Search

Helicobacter pylori is a class I carcinogen that infects more than 100 million individuals in the United States. Antimicrobial therapy for H. pylori has typically been prescribed empirically rather than based on susceptibility testing. Until recently, therapeutic recommendations have generally ignored the principles of antibiotic stewardship. A combination of a proton pump inhibitor (PPI), amoxicillin, and clarithromycin (triple therapy) remains popular despite increasing clarithromycin resistance and poor cure rates. Concomitant therapy (a PPI, amoxicillin, clarithromycin, and metronidazole) is recommended and widely used despite all patients receiving at least one unneeded antibiotic. In 2020, the Food and Drug Administration approved vonoprazan, amoxicillin, and clarithromycin triple therapy, which administers unneeded clarithromycin to >90% of patients (i.e., ~6 tons of unneeded clarithromycin/million treatments). In the late 1980s, the infectious disease community functionally transferred responsibility for the management of H. pylori to gastroenterology, which has managed the infection as another common gastrointestinal disease such as constipation. In 2022, both traditional and noninvasive molecular-based susceptibility testing for H. pylori became available in the United States. In order to reduce and prevent antibiotic misuse, the infectious disease community should reclaim responsibility for the management of this important infectious disease. [ABSTRACT FROM AUTHOR]

Clinical chorioamnionitis, the most common infection-related diagnosis in labor and delivery units, is an antecedent of puerperal infection and neonatal sepsis. The condition is suspected when intrapartum fever is associated with two other maternal and fetal signs of local or systemic inflammation (eg, maternal tachycardia, uterine tenderness, maternal leukocytosis, malodorous vaginal discharge or amniotic fluid, and fetal tachycardia). Clinical chorioamnionitis is a syndrome caused by intraamniotic infection, sterile intraamniotic inflammation (inflammation without bacteria), or systemic maternal inflammation induced by epidural analgesia. In cases of uncertainty, a definitive diagnosis can be made by analyzing amniotic fluid with methods to detect bacteria (Gram stain, culture, or microbial nucleic acid) and inflammation (white blood cell count, glucose concentration, interleukin-6, interleukin-8, matrix metalloproteinase-8). The most common microorganisms are Ureaplasma species, and polymicrobial infections occur in 70% of cases. The fetal attack rate is low, and the rate of positive neonatal blood cultures ranges between 0.2% and 4%. Intrapartum antibiotic administration is the standard treatment to reduce neonatal sepsis. Treatment with ampicillin and gentamicin have been recommended by professional societies, although other antibiotic regimens, eg, cephalosporins, have been used. Given the importance of Ureaplasma species as a cause of intraamniotic infection, consideration needs to be given to the administration of antimicrobial agents effective against these microorganisms such as azithromycin or clarithromycin. We have used the combination of ceftriaxone, clarithromycin, and metronidazole, which has been shown to eradicate intraamniotic infection with microbiologic studies. Routine testing of neonates born to affected mothers for genital mycoplasmas could improve the detection of neonatal sepsis. Clinical chorioamnionitis is associated with decreased uterine activity, failure to progress in labor, and postpartum hemorrhage; however, clinical chorioamnionitis by itself is not an indication for cesarean delivery. Oxytocin is often administered for labor augmentation, and it is prudent to have uterotonic agents at hand to manage postpartum hemorrhage. Infants born to mothers with clinical chorioamnionitis near term are at risk for early-onset neonatal sepsis and for long-term disability such as cerebral palsy. A frontier is the noninvasive assessment of amniotic fluid to diagnose intraamniotic inflammation with a transcervical amniotic fluid collector and a rapid bedside test for IL-8 for patients with ruptured membranes. This approach promises to improve diagnostic accuracy and to provide a basis for antimicrobial administration. [ABSTRACT FROM AUTHOR]

Introduction:Helicobacter pylori (H. pylori) is one of the most important infections globally, affecting more than 50% of the human population. Clarithromycin (CLA)-containing regimens are recommended for empirical eradication of H. pylori in populations with less than 15% resistance. The aim of this study was to estimate the prevalence of CLA resistance in samples collected from Zambian patients to determine if CLA is suitable for first-line H. pylori empirical treatment. Methodology: We used archival biopsy samples collected from dyspeptic patients undergoing endoscopy. The samples had been snap-frozen immediately after collection and stored at −80°C. We performed multiplex real-time PCR using Bosphore Helicobacter pylori Genotyping Kits v1, Istanbul, Turkey, to determine the presence of wild-type H. pylori and three mutations, A2142G, A2142C, and A2143G, of domain V in 23s rRNA gene. Results: We tested 259 gastric biopsy samples from patients with dyspepsia, of which 136 (53%) were from females. The median age was 48 years (IQR 40–61 years). Endoscopically, most of the patients, 164 (63%), had a normal gastric mucosa. CLA resistance was found in 48 (28%) samples, with A2142G mutation in 23 (13%), A2143G mutation in 32 (18%), and double mutations A2142C and A2143G in 6 (3%). Conclusions: The presence of significant levels of CLA resistance in Zambia suggests that it should not be used as first-line empirical treatment for H. pylori infection. However, with a limitation of suitable alternatives, there is an urgent need to formulate new treatment approaches. [ABSTRACT FROM AUTHOR]

One hundred and eighteen sputum specimens suspected of Mycobacterium abscessus infection were collected. Species level identification of M. abscessus was performed by rpoB sequencing. Clonality analysis was done by multilocus sequence typing (MLST) for M. abscessus. Antibiotic susceptibility testing was performed for clarithromycin, amikacin, ciprofloxacin and moxifloxacin. Altogether 128 isolates were obtained and were subjected to rpoB gene sequencing for definite identification. Among them 59 were identified as M. abscessus, and these included 22 (37.28%) isolates of M. abscessus subsp. abscessus, 22 (37.28%) isolates of M. abscessus subsp. massiliense, and 15 (25.42%) isolates of M. abscessus subsp. bolletii. All 59 M. abscessus complex isolates were analyzed by MLST in this study. Certain sequence types (STs) were identified among the 59 isolates and were specific for each subspecies. Two STs (ST40 and ST33) were specific to M. abscessus subsp. abscessus, one ST (ST20) was specific to M. abscessus subsp. bolletii, and one ST (ST15) was specific to M. abscessus subsp. massiliense. In antibiotic resistance, clarithromycin susceptibility testing of 22 M. abscessus subsp. abscessus strains detected 15 (68.18%) resistant strains, while among 22 M. abscessus subsp. massiliense strains 5 (22.72%) exhibited resistance, and among 15 M. abscessus subsp. bolletii 8 (53.33%) were resistant. Our study revealed a significant level of antibiotic resistance in isolates of the M. abscessus complex. [ABSTRACT FROM AUTHOR]

