Macrolide-resistant Mycoplasma Research Articles

Prevalence and Clinical Features of Community-Acquired Pneumonia Caused by Macrolide-Resistant Mycoplasma pneumoniae Isolated from Adults in Jeju Island.

Aims: Although the cases of macrolide-resistant Mycoplasma pneumoniae (MRMP) have been increasing substantially among children, there are very few studies that have focused on MRMP in adults. This study aimed to investigate the prevalence and clinical features of community-acquired pneumonia (CAP) caused by MRMP from adults in Jeju Island, Korea. Methods: We retrospectively recruited adult patients with CAP in whom M. pneumoniae infections had been confirmed for a 7-year period. Macrolide resistance was determined by identifying a mutation in the 23S rRNA gene using PCR. Results: In total, 70 subjects were included. Their mean age was 46.1 years and 36 (51.4%) were women. Only two isolates (2.9%) carried macrolide resistance mutations in the 23S rRNA gene, and all the mutations were A2063G transitions. No significant differences were observed in age, comorbidities, symptoms, duration of fever, and length of hospital stay between the MRMP and macrolide-sensitive Mycoplasma pneumoniae groups. The number of involved pulmonary lobes was greater in the MRMP group (3.50 vs. 1.44, p = 0.008). Conclusion: The prevalence of CAP caused by MRMP was relatively low in adults in Jeju Island. Patients with MRMP pneumonia tended to have multilobar pneumonic infiltrates.

2337. Clinical Characteristics of Children Infected With Macrolide-Resistant Mycoplasma Pneumonia in Central Ohio—Preliminary Data

BackgroundMacrolide-resistant Mycoplasma pneumoniae (MRMp) has emerged in the last 2 decades, with rates as high as 93% in Asia. Rates in the United Stated vary from 3.5 to 13.2%. By sequencing we identified our local resistance rate of 1.8% (9/477) in isolates collected from October 2015 to December 2017. Previous reports described increased morbidity in patients with MRMp. We evaluated the clinical characteristics of children infected with MRMp in Central Ohio.MethodsOf the 9 MRMp isolates identified, clinical data were available in 7 cases. We performed a case–control (1:3) analysis, where Mp patients were matched by month and year of presentation. Retrospective analysis of electronic health records (HER) was performed to identify clinical and treatment characteristics. Continuous variables are shown as medians and inter-quartile ranges (IQR), and categorical variables as percentages. For comparisons T, Mann–Whitney U, and Fisher’s exact tests were used as appropriate.ResultsBoth groups had similar demographics with no differences in age and gender. Median age (IQR) was 8.5 years (6–17) for the MRMp and 8 (IQR 3.5–11.5) for the Macrolide-susceptible Mp (MSMp). Duration of symptoms at presentation was similar, median (IQR) of 11 (4–14) days for MRMp, and 8 (6.25–13.25) days for MSMp (P = 0.7). All patients with MRMp had fever compared with 17 (81%) of the MSMp (P = 0.07). Tmax was similar in both groups (P = 0.11). All patients (100%) had cough. There were no differences in the frequency of oxygen requirement, fatigue, shortness of breath, sore throat, nasal congestion, rash, headache and chest radiographic findings. There were similar rates of hospitalization with 4 (57%) in the MRMp and 8 (38%) in the MSMp (P = 0.42). Among hospitalized children, there were no differences in duration hospitalization, median (IQR) 6 (1.25–21.25) days for MRMp and 2 (1–2.75) for MSMp (P = 0.31). None required invasive ventilation. One MRMp patient had encephalitis; this was the only patient requiring intensive care compared with none MSMp (P = 0.25). All patients were initially treated with azithromycin, but 2 (12%) of the MRMp were switched to levofloxacin (P = 0.06).ConclusionWe did not identify significant differences in clinical characteristics between patients with MRMp and MSMp. This could be related to our low local rate of MRMp.Disclosures O. Ramilo, Janssen Scientific Affairs, LLC: Consultant, Consulting fee. Sanofi: Scientific Advisor, Consulting fee. Merck: Scientific Advisor, Consulting fee and Speaker honorarium. Janssen: Grant Investigator and Scientific Advisor, Consulting fee, Grant recipient and Speaker honorarium. Pfizer: Consultant, Consulting fee and Speaker honorarium. A. Leber, Nationwide Children’s Hospital: Research Contractor, Research support.

