Analysis of Clinical Isolation Characteristics of Nontuberculous Mycobacteria and Drug Sensitivity of Rapidly Growing Mycobacteria in the General Hospital of Guangzhou, China.

Purpose: The clinical distribution characteristics of nontuberculous mycobacteria (NTM) in general hospital were explored to guide the clinical diagnosis and treatment of NTM infection. Methods: Samples with positive mycobacterium culture in the First Affiliated Hospital of Guangzhou Medical University were collected and identified through PCR. Phenotypic drug sensitivity experiments were conducted on 44 Mycobacteroides abscessus isolated from clinical departments with broth microdilution method, and rrl, rrs and erm (41) genes associated with drug resistance were detected. Results: From September 2020 to July 2023, 314 mycobacterium-positive isolates were separated from patients in the First Affiliated Hospital of Guangzhou Medical University, with 147 (46.8%) NTM isolates were included in our study. The samples were respiratory tract specimens mainly, with 64% bronchoalveolar lavage fluid. Of 144 cases identified, samples were from 133 patients (60 males and 73 females; gender ratio of 0.82:1). NTM was mainly isolated from the people aged 40 and above, especially females (χ2 = 10.688, P = 0.014). M. abscessus (61, 42.36%), M. intracellulare (35, 24.31%) were the two most NTMs in this hospital. Clinical strains of M. abscessus exhibited high resistance to antibiotics, except for cefoxitin (31.8%), linezolid (25.0%), amikacin (0%), and clarithromycin (18.2%). Among 8 strains of M. abscessus with clarithromycin acquired resistance, just 4 strains (50.0%) showed mutations (A2270G, A2271G) in rrl gene, but a new mutation (C2750T) was detected in 1 strain. Among 14 strains of M. abscessus with clarithromycin-induced resistance, 13 (93.0%) strains had T28 erm (41) gene and 1 (7.0%) strain had C28 erm (41) gene. Conclusion: M. avium-intracellulare complex was gradually becoming predominant strain in Guangzhou area. The resistant situation of M. abscessus in general hospital had shown severe. Potential mutation in rrl gene associated with clarithromycin acquired resistance of M. abscessus were found, but drug-resistant mechanism remained unclear.

Efficacy and safety of long-term macrolide therapy for non-cystic fibrosis bronchiectasis: A systematic review and meta-analysis.

BACKGROUND: Long-term macrolide therapy for non-cystic fibrosis bronchiectasis (NCFB) can play a significant role. However, such data are insufficient regarding the efficacy against severe exacerbation and adverse effects, including the emergence of macrolide-resistant pathogens and prolonged macrolide use beyond 1 year. METHODS: Randomized controlled trials (RCTs) and prospective observational studies comparing the efficacy and safety of macrolides and placebo in adult patients with NCFB were screened on April 10, 2024. The primary outcome was severe exacerbation frequency. RESULTS: Ten RCTs ≤1 year study durations were included. Most studies mainly included patients with a history of >2 exacerbations. Macrolides had a tendency to reduce the frequency of severe exacerbations compared with placebo (odds ratio = 0.54, 95% confidence interval (CI) = 0.25-1.18). Macrolides significantly reduced the frequency of exacerbations (rate ratio = 0.58, 95% CI = 0.48-0.69), prolonged the time to first exacerbation (rate ratio = 0.41, 95% CI = 0.30-0.55), improved the changes in SGRQ scores [mean difference (MD) = -3.99, 95% CI = -4.63-3.44] and percent predicted forced expiratory volume in 1 s (MD = -2.30, 95% CI = 0.26-4.33), and reduced sputum volume (gram) (MD = -7.44, 95% CI = -9.15-5.74). Additionally, macrolides did not increase drug-related adverse events leading to discontinuation. Qualitative SR of pathogens indicated macrolides might increase the number of macrolide-resistant oropharyngeal and sputum pathogens and the emergence of Pseudomonas aeruginosa. CONCLUSIONS: Our results support macrolide therapy for patients with NCFB. Studies with an observation period of >1 year or those focusing on patients with/without a minimal exacerbation history are required to determine the long-term effects on patients with NCFB.

Clarithromycin sustained-release tablet may be an improper therapy for the eradication of Helicobacter pylori.

