negative, and atypical pathogens, including MRMP.6 While clinical trials have established its efficacy for CABP, existing evidence is largely derived from controlled trials enrolling unselected CABP patients, with scarce real-world data focusing on genetically confirmed A2063G-mutated MRMP pneumonia. Data on clinical response, inflammatory resolution, radiological improvement, and safety profiles of omadacycline specifically in macrolide- and fluoroquinolone-refractory A2063G mutant MRMP infections remain insufficient to guide clinical decision-making. This case series reports the initial clinical experience with omadacycline for A2063G-mutated MRMP pneumonia, thereby evaluating its real-world efficacy and safety profile.
Methods
Study Design and Participants
This retrospective, single-center case series was conducted at The Third People’s Hospital of Hubei Province during the study period from January 2023 to December 2025. Inclusion Criteria: Presence of the 23S rRNA A2063G macrolide resistance mutation confirmed by mNGS; Age between 9 and 75 years; Treatment with intravenous omadacycline tosylate; Complete available medical records. Exclusion Criteria: Duration of omadacycline treatment < 72 hours; Incomplete clinical data or medical records. Adult patients received the standard recommended dosage of omadacycline: an initial intravenous dose of 200 mg administered over 60 minutes on day 1, followed by a maintenance intravenous dose of 100 mg infused over 30 minutes once daily for 6 consecutive days. The drug administered was omadacycline tosylate for injection (100 mg per vial, manufactured by Zhejiang Hisun Pharmaceutical Co., Ltd). For patients under 18 years of age, maintenance doses were adjusted based on body weight with reference to relevant literature.
Procedures
Data were retrieved from electronic medical records, including patient demographics, clinical symptoms and signs, chest computed tomography (CT), infection-related parameters: white blood cell count (WBC), neutrophil (NEU), C-reactive protein (CRP), and serum amyloid A (SAA), procalcitonin (PCT); biochemical indicators: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), gamma-Glutamyl Transferase (GGT), and Creatinine (CREA); details of prior antibiotic therapies and any adverse events (AEs). Metagenomic next-generation sequencing (mNGS) was used to comprehensively identify pathogens and detect resistance mutations. Serum-specific IgM and IgG antibodies against Mycoplasma pneumoniae were measured by enzyme-linked immunosorbent assay (ELISA). Mycoplasma pneumoniae deoxyribonucleic acid (DNA) was detected by real-time quantitative polymerase chain reaction (qPCR). Clinical improvement was defined as the resolution of fever, significant alleviation of cough and other respiratory symptoms, along with improvement in key inflammatory markers or radiological manifestations. Safety was assessed through monitoring liver function, renal function, gastrointestinal reactions, and allergic reactions.
Statistics
Descriptive statistical methods were used for data analysis. Continuous variables were tested for normality using the Shapiro–Wilk test. Normally distributed data were presented as the mean ± standard deviation (SD), and non-normally distributed data were summarized as the median (interquartile range, IQR). The independent samples t-test was applied for comparisons between two groups of normally distributed continuous variables. All statistical tests were two-sided, and a P-value < 0.05 was considered statistically significant. Statistical analyses were performed using SPSS software (version 26.0, IBM Corp., Armonk, NY, USA).
Results
Baseline Characteristics of Patients with MRMP Pneumonia
This study included 8 patients (4 males and 4 females) with mNGS testing results confirming MRMP pneumonia, with a mean sequence length of 21328.37 ± 22,119.01. The mean age of the patients was (37.63 ± 24.17) years. All patients presented with cough and fever, with a mean body temperature of (38.74 ± 0.85) °C. In terms of serological testing for Mycoplasma pneumoniae IgG, four patients showed positive results. One patient tested positive for Mycoplasma pneumoniae IgM, and five patients had positive results in the mycoplasma pneumoniae deoxyribonucleic acid detection. Seven patients had no mixed infections, while one patient had concomitant Aspergillus infection. Six patients received moxifloxacin prior to omadacycline therapy, whereas two patients were treated with azithromycin. The baseline characteristics of the patients are summarized in Table 1.
Table 1.