Background and aim: We conducted an equivalence trial of quadruple non-bismuth "concomitant" and "hybrid" regimens for H. pylori eradication in a high clarithromycin resistance area. Methods: There were 321 treatment-naïve H. pylori-positive individuals in this multicenter clinical trial randomized to either the hybrid (esomeprazole 40 mg/bid, amoxicillin 1 g/bid for 7 days, then 7 days esomeprazole 40 mg/bid, amoxicillin 1 g/bid, clarithromycin 500 mg/bid, and metronidazole 500 mg/bid) or the concomitant regimen (all medications given concurrently bid for 10 days). Eradication was tested using histology and/or a 13C-urea breath test. Results: The concomitant regimen had 161 patients (90F/71M, mean 54.5 years, 26.7% smokers, 30.4% ulcer) and the hybrid regimen had 160 (80F/80M, mean 52.8 years, 35.6% smokers, 31.2% ulcer). The regimens were equivalent, by intention to treat 85% and 81.8%, (p = 0.5), and per protocol analysis 91.8% and 87.8%, (p = 0.3), respectively. The eradication rate by resistance, between concomitant and hybrid regimens, was in susceptible strains (97% and 97%, p = 0.6), clarithromycin single-resistant strains (86% and 90%, p = 0.9), metronidazole single-resistant strains (96% and 81%, p = 0.1), and dual-resistant strains (70% and 53%, p = 0.5). The side effects were comparable, except for diarrhea being more frequent in the concomitant regimen. Conclusions: A 14-day hybrid regimen is equivalent to a 10-day concomitant regimen currently used in high clarithromycin and metronidazole resistance areas. Both regimens are well tolerated and safe. [ABSTRACT FROM AUTHOR]

Background: The Mycobacterium avium complex includes the commonest non-tuberculous mycobacteria associated with human infections. These infections have been associated with the production of biofilms in many cases, but there are only a few studies about biofilms produced by the species included in this group. Methods: Three collection strains (M. avium ATCC25291, M. intracellulare ATCC13950, and M. chimaera DSM756), three clinically significant strains (647, 657, and 655), and three clinically non-significant ones (717, 505, and 575) of each species were included. The clinical significance of the clinical isolates was established according to the internationally accepted criteria. The biofilm ultrastructure was studied by Confocal-Laser Scanning Microscopy by using BacLight Live–Dead and Nile Red stains. The viability, covered surface, height, and relative autofluorescence were measured in several images/strain. The effect of clarithromycin was studied by using the technique described by Muñoz-Egea et al. with modifications regarding incubation time. The study included clarithromycin in the culture medium at a concentration achievable in the lungs (11.3 mg/L), using one row of wells as the control without antibiotics. The bacterial viability inside the biofilm is expressed as a percentage of viable cells. The differences between the different parameters of the biofilm ultrastructure were analyzed by using the Kruskal–Wallis test. The correlation between bacterial viability in the biofilm and treatment time was evaluated by using Spearman's rank correlation coefficient (ρ). Results: The strains showed differences between them with all the studied parameters, but neither a species-specific pattern nor a clinical-significance-specific pattern were detected. For the effect of clarithromycin, the viability of the bacteria contained in the biofilm was inversely proportional to the exposure time of the biofilm (ρ > −0.3; p-value < 0.05), excluding two M. chimaera strains (M. chimaera DSM756 and 575), which showed a weak positive correlation with treatment time (0.2 < ρ < 0.39; p-value < 0.05). Curiously, despite a clarithromycin treatment of 216 h, the percentage of the biofilm viability of the strains evaluated here was not less than 40% at best (M. avium 717). Conclusions: All the M. avium complex strains studied can form biofilm in vitro, but the ultrastructural characteristics between them suggest that these are strain-specific characteristics unrelated to the species or the clinical significance. The clarithromycin effect on MAC species is biofilm-age/time-of-treatment-dependent and appears to be strain-specific while being independent of the clinical significance of the strain. [ABSTRACT FROM AUTHOR]

The carriage of methicillin-resistant S. aureus (MRSA) strains may determine the subsequent occurrence of infection, which mainly affects patients after surgeries. Therefore, its eradication with the use of antibiotics or antiseptics is a crucial method of preventing staphylococcal self-infections. The observed increase in bacterial resistance to known antibacterial substances poses a huge challenge to scientists. The aim of this study was to analyze the interaction of selected commercial antiseptics (Braunol, CITROclorex 2%, Microdacyn 60 Wound Care, Octenisept and Prontoderm Solution) with natural products (carvacrol, β-citronellol, geraniol, eugenol, farnesol, (-)-menthone, eucalyptol, limonene, linalyl acetate and trans-anethole) against the MRSA standard strain. The antistaphylococcal activity of commercial antiseptics in combination with natural products against MRSA was determined using the checkerboard method. The obtained results showed that most combinations decreased the MIC level of the commercial antiseptic and natural compounds. A statistically significant decrease in the MIC value of the antiseptic and natural constituent was observed for the Braunol–β-citronellol combination. Such a significant decrease in the MIC value of the natural compound against the analyzed strain was also detected for the Octenisept–β-citronellol and Prontoderm Solution–β-citronellol combinations. The interaction analysis showed that out of all 20 combinations of individual antiseptics with substances of natural origin, two combinations showed a synergistic effect (Braunol–β-citronellol, Braunol–carvacrol), and three combinations showed an additive effect (Braunol–eugenol, Braunol–geraniol, Prontoderm Solution–β-citronellol). The use of Braunol in combination with β-citronellol or carvacrol may become an alternative method of eradicating MRSA strains. However, further studies are needed to determine the toxicity of the analyzed combinations. [ABSTRACT FROM AUTHOR]

The common adverse effects and the complicated administration of tetracycline and metronidazole greatly affect the clinical application of the classical bismuth quadruple therapy (BQT) for Helicobacter pylori eradication. This pilot study aimed to evaluate the efficacy and safety of minocycline/amoxicillin-based BQT for H. pylori eradication. Firstly, consecutive H. pylori isolates collected at West China Hospital of Sichuan University between 2018 and 2021 were included for susceptibility testing of tetracycline and minocycline using E-test strips. Secondly, both treatment-naïve and experienced patients were included to receive a 14-day minocycline/amoxicillin-based BQT: esomeprazole 40 mg or vonoprazan 20 mg, bismuth colloidal pectin 300 mg, amoxicillin 1000 mg, and minocycline 100 mg, all given twice daily. Among a total of 101 H. pylori isolates, tetracycline resistance was 3.0%, whereas minocycline resistance was nil. A total of 114 patients (treatment-naïve/experienced, 72/42) received the minocycline/amoxicillin-based BQT. The overall intention-to-treat (ITT) and per protocol (PP) eradication rates were 94.7% (108/114) and 97.3% (108/111), respectively. The ITT and PP eradication rates were 91.7% (66/72) and 95.7% (66/69) among the treatment-naïve patients, and both were 100.0% among the treatment-experienced patients. No serious adverse event was recorded. This pilot study suggests that minocycline/amoxicillin-based BQT is an excellent therapy for H. pylori eradication. [ABSTRACT FROM AUTHOR]