Background: Clarithromycin plays an important role in eradicating Helicobacter pylori (H. pylori) through quadruple therapy. However, there is limited research on whether different forms of clarithromycin dosage have similar efficacies against H. pylori. Objective: We aimed to evaluate the efficacy of different forms of clarithromycin dosage in bismuth-containing quadruple therapy for eradicating H. pylori. Design: A single-center retrospective analysis comparing the efficacy of different forms of clarithromycin dosage in eradicating H. pylori. Methods: An analysis was conducted on patients diagnosed with H. pylori infection through the 13C-urea breath test (13C-UBT) at Henan Provincial People's Hospital, China from 2020 to 2022 who were treated with either a dispersible or sustained-release clarithromycin tablet (500 mg each), alongside amoxicillin (1000 mg), a standard dose of proton pump inhibitors (PPIs), and bismuth citrate (220 mg), administered twice daily as part of bismuth-containing quadruple therapy. Treatment efficacy was assessed using 13C-UBT at least 4 weeks after treatment completion. The H. pylori eradication rate was the primary outcome of this study, and factors influencing it were analyzed. Results: Among 2094 screened patients, 307 with H. pylori infection (mean age, 41.8 ± 0.7 years; 43% men) received bismuth-containing quadruple therapy. Univariate analysis of the dispersible and sustained-release tablet groups revealed a lower eradication rate with the sustained-release tablet compared with the dispersible clarithromycin tablet regimen (75.26% (73/97) vs 95.26% (200/210), respectively; p < 0.05). Other factors, such as smoking, age, and PPI type, were not significantly associated with the cure rate. Multivariate analysis identified the form of clarithromycin dosage (dispersible vs sustained-release) to be an independent risk factor for eradication failure using the bismuth-containing quadruple therapy (odds ratio = 0.145, 95% confidence interval: (0.065-0.323); p < 0.05). Conclusion: The clarithromycin dispersible tablet demonstrated a higher H. pylori eradication rate, and the sustained-release clarithromycin tablet may be inappropriate for H. pylori eradication.

Clarithromycin sustained-release tablet may be an improper therapy for the eradication of Helicobacter pylori The clarithromycin dispersible tablet therapy demonstrated a higher eradication rate for H. pylori infection, and clarithromycin sustained-release tablets may be inappropriate for the eradication of H. pylori.

Liquid crystal nanoparticles for oral combination antibiotic therapies: A strategy towards protecting commensal gut bacteria during treatment.

Antibiotics are essential for treating infections and reducing risks during medical interventions. However, many commonly used antibiotics lack the physiochemical properties for an efficient oral administration when treating systemic infection. Instead, we are reliant on intravenous delivery, which presents complications outside of clinical settings. Developing novel formulations for oral administration is a potential solution to this problem. We engineered hexosome and cubosome liquid crystal nanoparticles (LCNPs) characterized by small-angle X-ray scattering and cryogenic transmission electron microscopy, and could encapsulate the antibiotics vancomycin (VAN) and clarithromycin (CLA) with high loading efficiencies. By rationally choosing stable lipid building blocks, the loaded LCNPs demonstrated excellent resilience against enzymatic degradation in an in vitro gut model LCNP stability is crucial as premature antibiotic leakage can negatively impact the gut microbiota. In screens against the representative gut bacteria Enterococcus faecalis and Escherichia coli, our LCNPs provided a protective effect. Furthermore, we explored co-administration and dual loading strategies of VAN and CLA, and demonstrated effective loading, stability and protection for E. faecalis and E. coli. This work represents a proof of concept for the early-stage development of antibiotic-loaded LCNPs to treat systemic infection via oral administration, opening opportunities for combination antibiotic therapies.

Antimicrobial susceptibility analysis of isepamicin combination treatments in Mycobacterium abscessus species.

This study evaluated the antimicrobial potency of the combination of isepamicin (ISP) for Mycobacterium abscessus species (MABS). 34 clinical MABS strains were isolated from clinical samples. Of them, 11 (32.4 %) were M. abscessus subsp. abscessus (Mab), 22 (64.7 %) were M. abscessus subsp. massiliense (Mma), and one (2.9 %) was M. abscessus subsp. bolletii (Mbo). We compared susceptibility to sitafloxacin (STFX)-ISP and clarithromycin (CLR)-ISP combinations with those of the antimicrobial agents alone, and synergistic effects were observed in 41.2 % and 17.6 % when treated with STFX-ISP and CLR-ISP. By hierarchical cluster analysis, the isolates divided into treatment-sensitive and treatment-resistant groups. Non-Mma or rough colony isolates were significantly likely to belong to the treatment-sensitive group (p = 0.024, p < 0.001, respectively). These results suggest that the ISP-containing combination could be a new therapeutic strategy for MABS, especially in cases of non-Mma: treatment-refractory subspecies, and rough morphotypes: high-virulence morphotypes.

