Clostridioides Difficile: A Concise Review of Best Practices and Updates.

Clostridioides difficile infection (CDI) is one of the most common and severe nosocomial infections worldwide. It can also affect healthy individuals in the community. The incidence of CDI has been on the rise globally for the past decade, necessitating a proactive approach to combat its spread; new strategies are being developed to enhance diagnostic accuracy and optimize treatment outcomes. Implementing the 2-step testing has increased diagnostic specificity, reducing the usage of CD-specific antibiotics with no concomitant increase in surgical complication rates. In 2021, the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA) shifted its preference for initial treatment to fidaxomicin over vancomycin and metronidazole due to its lower recurrence rate. It also prioritized fidaxomicin for the treatment of recurrent CDI. There are new developments on the frontiers of fecal microbiota therapies, with RBX2660 and SER-109 approved recently by the FDA for prevention, with other microbiome-based therapies in various development and clinical trials. This review offers providers an updated and practical guide for CDI management.

Efficacy of Dequalinium Chloride vs Metronidazole for the Treatment of Bacterial Vaginosis: A Randomized Clinical Trial.

Importance: Bacterial vaginosis (BV) is a common cause of vaginal infection. First-line treatments of BV are metronidazole and clindamycin. Due to the increase in antibiotic resistance, effective nonantibiotic treatments for BV are needed. Objective: To examine whether dequalinium chloride, a broad-spectrum antiseptic, is noninferior to oral metronidazole for the treatment of BV. Design, Setting, and Participants: This phase 4, multicenter, triple-blind, double-dummy, parallel, noninferiority randomized clinical trial was conducted from July 29, 2021, to August 25, 2022, with a 1-month follow-up. Participants were premenopausal women 18 years or older with BV from 11 gynecologic practices and 1 hospital in Poland, Slovakia, and the Czech. Intervention: Patients were randomized to treatment with dequalinium chloride vaginal tablets (10 mg once daily for 6 days) or oral metronidazole (500 mg twice daily for 7 days). Double-dummy medication kits contained vaginal and oral tablets with placebo and active medication. Main Outcomes and Measures: The main outcome was the noninferiority margin (of 15 percentage points) in the absolute difference in clinical cure rates between dequalinium chloride and metronidazole 7 to 11 days after start of treatment (visit 1). Noninferiority was met if the lower 95% CI for the difference in clinical cure rate was less than 15 percentage points at visit 1. Results: A total of 147 women (mean [SD] age, 36.7 [9.0] years) were treated with dequalinium chloride (n = 72) or metronidazole (n = 75). The clinical cure rates at visit 1 were 64 of 69 (92.8%) for dequalinium chloride vs 69 of 74 (93.2%) for metronidazole in the intention-to-treat population, whereas in the per-protocol population, cure rates were 54 of 58 (93.1%) for dequalinium chloride vs 48 of 53 (90.6%) for metronidazole. The treatment differences of -0.5 percentage points (95% CI, -10.8 to 9.8 percentage points; P = .002) in the intention-to-treat population and 2.5 percentage points (95% CI, -9.4 to 14.4 percentage points; P = .001) in the per-protocol population confirmed the noninferiority of dequalinium chloride. The tolerability of dequalinium chloride was rated as very good by 30 of 50 patients (60.0%) but only by 21 of 54 (38.9%) for metronidazole. Three patients in the metronidazole group suspended treatment due to an adverse event. Conclusions and Relevance: This randomized clinical trial showed that dequalinium chloride was not inferior to metronidazole for the treatment of BV. Dequalinium chloride had a similarly high cure rate but with better tolerability and fewer adverse events. With a similar efficacy to metronidazole and clindamycin, dequalinium chloride warrants consideration as first-line treatment for BV to help reduce antibiotic consumption. Trial Registration: EudraCT: 2020-002489-15.

Comparison of the Efficacy of 12-day Concomitant Quadruple Therapy versus 14-day High dose Dual Therapy as a First-line H. pylori Eradication Regimen.

Background/Aims: Helicobacter pylori (H. pylori) is the most prevalent infection in the world and is strongly associated with gastric adenocarcinoma, lymphoma and gastric or duodenal ulcers. Different regimens have been used for H. pylori eradication. We aimed to compare the efficacy of two different regimens as first-line H. pylori eradication regimens, in an area with high antibiotic resistance. Methods: In this RCT, we assigned 223 patients with H. pylori infection, who were naïve to treatment. They were randomly divided into two groups to receive either 12-day concomitant quadruple therapy (consisting of pantoprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg every 12 hours) or 14-day high dose dual therapy (consisting of esomeprazole 40 mg and amoxicillin 1 g TDS). H. pylori eradication was assessed eight weeks after the end of treatment. Results: H. pylori eradication rate by PP analysis for 12-day concomitant quadruple therapy and 14-day high dose dual therapy were 90.4% and 79.1%, respectively (p=0.02). According to ITT analysis, the eradication rates were 86.2% and 76.3%, respectively (p=0.06). Adverse drug reactions were 12.3% in high dose dual therapy and 36.8% in concomitant quadruple therapy (p<0.001). Conclusions: Twelve-day concomitant therapy seems to be an acceptable regimen for first-line H. pylori eradication in Iran, a country with a high rate of antibiotic resistance. Although, high dose dual therapy did not result in an ideal eradication rate, but it had fewer drug side effects than the 12-day concomitant regimen.