The Baseline Characteristics of the MRMP Patients
| ID | Patients | Mean ± SD | |||||||
|---|---|---|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | ||
| Gender | F | F | F | F | M | M | M | M | |
| Age (years) | 32 | 15 | 71 | 56 | 17 | 20 | 20 | 70 | 37.63 ± 24.17 |
| Fever (°C) | 38.00 | 39.20 | 37.50 | 39.30 | 39.00 | 40.00 | 39.00 | 37.90 | 38.74 ± 0.85 |
| IgM antibody | N/A | – | – | – | + | – | N/A | – | |
| IgG antibody | N/A | N/A | + | + | – | – | + | + | |
| MP-DNA | + | + | - | + | + | + | - | - | |
| mNGS Sequence Count | 41926 | 47,915 | 83 | 4655 | 51,408 | 1995 | 4785 | 17,860 | 21,328.37 ± 22,119.01 |
| Co-infection | None | None | None | None | None | None | None | Aspergillus | |
| Initial Antimicrobial Regimen | Moxifloxacin | Azithromycin | Moxifloxacin | Moxifloxacin | Azithromycin | Moxifloxacin | Moxifloxacin | Voriconazole + Moxifloxacin | |
| Adjusted Antimicrobial Regimen | Omadacycline | Omadacycline | Omadacycline | Omadacycline | Omadacycline | Moxifloxacin+Omadacycline | Omadacycline | Voriconazole + Omadacycline+Meropenem | |
Abbreviations: ID, Identifier; M, Male; F, Female; MRMP, Macrolide-resistant Mycoplasma pneumoniae; mNGS, metagenomic next-generation sequencing; IgG, immunoglobulin G; IgM, immunoglobulin M; MP-DNA, Mycoplasma pneumoniae deoxyribonucleic acid; N/A, not available; “+”, positive; “−”, negative.
Infection-Related Parameters Results
The infection-related parameters before (Group a) and after (Group b) treatment are summarized in Table 2. Administration of omadacycline resulted in a decrease in the mean WBC count from (9.43 ± 2.92)×109/L to (7.54 ± 1.33)×109/L. However, statistical analysis via the Wilcoxon signed-rank test revealed no statistically significant reduction (t = 1.67, P = 0.14). Despite the small sample size, a significant reduction was observed in NEU count following treatment, with the mean value decreasing from (6.92 ± 2.13)×109/L to (4.67 ± 1.03)×109/L (t = 2.70, P = 0.02). The levels of acute-phase reactants exhibited a marked and statistically significant decline post-treatment. The mean CRP concentration exhibited a substantial decrease from (68.17 ± 50.35) mg/L to (14.77 ± 19.34) mg/L (t = 2.80, P = 0.01). Similarly, SAA levels decreased significantly from a mean of (497.28 ± 319.79) mg/L to (28.35 ± 32.28) mg/L (t = 4.13, P < 0.01). All patients had normal procalcitonin (PCT) levels at baseline, and no follow-up PCT re-examination was performed. Biochemical indicators before and after omadacycline treatment are shown in Table 3.
Table 2.
The Infection-Related Parameters Before (Group a) and After (Group b) Omadacycline Treatment
| ID | Group | Patients | Mean ± SD | t value | P value | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | |||||
| WBC (×109 cells/L) | a | 10.30 | 11.03 | 13.23 | 8.50 | 7.44 | 4.67 | 7.57 | 12.73 | 9.43 ± 2.92 | 1.67 | 0.14 |
| b | 8.60 | 8.16 | 5.70 | 7.79 | 5.45 | 8.34 | 7.25 | 9.05 | 7.54 ± 1.33 | |||
| NEU (×109 cells/L) | a | 6.76 | 7.89 | 8.87 | 7.27 | 5.46 | 3.11 | 6.05 | 9.98 | 6.92 ± 2.13 | 2.70 | 0.02 |
| b | 6.39 | 5.50 | 3.42 | 4.54 | 3.54 | 4.65 | 3.97 | 5.34 | 4.67 ± 1.03 | |||
| CRP (mg/L) | a | 73.24 | 62.94 | 172.82 | 60.70 | 15.58 | 17.70 | 45.20 | 97.20 | 68.17 ± 50.35 | 2.80 | 0.01 |
| b | 23.60 | 5.70 | 15.30 | 5.00 | 4.50 | 2.43 | 2.64 | 59.00 | 14.77 ± 19.34 | |||
| SAA (mg/L) | a | 100.02 | 574.58 | 1054.48 | 351.30 | 82.23 | 528.90 | 596.70 | 690.00 | 497.28 ± 319.79 | 4.13 | <0.01 |
| b | 2.80 | 4.70 | 8.50 | 3.90 | 8.10 | 81.81 | 57.55 | 59.45 | 28.35 ± 32.28 | |||
| PCT (ng/mL) | a | ND | ND | 0.15 | ND | ND | 0.20 | 0.09 | ND | – | – | – |
| b | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | – | |||
Abbreviations, ID, Identifier; WBC, White Blood Cell; NEU, Neutrophil; CRP, C-reactive protein; SAA, Serum Amyloid A; ND, Not Detected; N/A, Not Available; a, pre-treatment; b, post-treatment.