Evaluation of Lightmix Mycoplasma macrolide assay for detection of macrolide-resistant Mycoplasma pneumoniae in pneumonia patients

ObjectivesRapid detection of macrolide resistance–associated mutations in Mycoplasma pneumoniae is crucial for effective antimicrobial treatment. We evaluated the Lightmix Mycoplasma macrolide assay for the detection of point mutations at nucleotide positions 2063 and 2064 in the 23S ribosomal RNA (rRNA) gene of M. pneumoniae that confer macrolide resistance. MethodsSamples from 3438 patients with a respiratory tract infection were analysed by M. pneumoniae real-time PCR, and 208 (6%) of them were tested positive. In this retrospective study, 163 M. pneumoniae real-time PCR–positive samples were analysed by the Lightmix assay, and results were compared to targeted 23S rRNA sequencing. ResultsMacrolide-resistant M. pneumoniae were found in 15 (9%) of 163 retrospectively analysed samples. The Lightmix assay showed a sensitivity of 100% (95% confidence interval, 78.2–100) and a specificity of 100% (95% confidence interval, 97.5–100) as the detected M. pneumoniae genotype (148 wild type and 15 non–wild type) was confirmed by 23S rRNA sequencing in all samples. ConclusionsThe Lightmix assay is an easy-to-use and accurate molecular test that allows rapid determination of macrolide resistance in M. pneumoniae.

Rapid Detection of the Macrolide Sensitivity of Pneumonia-Causing Mycoplasma pneumoniae Using Quenching Probe Polymerase Chain Reaction (GENECUBE®).

Macrolide-resistant Mycoplasma pneumoniae (MR-MP) have been reported worldwide. Strategies for the treatment of MR-MP are a key focus of research. The GENECUBE® is a novel, fully automated rapid genetic analyzer. The goals of this study were to assess the macrolide sensitivity of M. pneumoniae (MP) isolates by analyzing 23S ribosomal RNA (rRNA) gene sequences using a GENECUBE®-based system and to determine the validity of this system in determining clinical treatment options for MP pneumonia. This was an observational retrospective study including 150 children with MP pneumonia. We used quenching probe polymerase chain reaction (Q-probe PCR) as implemented in the GENECUBE® system to detect macrolide resistance-causing mutations in the MP 23S rRNA gene. We compared the duration of fever between patients receiving initial empirical antibiotic treatment (Empirical T group) and those receiving treatment after Q-probe PCR (PCR First group) diagnosis. Selecting antibiotic treatment after Q-probe PCR significantly shortened the duration of fever compared to empirical antibiotic treatment (PCR First group, median: 6.0days [n = 32]; Empirical T group, median: 7.5days [n = 66]; p = 0.002). Comparison of macrolide sensitivity using Q-probe PCR and clinical diagnosis showed that the reliability of Q-probe PCR was nearly validated for macrolide sensitivity. Q-probe PCR as implemented by GENECUBE® is a useful tool for the diagnosis of MP pneumonia and enables optimization of the selection of antibiotics in order to rapidly improve the clinical course of disease.

Clinical effect and mechanism of compound herba houttuyniae mixture for the childern with macrolide-resistant myeoplasma pneumoniae