Postprandial hypoglycemia caused by the combination of clarithromycin and rifampicin in a patient with nontuberculous mycobacterial pulmonary disease.

Most cases of nontuberculous mycobacterial pulmonary disease (NTM-PD) have a progressive clinical course, and initiation of treatment is recommended rather than watchful waiting. The NTM-PD medications are frequently associated with adverse reactions, occasionally serious. Optimization of the methods for monitoring and managing adverse events in NTM-PD treatment is thus an important medical issue. Here we report a first case of postprandial hypoglycemia caused by the combination of clarithromycin (CAM) and rifampicin (RFP) in a patient with NTM-PD. A 73-year-old Japanese woman with NTM-PD was hospitalized for treatment with a combination of oral CAM, RFP, and ethambutol. She took the first doses of antibiotics before breakfast, and 3 h later went into a hypoglycemic state. Postprandial hypoglycemia occurred with high reproducibility and was accompanied by relative insulin excess. Continuous glucose monitoring with or without food and in combination with various patterns of medication revealed that the combination of CAM and RFP specifically induced postprandial hypoglycemia. Shifting the timing of administration of the CAM and RFP combination from morning to before sleep corrected the hypoglycemia and enabled continuation of the antimicrobial treatment. In conclusion, our report suggests the importance of introducing NTM-PD medication under inpatient management in order to closely monitor and early detect postprandial hypoglycemia and other serious adverse events.

Clinical evaluation of a real-time PCR assay for diagnosis of Helicobacter pylori infection and antibiotic resistance.

OBJECTIVES: Helicobacter pylori (H. pylori) is a globally prevalent bacterium that increases the risk of developing various gastrointestinal diseases, including gastric adenocarcinoma. This study aimed to evaluate the performances of real-time PCR assay in detecting H. pylori infection, as well as clarithromycin and levofloxacin resistance, in both stool and gastric biopsy specimens. METHODS: Stool and gastric biopsy specimens were collected from patients within one to three days post-hospitalization. All patients were analyzed for H. pylori infection and resistance to clarithromycin and levofloxacin using a real-time PCR based molecular assay. RESULTS: 169 patients (83 males) with a mean age of 43.6±13.1 years were included in the study. The prevalence of H. pylori was 89.9% (152/169) in stool and 90.5% (153/169) in gastric biopsy samples. The molecular diagnostics employed in this study exhibited a sensitivity of 99.3% and a specificity of 100%, resulting in a diagnostic accuracy rate of 99.6%. Resistance to clarithromycin was 36.1% (61/169) in stool and 44.4% (75/169) in gastric biopsy samples. The molecular tests for clarithromycin resistance demonstrated a sensitivity of 96.8% and a specificity of 86.8%, with an overall diagnostic accuracy of 90.5%. Furthermore, resistance to levofloxacin was 22.5% (38/169) and 26.6% (45/169) in stool and gastric biopsy samples, respectively. The molecular test demonstrated a sensitivity of 80.9% and a specificity of 94.3%, resulting in a diagnostic accuracy of 90.5%. CONCLUSION: The implementation of real-time PCR-based screening for H. pylori infection and resistance to clarithromycin and levofloxacin in the stool may enhance the success rate of eradication therapy.

Design and structure-activity relationships of ether-linked alkylides: Hybrids of 3-O-descladinosyl macrolides and quinolone motifs.

Ketolides (3-keto) such as TE-802 and acylides (3-O-acyl) like TEA0929 are ineffective against constitutively resistant pathogens harboring erythromycin ribosomal methylation (erm) genes. Following our previous work on alkylides (3-O-alkyl), we explored the structure-activity relationships of hybrids combining (R/S) 3-descladinosyl erythromycin with 6/7-quinolone motifs, featuring extended ether-linked spacers, with a focus on their efficacy against pathogens bearing constitutive erm gene resistance. Optimized compounds 17a and 31f not only reinstated efficacy against inducibly resistant pathogens but also demonstrated significantly augmented activities against constitutively resistant strains of Streptococcus pneumoniae and Streptococcus pyogenes, which are typically refractory to existing C-3 modified macrolides. Notably, hybrid 31f (coded ZN-51) represented a pioneering class of agents distinguished by its dual modes of action, with ribosomes as the primary target and topoisomerases as the secondary target. As a novel chemotype of macrolide-quinolone hybrids, alkylide 31f is a valuable addition to our armamentarium against macrolide-resistant bacteria.

