BACKGROUND: Owing to the high prevalence of antibiotic resistance in Helicobacter pylori ( H. pylori ) in China, bismuth-containing quadruple therapies have been recommended for H. pylori eradication. This study compared the efficacy and safety of quadruple regimens containing vonoprazan vs . esomeprazole for H. pylori eradication in a patient population in China. METHODS: This was a phase 3, multicenter, randomized, double-blind study. Patients with confirmed H. pylori infection were randomized 1:1 to receive quadruple therapy for 14 days: amoxicillin 1000 mg and clarithromycin 500 mg after meals, bismuth potassium citrate 600 mg before meals, plus either vonoprazan 20 mg or esomeprazole 20 mg before meals, all twice daily. The primary outcome was the eradication rate of H. pylori , evaluated using a 13 C urea breath test at 4 weeks after treatment. The non-inferiority margin was at 10%. RESULTS: The study included 510 patients, 506 of whom completed the follow-up assessment. The primary analysis revealed eradication rates of 86.8% (210/242) and 86.7% (208/240) for vonoprazan and esomeprazole therapy, respectively (treatment difference: 0.1%; 95% confidence interval [CI]: -5.95, 6.17; non-inferiority P  = 0.0009). Per-protocol analysis showed eradication rates of 87.4% for vonoprazan and 86.3% for esomeprazole (treatment difference: 1.2%; 95% CI: -5.03, 7.36; non-inferiority P  = 0.0004). Vonoprazan and esomeprazole were well tolerated, with similar safety profiles. CONCLUSION: Vonoprazan was found to be well-tolerated and non-inferior to esomeprazole for eradicating H. pylori in patients from China. TRIAL REGISTRATION ClinicalTrials.gov , NCT04198363.
Humans ; Esomeprazole/therapeutic use* ; Double-Blind Method ; Helicobacter Infections/drug therapy* ; Male ; Female ; Middle Aged ; Helicobacter pylori/pathogenicity* ; Pyrroles/therapeutic use* ; Sulfonamides/therapeutic use* ; Adult ; Clarithromycin/therapeutic use* ; Amoxicillin/therapeutic use* ; Aged ; Anti-Bacterial Agents/therapeutic use* ; Pyrrolidines/therapeutic use* ; Drug Therapy, Combination ; Proton Pump Inhibitors/therapeutic use*

OBJECTIVES: To investigate the efficacy and safety of prolonged azithromycin (PAZM) versus switching to doxycycline (SDXC) in the treatment of macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMPP) in children. METHODS: A total of 173 children with MUMPP who were hospitalized in Baoji Central Hospital, from January to December 2023 were selected as subjects. According to the choice of secondary antibiotic after 72 hours of initial macrolide therapy, they were divided into two groups: PAZM and SDXC. The efficacy and adverse drug reactions were compared between the two groups, and the risk factors for refractory Mycoplasma pneumoniae pneumonia (RMPP) were analyzed. RESULTS: Compared with the PAZM group, the SDXC group had significantly shorter time to defervescence and time to cough relief, a significantly lower proportion of patients using glucocorticoids, and a significantly higher proportion of patients with lung lesion absorption (P<0.05). No adverse reactions such as liver and kidney function impairment and tooth discoloration were observed in either group. RMPP occurred in 47 cases in the PAZM group. The univariate analysis showed that lactate dehydrogenase levels and age were risk factors for RMPP (P<0.05). CONCLUSIONS The efficacy of SDXC is superior to that of PAZM in children with MUMPP, and short-term use of doxycycline is relatively safe.
Humans ; Pneumonia, Mycoplasma/drug therapy* ; Doxycycline/administration & dosage* ; Female ; Male ; Azithromycin/administration & dosage* ; Child ; Child, Preschool ; Anti-Bacterial Agents/administration & dosage* ; Macrolides/administration & dosage* ; Adolescent ; Mycoplasma pneumoniae/drug effects*