ABSTRACT The high-consequence pathogen Bacillus anthracis causes human anthrax and often results in lethal infections without the rapid administration of effective antimicrobial treatment. Antimicrobial resistance profiling is therefore critical to inform post-exposure prophylaxis and treatment decisions, especially during emergencies such as outbreaks or where intentional release is suspected. Whole-genome sequencing using a rapid long-read sequencer can uncover antimicrobial resistance patterns if genetic markers of resistance are known. To identify genomic markers associated with antimicrobial resistance, we isolated B. anthracis derived from the avirulent Sterne strain with elevated minimal inhibitory concentrations to clarithromycin. Mutants were characterized both phenotypically through broth microdilution susceptibility testing and observations during culturing, as well as genotypically with whole-genome sequencing. We identified two different in-frame insertions in the L22 ribosomal protein-encoding gene rplV, which were subsequently confirmed to be involved in clarithromycin resistance through the reversion of the mutant gene to the parent (drug-susceptible) sequence. Detection of the rplV insertions was possible with rapid long-read sequencing, with a time-to-answer within 3 h. The mutations associated with clarithromycin resistance described here will be used in conjunction with known genetic markers of resistance for other antimicrobials to strengthen the prediction of antimicrobial resistance in B. anthracis.IMPORTANCEThe disease anthrax, caused by the pathogen Bacillus anthracis, is extremely deadly if not treated quickly and appropriately. Clarithromycin is an antibiotic recommended for the treatment and post-exposure prophylaxis of anthrax by the Centers for Disease Control and Prevention; however, little is known about the ability of B. anthracis to develop resistance to clarithromycin or the mechanism of that resistance. The characterization of clarithromycin-resistant isolates presented here provides valuable information for researchers and clinicians in the event of a release of the resistant strain. Additionally, knowledge of the genetic basis of resistance provides a foundation for susceptibility prediction through rapid genome sequencing to inform timely treatment decisions.

ABSTRACT The latest guidelines include azithromycin as a preferred regimen for treating Mycobacterium avium complex (MAC) pulmonary disease. However, serially collected susceptibility data on clinical MAC isolates are limited, and no breakpoints have been determined. We investigated the minimum inhibitory concentrations (MICs) of azithromycin and clarithromycin for all MAC strains isolated in 2021 from a single center in Japan, excluding duplicates. The MICs were determined using a panel based on the microbroth dilution method, according to the latest Clinical and Laboratory Standards Institute recommendations. The MICs were determined for 318 MAC strains. Although there was a significant positive correlation between the MICs of azithromycin and clarithromycin, the MICs of azithromycin tended to be higher than those of clarithromycin. Among the cases in which the strains were isolated, 18 patients initiated treatment, including azithromycin treatment, after sample collection. Some patients infected with stains with relatively high azithromycin MICs achieved a microbiological cure with azithromycin-containing regimens. This study revealed a higher MIC distribution for azithromycin than clarithromycin, raising questions about the current practice of estimating azithromycin susceptibility based on the clarithromycin susceptibility test result. However, this was a single-center study that included only a limited number of cases treated with azithromycin. Therefore, further multicenter studies that include a greater number of cases treated with azithromycin are warranted to verify the distribution of azithromycin MICs and examine the correlation between azithromycin MICs and treatment effectiveness.IMPORTANCEThe macrolides serve as key drugs in the treatment of pulmonary Mycobacterium avium complex infection, and the administration of macrolide should be guided by susceptibility test results. Azithromycin is recommended as a preferred choice among macrolides, surpassing clarithromycin; however, drug susceptibility testing is often not conducted, and clarithromycin susceptibility is used as a surrogate. This study represents the first investigation into the minimum inhibitory concentration of azithromycin on a scale of several hundred clinical isolates, revealing an overall tendency for higher minimum inhibitory concentrations compared with clarithromycin. The results raise questions about the appropriateness of using clarithromycin susceptibility test outcomes for determining the administration of azithromycin. This study highlights the need for future discussions on the clinical breakpoints of azithromycin, based on large-scale clinical research correlating azithromycin susceptibility with treatment outcomes.

A simple, rapid and novel method involving ultrahigh-performance liquid chromatography-electrospray ionization tandem triple quadrupole mass spectrometry (UHPLC-ESI–MS/MS) was developed to simultaneously detect erythromycin, its major metabolite and clarithromycin in chicken tissues (muscle, liver and kidney) and eggs (whole egg, albumen and yolk). Samples were extracted using acetonitrile–water (80:20, v/v), and a Cleanert MAS-Q cartridge was used to perform quick, easy, cheap, effective, rugged, and safe (QuEChERS) purification. The average recoveries were 87.78–104.22 %, and the corresponding intraday and interday relative standard deviations were less than 7.10 %. The decision limits and detection capabilities of the chicken tissues and eggs were 2.15–105.21 μg/kg and 2.26–110.42 μg/kg, respectively. For chicken tissues and eggs, the limits of detection and limits of quantification were 0.5 μg/kg and 2.0 μg/kg, respectively. The proposed method was successfully employed to analyse real samples, demonstrating its applicability.

Helicobacter pylori is a class I carcinogen that infects more than 100 million individuals in the United States. Antimicrobial therapy for H. pylori has typically been prescribed empirically rather than based on susceptibility testing. Until recently, therapeutic recommendations have generally ignored the principles of antibiotic stewardship. A combination of a proton pump inhibitor (PPI), amoxicillin, and clarithromycin (triple therapy) remains popular despite increasing clarithromycin resistance and poor cure rates. Concomitant therapy (a PPI, amoxicillin, clarithromycin, and metronidazole) is recommended and widely used despite all patients receiving at least one unneeded antibiotic. In 2020, the Food and Drug Administration approved vonoprazan, amoxicillin, and clarithromycin triple therapy, which administers unneeded clarithromycin to >90% of patients (i.e., ~6 tons of unneeded clarithromycin/million treatments). In the late 1980s, the infectious disease community functionally transferred responsibility for the management of H. pylori to gastroenterology, which has managed the infection as another common gastrointestinal disease such as constipation. In 2022, both traditional and noninvasive molecular-based susceptibility testing for H. pylori became available in the United States. In order to reduce and prevent antibiotic misuse, the infectious disease community should reclaim responsibility for the management of this important infectious disease.