Table 3.
Biochemical Indicator Before and After Omadacycline Treatment
| ID | Group | Patients | Mean ± SD | t value | P value | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | |||||
| AST (U/L) | a | 12.70 | 63.70 | 18.90 | 29.80 | 17.80 | 22.90 | 34.50 | 12.10 | 26.55 ± 16.92 | −0.20 | 0.83 |
| b | 16.40 | 24.30 | 20.20 | 18.20 | 18.90 | 53.40 | 59.40 | 15.40 | 28.28 ± 17.64 | |||
| ALT (U/L) | a | 7.70 | 31.20 | 12.90 | 161.10 | 13.30 | 20.40 | 63.20 | 15.30 | 40.64 ± 51.77 | −0.20 | 0.82 |
| b | 10.00 | 20.50 | 39.40 | 63.90 | 15.30 | 115.30 | 87.10 | 10.00 | 45.19 ± 39.70 | |||
| GGT (U/L) | a | 16.30 | 19.20 | 98.60 | 196.50 | 27.90 | 45.70 | 23.10 | 95.90 | 65.40 ± 62.51 | −0.16 | 0.80 |
| b | 16.90 | 13.90 | 240.20 | 156.20 | 23.80 | 38.00 | 44.00 | 35.80 | 71.10 ± 82.25 | |||
| CREA (μmol/L) | a | 66.44 | 64.21 | 55.08 | 42.00 | 74.57 | 72.00 | 84.07 | 61.00 | 64.92 ± 12.82 | 0.41 | 0.46 |
| b | 68.00 | 43.00 | 39.00 | 52.00 | 75.76 | 78.70 | 79.07 | 60.10 | 61.95 ± 15.99 | |||
Abbreviations: ID, Identifier; AST, Aspartate Aminotransferase; ALT, Alanine Aminotransferase; GGT, gamma-Glutamyl Transferase; CREA, Creatinine; a, pre-treatment; b, post-treatment.
Changes of Chest CT
Chest CT images of all eight enrolled patients are shown in Figures 1–8, corresponding to patients 1 to 8. Subpanel “ a ” shows the baseline image before omadacycline treatment, and subpanel “ b ” shows the post-treatment image. All paired CT scans were acquired at the same slice level for each patient. Cases 1 to 7 exhibited improved clinical manifestations. CT scans revealed that the extent and density of pulmonary consolidation and infiltrative lesions were significantly reduced after omadacycline treatment compared with baseline. In contrast, Case 8 was complicated by pulmonary aspergillosis, with poor radiological and clinical improvement.
Figure 1.
Chest CT (lung window) of patient 1. (a) Pre-treatment: patchy consolidation with surrounding ground-glass opacities was observed in the right middle and lower lobes; red arrows indicate inflammatory lesions. (b) Post-treatment: consolidation and ground-glass opacities were markedly absorbed, with minimal residual fibrous streaks; red arrows show significant resolution of the primary lesions.
Figure 2.
Chest CT (lung window) of patient 2. (a) Pre-treatment: Extensive patchy and nodular ground-glass opacities with linear consolidation in the anterior segment of the right upper lobe, with ill-defined margins and heterogeneous density; red arrows indicate inflammatory lesions. (b) Post‑treatment: Marked resolution of ground‑glass opacities and consolidation in the anterior segment of the right upper lobe; red arrows demonstrate significant absorption of the original inflammatory lesions.
Figure 3.
Chest CT (lung window) of patient 3. (a) Pre-treatment: Increased and indistinct markings in both upper lobes, with scattered patchy and nodular ground-glass opacities; red arrows indicate inflammatory lesions in the right upper lobe. (b) Post-treatment: Clear markings in both upper lobes, with marked resolution and disappearance of the original ground-glass opacities; red arrows show significant absorption of the initial inflammatory lesions.
Figure 4.
Chest CT (lung window) of patient 4. (a) Pre-treatment: Linear and patchy consolidation in the right upper lobe, with ill-defined borders and heterogeneous density; red arrows indicate consolidation in the right upper lobe. (b) Post-treatment: Marked resolution of consolidation in the right upper lobe; red arrows indicate complete absorption of the original inflammatory lesions.
Figure 5.
Chest CT (lung window) of patient 5. (a) Pre-treatment: A large area of consolidation and patchy ground-glass opacities in the lingular segment of the left upper lobe, with ill-defined borders; red arrows indicate inflammatory lesions in the lingular segment of the left upper lobe. (b) Post-treatment: Significant resolution of the original consolidation in the lingular segment of the left upper lobe, with improved lucency of the local lung field; red arrows indicate marked absorption of the initial inflammatory lesions.