Objective To observe the clinical effect of the Compound herba houttuyniae mixture combined with azithromycin for the children with macrolide-resistant mycoplasma pneumoniae(MRMPP) and investigate the bi-directional control mechanism of inflammatory response. Methods A total of 60 patients with MRMPP were randomly divided into control group and observation group of 30 patients each by random number table. Patients in control group took azithromycin, while patients in observation group took azithromycin and compound herba houttuyniae mixture. Both groups were treated 21 days. Results The total effective rate of observation group was 86.67%, while the control group was 56.67%, and the difference was statistical significance (χ2=5.253, P=0.022). The duration of fever (1.2 ± 0.3 d vs. 3.7 ± 2.2 d, t=6.293), cough (7.5 ± 2.3 d vs. 14.9 ± 3.7 d, t=9.232) in the observation group were significantly better than those in the control group (P<0.01). The serum concentrations of IL-6 (14.69 ± 8.26 pg/ml vs. 8.41 ± 5.26 pg/ml, t=3.512), IL-10 (6.23 ± 1.79 pg/ml vs. 3.47 ± 2.18 pg/ml, t=5.359), IL-17 (5.61 ± 2.77 pg/m vs. 2.09 ± 1.53 pg/ml, t=6.093) in the observation group were significantly decreased than the control group (P<0.01). There were fewer cases of gastrointestinal adverse events in the treatment group than in the control group (3 vs. 11 cases; χ2=4.565, P<0.05) and the number of abnormal liver function (2 vs. 9 cases; χ2=4.007, P<0.05). Conclusions Compound herba houttuyniae mixture combined with azithromycin could improve the clinical symptoms and signs, and shorten the symptoms duration and reduce the side reaction. Key words: Pneumonia, Mycoplasma; Child; Macrolides; Drug resistance; Compound herba houttuyniae mixture; Integrated Chinese traditional and western medicine therapy

Clinical features and seasonal variations in the prevalence of macrolide-resistant Mycoplasma pneumoniae.

Background Mycoplasma pneumoniae is a common pathogen causing pneumonia; macrolide‐resistant strains are rapidly spreading across Japan. However, the clinical features of macrolide‐resistant M. pneumoniae pneumonia have not been well established. Here, we evaluated the clinical characteristics and seasonal variations in the prevalence of M. pneumoniae with macrolide‐resistant mutations (MRM).MethodsThe monthly prevalence of MRM in M. pneumoniae strains isolated from May 2016 to April 2017 was retrospectively analyzed, and the clinical characteristics of pneumonia cases with MRM were compared to those of cases without MRM. The M. pneumoniae isolates and point mutations at site 2063 or 2064 in domain V of 23S rRNA were evaluated by the GENECUBE system and GENECUBE Mycoplasma detection kit.Results Mycoplasma pneumoniae infection was identified in 383 cases, including 221 cases of MRM (57.7%). The MRM prevalence was 86.3% (44/51) between May and July 2016, demonstrating an apparent decrease in September 2016, subsequently reaching 43.0% (34/79) in November 2016. Mycoplasma pneumoniae pneumonia was diagnosed in 275 cases, including 222 pediatric and 53 adult cases. Macrolide use preceding evaluation was found to be the only feature of MRM pneumonia cases both in children (odds ratio [OR] 3.86, 95% confidence interval [CI]:1.72–8.66) and in adults (OR 7.43, 95% CI: 1.67–33.1).ConclusionsThe determination rate of MRM varied widely throughout the year, and our study demonstrated the challenges in predicting M. pneumoniae with MRM based on clinical features at diagnosis. Therefore, continuous monitoring of the prevalence of MRM is warranted, which may help in selecting an effective treatment.

Increased procalcitonin level is a risk factor for prolonged fever in children with Mycoplasma pneumonia.

Purpose Macrolide-resistant Mycoplasma pneumoniae pneumonia (MPP) is characterized by prolonged fever and radiological progression despite macrolide treatment. Few studies have examined serum procalcitonin (PCT) level in children with MPP. We aimed to investigate the association of acute inflammation markers including PCT with clinical parameters in children with MPP. Methods A total of 147 children were recruited. The diagnosis of MPP relied on serial measurement of IgM antibody against mycoplasma and/or polymerase chain reaction. We evaluated the relationships between C-reactive protein (CRP), PCT, and lactate dehydrogenase (LDH) levels and white blood cell (WBC) counts, and clinical severity of the disease. We used multivariate logistic regression analysis to estimate the odds ratio for prolonged fever (>3 days after admission) and hospital stay (> 6 days), comparing quintiles 2–5 of the PCT levels with the lowest quintile. Results The serum PCT and CRP levels were higher in children with fever and hospital stay than in those with fever lasting ≤ 3 days after admission and hospital stay ≤ 6 days. CRP level was higher in segmental/lobar pneumonia than in bronchopneumonia. The LDH level and WBC counts were higher in children with fever lasting for >3 days before compared to those with fever lasting for ≤ 3 days. The highest quintile of PCT levels was associated with a significantly higher risk of prolonged fever and/or hospital stay than the lowest quintile. Conclusion Serum PCT and CRP levels on admission day were associated with persistent fever and longer hospitalization in children with MPP.