Abstract Background Leprosy is an infectious disease with a slow decline in global annual caseload in the past two decades. Active case finding and post-exposure prophylaxis (PEP) with a single dose of rifampicin (SDR) are recommended by the World Health Organization as measures for leprosy elimination. However, more potent PEP regimens are needed to increase the effect in groups highest at risk (i.e., household members and blood relatives, especially of multibacillary patients). The PEP++ trial will assess the effectiveness of an enhanced preventive regimen against leprosy in high-endemic districts in India, Brazil, Bangladesh, and Nepal compared with SDR-PEP. Methods The PEP++ study is a cluster-randomised controlled trial in selected districts of India, Brazil, Bangladesh, and Nepal. Sub-districts will be allocated randomly to the intervention and control arms. Leprosy patients detected from 2015 − 22 living in the districts will be approached to list their close contacts for enrolment in the study. All consenting participants will be screened for signs and symptoms of leprosy and tuberculosis (TB). In the intervention arm, eligible contacts receive the enhanced PEP++ regimen with three doses of rifampicin (150 − 600 mg) and clarithromycin (150 − 500 mg) administered at four-weekly intervals, whereas those in the control arm receive SDR-PEP. Follow-up screening for leprosy will be done for each individual two years after the final dose is administered. Cox’ proportion hazards analysis and Poisson regression will be used to compare the incidence rate ratios between the intervention and control areas as the primary study outcome. Discussion Past studies have shown that the level of SDR-PEP effectiveness is not uniform across contexts or in relation to leprosy patients. To address this, a number of recent trials are seeking to strengthen PEP regimens either through the use of new medications or by increasing the dosage of the existing ones. However, few studies focus on the impact of multiple doses of chemoprophylaxis using a combination of antibiotics. The PEP++ trial will investigate effectiveness of both an enhanced regimen and use geospatial analysis for PEP administration in the study communities. Trial registration NL7022 on the Dutch Trial Register on April 12, 2018. Protocol version 9.0 updated on 18 August 2022 https://www.onderzoekmetmensen.nl/en/trial/23060

Variya Nemidkanam,1 Wijit Banlunara,2 Nuntaree Chaichanawongsaroj3 1Department of Clinical Chemistry, Graduate Program in Clinical Biochemistry and Molecular Medicine, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand; 2Department of Pathology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand; 3Department of Transfusion Medicine and Clinical Microbiology, Research Unit of Innovative Diagnosis of Antimicrobial Resistance, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, ThailandCorrespondence: Nuntaree Chaichanawongsaroj, Department of Transfusion Medicine and Clinical Microbiology, Research Unit of Innovative Diagnosis of Antimicrobial Resistance, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand, Tel +66 838199988, Email nuntaree@gmail.comPurpose: Kaempferia parviflora extracellular vesicles (KPEVs) have been reported as promising nanovesicles for drug delivery. This study aimed to load clarithromycin (CLA) into KPEVs (KPEVS-CLA) and determine the physical properties, drug-releasing efficiency, gastric cell uptake, anti-H. pylori activities, and anti-inflammatory responses in comparison with free CLA and KPEVs.Methods: The size and surface charge of KPEVs-CLA were evaluated using dynamic light scattering and visualized using a transmission electron microscope. The encapsulation efficiency (EE%), loading capacity (LC%), and drug release of KPEVs-CLA were examined using HPLC. Anti-H. pylori growth and anti-adhesion were evaluated. IL-8 gene expression, NF-κB signaling proteins, and anti-inflammatory profiles were examined using qRT-PCR, Western blotting, and Bio-Plex immunoassay, respectively. Anti-chemotaxis was then examined using a Transwell assay.Results: KPEVs-CLA were intact and showed a negative surface charge similar to that of KPEVs. However, slightly enlarged KPEVs were observed. CLA was successfully loaded into KPEVs with EE of 93.45% ± 2.43%, LC of 9.3% ± 3.02%. CLA release in the PBS and gastric mimic buffer with Fickian diffusion (n ≤ 0.43) according to Korsmeyer-Peppas kinetic model (R2=0.98). KPEVs-CLA was localized in the gastric cells’ cytoplasm and perinuclear region. Anti-H. pylori growth and anti-H. pylori adhesion of KPEVs-CLA were compared with those of free CLA with no cytotoxicity to adenocarcinoma gastric cells. KPEVs-CLA significantly reduced IL-8, G-CSF, MIP-1α, and MIP-1β levels. Moreover, KPEVs-CLA showed a superior effect over CLA in reducing G-CSF, MIP-1α, and NF-κB phosphorylation and monocyte chemotactic activities.Conclusion: KPEVs serve as potential carriers of CLA. They exhibited a higher efficiency in inhibiting gastric cell inflammation mediated by H. pylori infection than free CLA. The establishment of KPEVs-CLA as a nanodrug delivery model for H. pylori treatment could be applied to other plant extracellular vesicles or loaded with other cancer drugs for gastric cancer treatment.Keywords: extracellular vesicle, clarithromycin, Kaempferia parviflora, Helicobacter pylori, inflammation

Different polylactic acid (PLA) thin films containing clarithromycin and a number of metal oxide nanoparticles (magnesium, titanium, zinc, and nickel) dioxides were created. Low dosages of metal oxides (0.01% by weight) and clarithromycin (0.5% by weight) were used to make transparent films. The role of metal oxide nanoparticles and clarithromycin as UV blockers for PLA photodegradation was looked at. The durability of polymeric materials is improved more by clarithromycin in combination with metal oxides than by clarithromycin alone in PLA films. An analysis of the weight loss, surface morphology, and changes in infrared spectra of irradiated polymeric blends revealed that nickel oxide and clarithromycin together function as effective UV blockers and offer PLA a high degree of protection. Nickel oxide nanoparticles were the best addition for PLA stability. Highly alkaline metal oxides are present. Contrarily, the heteroatom and aromatic nature of clarithromycin enables it to absorb damaging radiation and function as an ultraviolet absorption. Thus, the adaptability of PLA to photodegradation was significantly improved by using a mixture of metal oxide nanoparticles and clarithromycin.

Idiopathic facial aseptic granuloma (IFAG) is a rare granulomatous lesion typically occurring in early childhood. It is often considered part of the childhood rosacea spectrum. These lesions frequently occur together with concomitant eyelid chalazion, further strengthening their association with rosacea. Here we present the case of a 12-year-old girl diagnosed with large IFAG and successfully treated with oral clarithromycin and topical metronidazole ointment. [ABSTRACT FROM AUTHOR]

Just as we prioritize personalized medicine for various other medical conditions, we should also include a neglected disease like leprosy, ensuring that patients receive the best care possible and improving their quality of life. Our case highlights the importance of instituting an alternate therapeutic regimen in a scenario where there is a lack of clinical response to multidrug therapy, even in the absence of documented drug resistance of the currently available molecular diagnostics. The search for the perfect regimen tailored for each individual leprosy patient should continue. Alternate anti-leprosy therapy is highly useful in cases with confirmed drug resistance or clinically non-responsive cases; however, their misuse should also be strictly avoided to prevent the development of resistance to them. [ABSTRACT FROM AUTHOR]