BACKGROUND: With the development of traditional Chinese medicine research, berberine has shown good efficacy and safety in the eradication of Helicobacter pylori (H. pylori). The present study aimed to evaluate the efficacy and safety of triple therapy containing berberine, amoxicillin, and vonoprazan for the initial treatment of H. pylori. METHODS: This study was a single-center, open-label, parallel, randomized controlled clinical trial. Patients with H. pylori infection were randomly (1:1:1) assigned to receive berberine triple therapy (berberine 500 mg, amoxicillin 1000 mg, vonoprazan 20 mg, A group), vonoprazan quadruple therapy (vonoprazan 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, B group), or rabeprazole quadruple therapy (rabeprazole 10 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, C group). The drugs were taken twice daily for 14 days. The main outcome was the H. pylori eradication rate. The secondary outcomes were symptom improvement rate, patient compliance, and incidence of adverse events. Furthermore, factors affecting the eradication rate of H. pylori were further analyzed. RESULTS: A total of 300 H. pylori-infected patients were included in this study, and 263 patients completed the study. An intention-to-treat (ITT) analysis showed that the eradication rates of H. pylori in berberine triple therapy, vonoprazan quadruple therapy, and rabeprazole quadruple therapy were 70.0% (70/100), 77.0% (77/100), and 69.0% (69/100), respectively. The per-protocol (PP) analysis showed that the eradication rates of H. pylori in these three groups were 81.4% (70/86), 86.5% (77/89), and 78.4% (69/88), respectively. Both ITT analysis and PP analysis showed that the H. pylori eradication rate did not significantly differ among the three groups (P >0.05). In addition, the symptom improvement rate, overall adverse reaction rate, and patient compliance were similar among the three groups (P >0.05). CONCLUSIONS The efficacy of berberine triple therapy for H. pylori initial treatment was comparable to that of vonoprazan quadruple therapy and rabeprazole quadruple therapy, and it was well tolerated. It could be used as one choice of H. pylori initial treatment.
Humans ; Amoxicillin/therapeutic use* ; Helicobacter pylori ; Anti-Bacterial Agents ; Clarithromycin/therapeutic use* ; Rabeprazole/therapeutic use* ; Berberine/therapeutic use* ; Bismuth ; Helicobacter Infections/drug therapy* ; Drug Therapy, Combination ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

Objective: To explore the clinical characteristics, common pathogens in children with vulvovaginitis. Methods: This was a retrospective cases study. A total of 3 268 children with vulvovaginitis were enrolled, who visited the Department of Pediatric and Adolescent Gynecology, Children's Hospital, Zhejiang University School of Medicine from January 2009 to December 2019. Patients were divided into 3 groups according to the age of <7, 7-<10 and 10-18 years. Patients were also divided in to 4 groups according to the season of first visit. The pathogen distribution characteristics of infective vulvovaginitis were compared between the groups. Their clinical data were collected and then analyzed by χ² test. Results: The were 3 268 girls aged (6.2±2.5) years. There were 1 728 cases (52.9%) aged <7 years, 875 cases (26.8%) aged 7-<10 years, and 665 cases (20.3%) aged 10-18 years. Of these cases, 2 253 cases (68.9%) were bacterial vulvovaginitis, 715 cases (21.9%) were fungal vulvovaginitis and 300 cases (9.2%) were vulvovaginitis infected with other pathogens. Bacterial culture of vaginal secretions was performed in 2 287 cases, and 2 287 strains (70.0%) of pathogens were detected, of which the top 5 pathogens were Streptococcus pyogenes (745 strains, 32.6%), Haemophilus influenzae (717 strains, 31.4%), Escherichia coli (292 strains, 12.8%), Staphylococcus aureus (222 strains, 9.7%) and Klebsiella pneumoniae (67 strains, 2.9%). Regarding different age groups, H.influenzae was the most common in children under 7 years of age (40.3%, 509/1 263), S.pyogenes (41.9%, 356/849) was predominantly in children aged 7 to 10 years, and E.coli was predominant in children aged 10 to 18 years (26.3%, 46/175). Susceptibility results showed that S.pyogenes was susceptible to penicillin G (610/610, 100.0%), ceftriaxone (525/525, 100.0%), and vancomycin (610/610, 100.0%); the resistance rates to erythromycin and clindamycin were 91.9% (501/545)and 90.7% (495/546), respectively. For H.influenzae, 32.5% (161/496) produced β-elactamase, and all strains were sensitive to meropenem (489/489, 100.0%) and levofloxacin (388/388, 100.0%), while 40.5% (202/499) were resistant to ampicillin. Among E.coli, all strains were sensitive to imipenem(100%, 175/175). The resistance rates of E.coli to levofloxacin and ceftriaxone were 29.1% (43/148) and 35.1% (59/168), respectively. A total of 48 strains of methicillin-resistant Staphylococcus aureus (MRSA) were isolated with a proportion of 28.3% (45/159) in 3 268 patients. The results of drug susceptibility test showed that all MRSA strains were sensitive to linezolid 100.0% (40/40), vancomycin (45/45, 100.0%), and tigecycline (36/36, 100.0%); the resistance rates of MRSA to penicillin G, erythromycin and clindamycin were 100% (45/45), 95.6% (43/45) and 88.9% (40/45), respectively. All methicillin-sensitive Staphylococcus aureus (MSSA) strains were sensitive to oxacillin (114/114, 100.0%), linezolid (94/94, 100.0%), vancomycin (114/114, 100.0%), and tigecycline (84/84, 100.0%); it's resistance rates to penicillin G, erythromycin and clindamycin were 78.1% (89/114), 59.7% (68/114) and 46.5% (53/114), respectively. The drug resistance rate of MSSA to penicillin G, erythromycin and clindamycin were lower than those of MRSA (χ²=11.71,19.74,23.95, respectively, all P<0.001). Conclusions: The age of consultation for pediatric infectious vulvovaginitis is mainly around 6 years. The most common pathogens are S.pyogenes, H.influenzae and Escherichia coli. Third generation cephalosporins can be used as the first choice of empirical anti-infection drugs. However, the results of drug susceptibility should be considered for targeted treatment.
Female ; Adolescent ; Child ; Humans ; Anti-Bacterial Agents/therapeutic use* ; Vancomycin/therapeutic use* ; Methicillin-Resistant Staphylococcus aureus ; Clindamycin/therapeutic use* ; Ceftriaxone/therapeutic use* ; Tigecycline/therapeutic use* ; Linezolid/therapeutic use* ; Levofloxacin/therapeutic use* ; Retrospective Studies ; Microbial Sensitivity Tests ; Staphylococcus aureus ; Staphylococcal Infections/drug therapy* ; Erythromycin/therapeutic use* ; Methicillin ; Penicillin G/therapeutic use* ; Escherichia coli ; Drug Resistance, Bacterial