Clinical features and treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children

To study the clinical features of macrolide-resistant Mycoplasma pneumoniae pneumonia and its treatment regimens in children. The samples of throat swab or bronchoalveolar lavage fluid were collected from 136 children with Mycoplasma pneumoniae pneumonia. Quantitative real-time PCR was used to detect 2063/2064 A:G mutation in 23S rRNA, and according to such results, the children were divided into drug-resistance group with 81 children and sensitive group with 55 children. The two groups were compared in terms of age composition, respiratory symptoms, extrapulmonary complications, laboratory markers, imaging changes, treatment regimens, and length of hospital stay. Compared with the sensitive group, the drug-resistance group had significantly longer duration of pyrexia and severe fever, a significantly higher percentage of children with reduced blood oxygen saturation, and significantly higher levels of alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) (P<0.05). The conventional azithromycin treatment had a good clinical effect in the sensitive group, while corticosteroid therapy was usually needed in the drug-resistance group. Macrolide-resistant Mycoplasma pneumoniae infection cannot be identified based on a single clinical feature, but prolonged duration of pyrexia and severe fever, reduced blood oxygen saturation, and increased ALT and LDH can suggest the presence of this disease. Azithromycin combined with glucocorticoids may be a good treatment regimen for children with macrolide-resistant Mycoplasma pneumoniae pneumonia.

In vitro activity of zoliflodacin (ETX0914) against macrolide-resistant, fluoroquinolone-resistant and antimicrobial-susceptible Mycoplasma genitalium strains.

Mycoplasma genitalium is estimated to be the second most common cause of bacterial sexually transmitted infection in Europe. It is of increasing public health concern due to the rapid development of resistance to different antimicrobial classes, including the preferred first- and second-line treatments azithromycin and moxifloxacin. Thus, new antimicrobial agents are urgently needed, especially for the treatment of MDR strains. The in vitro activity of the new spiropyrimidinetrione zoliflodacin against 47 M. genitalium strains was assessed by growing M. genitalium in Vero cell culture and measuring growth by quantitative PCR. The collection included 34 moxifloxacin-susceptible (MIC <1 mg/L) and 13 moxifloxacin-resistant (MIC ≥1 mg/L) strains. Twenty-three of the strains were azithromycin resistant (MIC ≥16 mg/L) and 12 of these strains were MDR. Only one (2.1%) strain with substantially increased MIC (4 mg/L) and potential resistance to zoliflodacin was found. Zoliflodacin was overall more potent than moxifloxacin (P = 0.009) and no cross-resistance was observed between the two drug classes of topoisomerase II inhibitors. Differences in the MICs of zoliflodacin and azithromycin were not statistically significant; however, 23 (48.9%) compared with potentially 1 (2.1%) of the strains were resistant to azithromycin and zoliflodacin, respectively. Zoliflodacin is a promising candidate for the treatment of M. genitalium and it is important to further develop and evaluate this drug.

The timing of azithromycin treatment is not associated with the clinical prognosis of childhood Mycoplasma pneumoniae pneumonia in high macrolide-resistant prevalence settings.

BackgroundMycoplasma pneumoniae infection is a major cause of community-acquired pneumonia in children. We performed a retrospective study to evaluate the clinical impact of the timing of azithromycin treatment in children with Mycoplasma pneumoniae pneumonia in high macrolide-resistant prevalence settings.Methods and findingsA total of 623 patients were enrolled in this study and were divided into 2 groups according to the timing of azithromycin therapy. Children who received azithromycin within 3 days (72 hours) after the onset of Mycoplasma pneumoniae pneumonia were classified into the early azithromycin treatment group (n = 174), whereas the late azithromycin treatment group (n = 449) comprised children treated with azithromycin more than 72 hours after symptom onset. We evaluated clinical prognosis according to demographic, clinical and laboratory characteristics. Although the early azithromycin treatment group exhibited a longer fever duration after azithromycin administration (7.17±4.12 versus 4.82±3.99 days, P<0.01), the total fever duration exhibited no significant difference (9.02±4.58 versus 9.57±4.91 days, P = 0.212). After azithromycin therapy, the two groups exhibited no significant differences with respect to improvements in the laboratory and radiological findings (all P>0.05).ConclusionThe timing of azithromycin treatment is not associated with the clinical prognosis of Mycoplasma pneumoniae pneumonia in children in high macrolide-resistant Mycoplasma pneumoniae prevalence settings.