Objectives The A2142G and A2143G mutations in the 23S ribosomal ribonucleic acid (rRNA) of Helicobacter pylori are the most common mutations associated with clarithromycin resistance. This study aimed to determine the differences in H. pylori eradication rates in patients infected with bacteria carrying the A2142G and A2143G mutations who were treated with clarithromycin-based triple therapy. Methods Data from a previous randomized controlled trial were analyzed retrospectively. Eradication rates were compared based on the presence of H. pylori carrying the A2142G and A2143G mutations. A meta-analysis was also conducted of relevant studies containing data regarding patients who received clarithromycin-based therapy due to infections with H. pylori harboring 23S rRNA mutations. Results No significant difference was observed in H. pylori eradication rates between patients infected with wild-type bacteria (95.7% [44/46]) compared with those infected with bacteria carrying the A2142G mutation (100.0% [3/3]; p>0.9). However, the eradication rate was significantly lower for patients infected with bacteria carrying the A2143G mutation (16.7% [1/6]; p

Background/Objectives: Stomach infections by Helicobacter pylori can cause acute or chronic gastritis, peptic ulcers, and gastric cancer. The rise in antibiotic resistance is a significant health issue highlighted by the World Health Organization. The increasing number of treatment failures underscores the necessity for antibiotic susceptibility testing (AST). The study aimed to investigate the current prevalence and resistance to fluoroquinolones and clarithromycin with their detected mutations. Methods: Stomach biopsies from symptomatic patients were subjected to molecular testing by GenoType Helico DR kit (Hain Lifescience GmbH, Nehren, Germany). Results: Positive findings on the presence of H. pylori were detected in 42.4% of symptomatic patients, with the significant majority of patients (69%) having previously failed treatments. The resistance rates to fluoroquinolones and clarithromycin were 53.9% and 58.5%, respectively, with significantly higher rates in secondary resistant strains. The main resistance markers in fluoroquinolones and clarithromycin were N87K (27.4%) and A2147G (78.6%), respectively. Hetero-resistance or mixed genotypes were detected in over 20% of tested patients. During the study period, a significant increase in trends in both fluoroquinolones and clarithromycin resistance rates was observed. Conclusions: Results indicate the need for the implementation of the latest Maastricht VI Consensus recommendations for both AST whenever possible and the use of tailored guided therapy options due to high resistance rates and possible treatment failures. The GenoType Helico DR kit is a useful tool for AST, especially in cases of mixed H. pylori genotypes.

Objective: This study aimed to compare the efficacy and tolerability of azithromycin and clarithromycin in pediatric Campylobacter enterocolitis. Methods: A prospective, randomized, controlled trial was conducted at a single center. Patients with confirmed Campylobacter enterocolitis were randomly assigned to receive either a 3-day course of azithromycin or a 5-day course of clarithromycin. Symptoms were monitored daily, and changes in laboratory markers (WBC counts, CRP levels, and stool calprotectin) were compared. Results: A total of 29 pediatric patients were included, with 14 patients in the azithromycin group and 15 patients in the clarithromycin group. The median age of patients in the azithromycin group was 10.0 years (interquartile range [IQR]: 5.0–13.0), and in the clarithromycin group, the median age was 9.0 years (IQR: 7.0–13.0) (p = 0.793). The median time to clinical resolution was 3.0 days (IQR: 2.0–3.0) in the azithromycin group and 2.0 days (IQR: 2.0–3.0) in the clarithromycin group (p = 0.132). There were no significant differences in the duration of individual symptoms, including fever, vomiting, and abdominal pain. The length of hospital stay was also similar, with a median stay of 4 days (IQR: 3.0–5.0) in both groups (p = 0.394). Both antibiotics were well-tolerated, with no significant adverse events or treatment discontinuation reported. Conclusions: Clarithromycin was found to be as effective as azithromycin in treating pediatric Campylobacter enterocolitis, with similar clinical outcomes and improvements in laboratory markers.

Background: The issue of Helicobacter pylori (H. pylori) resistance to clarithromycin (CLR) has consistently posed challenges for clinical treatment. Hence, a rapid susceptibility testing (AST) method urgently needs to be developed. Methods: In the present study, 35 isolates of H. pylori were isolated from 203 gastritis patients of the Guangzhou cohort, and the antimicrobial resistance phenotypes were associated with their genomes to analyze the relevant mutations. Based on these mutations, a rapid detection system utilizing high-resolution melting (HRM) curve analysis was designed and verified by the Shenzhen cohort, which consisted of 38 H. pylori strains. Results: Genomic analysis identified the mutation of the 2143 allele from A to G (A2143G) of 23S rRNA as the most relevant mutation with CLR resistance (p < 0.01). In the HRM system, the wild-type H. pylori showed a melting temperature (Tm) of 79.28 ± 0.01 °C, while the mutant type exhibited a Tm of 79.96 ± 0.01 °C. These differences enabled a rapid distinction between two types of H. pylori (p < 0.01). Verification examinations showed that this system could detect target DNA as low as 0.005 ng/μL in samples without being affected by other gastric microorganisms. The method also showed a good performance in the Shenzhen validation cohort, with 81.58% accuracy, and 100% specificity. Conclusions: We have developed an HRM system that can accurately and quickly detect CLR resistance in H. pylori. This method can be directly used for the detection of gastric microbiota samples and provides a new benchmark for the simple detection of H. pylori resistance.

Objectives: In the present study, we aimed to clarify the mechanisms by which periodontal pathogens, particularly Prevotella intermedia, induce severe neutrophilic inflammation. In addition, we aimed to test the efficacy of macrolides, which has not been resolved in the neutrophilic inflammation induced by P. intermedia. Methods: NCl-H292 human airway epithelial cells were pre-incubated with clarithromycin for 2 h before incubation with P. intermedia supernatants. Then, C-X-C motif chemokine ligand 8 (CXCL8) transcription and interleukin (IL)-8 production were measured. To elucidate the signaling pathway, mitogen-activated protein kinase inhibitors were added to the cell culture, and the cells were subjected to Western blotting. Results:P. intermedia supernatants promoted CXCL8 transcription and IL-8 production, and the reactions were significantly suppressed by clarithromycin pretreatment. Only trametinib, the selective mitogen-activated extracellular signal-regulated kinase inhibitor, downregulated CXCL8 transcription and IL-8 production. Furthermore, Western blotting revealed that stimulation with P. intermedia supernatants specifically induces extracellular signal-regulated kinases (ERK) 1/2 phosphorylation, which is suppressed by clarithromycin pretreatment. Notably, the interference analysis revealed that ERK3 might be dispensable for IL-8 production under the stimulation of P. intermedia supernatants. Conclusions: Our results provide new insight into the mechanism underlying P. intermedia-induced production of IL-8 from human airway epithelial cells. Furthermore, macrolides might have therapeutic potential in regulating periodontal pathogen-induced neutrophilic inflammation in the lungs.

