Observational retrospective clinical study on clinical features of macrolide-resistant Mycoplasma pneumoniae pneumonia in Chinese pediatric cases.

This study aimed to investigate differences in clinical characteristics and laboratory findings between children infected with Macrolide-Sensitive Mycoplasma pneumoniae (MSMP) and Macrolide-Resistant Mycoplasma pneumoniae (MRMP). Additionally, the research sought to identify laboratory markers for rapidly distinguishing refractory Mycoplasma pneumoniae pneumonia (RMPP) from ordinary Mycoplasma pneumoniae pneumonia (OMPP). In total, 265 Mycoplasma pneumoniae (MP) patients were included, with MRMP identified by specific point mutations in domain V of the 23S rRNA gene. A retrospective analysis compared the clinical courses and laboratory data, revealing that MRMP patients experienced prolonged febrile days (P = 0.004), elevated CRP levels (P < 0.001), and higher MP DNA loads than MSMP patients (P = 0.037). Based on clinical symptoms, MRMP was divided into RMPP (n = 56) and OMPP (n = 70), with RMPP demonstrating significantly increased IL-18, community-acquired respiratory distress syndrome (CARDS) toxins in nasopharyngeal aspirate, and serum CRP levels (P < 0.001; P = 0.006; P < 0.001). In conclusion, timely recognition of RMPP is crucial for enhancing prognosis. The identification of MRMP, coupled with proinflammatory cytokines such as IL-18, CARDS toxins, and CRP, emerges as promising markers with the potential to contribute significantly to diagnostic accuracy and prognosis assessment.

Clozapine-induced pneumonitis mimicking an atypical pneumonia.

Clozapine is an antipsychotic used for treatment-resistant schizophrenia with a significant side effect profile, including agranulocytosis, myocarditis and fever. Clozapine-induced fever often occurs in the first 2 weeks of treatment and settle after a few days. We report a case of a woman in her mid-30s who developed fever and infective symptoms suggestive of an atypical pneumonia while on clozapine titration. She was on clozapine for 16 days before developing high-grade fever, dry cough, diarrhoea, headache and photophobia with a very high CRP. We performed an extensive infection workup that returned negative results except for bilateral upper lobe ground glass changes of the lungs on CT. Despite antibiotic therapy, which would cover an atypical pneumonia, her CRP remained elevated and her fever persisted. Focus was directed to clozapine-induced pneumonitis as the cause for her symptoms. Her antibiotics were ceased, and clozapine was downtitrated. With the adjustment of her clozapine dose, her fevers and associated symptoms resolved, and CRP downtrended. Her fevers did not return when clozapine was uptitrated in the community subsequently. Clozapine-induced fever or other immune-allergic reactions should be systematically considered when patients develop fever during the initiation phase of clozapine therapy. Ruling out infective causes is desirable prior to attributing fevers to clozapine especially when they are accompanied by infective symptoms and high inflammatory markers. Careful downtitration of clozapine should be considered rather than abrupt cessation in managing clozapine-induced fevers and subsequent slow uptitration could be considered.

Efficacy of doxycycline therapy for macrolide-resistant Mycoplasma pneumoniae pneumonia in children at different periods.

BACKGROUND: The prevalence of macrolide-resistant Mycoplasma pneumoniae has increased considerably. Treatment in children has become challenging. This study aimed to evaluate the efficacy of doxycycline therapy for macrolide-resistant Mycoplasma pneumoniae pneumonia in children at different periods. METHODS: We retrospectively analyzed the data of patients with macrolide-resistant Mycoplasma pneumoniae pneumonia hospitalized between May 2019 to August 2022. According to treatment, patients were divided into three groups: oral doxycycline treatment alone (DOX group), changed from intravenous azithromycin to oral doxycycline (ATD group), and intravenous azithromycin treatment alone (AZI group). ATD group cases were separated into two sub-groups: intravenous azithromycin treatment<3 days (ATD1 group) and ≥ 3 days (ATD2 group). Clinical symptoms were compared in each group and adjusted by Propensity score matching (PSM) analysis. RESULTS: A total of 106 were recruited in this study. 17 (16%) were in DOX group, 58 (55%) in ATD group, and 31(29%) in AZI group. Compared with ATD group and AZI group, the DOX group showed shorter hospitalization duration and fever duration after treatment, while higher rate of chest radiographic improvement. After using PSM analysis, shorter days to hospitalization duration (P = 0.037) and to fever duration after treatment (P = 0.027) in DOX + ATD1 group than in ATD2 group was observed. A higher number of patients in the DOX + ATD1 group achieved defervescence within 72 h (P = 0.031), and fewer children received glucocorticoid adjuvant therapy (P = 0.002). No adverse reactions associated with doxycycline was observed during treatment. CONCLUSIONS: Children receiving early oral doxycycline had a shorter duration of fever and hospitalization in macrolide-resistant Mycoplasma pneumoniae patients.