Figure 6.
Chest CT (lung window) of patient 6. (a) Pre-treatment: Patchy ground-glass opacities in the dorsal segment of the right lower lobe, with poorly defined borders; red arrows indicate inflammatory lesions in the right lower lobe. (b) Post-treatment: Obvious resolution of the original ground-glass opacities in the dorsal segment of the right lower lobe; red arrows indicate marked absorption of the initial inflammatory lesions.
Figure 7.
Chest CT (lung window) of patient 7. (a) Pre-treatment: Extensive consolidation and patchy ground-glass opacities in the apicoposterior segment of the left upper lobe, with ill-defined borders and heterogeneous density; red arrows indicate inflammatory infiltration in the apicoposterior segment of the left upper lobe. (b) Post-treatment: Marked resolution of the original consolidation and ground-glass opacities in the apicoposterior segment of the left upper lobe; red arrows indicate nearly complete absorption of the initial inflammatory lesions.
Figure 8.
Chest CT (lung window) of patient 8. (a) Pre-treatment: Multiple patchy, nodular, and sheet-like high-density opacities in the right middle lobe and bilateral lower lobes, accompanied by pulmonary interstitial fibrosis and honeycomb changes; red arrows indicate inflammatory lesions and fibrotic areas in both lungs. (b) Post-treatment: Partial absorption of the original inflammatory infiltrates in the right lower lobe, with an increased extent of consolidation in the left lower lobe; red arrows indicate the inflammatory changes in both lungs.
Adverse Reaction Profile
The results showed that there were no statistically significant differences in AST, ALT, GGT, and CREA levels between pre- and post-treatment in all patients (P > 0.05). Nevertheless, post-treatment AST and ALT levels in patients 6 and 7 were elevated compared with baseline and exceeded the normal reference range. No abnormal biochemical parameters were observed in the remaining patients.
Discussion
Macrolides, fluoroquinolones, and tetracyclines are commonly employed as first-line agents for the treatment of Mycoplasma pneumoniae infections. Studies have demonstrated that Mycoplasma pneumoniae exhibits high resistance to macrolides, while showing relatively high susceptibility to fluoroquinolones and tetracyclines.2 However, data on the susceptibility of MRMP to fluoroquinolones remain limited. Furthermore, fluoroquinolones may induce chondrodysplasia in pediatric patients, rendering them contraindicated for adolescent treatment.7 In this study, patients in Case 2 and Case 5 were under 18 years of age and treated with azithromycin, whereas the other patients received quinolone antibiotics. However, no clinical improvement was observed in all patients, so treatment was promptly switched to omadacycline monotherapy or combination therapy containing omadacycline. Warnings of tooth discoloration linked to tetracycline antibiotics mainly stem from studies on first-generation agents.5 The risk of dental discoloration from short-term omadacycline administration may remain relatively low,8 though potential hazards cannot be entirely ruled out. Case 2 was a 15-year-old adolescent weighing 60 kg, and Case 5 was a 17-year-old patient weighing 62 kg. Calculated based on the pediatric dose of 2.4 mg/kg reported in a retrospective study,8 the resultant dose exceeded the daily maintenance dose of 100 mg specified in the drug instructions. Both patients were therefore treated with a maintenance dose of 100 mg once daily.
In this investigation, seven patients demonstrated significant improvement in clinical symptoms, systemic inflammatory markers, and resolution of pulmonary inflammatory infiltrates following omadacycline treatment. Following omadacycline therapy, the high-density lesions in the right lung of Case 8 were markedly reduced, and no new consolidation was detected. Left lung lesions showed only slight improvement, with an unsatisfactory overall clinical response. This condition was presumed to be largely associated with concurrent fungal infection. Research findings are consistent with recent academic literature. A real-world study conducted in China in 2024, which included 183 patients with diverse infections, reported a 71.0% clinical success rate for omadacycline, validating its broad-spectrum efficacy.9 A case report in 2025 documented the successful compassionate use of intravenous omadacycline in a critically ill preschool-aged child with Down syndrome and MRMP pneumonia.10 These findings suggest that omadacycline may serve as a viable alternative anti-infective agent for the management of Mycoplasma pneumoniae pneumonia harboring the 23S rRNA A2063G mutation.