Background: Leprosy is an infectious disease with a slow decline in global annual caseload in the past two decades. Active case finding and post-exposure prophylaxis (PEP) with a single dose of rifampicin (SDR) are recommended by the World Health Organization as measures for leprosy elimination. However, more potent PEP regimens are needed to increase the effect in groups highest at risk (i.e., household members and blood relatives, especially of multibacillary patients). The PEP++ trial will assess the effectiveness of an enhanced preventive regimen against leprosy in high-endemic districts in India, Brazil, Bangladesh, and Nepal compared with SDR-PEP. Methods: The PEP++ study is a cluster-randomised controlled trial in selected districts of India, Brazil, Bangladesh, and Nepal. Sub-districts will be allocated randomly to the intervention and control arms. Leprosy patients detected from 2015 − 22 living in the districts will be approached to list their close contacts for enrolment in the study. All consenting participants will be screened for signs and symptoms of leprosy and tuberculosis (TB). In the intervention arm, eligible contacts receive the enhanced PEP++ regimen with three doses of rifampicin (150 − 600 mg) and clarithromycin (150 − 500 mg) administered at four-weekly intervals, whereas those in the control arm receive SDR-PEP. Follow-up screening for leprosy will be done for each individual two years after the final dose is administered. Cox' proportion hazards analysis and Poisson regression will be used to compare the incidence rate ratios between the intervention and control areas as the primary study outcome. Discussion: Past studies have shown that the level of SDR-PEP effectiveness is not uniform across contexts or in relation to leprosy patients. To address this, a number of recent trials are seeking to strengthen PEP regimens either through the use of new medications or by increasing the dosage of the existing ones. However, few studies focus on the impact of multiple doses of chemoprophylaxis using a combination of antibiotics. The PEP++ trial will investigate effectiveness of both an enhanced regimen and use geospatial analysis for PEP administration in the study communities. Trial registration: NL7022 on the Dutch Trial Register on April 12, 2018. Protocol version 9.0 updated on 18 August 2022 https://www.onderzoekmetmensen.nl/en/trial/23060 [ABSTRACT FROM AUTHOR]

The main objective of this study is to investigate the effect of mixtures of seven widely used human antibiotics (ciprofloxacin, clarithromycin, erythromycin, metronidazole, ofloxacin, sulfamethoxazole, and trimethoprim) on the growth, pH, pigment production, and antibiotics removal of three microalgal species (Auxenochlorella protothecoides, Tetradesmus obliquus, and Chlamydomonas acidophila). Batch assays were conducted with media with antibiotic mixtures at 10, 50, and 100 μg L−1 for each antibiotic. The three microalgae species effectively removed the antibiotics without any growth inhibition, even when exposed to the highest antibiotic concentrations. Biosorption was reported as the primary mechanism for ciprofloxacin, clarithromycin, metronidazole, and ofloxacin, with up to 70% removal, especially in A. protothecoides and C. acidophila. A. protothecoides, a species never investigated for antibiotic removal, was the only microalgae exhibiting bioaccumulation and biodegradation of specific antibiotics, including sulfamethoxazole. Furthermore, in media with the highest antibiotic concentration, all three species exhibited increased chlorophyll (up to 37%) and carotenoid (up to 32%) production, accompanied by a pH decrease of 3 units. Generally, in the present study, it has been observed that physiological responses and the removal of antibiotics by microalgae are interlinked and contingent on the antibiotic levels and types. [ABSTRACT FROM AUTHOR]

Background: There are concerns that Helicobacter pylori eradication therapy may worsen kidney function in patients with decreased renal function. This study aimed to systematically review the literature regarding Helicobacter pylori eradication in patients with renal impairment. Methods: PubMed, the Cochrane Library, and Igaku Chuo Zasshi were searched for comparative studies on H. pylori eradication in patients with renal impairment. Results: Five articles were included in this systematic review. According to a randomized trial comparing a proton pump inhibitor (PPI) + clarithromycin + metronidazole and PPI + clarithromycin + amoxicillin in patients with decreased renal function, the incidence of acute renal failure was significantly lower in PPI + clarithromycin + metronidazole (2%: 1/44) than in PPI + clarithromycin + amoxicillin (18%: 8/44). The eradication rate in PPI + clarithromycin + metronidazole (92.5%) was significantly better than that in PPI + clarithromycin + amoxicillin (76.3%). According to four reports on eradication treatment using PPI + clarithromycin + amoxicillin in patients with and without decreased renal function, the eradication rates and adverse effects were similar in both groups. Regarding dose adjustment, three reports reduced the dose of antibiotics by half in patients with a creatinine clearance of 30 mL/min or less. Conclusions: The regimen with PPIs, clarithromycin, and metronidazole is recommended for renal impairment. The combination of PPIs, clarithromycin, and amoxicillin, at reduced doses depending on the renal function, is also a potential option. [ABSTRACT FROM AUTHOR]

• In a systematic review, no significant differences regarding mortality, hospital length of stay or clinical complications were identified when comparing fluoroquinolones vs macrolides administration in hospitalized patients with moderate severity Legionella pneumonia. • When data from the three cohorts with severe pneumonia were pooled together, mortality with fluoroquinolones alone was statistically superior to macrolides alone (72.8 % vs 30.7 %, p value 0.027). • A randomized controlled trial in severe pneumonia is an unmet clinical need to determine if one class of antibiotic is superior to another or whether a combination therapy regimen provides any significant clinical benefit over monotherapy. The optimal antimicrobial regimen for adults with respiratory failure due to Legionella pneumonia remains controversial. A systematic review was performed to assess the impact on outcomes comparing quinolones versus macrolides. A literature search was conducted in PubMed, Cochrane Library and Web of Science between 2012 and 2022. It yielded 124 potentially articles and ten observational studies met the inclusion criteria. A total of 4271 patients were included, 2879 (67 %) were male. A total of 1797 (42 %) subjects required intensive care unit (ICU) admission and 942 (52 %) mechanical ventilation. Fluoroquinolones and macrolides alone were administered in 1397 (33 %) and 1500 (35 %) subjects, respectively; combined therapy in 204 (4.8 %) patients. Overall mortality was 7.4 % (319 patients), with no difference between antibiotics. When data from the three studies with severe pneumonia were pooled together, mortality with fluoroquinolones alone was statistically superior to macrolides alone (72.8 % vs 30.8 %, p value 0.027). Hospital length of stay and complications were comparable. Our findings suggest that macrolides and quinolones were comparable for hospitalized Legionella pneumonia. However, in severe pneumonia, a randomized clinical trial is an unmet clinical need. PROSPERO registration number: CRD42023389308. [ABSTRACT FROM AUTHOR]

The article describes three cases of infections by Mycoplasma pneumoniae (MP), an important agent of disease in childhood with multiple clinical presentations. These include a 15-year-old previously healthy female with fever and complained of progressively worsening headache, vomiting and lethargy, a previously healthy 16-year-old male who reported the appearance of multiple oral ulcers and odynophagia, and a 17-year-old male with a relevant medical history of atopic dermatitis and asthma.