Randomized, Double-Blind, Placebo-Controlled Study of Anti-Mycobacterial Therapy (RHB-104) in Active Crohn's Disease.

This study, conducted between 4 October 2013, and 30 November 2018, tested the hypothesis that triple antimicrobial therapy, targeting Mycobacterium avium subspecies paratuberculosis (MAP), long considered a putative cause, would favorably affect Crohn's disease. A double-blind multicenter study of adults with active Crohn's disease, (i.e., Crohn's Disease Activity Index [CDAI] 220-450 plus C-reactive protein ≥ 1.0 mg/dL, fecal calprotectin (FCP) >162.9 µg/g stool, or recent endoscopic or radiographic confirmation of active disease) receiving concomitant standard-of-care Crohn's disease treatment (Clinicaltrials.gov: NCT01951326) were stratified by anti-tumor necrosis factor use and randomized (1:1) to anti-MAP RHB-104 (clarithromycin 95 mg, rifabutin 45 mg, and clofazimine 10 mg per capsule) (n = 166), resulting in clarithromycin 950 mg/day, rifabutin 450 mg/day, and clofazimine 100 mg/day, or placebo (n = 165) for up to 52 weeks. A greater proportion of RHB-104 versus placebo-treated patients met the primary endpoint-remission (i.e., CDAI < 150)-at week 26 (36.7% [61/166] vs. 22.4% [37/165], respectively; 95% CI for difference: 4.6, 24.0, p = 0.0048; chi-square test). Clinical response (reduction of CDAI by ≥100 points from baseline) at week 26 (first secondary endpoint) was also higher among the patients treated with RHB-104 (73/166 [44.0%]) compared with placebo (50/165 [30.3%]; 95% CI for difference: 3.4, 24.0, p = 0.0116), and it remained higher at week 52 among the patients treated with RHB-104 (59/166 [35.5%] vs. (35/165 [21.2%] for placebo; 95% CI for difference: 4.7, 23.9, p = 0.0042). A statistically significantly greater decline in FCP (another prospective efficacy endpoint) was also observed in RHB-104-treated patients, compared with placebo, at weeks 12, 26, and 52. The rates of serious adverse events were similar between groups (RHB-104: 18.7%; placebo: 18.8%). No patient died during the study. Antimicrobial therapy directed against MAP resulted in significantly greater improvement in clinical and laboratory (FCP) measures of active Crohn's disease.

Preparation and Evaluation of Clarithromycin Taste-Masking Dry Suspension Using Hot Melt Extrusion Based on Solid Dispersion Technology.

Clarithromycin (CLA) is the preferred drug for treating respiratory infections in pediatric patients, but it has the drawbacks of extreme bitterness and poor water solubility. The purpose of this study was to improve solubility and mask the extreme bitterness of CLA. We use Hot Melt Extrusion (HME) to convert CLA and Eudragit® E100 into Solid Dispersion (SD). Differential scanning calorimetry (DSC) and Powder X-ray diffraction (PXRD) were used to identify the crystalline form of the prepared SDs, which showed that the crystalline CLA was converted to an amorphous form. At the same time, an increase in dissolution rate was observed, which is one of the properties of SD. The results showed that the prepared SD significantly increased the dissolution rate of crystalline CLA. Subsequently, the SD of CLA was prepared into a dry suspension with excellent suspending properties and a taste-masking effect. The bitterness bubble chart and taste radar chart showed that the SD achieved the bitter taste masking of CLA. Principal components analysis (PCA) of the data generated by the electronic tongue showed that the bitter taste of CLA was significantly suppressed using the polymer Eudragit® E100. Subsequently, a dry suspension was prepared from the SD of CLA. In conclusion, this work illustrated the importance of HME for preparing amorphous SD of CLA, which can solve the problems of bitterness-masking and poor solubility. It is also significant for the development of compliant pediatric formulations.