Outbreak of Mycoplasma pneumoniae pneumonia in hospitalized patients: Who is concerned? Nord Franche-Comté Hospital, France, 2023-2024.

We report an outbreak of confirmed Mycoplasma pneumoniae community-acquired pneumonia (CAP) in Nord Franche-Comté Hospital, France, from 14 November 2023 to 31 January 2024. All 13 inpatients (11 adults with a mean age of 45.5 years and 2 children) were diagnosed with positive serology and/or positive reverse transcription polymerase chain reaction (RT-PCR) on respiratory specimens. All patients were immunocompetent and required oxygen support with a mean duration of oxygen support of 6.2 days. Two patients were transferred to the intensive care unit (ICU) but were not mechanically ventilated. Patients were treated with macrolides (n = 12, 92.3%) with recovery in all cases. No significant epidemiological link was reported in these patients.

Molecular epidemiology of Mycoplasma pneumoniae pneumonia in children, Wuhan, 2020-2022.

BACKGROUND: Mycoplasma pneumoniae (M. pneumoniae) is an important pathogen of community-acquired pneumonia in children. The factors contributing to the severity of illness caused by M. pneumoniae infection are still under investigation. We aimed to evaluate the sensitivity of common M. pneumoniae detection methods, as well as to analyze the clinical manifestations, genotypes, macrolide resistance, respiratory microenvironment, and their relationship with the severity of illness in children with M. pneumoniae pneumonia in Wuhan. RESULTS: Among 1,259 clinical samples, 461 samples were positive for M. pneumoniae via quantitative polymerase chain reaction (qPCR). Furthermore, we found that while serological testing is not highly sensitive in detecting M. pneumoniae infection, but it may serve as an indicator for predicting severe cases. We successfully identified the adhesin P1 (P1) genotypes of 127 samples based on metagenomic and Sanger sequencing, with P1-type 1 (113/127, 88.98%) being the dominant genotype. No significant difference in pathogenicity was observed among different genotypes. The macrolide resistance rate of M. pneumoniae isolates was 96% (48/50) and all mutations were A2063G in domain V of 23S rRNA gene. There was no significant difference between the upper respiratory microbiome of patients with mild and severe symptoms. CONCLUSIONS: During the period of this study, the main circulating M. pneumoniae was P1-type 1, with a resistance rate of 96%. Key findings include the efficacy of qPCR in detecting M. pneumoniae, the potential of IgM titers exceeding 1:160 as indicators for illness severity, and the lack of a direct correlation between disease severity and genotypic characteristics or respiratory microenvironment. This study is the first to characterize the epidemic and genomic features of M. pneumoniae in Wuhan after the COVID-19 outbreak in 2020, which provides a scientific data basis for monitoring and infection prevention and control of M. pneumoniae in the post-pandemic era.

Increase of respiratory illnesses among children in Beijing, China, during the autumn and winter of 2023.

In 2023, through an ongoing respiratory pathogen surveillance system, we observed from mid-September onwards, an increase of respiratory illness among children aged ≤ 15 years presenting at hospital outpatient clinics in Beijing, China. Data indicated that illness was caused by multiple pathogens, predominantly Mycoplasma pneumoniae. Seasonality, periodicity and high prevalence of resistance to macrolide (30 of 30 strains sequenced with the A2063G mutation) were important characteristics of the M. pneumoniae epidemic, which resulted in a rise in consultations at specialised paediatric hospitals.

Mycoplasma pneumoniae epidemic in Denmark, October to December, 2023.