Related factors for and changes in clinical manifestations in mycoplasma pneumonia nonresponsive to macrolide treatment

Purpose: Mycoplasma pneumonia is known to be a major cause of community-acquired pneumonia in children. Macrolide has been the first-line treatment for mycoplasma pneumonia, but recently there has been an increasing tendency of macrolide-resistant Mycoplasma pneumoniae (MRMP). Therefore, this study aimed to investigate the clinical tendency and the therapeutic responsibility of mycoplasma pneumonia in terms of the fever duration after treatment and its associated factors. Methods: A total of 346 children admitted with mycoplasma pneumonia during 3 recent periods (2008-2009, 2011-2012, and 2015-2016) were investigated with clinical manifestations, laboratory test results and chest x-ray findings. Patients were grouped according to fever duration and analyzed for differences in clinical features. Results: There was no statistically significant difference in age or sex between the 3 periods (P=0.284 and P=0.559, respectively). Total fever duration during mycoplasma pneumonia was increased with time (P for trend <0.001). The patients with a longer fever duration (≥3 days) after macrolide treatment presented with a higher CRP (P<0.001) and with lobar-type pneumonia (P=0.020) compared to those with a shorter fever duration. Fever duration after steroid treatment became longer in the longer fever group in 2011 (P=0.015) and 2015 (P<0.001), but not in 2008 (P=0.536). Conclusion: This study showed that the therapeutic effect of macrolide or steroid for mycoplasma pneumonia is recently attenuat ing and that high CRP, lobar-type pneumonia and presence of pleural effusion were the associated factors. Therefore, efforts to de crease MRMP and to develop better treatment guidelines for mycoplasma pneumonia are needed in the future. (Allergy Asthma Respir Dis 2018;6:116-121)

Macrolide-resistant Mycoplasma pneumoniae prevalence and clinical aspects in adult patients with community-acquired pneumonia in China: a prospective multicenter surveillance study.

Drug resistant Mycoplasma pneumoniae (MP) is a rising issue in the management of community-acquired pneumonia (CAP). Epidemiological monitoring is essential for identifying resistant patterns of MP isolates against various antibiotics in adult CAP patients. This is a prospectively designed multicenter study conducted on adult patients with CAP visiting six teaching hospitals in the cities of Beijing, Shanghai and Guangzhou between September 2010 and June 2012. A total of 520 adult patients (mean age: 45.7±26.2 years) with CAP visiting teaching hospitals in the cities of Beijing, Shanghai and Guangzhou were included. Of the 520 patients, only 75 (14.42%) were confirmed MP positive by means of culture and real-time PCR methods. Quinolones were the most common initially prescribed antimicrobial, followed by β-lactams and β-lactams plus quinolones. Macrolide resistance was as high as 80% and 72% against erythromycin (ERY) and azithromycin (AZM) respectively, which were associated with the A2063G transition mutation in domain V of the 23S ribosomal RNA (rRNA) gene. Six strains with mild to moderate ERY-resistant level were still susceptible to AZM. Tetracycline (TET), minocycline (MIN) and quinolones [moxifloxacin (MOX) and fluoroquinolones] had no signs of resistance. High resistance was observed with macrolides, whereas, none of the MP strains were resistant to fluoroquinolones and TET. Hence, macrolide resistant MP (MRMP)_infections could be well treated with fluoroquinolones. However, few isolated strains had minimal inhibitory concentration (MIC) values on the edge of resistance to quinolones, alarming a quinolone-resistant MP in the near future.