Comparison of vonoprazan bismuth-containing triple therapy with quadruple therapy in Helicobacter pylori-infected treatment-naive patients: a prospective multicenter randomized controlled trial.

BACKGROUND AND AIM: Helicobacter pylori infection is linked to various gastrointestinal conditions, such as chronic active gastritis, peptic ulcers, and gastric cancer. Traditional treatment options encounter difficulties due to antibiotic resistance and adverse effects. Therefore, the aim of this study was to explore the effectiveness of a new treatment plan that combines vonoprazan (VPZ), amoxicillin, and bismuth for the eradication of H. pylori. METHODS: A total of 600 patients infected with H. pylori were recruited for this multicenter randomized controlled trial. Patients treated for H. pylori elimination were randomly assigned at a 1:1 ratio to receive 14 days of vonoprazan-based triple therapy (vonoprazan + amoxicillin + bismuth, group A) or standard quadruple therapy (esomeprazole + clarithromycin + amoxicillin + bismuth, group B). Compliance and adverse effects were tracked through daily medication and side effect records. All patients underwent a 13C/14C-urea breath test 4 weeks after treatment completion. RESULTS: Intention-to-treat (ITT) and per-protocol (PP) analyses revealed no substantial differences in H. pylori eradication rates between groups A and B (ITT: 83.7% vs 83.2%; PP: 90.9% vs 89.7%). However, significant differences were observed in the assessment of side effects (13.7% vs 28.6%, P < 0.001). Specifically, group A had significantly fewer "bitter mouths" than group B did (3.7% vs 16.2%, P < 0.001). CONCLUSION: Triple therapy comprising vonoprazan (20 mg), amoxicillin (750 mg), and bismuth potassium citrate (220 mg) achieved a PP eradication rate ≥90%, paralleling standard quadruple therapy, and had fewer adverse events and lower costs (¥306.8 vs ¥645.8) for treatment-naive patients.

Clarithromycin attenuates airway epithelial-mesenchymal transition in ovalbumin-induced asthmatic mice through modulation of Kv1.3 channels and PI3K/Akt signaling.

Airway epithelial-mesenchymal transition (EMT) is the important pathological feature of airway remodeling in asthma. While macrolides are not commonly used to treat asthma, they have been shown to have protective effects on the airways, in which mechanisms are not yet fully understood. This study aims to investigate the impact of clarithromycin on airway EMT in asthma and its potential mechanism. The results revealed an increase in Kv1.3 expression in the airways of ovalbumin (OVA)-induced asthmatic mice, with symptoms and pathological changes being alleviated after treatment with the Kv1.3 inhibitor 5-(4-phenoxybutoxy)psoralen (PAP-1). Clarithromycin was found to attenuate airway epithelial-mesenchymal transition through the inhibition of Kv1.3 and PI3K/Akt signaling. Further experiments in vitro confirmed that PAP-1 could mitigate EMT by modulating the PI3K/Akt signaling in airway epithelial cells undergoing transformation into mesenchymal cells. These findings confirmed that clarithromycin might have a certain protective effect on asthma-related airway remodeling and represent a promising treatment strategy.

Simultaneous Detection of Helicobacter pylori and Clarithromycin Resistance Mutations Using RAA-CRISPR/Cas13a Assay.

Background: Infection caused by Helicobacter pylori (H. pylori) affects approximately 50% of the global population. It is a major pathogenic factor for chronic gastritis and gastric cancer. Besides, the resistance to antibiotics such as clarithromycin could reduce the eradication rate. Currently, there is an urgent need for a swift, easy to perform, and highly sensitive detection method for H. pylori and clarithromycin resistance. Methods: We used FAM/Digoxin labeled primers to amplify specific H. pylori 23S rRNA fragments by Recombinase Aided Amplification (RAA), and resistance mutations were distinguished using CRISPR/Cas13a system combined with lateral flow strip. Twenty-eight saliva samples were analyzed using qPCR, gene sequencing and this method to evaluate the detection efficiency. Results: We developed a simultaneous detection method for H. pylori and clarithromycin resistance mutations named sensitive H. pylori easy-read dual detection (SHIELD). The results showed both A2142G and A2143G mutant DNAs causing clarithromycin resistance could be distinguished from the wild type with a concentration of 50 copies/µL, and no cross-reaction with other 5 common gastrointestinal bacteria was observed. For the detection of H. pylori in 28 saliva samples, the positive predictive value of this method was 100% (19/19) in comparison with qPCR. For detecting clarithromycin resistance, the positive predictive value of this method was 84.6% (11/13) compared with gene sequencing. Conclusion: SHIELD assay showed high sensitivity and specificity in detecting H. pylori and clarithromycin resistance mutations. It could be a potential measure in the rapid detection of H. pylori, large-scale screening and guiding clinical medication.