We report a surge of patients, especially children and adolescents, with respiratory disease caused by Mycoplasma pneumoniae in Denmark since October 2023. While the surge has reached an epidemic level, no impact on hospital capacity has been observed; only 14% (446/3,195) of cases, primarily adults, required hospitalisation. Macrolide resistance was detected in less than 2% of samples tested. Timely monitoring of hospitalisations linked to M. pneumoniae infections has been established to inform the healthcare system, decisionmakers and the public.

In vitro and in vivo study of andrographolide nanoparticles for the treatment of Mycoplasma pneumoniae pneumonia.

OBJECTIVE(S): The emergence of antibiotic resistance has led to suboptimal treatment outcomes for Mycoplasma pneumoniae pneumonia (MPP). Exploring naturally occurring drug components that are both effective against MPP and non-toxic may be a promising choice. This study aimed to investigate the therapeutic effect of andrographolide nanoparticles on pneumonia caused by Mycoplasma pneumoniae infection. METHODS: Andrographolide alginate-poloxamer nanoparticles (AND-ALG-POL/NPs) were obtained by wet medium grinding, and the characterization and in vitro release of the prepared andrographolide nanoparticles were examined by high performance liquid chromatography, particle size analyzer, zeta potential meter and transmission electron microscopy. The cytotoxicity and anti-inflammatory effects of AND-ALG-POL/NPs were evaluated in vitro by MP-infected lung epithelial cells BEAS-2B. Symptoms of pneumonia, total cell count, total protein content and inflammatory factor levels in BALF were assessed by MP-induced pneumonia in BALB/c mice treated with AND-ALG-POL/NPs, and histopathological studies were performed on lung tissues from experimental animals. RESULTS: The results showed that the prepared AND-ALG-POL/NPs were homogeneous spherical with a diameter of 180 ± 23 nm, a zeta potential of (-14.4 ± 2.1) mV, an average encapsulation rate of 87.74 ± 0.87 %, and an average drug loading of 13.17 ± 0.54 %. AND-ALG-POL/NPs were capable of slow release in vitro and showed significant inhibitory ability against MP (P < 0.001). However, AND-ALG-POL/NPs were not cytotoxic to normal cells and alleviated MP infection-induced apoptosis and elevated inflammatory factors. In the in vivo experiments, AND-ALG-POL/NPs alleviated the symptoms of pneumonia in MPP mice, reduced the abnormally elevated total cell count, total protein content and inflammatory factor levels in BALF, and alleviated lung tissue edema, inflammatory cell infiltration and apoptosis (P < 0.001). Meanwhile, the therapeutic effects of AND-ALG-POL/NPs on MPP were similar to those of azithromycin (AZM) and higher than those of andrographolide (AND) free monotherapy (P < 0.001). CONCLUSION: In summary, the prepared AND-ALG-POL/NPs can effectively inhibit MPP in vitro and in vivo, and the effect is similar to that of AZM. Therefore, AND- ALG - POL/NPs have the potential to replace AZM as a potential drug for the treatment of MPP.

Clinical significance of serum microRNA-146a and inflammatory factors in children with Mycoplasma pneumoniae pneumonia after azithromycin treatment.

OBJECTIVE: This study aimed to investigate the clinical significance of serum microRNA-146a and pro-inflammatory factors in children with Mycoplasma pneumoniae pneumonia after azithromycin treatment. microRNA-146a is known to regulate inflammatory responses, and excessive inflammation is a primary characteristic of MPP. METHODS: Children with MPP received conventional symptomatic therapy along with intravenous administration of azithromycin for one week. Serum levels of microRNA-146a and pro-inflammatory factors were measured using RT-qPCR and ELISA kits, respectively. The correlation between microRNA-146a and pro-inflammatory factors was analyzed by the Pearson method. Pulmonary function indexes were assessed using a pulmonary function analyzer, and their correlation with microRNA-146a and pro-inflammatory factors after treatment was evaluated. Children with MPP were divided into effective and ineffective treatment groups, and the clinical significance of microRNA-146a and pro-inflammatory factors was evaluated using receiver operating characteristic curves and logistic multivariate regression analysis. RESULTS: Serum microRNA-146a was downregulated in children with MPP but upregulated after azithromycin treatment, contrasting with the trend observed for pro-inflammatory factors. MicroRNA-146a showed a negative correlation with pro-inflammatory cytokines. Pulmonary function parameters were initially reduced in children with MPP, but increased after treatment, showing positive/inverse associations with microRNA-146a and pro-inflammatory factors. Higher microRNA-146a and lower pro-inflammatory factors predicted better efficacy of azithromycin treatment. MicroRNA-146a, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) were identified as independent factors influencing treatment efficacy. CONCLUSION: Azithromycin treatment in children with MPP upregulates microRNA-146a, downregulates pro-inflammatory factors, and effectively improves pulmonary function.