14-day tailored PCR-guided triple therapy versus 14-day non-Bismuth concomitant quadruple therapy for Helicobacter pylori eradication: A multicenter, open-label randomized noninferiority controlled trial.

BACKGROUND: The systematic use of susceptibility testing and tailored first-line treatment for Helicobacter pylori eradication has yet to be established. AIM: To compare 14-day tailored PCR-guided triple therapy to 14-day non-Bismuth concomitant quadruple therapy for first-line Helicobacter pylori eradication. PATIENTS AND METHODS: We performed a multicenter, parallel-group, randomized noninferiority controlled trial. Naive adult patients with Helicobacter pylori infection were treated with 14-day tailored PCR-guided triple therapy (esomeprazole 40 mg and amoxicillin 1000 mg b.d. plus clarithromycin 500 mg or levofloxacin 500 mg b.d. according to clarithromycin susceptibility) or 14-day non-Bismuth concomitant quadruple therapy (esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg b.d.). The primary endpoint was H. pylori eradication. RESULTS: We screened 991 patients for eligibility and randomized 241 patients. The first-line eradication rate was 99.2% in the tailored PCR-guided group and 95.9% in the control group (ITT population; absolute difference of +3.30%, with a lower bound of CI at -0.68%). Both first-line therapies were well tolerated, with a formally significant difference in favor of the tailored PCR-guided group (61.4% vs. 41.2%, p = 0.003). Economic analyses revealed a lower cost of the tailored PCR-guided arm, with a 92% chance of being jointly more effective and less expensive than the control arm in the ITT population. CONCLUSION: In a country with a high level of clarithromycin resistance, the results of our study demonstrated the noninferiority of 14-day tailored PCR-guided triple therapy as a first-line H. pylori eradication therapy compared to 14-day non-Bismuth quadruple therapy (ClinicalTrials.gov NCT02576236).

Synthesis of new trypanocidal agents from the hybridisation of metronidazole and eugenol analogues.

Nitroimidazole compounds are well-known bioactive substances, and the structural activity relationship has been reported whereby the position of the nitro group within the imidazole ring has a large influence on the activity. This study focuses on synthesising new trypanocidal agents from the hybridisation of metronidazole with different natural phenols (eugenol, dihydroeugenol and guaiacol). Two different coupling methodologies have been explored in order to analyse the influence of the connector on bioactivity: i) classic direct esterification (AD compounds) and ii) "click" chemistry using a triazole connector (AC compounds). The in vitro trypanocidal tests show good results for both AC and AD hybrid compounds against both epimastigote and trypomastigote forms of T. cruzi. In silico studies showed positive data for most of the synthesised compounds and, in general present low toxicological risks. The AC compounds present lower ClogP (lipophilicity) values than those found for the AD series and higher TPSA (topological polar surface area) values, suggesting lower lipophilicity may be related to the presence of the triazole connector. The AD series compounds have higher Drug Score values than the AC series derivatives, suggesting better general properties for a pharmacological action.

High antibiotic resistance rates in Helicobacter pylori strains in Turkey over 20 years: implications for gastric disease treatment.