Validated chromatographic approach for determination of two ternary mixtures in newly approved formulations for helicobacter pylori eradication: assessment of greenness profile and content uniformity.

A new, sensitive, and rapid isocratic reversed phase chromatographic method (RP-HPLC-UV) was developed for simultaneous separation of two newly co-formulated antiulcer mixtures; Amoxicillin, Vonoprazan and Clarithromycin [Mixture (I)], and Amoxicillin, Lansoprazole and Clarithromycin [Mixture (II)]. Analytical separation was performed using a Promosil C18 column and ultraviolet detection at 210 nm. The separation was achieved within only 8 min. For both mixtures, an aqueous solution, composed of (Acetonitrile: Methanol: 0. 2 M phosphoric acid) within ratio of (30: 30: 40) adjusted to final pH 3.0, was the mobile phase. This method was validated as per the International Conference on Harmonization guidelines. The linearity ranges of these proposed method of the (Mixture (I)) were 25.0-400.0 µg/mL Amoxicillin, 0.5-8.0 µg/mL Vonoprazan, and 12.5-200.0 µg/mL Clarithromycin. And the linearity ranges of the (Mixture (II)) were 10.0-300.0 µg/mL Amoxicillin, 0.3-9.0 µg/mL Lansoprazole and 5.0-150.0 µg/mL Clarithromycin. This method was firstly applied for effective separation of Amoxicillin, Vonoprazan and Clarithromycin [Mixture (I)]. It fulfilled good repeatability, sensitivity, and accuracy (R.S.D. < 2.0%). The mean recoveries of the analytes in their Tri-Pak formulations were acceptable. The greenness of the developed chromatographic methods was assessed using an Eco-scale method and it was applied for content uniformity testing as per the United States Pharmacopoeia (USP) and the acceptance value of Amoxicillin, in Mixture (I) was 2.88, the acceptance values for Amoxicillin, Lansoprazole in Mixture (II) were 2.592, 2.424, respectively.

Formulation and Stability of a 1% Clarithromycin-Based Topical Skin Cream: A New Option to Treat Buruli Ulcers?

There are more than 170 known species of non-tuberculous mycobacteria, and some are responsible for serious diseases in people infected with them. One of these is Buruli ulcers, a neglected tropical disease endemic in more than 33 countries and caused by Mycobacterium ulcerans, which infects skin tissue. Treatment consists of a long-term regimen combining the use of oral rifampin with another anti-tuberculosis drug (e.g., clarithromycin). Patients in these countries face difficulties in accessing and adhering to this therapy. This study investigates the feasibility of formulating stable, optimized clarithromycin as a topical cutaneous cream. The cream was formulated, and its stability was evaluated under different storage temperature conditions and using a stability indicator method. The results showed that the clarithromycin cream was stable for at least 60 days, even at extreme temperatures (40 °C). In conclusion, the data presented here demonstrate the stability of a new form of topical cutaneous clarithromycin, which may offer a new approach to the treatment of Buruli ulcers and clarithromycin-sensitive infections.

Prophylactic Effect of Clarithromycin on Radiation Pneumonitis in IMRT for Lung Cancer.

BACKGROUND/AIM: To evaluate the association between prophylactic administration of clarithromycin (CAM) and the development of radiation pneumonitis (RP) in patients treated with intensity modulated radiation therapy (IMRT) for lung cancer. PATIENTS AND METHODS: A total of 89 patients who underwent definitive or salvage IMRT for lung cancer were retrospectively evaluated. The median total and daily doses were 60 Gy and 2 Gy, respectively. A total of 39 patients (44%) received CAM for a median of three months after the start of IMRT. The relationship between the development of RP and certain clinical factors was analyzed. RESULTS: RP of Grade ≥2 was recognized in 10 (11%) patients; Grade 2 in six patients and Grade 3 in four patients. The incidence of Grade ≥2 RP was 3% (1/39) in patients treated with CAM, which was significantly lower than that of 18% (9/50) in patients without CAM. The median lung V20 and V5 in the 10 patients with RP Grade ≥2 were 24% and 46%, respectively, compared with 18% and 37% in the 79 patients with RP Grade 0-1, and the differences were significant. Durvalumab administration after IMRT was also a significant factor for RP Grade ≥2. CONCLUSION: Prophylactic administration of CAM may reduce Grade ≥2 RP in patients treated with IMRT for lung cancer. Therefore, further clinical trials are warranted.