Antibiotic treatment of Mycoplasma ovipneumoniae in domestic sheep (Ovis aries): Working at the livestock-wildlife interface in Yukon, Canada.

Domestic sheep (Ovis aries) can carry the bacterium Mycoplasma ovipneumoniae (M. ovipneumoniae) in their upper respiratory tract, often with little effect on health and productivity. However, for bighorn sheep (Ovis canadensis) populations, there is a link between M. ovipneumoniae infection and pneumonia, poor lamb recruitment, and high fatality rate. Because of these outcomes, preventing transmission of M. ovipneumoniae to free-ranging wild sheep has garnered interest from both the livestock and wildlife sectors. We hypothesized that treatment with intranasal and systemic enrofloxacin would reduce the prevalence of M. ovipneumoniae-positive animals in a flock of domestic sheep. Initially, the prevalence decreased in the treated group; but by 34 d post-treatment, the number of M. ovipneumoniae-positive sheep returned to near pretreatment prevalence. Key clinical message: Test-and-slaughter is a method used to reduce the risk of transmission of pneumonia-causing M. ovipneumoniae from domestic sheep and goats to free-ranging wild sheep. In an effort to find an alternative, we used enrofloxacin to treat a flock of M. ovipneumoniae-positive domestic sheep; however, long-term reduction of M. ovipneumoniae prevalence in the flock was not achieved.

Traitement antibiotique de Mycoplasma ovipneumoniae chez le mouton domestique (Ovis aries): travail à l'interface bétail-faune au Yukon, Canada. Les moutons domestiques (Ovis aries) peuvent être porteurs de la bactérie Mycoplasma ovipneumoniae (M. ovipneumoniae) dans leurs voies respiratoires supérieures, avec souvent peu d'effets sur la santé et la productivité. Cependant, pour les populations de mouflons d'Amérique (Ovis canadensis), il existe un lien entre l'infection à M. ovipneumoniae et la pneumonie, un faible recrutement d'agneaux et un taux de mortalité élevé. En raison de ces résultats, la prévention de la transmission de M. ovipneumoniae aux moutons sauvages en liberté a suscité l'intérêt des secteurs de l'élevage et de la faune sauvage. Nous avons émis l'hypothèse qu'un traitement par enrofloxacine intranasale et systémique réduirait la prévalence d'animaux positifs à M. ovipneumoniae dans un troupeau de moutons domestiques. Initialement, la prévalence a diminué dans le groupe traité; mais 34 jours après le traitement, le nombre de moutons positifs à M. ovipneumoniae est revenu à une prévalence proche de celle précédant le traitement.Message clinique clé :L'essai et l'abattage sont une méthode utilisée pour réduire le risque de transmission de M. ovipneumoniae, responsable de la pneumonie, des moutons et chèvres domestiques aux moutons sauvages en liberté. Dans le but de trouver une alternative, nous avons utilisé l'enrofloxacine pour traiter un troupeau de moutons domestiques positifs à M. ovipneumoniae; cependant, aucune réduction à long terme de la prévalence de M. ovipneumoniae dans le troupeau n'a été obtenue.(Traduit par Dr Serge Messier).

In vitro pharmacodynamics of nemonoxacin and other antimicrobial agents against Mycoplasma pneumoniae.

IMPORTANCE: This study first reported the in vitro effector kinetics of the new non-fluorinated quinolone, nemonoxacin, against macrolide-resistant M. pneumoniae (MRMP) and macrolide susceptible M. pneumoniae (MSMP) strains along with other antimicrobial agents. The time-kill assays and pharmacodynamic analysis showed that nemonoxacin has significant mycoplasmacidal activity against MRMP and MSMP. This study paves the road to establish appropriate dosing protocols of a new antimicrobial drug for children infected with M. pneumoniae.