OBJECTIVE: Helicobacter pylori (Hp) eradication therapy is crucial for preventing the development of gastritis, peptic ulcers, and gastric cancer. An increase in resistance against antibiotics used in the eradication of Hp is remarkable. This meta-analysis aims to examine the resistance rates of Hp strains isolated in Turkey over the last 20 years against clarithromycin (CLR), metronidazole (MTZ), levofloxacin (LVX), tetracycline (TET), and amoxicillin (AMX) antibiotics. BASIC METHODS: Literature search was carried out in electronic databases, by searching articles published in Turkish and English with the keywords ' helicobacter pylori ' or 'Hp' and 'antibiotic resistance' and 'Turkey'. That meta-analysis was carried out using random-effect model. First, the 20-year period data between 2002 and 2021 in Turkey were planned to be analyzed. As a second stage, the period between 2002 and 2011 was classified as Group 1, and the period between 2012 and 2021 as Group 2 for analysis, with the objective of revealing the 10-year temporal variation in antibiotic resistance rates. MAIN RESULTS: In gastric biopsy specimens, 34 data from 29 studies were included in the analysis. Between 2002-2021, CLR resistance rate was 30.9% (95% CI: 25.9-36.2) in 2615 Hp strains. Specifically, in Group 1, the CLR resistance rate was 31% in 1912 strains, and in Group 2, it was 30.7% in 703 strains. The MTZ resistance rate was found to be 31.9% (95% CI: 19.8-45.4) in 789 strains, with rates of 21.5% in Group 1 and 46.6% in Group 2. The overall LVX resistance rate was 25.6%, with rates of 26.9% in Group 1 and 24.8% in Group 2. The 20-year TET resistance rate was 0.8%, with 1.50% in Group 1 and 0.2% in Group 2. The overall AMX resistance rate was 2.9%, 3.8% between 2002-2011, and 1.4% between 2012-2021. PRINCIPAL CONCLUSION: Hp strains in Turkey exhibit high resistance rates due to frequent use of CLR, MTZ, and LVX antibiotics. However, a significant decrease has been observed in TET and AMX resistance to Hp in the last 10 years. Considering the CLR resistance rate surpasses 20%, we suggest reconsidering the use of conventional triple drug therapy as a first-line treatment. Instead, we recommend bismuth-containing quadruple therapy or sequential therapies (without bismuth) for first-line treatment, given the lower rates of TET and AMX resistance. Regimens containing a combination of AMX, CLR, and MTZ should be given priority in second-line therapy. Finally, in centers offering culture and antibiogram opportunities, regulating the Hp eradication treatment based on the antibiogram results is obviously more appropriate.

A comparative analysis of univariate versus multivariate eco-friendly spectrophotometric manipulations for resolving severely overlapped spectra of vonoprazan and amoxicillin new combination.

Vonoprazan and amoxicillin are pharmacological combinations that demonstrate synergistic effects in treating Helicobacter pylori (H. pylori), a global public health concern associated with peptic ulcer disease and gastric cancer. Four spectrophotometric methods were developed, including two univariate techniques (Fourier self-deconvolution and ratio difference) and two multivariate chemometric approaches (partial least squares and principal component regression). These methods provide innovative solutions for effectively resolving and accurately quantifying the overlapping spectra of vonoprazan and amoxicillin. The concentration ranges covered were 3-60 µg ml-1 for vonoprazan and 5-140 µg ml-1 for amoxicillin. To assess the environmental sustainability of the methodologies, various measures such as the Green Analytical Procedure Index (GAPI), National Environmental Method Index (NEMI), Analytical GREEnness Calculator, and Analytical Eco-scale, as well as RGB12 and hexagon toll were implemented. The validation of the developed techniques was carried out in compliance with ICH standards. The present study is highly significant because it is the first time that the mixture has been determined using the current approaches. The comparative analysis demonstrated no significant difference in terms of accuracy and precision compared to reference HPLC method (p = 0.05). The established spectrophotometric methods offer a straightforward, rapid, and cost-effective alternative to complex analytical techniques for determining the vonoprazan and amoxicillin mixture. They show potential for routine analysis in research laboratories and pharmaceutical industries.

Conserved signatures of the canine faecal microbiome are associated with metronidazole treatment and recovery.

Antibiotic resistance is recognised as one of the biggest global threats to human and animal health. Understanding the influence of antibiotics on the canine microbiome is important to know the potential mid-to-long term effects on dysbiosis and mitigate side-effects such as antibiotic-associated diarrhoea. In this study, metronidazole was prescribed to 22 dogs for suspected giardiasis after exhibiting gastrointestinal symptoms such as diarrhoea and/or vomiting. Faecal samples were collected before, during seven days of treatment, and six months post-cessation. Faecal microbiota was assessed with 16S rRNA sequencing. Shannon diversity was reduced for up to three days after the treatment ended, and an altered community persisted for four to six weeks. All dogs recovered to a similar microbiome composition as pre-treatment. Immediately after receiving metronidazole, an increase in the relative abundance of the genera Lactobacillus, Bifidobacterium, and Enterococcus was observed. This may be due to antibiotic resistance commonly exhibited by these organisms. One-to-two weeks post-cessation, several other genera that were sensitive to the antibiotic recovered in abundances, with taxa belonging to the Erysipelotrichaceae family particularly driving composition change. Many of the bacteria initially reduced were associated with carbohydrate fermentation. This suggests scope exists to explore interventions to augment gastrointestinal health and support the re-establishment of the microbiome.

Effective treatment of Clostridioides difficile infection improves survival and affects graft-versus-host disease: a multicenter study by the Polish Adult Leukemia Group.