Objective To explore the inhibitory effects and mechanisms of benzodiazepines on Helicobacter pylori (Hp).Methods The Hp international standard strain ATCC43504 was treated with benzodiazepines diazepam,midazolam,and remimazolam,respectively.The treatments with amoxicillin and clarithromycin were taken as the positive controls,and that with water for injection as the negative control.The inhibition zone of each drug was measured by the disk diffusion method.The minimum inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of each drug against Hp were determined.Hp suspension was configured and treated with diazepam and midazolam,respectively.The bacterial suspension without drug added was used as the control group.The concentration of K⁺ in each bacterial suspension was measured by an automatic biochemical analyzer before drug intervention(T₀)and 1(T₁),2(T₂),3(T₃),4(T₄),5(T₅),6(T₆),and 7 h(T₇)after intervention.Hp urease was extracted and treated with 1/2 MIC diazepam,1 MIC diazepam,2 MIC diazepam,1/2 MIC midazolam,1 MIC midazolam,2 MIC midazolam,1 mg/ml acetohydroxamic acid,and water for injection,respectively.The time required for the rise from pH 6.8 to pH 7.7 in each group was determined by the phenol red coloring method.Results The inhibition zones of diazepam,midazolam,remimazolam,amoxicillin,clarithromycin,and water for injection against Hp were 52.3,42.7,6.0,72.3,60.8,and 6.0 mm,respectively.Diazepam and midazolam showed the MIC of 12.5 μg/ml and 25.0 μg/ml and the MBC of 25 μg/ml and 50 μg/ml,respectively,to Hp.The concentrations of K⁺ in the diazepam,midazolam,and control groups increased during T₁-T₇ compared with those at T₀(all P<0.01).The concentration of K⁺ in diazepam and midazolam groups during T₁-T₄ was higher than that in the control group(all P<0.01).The time of inhibiting urease activity in the 1/2 MIC diazepam,1 MIC diazepam,2 MIC diazepam,1/2 MIC midazolam,1 MIC midazolam,and 2 MIC midazolam groups was(39.86±5.11),(36.52±6.65),(38.58±4.83),(39.25±6.19),(36.36±4.61),and(35.81±6.18)min,respectively,which were shorter than that in the acetohydroxamic acid group(all P<0.01)and had no significance differences from that in the water for injection group(all P>0.05).Conclusion Diazepam and midazolam exerted inhibitory effects on Hp,which may be related to the cleavage of Hp cells rather than inhibiting urease.
Midazolam ; Helicobacter pylori ; Urease ; Clarithromycin/pharmacology* ; Benzodiazepines/pharmacology* ; Diazepam/pharmacology* ; Amoxicillin ; Water ; Anti-Bacterial Agents/pharmacology*