Clinical features and risk factors of plastic bronchitis caused by Mycoplasma pneumoniae pneumonia in children.

BACKGROUND: We analyzed the clinical characteristics of children with plastic bronchitis (PB) caused by Mycoplasma pneumoniae (MP) and explored its risk factors. METHODS: We prospectively analyzed clinical data of children with MP pneumonia (MPP) treated with fiberoptic bronchoscopy (FB). Patients were classified into a PB and non-PB group. General information, clinical manifestations, laboratory tests, results of computed tomography scan, and FB findings were compared between groups. We conducted statistical analysis of risk factors for developing PB. RESULTS: Of 1169 children who had MPP and were treated with FB, 133 and 1036 were in the PB and non-PB groups, respectively. There were no significant differences in sex, age, and incident season between groups (P > 0.05). The number of children in the PB group decreased during the COVID-19 pandemic. Compared with children in the non-PB group, those in the PB group had longer duration of hospitalization, increased levels of neutrophil (N), C-reactive protein (CRP), procalcitonin (PCT), D-dimer, lactate dehydrogenase (LDH), alanine transaminase (ALT) and aspartate transaminase (AST); lower levels of lymphocyte (L) and platelet (PLT); and higher incidence of lack of appetite, decreased breath sounds, single lobar infiltrate, pleural effusion, pericardial effusion, mucosal erosion and/or necrosis, and bronchial embolization. L levels and pleural effusion were identified as risk factors in multivariate logistic regression. CONCLUSIONS: Children with PB caused by MPP had a strong and local inflammatory response. L levels and pleural effusion were independent risk factors of PB with MPP in children. Our findings will help clinicians identify potential PB in pediatric patients for early and effective intervention.

Clinical efficacy of budesonide combined with acetylcysteine in the treatment of mycoplasma pneumonia infection.

OBJECTIVE: Mycoplasma pneumoniae pneumonia (MPP) is a common respiratory tract infectious disease in children. The study aimed to elucidate the therapeutic efficacy of aerosolized budesonide and N-acetylcysteine combination therapy for MP infection in children. METHODS: One hundred and twenty children with MP infection were included and divided into the control group (received aerosol inhalation of budesonide) and the experimental group (aerosolized budesonide and N-acetylcysteine). After treatment, the disappearance time of clinical symptoms and efficacy were contrasted between the two groups. RESULTS: With the passage of treatment time, the children's cough score of the two groups were gradually reduced. The children in the experimental group got well from the cough faster than the control group, and the difference reached a significant level on the 5th and 7th days. The time required for fever, rale, and cough to disappear in the experimental group was shorter than those in the control group. As the treatment progressed, a gradual decrease in serum interleukin-6, tumor necrosis factor-α, and C-reactive protein values was detected in both groups, and the decrease was more significant in the experimental group. The total effective rate of the experimental group was 98.33%, which surpassed the control group (93.33%). CONCLUSION: Budesonide and N-acetylcysteine combination therapy in the treatment of MP infection in children has a significant effect, and can quickly relieve the clinical symptoms of children with good safety. It is worthy of widespread clinical use.

Primary symptoms of severe mycoplasma pneumoniae pneumonia with acute abdomen, scrotal swelling and pain, and fever: A case report.

BACKGROUND INTRODUCTION: In recent years, there has been an increase in the number of patients diagnosed with pediatric diseases who have severe Mycoplasma pneumoniae (MP) pneumonia, and there has also been an increased attention to serious extrapulmonary complications. However, cases with abdominal pain, acute abdomen, scrotal swelling and pain, and fever as the primary symptoms have been rarely reported. CASE DESCRIPTION: A 3-years-and-8-months-old male patient diagnosed with pediatric disease was reported with abdominal pain, scrotal swelling and pain, and fever as the primary symptoms in the present study. No respiratory symptoms were observed throughout the disease. Through computed tomography (CT) scanning, the patient was diagnosed with severe MP pneumonia based on the symptoms of abdominal pain and fever, as well as pulmonary infection, pleural effusion, and retroperitoneal exudation. Laboratory tests supported the diagnosis of MP infection, and the diagnosis was confirmed by severe MP pneumonia. The therapeutic effects of azithromycin were poor, and the symptoms were quickly alleviated with the addition of gamma globulin and methylprednisolone. After discharge, azithromycin sequential therapy was administered. The chest CT was normal at the follow-up 1-month later. CONCLUSION: Severe MP pneumonia in patients with pediatric diseases may include abdominal pain, scrotal swelling and pain, and fever as the primary symptoms. Care should be taken to avoid missed diagnoses and misdiagnoses in clinical practice.