High levels of macrolide-resistant Mycoplasma genitalium in Queensland, Australia.

The macrolide azithromycin is recommended for treatment of Mycoplasma genitalium infection; however, M. genitalium strains possessing macrolide resistance-mediating mutations (MRMMs) are increasingly being reported. Here, we used the SpeeDx ResistancePlus MG kit, which provides simultaneous detection of M. genitalium and MRMMs, to assess MRMM carriage among M. genitalium infections in Queensland, Australia. Performance characteristics of the ResistancePlus MG kit for M. genitalium detection were compared to in-house PCR. Available M. genitalium PCR-positive (n=67) and negative (n=281) samples from the years 2011 to 2017 were tested using the SpeeDx ResistancePlus MG kit. In total, 63.6 % M. genitalium-positive samples were indicated to harbour MRMMs. The ResistancePlus MG method provided sensitivity and specificity of 97 and 99.6 % respectively compared to in-house PCR for M. genitalium detection. Such high levels of macrolide-resistant M. genitalium raise further concerns over future use of azithromycin for treatment of M. genitalium infection.

Whole Genome Analysis Reveals New Insights into Macrolide Resistance in Mycoplasma pneumoniae

ObjectiveMutations in 23S rRNA gene are known to be associated with macrolide resistance in Mycoplasma pneumoniae (M. pneumoniae). However, these mutations alone do not fully explain the high resistance rates in Asia. The aim of this study was to investigate other possible mutations involved in macrolide resistance in M. pneumoniae. MethodsThe whole genomes of 10 clinical isolates of M. pneumoniae with macrolide resistance were sequenced by Illumina HiSeq2000 platform. The role of the macrolide-specific efflux transporter was assessed by efflux-pump inhibition assays with reserpine and carbonyl cyanide m-chlorophenyl-hydrazone (CCCP). ResultsA total of 56 single nucleotide polymorphisms (SNPs) were identified in 10 clinical isolates in comparison to the reference strains M129 and FH. Strikingly, 4 of 30 SNPs causing non-synonymous mutations were clustered in macrolide-specific efflux system gene macB encoding macrolide-specific efflux pump protein of the ATP-binding cassette transporter family. In assays of the minimal inhibitory concentrations (MIC) of macrolide antibiotics in the presence of the efflux pump inhibitors caused a significant decrease of MICs, even under detectable levels in some strains. ConclusionOur study suggests that macrolide efflux pump may contribute to macrolide resistance in M. pneumoniae in addition to the common point mutations in 23S rRNA gene.

Killing kinetics of minocycline, doxycycline and tosufloxacin against macrolide-resistant Mycoplasma pneumoniae

Macrolide-resistant Mycoplasma pneumoniae (MRMP) has emerged and is increasing worldwide. In a 2011 outbreak of MRMP infections in Japan, symptoms failed to improve in many patients who initially received macrolides; the therapeutic agent was then changed to minocycline (MIN), doxycycline (DOX) or tosufloxacin (TFX). In this study, the bactericidal effects of these three agents against MRMP were evaluated. Time–kill kinetics against MRMP and macrolide-susceptible M. pneumoniae (MSMP) were determined for 5 days at concentrations corresponding to the respective minimum inhibitory concentration (MIC) and 2 × MIC, i.e. 1 µg/mL and 2 µg/mL for MIN, 0.5 µg/mL and 1 µg/mL for DOX, and 0.5 µg/mL and 1 µg/mL for TFX. The post-antibiotic effects (PAE) of these agents in culture against MRMP were also examined based on their pharmacokinetic parameters in children. Following exposure of MRMP and MSMP to up to twice the respective MICs of MIN, DOX and TFX, viable cells initially numbering 106 CFU/mL had decreased similarly to 103 CFU/mL after 4 days. Clarithromycin and azithromycin showed good bactericidal action against MSMP but not against MRMP. PAEs against MRMP appeared superior with MIN and DOX compared with TFX. In infection with M. pneumoniae having a generation time exceeding 6 h, a therapeutic agent must be selected in consideration of pharmacokinetic parameters, not MICs alone.