Objective: To investigate the molecular characteristics of ciprofloxacin-cefotaxime-azithromycin co-resistant Salmonella enterica serovar Thompson (S. Thompson) isolates from sporadic cases of foodborne diseases and aquatic foods in Hunan province. Methods: Ciprofloxacin-cefotaxime-azithromycin co-resistant S. Thompson isolates were selected from samples, and broth microdilution method was used to determine the resistance to 11 antibiotics of these isolates in vitro. Whole genome sequencing was used for investigating antimicrobial resistance gene patterns and phylogenetic relationships of strains. Results: Nine ciprofloxacin-cefotaxime-azithromycin co-resistant isolates were recovered from 19 S. Thompson isolates. Among nine ciprofloxacin-cefotaxime-azithromycin co-resistant isolates, eight of them harbored IncC plasmids, simultaneously carrying plasmid-mediated quinolone resistance (PMQR) genes qepA and qnrS1, β-lactamase resistance gene bla_CMY-2, azithromycin resistance gene mph(A), and one isolate harbored IncR plasmid, and carried PMQR genes qnrB4 and aac(6')-Ib-cr, bla_OXA-10 and mph(A). Genetic environment analysis showed that qnrS1, qepA, mph(A) and bla_CMY-2 genes might be integrated on genomes of strains by ISKra4, IS91, IS6100 and ISEcp1, respectively. Phylogenetic core genome comparisons demonstrated that ciprofloxacin-cefotaxime-azithromycin co-resistant isolates from patients and aquatic foods were genetically similar and clustered together. Conclusion: Ciprofloxacin-cefotaxime-azithromycin co-resistant S. Thompson isolates have been isolated from both human and aquatic food samples, suggesting that the spread of multidrug resistant Salmonella between human and aquatic animals.
Animals ; Humans ; Ciprofloxacin ; Cefotaxime ; Azithromycin ; Serogroup ; Phylogeny ; Drug Resistance, Multiple, Bacterial/genetics* ; Anti-Bacterial Agents/pharmacology* ; Salmonella ; Quinolones ; Foodborne Diseases ; Plasmids ; Salmonella enterica ; Microbial Sensitivity Tests

Erythromycin is a macrolide antibiotic produced by Saccharopolyspora erythraea. Its yield is greatly affected by the fermentation conditions and the bioreactor configurations. In this study, a novel scale-up method for erythromycin fermentation was developed based on computational fluid dynamics (CFD) and time constant analysis. Firstly, the dissolved oxygen (DO) was determined as a key parameter according to the physiological properties of S. erythraea cultivated in a 50 L bioreactor. It was found that the time constant of oxygen supply (t_mt) in a 500 m³ bioreactor should be less than 6.25 s in order to satisfy the organism's oxygen uptake rate (OUR). Subsequently, a 500 m³ bioreactor was designed using the time constant method combined with empirical correlations. The impeller combination with one BDT8 impeller at bottom and two MSX4 impellers at upper part was determined, and then validated by numerical simulation. The results indicated that the t_mt of the bioreactor (< 6.25 s) and the fluid properties, including gas hold-up, shear stress and fluid vector, met the requirements of erythromycin fermentation. Finally, the industrial production of erythromycin in the 500 m³ showed the design method was applicable in large scale fermentation.
Erythromycin ; Saccharopolyspora/genetics* ; Bioreactors ; Fermentation ; Anti-Bacterial Agents