Case Report: Omadacycline in the treatment of macrolide-unresponsive Mycoplasma pneumoniae pneumonia in an adolescent patient.

Omadacycline is a novel tetracycline antibiotic that exhibits good in vitro antibacterial activity against atypical pathogens such as Mycoplasma pneumoniae. It is approved for the treatment of adults with community-acquired bacterial pneumonia. However, the safety and efficacy of omadacycline in pediatric patients under 18 years of age have not yet been established. In the present paper, we report a case of pediatric community-acquired pneumonia in which initial empirical anti-infective therapy had failed. The patient received empirical anti-infective therapy with azithromycin and other antimicrobial agents upon admission but showed a poor clinical response and developed secondary tinnitus and liver dysfunction. After the confirmation of M. pneumoniae infection through metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid, an antibiotic switch to omadacycline was made. Thereafter, the patient's condition improved, and no adverse reactions were observed. These findings demonstrate that mNGS enables the identification of infection-causing pathogens in patients with unresponsive pneumonia. Omadacycline can be considered as an alternative option for anti-infective therapy in pediatric M. pneumoniae pneumonia, especially when the presence of bacterial resistance, adverse drug reactions, or organ failure are taken into consideration.

Differentiate Clinical Characteristics Between Viral Pneumonia and Mycoplasma pneumoniae and Nomograms for Predicting Mycoplasma pneumoniae : A Retrospective Study in Primary Hospitals.

OBJECTIVE: To identify the difference in clinical characteristics between viral pneumonia and Mycoplasma pneumoniae , providing cues on their differential diagnosis for primary hospitals with the insufficient pathogen detection capacity. METHODS: We retrospectively reviewed the medical records of hospitalized children with acute respiratory tract infections, and pathogenic microbes test results were analyzed. Clinical characteristics, routine blood parameters and hospitalization duration and fee were compared between M. pneumoniae and viral pneumonia. We used in the multivariable logistic regression to predict the probability of children with M. pneumoniae and graphically represented by a dynamic nomogram. The discrimination and clinical utility of the model were confirmed by receiver operating characteristic and decision curve analysis curves. RESULT: A total of 375 children with community-acquired pneumonia were included. Mycoplasma infection accounted for the largest proportion (22.13%). The incidence of both hypothermia and vomiting was lower in M. pneumoniae compared to viral pneumonia (hypothermia: 10.50% vs. 0.00%; vomiting: 7.90% vs. 0.00%). The prevalence of hyperthermia was higher in M. pneumoniae (hyperthermia: 89.5% vs. 100%). Procalcitonin, peripheral blood white blood cell count and lymphocyte levels were higher in the viral pneumonia group, and eosinophil levels were conversely lower. As for the duration of illness, the mean length of stay was 5.20 ± 2.12 (viral pneumonia) and 6.27 ± 2.48 days ( M. pneumoniae ). Children with M. pneumoniae had higher overall hospital costs and required more medical treatment. The above were all statistically significant with a P < 0.05. The scoring system was established based on the above results. Receiver operating characteristic curves showed good model-discrimination ability with 0.844 of the area under the curve in the training set and 0.778 in the test set. Decision curve analysis curves demonstrated the discriminative superiority of this model. The web-based dynamic nomogram calculator is accessible at https://zhxylxy0160128.shinyapps.io/Nomogram/ . CONCLUSION: Nomograms have satisfactory discrimination, and clinical utility may benefit in predicting the probability of developing M. pneumoniae in children. Children with M. pneumoniae have a higher burden than those with viral pneumonia and may require more intensive in-hospital monitoring.