Analysis of clinical characteristics and epidemic genotypes of children with Mycoplasma pneumoniae pneumonia

Objective To explore the clinical features of children infected with macrolide-resistant (MR) Mycoplasma pneumonia(MP) isolates and genetic typing of all isolates. Methods Polymerase chain reaction(PCR) of MP positive in 96 nasopharyngeal or bronchoalveolar lavage fluid (BALF) samples were collected from patients diagnosed as MP pneumonia in the Affiliated Children′s Hospital of the Capital Institute of Pediatrics from January 2013 to October 2015.Fifty-five cases were male, 41 cases were female; 19 cases(19.8%) were 1 to 3 years old, 18 cases(18.7%) were more than 3 to 5 years old, 59 cases(61.5%) were more than 5 to 13 years and 2 months old.These samples were tested for MR associated mutations in the 23S rRNA of MP, and were divided into the MR group and the macrolide-sensitive (MS) group.Furthermore, the genotype of all the isolates were performed by conducting P1- restriction fragment length polymorphism(P1-RFLP) analysis and multiple-locus variable-number tandem-repeat analysis(MLVA) method.The clinical characteristics including the age, gender, hospitalization duration, symptoms, signs, fever duration, fever duration after macrolide therapy, white blood cell count, C-reactive protein (CRP), chest X-ray and/or chest computed tomography, which were compared between different groups.SPSS 11.5 software was used to analyze the statistical data.Statistical significance was determined at the 0.05 level of a two-tailed test. Results MR mutations were identified in the 23S rRNA gene in 81 specimens(84%), and the 96 specimens were divided into MR group(81 cases) and MS group(15 cases). There were statistical differences in fever duration, hospitalization duration, the incidence of complications and CRP level between the MR group and MS group (t=2.061, Z=-3.368, χ2=5.856, Z=-2.165, all P 0.05). All the 96 isolates were performed by adopting P1-RFLP typing, but 5 isolates were not typed successfully, while 81 cases(89.0%)isolates were typed as P1-Ⅰ and 10 isolates(11%) were typed as P1-Ⅱc.The hospitalization duration and the fever duration after macrolide therapy in the P1-Ⅰ were longer than the P1-Ⅱc group, and the difference was statistically significant (Z=-2.197, 2.237, all P 0.05). Seventy-three cases (90%)of P1-Ⅰ group were MR isolates, 8 cases (10%) were MS isolates; 3 cases(30%) of the P1-Ⅱc group were MR isolates, 7 cases (70%) were MS isolates.The MR isolates in P1-Ⅰ group were much more than P1-Ⅱc group.There was obvious statistical difference in the proportion of MR isolates between 2 groups(χ2=19.209, P 0.05). Seventy-four cases (90%)of the M4-5-7-2 group were MR isolates, 8 cases (10%) were MS isolates; 4 cases (36%) of the M3-5-6-2 group were MR isolates, 7 cases (64%) were MS isolates.The MR isolates in M4-5-7-2 group were much more than M3-5-6-2 group.There was obviously statistical difference in the proportion of MR isolates between 2 groups(χ2=17.022, P<0.01). Conclusions In the MR group, the children had longer fever duration and hospitalization duration, higher incidence of complications and higher CRP level than those in the MS group.The MR rates of MP in China was high.P1-Ⅰ and M4-5-7-2 are the predominate genotypes.There may be a correlation between genotype and MR. Key words: Mycoplasma pneumoniae; Drug resistance; Macrolides; Genotype

Therapeutic efficacy of azithromycin, clarithromycin, minocycline and tosufloxacin against macrolide-resistant and macrolide-sensitive Mycoplasma pneumoniae pneumonia in pediatric patients.