Triple-Antibiotic Combination Exerts Effective Activity against Mycobacterium avium subsp. hominissuis Biofilm and Airway Infection in an In Vivo Murine Model.

OBJECTIVES: Slow-growing nontuberculous mycobacteria (NTMs) are highly prevalent and routinely cause opportunistic intracellular infectious disease in immunocompromised hosts. METHODS: The activity of the triple combination of antibiotics, clarithromycin (CLR), rifabutin (RFB), and clofazimine (CFZ), was evaluated and compared with the activity of single antibiotics as well as with double combinations in an in vitro biofilm assay and an in vivo murine model of Mycobacterium avium subsp. hominissuis (M. avium) lung infection. RESULTS: Treatment of 1-week-old biofilms with the triple combination exerted the strongest effect of all (0.12 ± 0.5 × 107 CFU/mL) in reducing bacterial growth as compared to the untreated (5.20 ± 0.5 × 107/mL) or any other combination (≥0.75 ± 0.6 × 107/mL) by 7 days. The treatment of mice intranasally infected with M. avium with either CLR and CFZ or the triple combination provided the greatest reduction in CLR-sensitive M. avium bacterial counts in both the lung and spleen compared to any single antibiotic or remaining double combination by 4 weeks posttreatment. After 4 weeks of treatment with the triple combination, there were no resistant colonies detected in mice infected with a CLR-resistant strain. No clear relationships between treatment and spleen or lung organ weights were apparent after triple combination treatment. CONCLUSIONS: The biofilm assay data and mouse disease model efficacy results support the further investigation of the triple-antibiotic combination.

Acneiform Eruptions Possibly Triggered by Clarithromycin During Sirolimus Treatment.

Acneiform eruption is the recognized dermatological side effect of sirolimus, an inhibitor of the mammalian target of rapamycin, although the pathophysiological mechanisms and dose dependency of this side effect remain unclear. This case report describes a case of a 40-year-old Japanese woman treated with systemic sirolimus who developed acneiform eruptions following the administration of clarithromycin. The acneiform eruption resolved after discontinuation of sirolimus and relapsed with the resumption. Since sirolimus and clarithromycin have a potential drug-drug interaction mediated by cytochrome P450 3A (CYP3A), this case suggests that the acneiform eruption developed in association with elevated blood levels of sirolimus. We conclude that clinicians should be aware of the possibility of developing acneiform eruption during sirolimus treatment, especially when administered with medications that inhibit CYP3A.

Exploring the Molecular Mechanisms of Macrolide Resistance in Laboratory Mutant Helicobacter pylori.

Resistance to clarithromycin, a macrolide antibiotic used in the first-line treatment of Helicobacter pylori infection, is the most important cause of treatment failure. Although most cases of clarithromycin resistance in H. pylori are associated with point mutations in 23S ribosomal RNA (rRNA), the relationships of other mutations with resistance remain unclear. We examined possible new macrolide resistance mechanisms in resistant strains using next-generation sequencing. Two resistant strains were obtained from clarithromycin-susceptible H. pylori following exposure to low clarithromycin concentrations using the agar dilution method. Sanger sequencing and whole-genome sequencing were performed to detect resistance-related mutations. Both strains carried the A2142G mutation in 23S rRNA. Candidate mutations (T1495A, T1494A, T1490A, T1476A, and G1472T) for clarithromycin resistance were detected in the Mutant-1 strain. Furthermore, a novel mutation in the gene encoding for the sulfite exporter TauE/SafE family protein was considered to be linked to clarithromycin resistance or cross-resistance, being identified as a target for further investigations. In the Mutant-2 strain, a novel mutation in the gene that encodes DUF874 family protein that can be considered as relevant with antibiotic resistance was detected. These mutations were revealed in the H. pylori genome for the first time, emphasizing their potential as targets for advanced studies.