The therapeutic effects observed in this study are attributed to the unique aminomethylcycline structure of omadacycline, which is specifically engineered to circumvent the two primary tetracycline resistance mechanisms: ribosomal protection (eg., mediated by tet(M) genes) and efflux pump systems.1,11,12 This mechanistic advantage distinguishes it from first-generation tetracyclines such as doxycycline. Omadacycline exhibits high-affinity binding to the bacterial 30S ribosomal subunit at a site distinct from macrolides, rendering the A2063G mutation inconsequential to its antimicrobial activity.13 Furthermore, studies have demonstrated that Mycoplasma pneumoniae infection can induce a variety of extrapulmonary manifestations affecting the neurological, dermatological, cardiovascular, and other organ systems. These complications are predominantly immune-mediated and have been well documented in both children14 and adults.15 The underlying pathogenesis involves excessive production of proinflammatory cytokines, generation of autoantibodies, and deposition of immune complexes. Notably, MRMP strains have been associated with a higher incidence of extrapulmonary manifestations16 and more severe respiratory diseases.17,18 Moreover, underlying immunological defects may influence the clinical expression of Mycoplasma pneumoniae infection and the host response to therapy.19 Emerging evidence indicates that omadacycline possesses immunomodulatory properties, including the suppression of pro-inflammatory cytokines (eg., TNF-α, IL-6) in vitro.20,21 Therefore, we hypothesize that omadacycline exerts a dual role in severe MRMP pneumonia: direct antibacterial activity and potential modulation of the excessive host inflammatory response. This dual effect may partially explain the concurrent reductions in systemic inflammatory markers (NEU, CRP, SAA) and pulmonary infiltrates observed in our study. However, these immunomodulatory effects remain speculative. Further basic and clinical studies are needed to confirm its anti-inflammatory activity in Mycoplasma pneumoniae infection. In addition, given the inevitable residual effects of prior administration of moxifloxacin and azithromycin, certain confounding factors exist in this study.
The clinical presentations, laboratory examinations, and imaging characteristics of Mycoplasma pneumoniae infection frequently lack specificity. Diagnosis primarily relies on serological assays and PCR testing. Nevertheless, serological tests generally exhibit low sensitivity for detecting IgM antibodies, with only one patient showing positive IgM results in this study. PCR exhibits high sensitivity and specificity but cannot detect drug resistance markers. In contrast, mNGS is a high-throughput technology that facilitates the identification of pathogens and resistance genes.22,23 In this study, all patients were confirmed to have MRMP pneumonia harboring the 23S rRNA A2063G mutation via mNGS. Literature has demonstrated that mNGS allows early and precise diagnosis in cases with unidentified infectious pathogens and pneumonia unresponsive to conventional treatment. In our small-scale study, no significant adverse events were observed. Only two patients experienced transient elevation of transaminases, which all resolved after treatment with compound glycyrrhizin injection, consistent with the generally favorable tolerability profile of this drug.24 Nevertheless, comprehensive safety monitoring is of utmost importance. A pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) in 2024 identified potential safety signals that were not initially emphasized in the tetracycline-class drug labels, such as ototoxicity and tongue discoloration.25 Although these reports need to be confirmed through controlled studies, they highlight the significance of vigilant post-marketing surveillance and patient monitoring.
Our study has limitations. First, the retrospective single-center design and small sample size (n=8) may cause inherent bias and limited generalizability, with insufficient power to control confounders. Second, the absence of a control group hinders efficacy comparison between omadacycline and conventional regimens. Moreover, all enrolled patients received omadacycline as salvage therapy for refractory pulmonary infections, which may lead to selection bias and restrict the extrapolation of our results. Larger prospective multicenter studies are needed to further validate the clinical value and standardized application of omadacycline. Nevertheless, this study supplements real-world evidence for omadacycline in refractory pulmonary infections and provides useful clinical insights.
Conclusion
Despite its limitations, based on the findings of this case series, we speculate that omadacycline may serve as an effective and well-tolerated therapeutic option for patients with MRMP pneumonia harboring the A2063G mutation. It can be regarded as a salvage therapy in the presence of severe drug resistance or drug intolerance. Notably, omadacycline is currently regarded only as an adjuvant therapy for refractory cases, and it should not replace first-line treatment regimens until robust evidence from large-scale prospective studies is available. Further large-sample prospective studies are warranted to clarify its optimal clinical application status and establish standardized medication guidelines in the future.
Funding Statement
This research was supported by ZhongNanShan Medical Foundation of Guangdong Province, No. ZNSXS-20240074.
Ethics Approval and Informed Consent
The study protocol was approved by the institutional ethics committee (IRB: KY2024032), and the requirement for informed consent was waived in view of the retrospective design.
Disclosure
The authors declare no conflicts of interest in this work.
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