Background: non-bismuth sequential therapy (SEQ) was suggested as a first-line anti-Helicobacter pylori treatment alternative to standard triple therapy (STT). Methods: We conducted a systematic review with a meta-analysis of randomized controlled trials (RCTs) comparing the efficacy of 10-day SEQ vs. STT (of at least 7 days) using bibliographical searches up to July 2021, including treatment-naïve adult or children. The intention-to-treat (ITT) eradication rate and the risk difference (RD) were calculated. Results: Overall, 69 RCTs were evaluated, including 19,657 patients (9486 in SEQ; 10,171 in STT). Overall, SEQ was significantly more effective than STT (82% vs. 75%; RD 0.08; p < 0.001). The results were highly heterogeneous (I2 = 68%), and 38 studies did not demonstrate differences between therapies. Subgroup analyses suggested that patients with clarithromycin resistance only and all geographical areas but South America could benefit more from SEQ. Both therapies have evolved over the years, showing similar results when STT lasted 14 days; however, a tendency toward lower SEQ efficacy was noted from 2010 onwards. Conclusions: Prior to 2010, SEQ was significantly more effective than STT, notably when 7-day STT was prescribed. A tendency toward lower differences between SEQ and STT has been noted, especially when using 10-day STT. None of the therapies achieved an optimal efficacy and therefore cannot be recommended as a valid first-line H. pylori treatment. [ABSTRACT FROM AUTHOR]

Objective: To observe the efficacy and safety of postoperative long-term low-dose oral administration of clarithromycin in patients with refractory chronic rhinosinusitis (RCRS), to explore the characteristics of postoperative microbiota in the nasal cavity in patients with RCRS, and to compare the differences and changes in microbiota in the nasal cavity before and after medication. Methods: This was a prospective, self-controlled study. Eighteen patients with RCRS who had persistent symptoms after endoscopic sinus surgery and standard therapy with normal immunoglobulin E and eosinophil level were included. Low dose (250 mg, once daily) clarithromycin was orally administrated for 12 weeks. Symptom severity and endoscopic findings were evaluated before, after 4 weeks, and 12 weeks of treatment, and nasal cavity microbiota was analyzed simultaneously. Results: A total of 18 patients with RCRS were enrolled and 17 patients completed the study. Four weeks after oral administration of clarithromycin, significant improvement was observed in subjective symptoms including nasal congestion, rhinorrhea, postnasal drip, and general discomfort, as well as endoscopic findings including general surgical cavity condition, rhinedema, and rhinorrhea (P <.05). After continuous treatment to the 12th week, symptoms showed significant improvement compared with baseline, and endoscopic score showed significant improvement compared with both baseline and 4 weeks after treatment. Analysis of middle nasal meatus flora revealed a significant decrease of Streptococcus pneumoniae after 12 weeks of clarithromycin treatment (P <.05), while the richness, composition, and diversity were similar before and after treatment. Patients enrolled experienced no adverse drug reaction or allergic reaction, nor clinical significant liver function impairment observed. Conclusion: Postoperative low-dose long-term oral administration of clarithromycin in patients with RCRS can improve the clinical symptoms and facilitate the mucosal epithelialization, with good tolerance and safety. The efficacy of clarithromycin in patients with RCRS may be related to its regulatory effect on nasal cavity microbiota. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to explore the efficacy and safety of tailored therapy guided by genotypic resistance in the first‐line treatment of Helicobacter pylori (H. pylori) infection in treatment‐naive patients. Methods: Gastric mucosal specimens were taken during gastroscopy, and main mutations of clarithromycin‐ and levofloxacin‐resistant genes were detected by polymerase chain reaction (PCR). Sensitive antibiotics were selected individually for treating H. pylori infection with tailored bismuth‐containing quadruple therapy (BQT) consisting of esomeprazole 20 mg twice daily, bismuth potassium citrate 220 mg twice daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily, or levofloxacin 500 mg once daily, or metronidazole 400 mg four times daily. Safety and patient compliance were assessed 1–3 days after eradication. Treatment outcome was evaluated by urea breath test 4–8 weeks after eradication. Results: One hundred and thirty‐two treatment‐naive patients with H. pylori infection were included. PCR results suggested resistance rates of 47.7% and 34.9% for clarithromycin and levofloxacin, respectively, and a dual resistance rate of 18.2%. Eradication rates of tailored BQT were 87.1% and 95.8% by intention‐to‐treat (ITT) analysis and per‐protocol (PP) analysis, respectively. There was no statistically significant difference in the efficacy of 7‐day clarithromycin‐containing, 7‐day levofloxacin‐containing, and 14‐day full‐dose metronidazole‐containing BQT (ITT analysis: P = 0.488; PP analysis: P = 0.833). The incidence of adverse events was 19.7%, and patient compliance was 97.7%. Conclusion: Tailored BQT guided by genotypic resistance can achieve satisfactory efficacy, safety, and patient compliance in the first‐line treatment of H. pylori infection. [ABSTRACT FROM AUTHOR]

The long-term use of pediatric medications can lead to discoloration of dental restorations, which affects their durability and longevity. The present in vitro study evaluated the effects of commonly used pediatric medications on the color stability of a conventional and a bulk-fill composite resin. For this study, 80 disc-shaped specimens of each composite were prepared in molds with a diameter of 6 mm and thicknesses of 2 or 4 mm (n = 40 per thickness per material). A spectrophotometer was used toevaluate the baseline color of the specimens in the International Commission on Illumination L*a*b* color space. Each specimen was immersed separately in a container holding 1 of 8 liquid medications (n = 5 per thickness per medication): amoxicillin/clavulanate, clarithromycin, cephalexin, acetaminophen, ibuprofen, levetiracetam, multivitamin, or albuterol. After the container was shaken for 2 minutes, the specimen was removed from the medication and stored in artificial saliva. The cycle was repeated every 8 hours for 1 week. The color measurements were repeated after 1 week of immersion cycles, and the overall color change (82*) was calculated; a value of AE* > 3.3 was considered clinically perceptible. The data were analyzed with 1-way and 2-way analyses of variance as well as the Levene test and Games-Howell post hoc test (P < 0.05). All specimens displayed clinically perceptible color changes after exposure to medications commonly used by children. The mean color change in the 4-mm bulk-fill composite resin group was significantly greater than that in all other groups (P < 0.05). However, there was no significant difference in color change based on the immersion drug for either of the composites (P > 0.05). Thestudy findings show that exposure of composite resin to certain commonly used pediatric drugs causes color changes that are clinically perceptible. [ABSTRACT FROM AUTHOR]

Bronchiectasis is a chronic disease syndrome manifested by a productive cough, subsequent to structural changes in the bronchial walls resulting from bacterial infection and leading to the retention of secretions. In some patients, the cause of bronchiectasis is chronic diseases, such as cystic fibrosis, ciliary dyskinesia, α1-antitrypsin deficiency, or congenital immune disorders. However, there are cases of bronchiectasis without underlying chronic disease, e.g. as a consequence of severe lower respiratory tract infection (bacterial or viral) or local airway obstruction, caused by foreign body aspiration or external pressure. Currently, it is believed that in some patients bronchial deformations may be reversible with a sufficiently quick diagnosis and implementation of treatment. The paper presents the cases of 3 children in whom the resolution of dilated lesions was confirmed by computed tomography. [ABSTRACT FROM AUTHOR]