ObjectiveTo clarify therapeutic effects of azithromycin, clarithromycin, minocycline and tosufloxacin against macrolide-resistant Mycoplasma pneumoniae (MRMP) pneumonia and against macrolide-sensitive Mycoplasma pneumoniae (MSMP) pneumonia in pediatric patients.MethodsA prospective, multicenter observational study was conducted from July 2013 to August 2015. The therapeutic effects of azithromycin, clarithromycin, minocycline and tosufloxacin were evaluated in 59 patients with pneumonia caused by MRMP and in 50 patients with pneumonia caused by MSMP. In vitro activities of antimicrobial agents against isolates of Mycoplasma pneumoniae were also measured.ResultsMean durations of fever following commencement of treatment in patients infected with MRMP and MSMP were 5.2 and 1.9 days, respectively (log-rank test, P < 0.0001). Among patients infected with MRMP, mean durations of fever were 4.6, 5.5, 1.0 and 7.5 days for patients treated with azithromycin, clarithromycin, minocycline and tosufloxacin, respectively (log-rank test, P < 0.0001). Among patients infected with MSMP, mean durations of fever were 2.5, 1.7, 0.9 and 4.3 days for patients treated with azithromycin, clarithromycin, minocycline and tosufloxacin, respectively (log-rank test, P = 0.0162). The MIC90s of azithromycin and clarithromycin among the 27 isolates of MRMP were 64 and 256 μg/ml, respectively, and those among the 23 isolates of MSMP were <0.000125 and 0.001 μg/ml, respectively. The MIC90s of minocycline and tosufloxacin among the 27 isolates of MRMP were 1.0 and 0.25 μg/ml, respectively, and those among the 23 isolates of MSMP were 1.0 and 0.5 μg/ml, respectively.ConclusionBoth minocycline and tosufloxacin showed good in vitro activities against MRMP. Minocycline, but not tosufloxacin, shortened the duration of fever in pediatric patients infected with MRMP compared to the duration of fever in patients treated with macrolides.

Development of an in-house real-time pcr to monitor the prevalence of macrolide-resistant Mycoplasma pneumoniae in Hong Kong

Development of an in-house real-time pcr to monitor the prevalence of macrolide-resistant Mycoplasma pneumoniae in Hong Kong

In Vitro Activities of Lefamulin and Other Antimicrobial Agents against Macrolide-Susceptible and Macrolide-Resistant Mycoplasma pneumoniae from the United States, Europe, and China.

Lefamulin, an investigational pleuromutilin, was tested against a collection of 18 macrolide-susceptible and 42 macrolide-resistant Mycoplasma pneumoniae strains, and the results were compared with those of azithromycin, erythromycin, tetracycline, doxycycline, and moxifloxacin testing. Lefamulin was highly active against all strains tested, with all MICs at ≤0.008 μg/ml. The lefamulin MIC90 (0.002 μg/ml) for macrolide-resistant strains was the lowest among all drugs tested. Minimum bactericidal concentrations were within 2 dilutions of the MIC values, indicating a bactericidal effect.

Mechanism of resistance acquisition and treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children.

Mycoplasma pneumoniae pneumonia (MPP) is one of the most common forms of community-acquired pneumonia in children and adolescents. Outbreaks of MPP occur in 3- to 7-year cycles worldwide; recent epidemics in Korea occurred in 2006–2007, 2011, and 2015–2016. Although MPP is known to be a mild, self-limiting disease with a good response to macrolides, it can also progress into a severe and fulminant disease. Notably, since 2000, the prevalence of macrolide-resistant MPP has rapidly increased, especially in Asian countries, recently reaching up to 80%–90%. Macrolide-resistant Mycoplasma pneumoniae (MRMP) harbors a point mutation in domain V of 23S rRNA with substitutions mainly detected at positions 2063 and 2064 of the sequence. The excessive use of macrolides may contribute to these mutations. MRMP can lead to clinically refractory pneumonia, showing no clinical or radiological response to macrolides, and can progress to severe and complicated pneumonia. Refractory MPP is characterized by an excessive immune response against the pathogen as well as direct injury caused by an increasing bacterial load. A change of antibiotics is recommended to reduce the bacterial load. Tetracyclines or quinolones can be alternatives for treating MRMP. Otherwise, corticosteroid or intravenous immunoglobulin can be added to the treatment regimen as immunomodulators to down-regulate an excessive host immune reaction and alleviate immune-mediated pulmonary injury. However, the exact starting time point, dose, or duration of immunomodulators has not been established. This review focuses on the mechanism of resistance acquisition and treatment options for MRMP pneumonia.