INTRODUCTION: H. pylori eradication reduces the risk of gastric malignancies and peptic ulcer disease. First-line therapies include 14-day PAC (proton pump inhibitor [PPI], amoxicillin, clarithromycin) and PBMT (PPI, bismuth, metronidazole, tetracycline). Second-line therapies include 14-day PBMT and PAL (PPI, amoxicillin, levofloxacin). This clinical audit examined current treatment outcomes in Singapore. METHODS: Clinical data of H. pylori-positive patientswho underwent empirical first- and second-line eradication therapies from 1 January 2017 to 31 December 2018 were reviewed. Treatment success was determined by ¹³C urea breath test performed at least 4 weeks after treatment and 2 weeks off PPI. RESULTS: A total of 963 patients (862 PAC, 36 PMC [PPI, metronidazole, clarithromycin], 18 PBMT, 13 PBAC [PAC with bismuth], 34 others) and 98 patients (62 PMBT, 15 PAL, 21 others) received first-and second-line therapies respectively. A 14-day treatment duration was appropriately prescribed for first- and second-line therapies in 65.2% and 82.7% of patients, respectively. First-line treatment success rates were noted for PAC (seven-day: 76.9%, ten-day: 88.3%, 14-day: 92.0%), PMC (seven-day: 0, ten-day: 75.0%, 14-day: 69.8%), PBMT (ten-day: 100%, 14-day: 87.5%) and PBAC (14-day: 100%). 14-day treatment was superior to seven-day treatment (90.8% vs. 71.4%; P = 0.028). PAC was superior to PMC (P < 0.001) but similar to PBMT (P = 0.518) and PBAC (P = 0.288) in 14-day therapies. 14-day second-line PAL and PBMT had similar efficacy (90.9% vs. 82.4%; P = 0.674). CONCLUSION First-line empirical treatment using PAC, PBMT and PBAC for 14 days had similar efficacy. Success rates for second-line PBMT and PAL were similar.
Humans ; Helicobacter pylori ; Clarithromycin/therapeutic use* ; Helicobacter Infections/drug therapy* ; Metronidazole/therapeutic use* ; Bismuth/therapeutic use* ; Singapore ; Drug Therapy, Combination ; Amoxicillin/therapeutic use* ; Proton Pump Inhibitors/therapeutic use* ; Anti-Bacterial Agents/therapeutic use* ; Treatment Outcome ; Clinical Audit

Background: Acne vulgaris is a common chronic inflammatory skin disease. Long term therapy involving antibiotics warrants for drug with a long half-life to increase compliance of patients. Methods: A twelve-week prospective randomized study was performed on 40 subjects with moderate to severe facial acne to compare the efficacy of oral azithromycin with oral doxycycline. Thirty-six subjects completed the study. Subjects in azithromycin group received azithromycin 250mg three times a week plus topical benzoyl peroxide 5% (BPO), whereas subjects in doxycycline group received doxycycline 100mg daily plus topical BPO 5%. Efficacy evaluation included treatment success rate (Comprehensive Acne Severity Score /CASS of 0 or 1 or improvement of two grades from baseline) and lesion counts. Results: Treatment was successful in 94.4% of subjects in azithromycin group, compared to 88.9% in doxycycline group (p=1.000) at week 12.However, percentage of clear or almost clear by CASS was higher in the doxycycline group ( 83.3% vs 66.7%; p= 0.443).Percentage reduction of inflammatory lesion counts in azithromycin and doxycycline group following treatment for 12 weeks were 78.3% and 85.3% (p=0.133) respectively, whereas for non-inflammatory lesion counts were 77.7% and 78.8% (p=0.852) respectively. Nausea was reported in 77.8% at week 6 and 66.7% at week 12 in doxycycline group, but none in azithromycin group. There were no significant differences in incidence of diarrhoea and abdominal pain. Conclusion Azithromycin 250mg three times a week plus topical BPO 5% is as effective as doxycycline 100mg daily plus topical BPO 5%.
Azithromycin ; Doxycycline ; Acne Vulgaris--therapy

Aims: Staphylococcus aureus is an important opportunistic human pathogen. The emergence of macrolide and vancomycin resistant S. aureus is of great concern for treatment of S. aureus infections. The current study aimed to investigate the pattern of antibiotic resistance in S. aureus clinical isolates recovered from El Boos Students’ hospital in Cairo, Egypt. Methodology and results: Sixty unduplicated S. aureus isolates were recovered from El Boos Students’ hospital in Cairo, Egypt for 11 months period. The antibiotic susceptibility test revealed that all isolates were resistant to eleven antibiotics, but only 49 S. aureus isolates were resistant to cefoxitin. The minimum inhibitory concentrations (MIC) of both erythromycin and vancomycin were determined by broth microdilution method. Two methicillin resistant S. aureus (MRSA) isolates showing tolerance to both erythromycin and vancomycin at high concentration were selected for further characterization. One isolate was recovered from eye infection and had MIC at 256 µg/mL of both erythromycin and vancomycin. While another isolate was recovered from throat infection and had MIC of erythromycin and vancomycin up till 512 µg/mL. The presence of resistance genes (ermA, ermB, ermC, mef, msrA, vanA and vanB) were confirmed by polymerase chain reaction (PCR). Both MRSA isolates carried all tested resistance genes. Conclusion, significance and impact of study This study highlights the concern of presence of multidrug-resistant S. aureus which showed resistance to high concentrations of erythromycin, vancomycin and carried ermA, ermB, ermC, mef, msrA, vanA and vanB genes, therefore imposes risk of failure to treat such infections.
Vancomycin-Resistant Staphylococcus aureus ; Erythromycin