Background: Nontuberculous mycobacteria are mycobacteria other than those that cause tuberculosis and leprosy and can cause infections in various parts of the body, predominantly the lungs. Of approximately 200 species of nontuberculous mycobacteria, only about 10 are linked to pulmonary infections, with Mycobacterium avium complex (MAC) being the most common. Current Concepts: The standard treatment for pulmonary diseases caused by the MAC is combination therapy, including macrolide antibiotics and other antibiotics such as ethambutol and rifampin. Among macrolide antibiotics, azithromycin and clarithromycin are commonly used for managing MAC pulmonary diseases, and in cases with extensive lesions, amikacin injections are administered concurrently during the initial stages of treatment. Ensuring an overall treatment duration of an additional 12 months after negative culture conversion is recommended in affected patients. However, despite an extended treatment period, the cure rate remains at 60~70%. Recently, an inhalable liposomal form of amikacin, marketed as ARIKAYCE, has been developed. It has been approved by the US Food and Drug Administration as an effective treatment for refractory MAC pulmonary diseases. When ARIKAYCE was used for an additional 6 months or more in patients with refractory MAC pulmonary diseases, approximately 29% of patients achieved additional treatment success. However, it has yet to be officially imported into South Korea, and a high monthly cost restricts its practical use in the country. Therefore, the treatment of MAC pulmonary disease in South Korea will remain a challenge, unless a more effective treatment emerges. Discussion and Conclusion: MAC pulmonary disease requires long-term combination antibiotic therapy, usually with macrolides, ethambutol, and rifampin, and amikacin injections are recommended for cases with extensive lesions. The lack of effective drugs hampers treatment, increasing the burden of antibiotic side effects. Therefore, more research is urgently needed for better treatment of MAC pulmonary disease. [ABSTRACT FROM AUTHOR]

The group of nontuberculous mycobacteria (NTM) includes about 200 mycobacteria that are widespread in the natural environment as free-living saprophytic bacteria, commensals or symbionts. NTM, also referred to as atypical mycobacteria, are mostly apathogenic; nowadays, they are increasingly important environmental opportunistic pathogens. This study continues the work of previous studies which investigated the individual and synergistic effect of different essential oils (EOs) on NTM. The aim was to investigate the effect of the interaction of the common juniper (Juniperus communis) EO and the antimicrobials, amikacin, clarithromycin and rifampicin, against Mycobacterium avium and M. intracellulare using the checkerboard synergy method in an enriched Middlebrook 7H9 broth. Morphological changes of treated NTM cells were observed with a transmission electron microscope. The most synergistic combinations were found at subinhibitory concentrations of the common juniper EO and rifampicin against both tested NTM and this EO and clarithromycin against M. avium. A slightly smaller number of synergistic effects on both NTM were found using a combination of this EO and amikacin. Combinations of clarithromycin and the common juniper EO showed no synergism against M. intracellulare. The exposure of both NTM to synergistic combinations of this EO and antimicrobials caused significant morphological changes in mycobacterial cells. Synergism with the combined use of EOs and antimicrobials allows the use of low effective concentrations via the sustained antimicrobial effect of the tested substances, but with potentially reduced toxicity. [ABSTRACT FROM AUTHOR]

Mycobacterium indicus pranii (MIP) vaccine is widely used in dermatology as immunotherapy for warts as well as in patients with leprosy. During the COVID-19 pandemic, a positive role of MIP as an immunomodulator in SARS-CoV-2 disease was reported after pilot research, with minor adverse effects. We report a case of a 65-year-old male, presenting with skin lesions suggestive of noninfective granulomatous dermatitis for 4 months, at the sites of MIP intradermal injections, allegedly received during a hospital stay for severe COVID-19 disease. The patient presented with nonhealing nodulo-ulcerative lesions at the sites of injection, which persisted for 4 months associated with intermittent serous discharge and showed no signs of healing despite supportive treatment. The patient was started on a combination therapy of ofloxacin 400mg/day and clarithromycin 500mg 12 hourly for 2 months. At the end of 2 months, all the lesions showed complete healing with a resolution of discharge and nodularity, leaving behind postinflammatory hypopigmentation and atrophic scarring. The patient was followed up for 4 months after stopping treatment during which time he had no relapse of the lesions. This case has been reported to the India Pharmacopoeia. [ABSTRACT FROM AUTHOR]

Limited data are available regarding the in vitro activity of SPR719, a derivative of benzimidazole, against diverse nontuberculous mycobacteria (NTM) species. We investigated the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of SPR719 against clinical NTM isolates, including clarithromycin- and amikacin-resistant strains. NTM isolates were obtained from patients with NTM-pulmonary disease caused by various NTM species, including Mycobacterium avium complex, M. abscessus (subspecies abscessus and massiliense), M. kansasii, and M. fortuitum. Regardless of clarithromycin or amikacin resistance, the MIC and MBC values of SPR719 were comparable among these major pathogenic NTM species. In over 70% of the isolates, the MIC values were = 2 µg/mL with MBC values of = 4 µg/mL. The MIC and MBC values of M. kansasii were relatively lower than those of the other species with little difference between them, demonstrating the bactericidal properties of SPR719. The in vitro activity of SPR719 against major clinical NTM species suggests that SPR719 can serve as a novel treatment option for NTM-pulmonary disease. [ABSTRACT FROM AUTHOR]

Clarithromycin as a macrolide antibiotic and zinc oxide (ZnO) nanoparticles with antibacterial and anti-inflammatory properties was incorporated into the chitosan/gelatin/polyurethane (PU) core-shell nanofibers prepared by the coaxial electrospinning method. The morphology and structure of nanofibers were characterized using SEM, FTIR, water contact angle, degradation rate, and swelling tests. The mean fiber diameters of the chitosan/gelatin/PU (CGP), CGP containing 1000 lM clarithromycin, CGP containing 2000 lM clarithromycin, CGP containing 0.5% ZnO, CGP containing 1 wt% ZnO, CGP containing 1000 lM clarithromycin, and 0.5 wt% ZnO and CGP containing 2000 lM clarithromycin, and 1 wt% ZnO were 210 ± 110 nm, 235 ± 100 nm, 250 ± 120 nm, 300 ± 120 nm, 360 ± 130 nm, 410 ± 130 nm, and 460 ± 140 nm, respectively. The gradual faster release of ZnO nanoparticles from core-shell nanofibers was obtained within 24 h; whereas, the sustained release of clarithromycin was achieved during 120 h. Loading of clarithromycin and ZnO nanoparticles into the nanofibers resulted in 100% bactericidal activity of core-shell nanofibers against both Escherichia coli and Staphylococcus aureus. The cell viability results indicated that loading of 0.5 wt% ZnO nanoparticles and 2000 lM clarithromycin was suitable for the development of the synthesized core-shell nanofibers as a potential wound dressing. [ABSTRACT FROM AUTHOR]