Clostridioides difficile infection (CDI) is the most common cause of infectious diarrhea after allogeneic hematopoietic cell transplantation (allo-HCT). The impact of CDI and its treatment on allo-HCT outcomes and graft-versus-host disease (GVHD), including gastrointestinal GVHD (GI-GVHD) is not well established. This multicenter study assessed real-life data on the first-line treatment of CDI and its impact on allo-HCT outcomes. Retrospective and prospective data of patients with CDI after allo-HCT were assessed. We noted statistically significant increase in the incidence of acute GVHD and acute GI-GVHD after CDI (P = 0.005 and P = 0.016, respectively). The first-line treatment for CDI included metronidazole in 34 patients, vancomycin in 64, and combination therapy in 10. Treatment failure was more common with metronidazole than vancomycin (38.2% vs. 6.2%; P < 0.001). The need to administer second-line treatment was associated with the occurrence or exacerbation of GVHD (P < 0.05) and GI-GVHD (P < 0.001) and reduced overall survival (P < 0.05). In the multivariate analysis, the risk of death was associated with acute GVHD presence before CDI (hazard ratio [HR], 3.19; P = 0.009) and the need to switch to second-line treatment (HR, 4.83; P < 0.001). The efficacy of the initial CDI treatment affects survival and occurrence of immune-mediated GI-GVHD after allo-HCT. Therefore, agents with higher efficacy than metronidazole (vancomycin or fidaxomicin) should be administered as the first-line treatment.

In vitro anti-Trichomonas gallinae effects of Ziziphus vulgaris L. and Camellia sinensis (L.) Kuntze extracts.

BACKGROUND: Trichomonas gallinae is a parasite that causes canker and severe loss and death, especially in young pigeons. Metronidazole (MTZ) is the recommended drug for treating avian trichomoniasis. Due to drug resistance, non-chemical alternatives, such as medicinal plant extracts, are also considered possible therapies for this disease. OBJECTIVES: This study compares the antitrichomonal effects of MTZ with extracts of Camellia sinensis and Ziziphus vulgaris on T. gallinae in vitro. METHODS: Samples of T. gallinae were taken from infected pigeons. Multi-well plates with different concentrations (5, 10, 25, 50 and 100 µg/mL) of plant extracts were used for the in vitro study. RESULTS: The minimum inhibitory concentration (MIC) of C. sinensis extract was 25 µg/mL over 24 h, compared to 50 µg/mL for MTZ. The MIC value of the Z. vulgaris extracts was 50 µg/mL. CONCLUSIONS: The results suggest that the extracts of Z. vulgaris and C. sinensis, as potential natural agents, could have anti-avian trichomoniasis properties. This study also shows that MTZ, C. sinensis and Z. vulgaris are equally effective in preventing the growth of T. gallinae trophozoites in the culture.

Microencapsulated Benzoyl Peroxide for Rosacea in Context: A Review of the Current Treatment Landscape.

Rosacea, a chronic skin condition affecting millions of people in the USA, leads to significant social and professional stigmatization. Effective management strategies are crucial to alleviate symptoms and improve patients' quality of life. Encapsulated benzoyl peroxide 5% (E-BPO 5%) is a newly FDA-approved topical treatment for rosacea that shows promise in enhancing therapeutic response and minimizing skin irritation. This review aims to assess the role of recently FDA approved E-BPO 5% in the current treatment landscape for rosacea management, as it is not yet included in clinical guidelines that predominantly rely on older approved therapies. The review focuses on randomized controlled trials conducted in English-speaking adults. It evaluates the efficacy, safety, and tolerability of various US Food and Drug Administration (FDA)-approved agents used for rosacea treatment, including E-BPO cream, metronidazole gel, azelaic acid gel and foam, ivermectin cream, minocycline foam, oral doxycycline, brimonidine gel, and oxymetazoline HCl cream. Existing therapies have been effective in reducing papulopustular lesions and erythema associated with rosacea for many years. E-BPO 5% offers a promising addition to the treatment options due to its microencapsulation technology, which prolongs drug delivery time and aims to improve therapeutic response while minimizing skin irritation. Further research is necessary to determine the exact role of E-BPO 5% in the therapeutic landscape for rosacea. However, based on available evidence, E-BPO 5% shows potential as a valuable treatment option for managing inflammatory lesions of rosacea, and it may offer benefits to patients including: rapid onset of action, demonstrated efficacy by Week 2, excellent tolerability, and sustained long-term results for up to 52 weeks of treatment.

The efficacy of combining adjuvants with non-surgical periodontal therapy in individuals with type 2 diabetes: A Bayesian network meta-analysis.

AIM: This Bayesian network meta-analysis of randomized controlled trials assessed the effect of adjuvant periodontal treatment in both periodontal and HbA1c outcomes in adult individuals with type 2 diabetes (T2DM). MATERIALS AND METHODS: A systematic search was done up to February 2023 comparing sub-gingival debridement (SD) in combination with local or systemic adjuvant treatment with SD alone for individuals with T2DM. The primary outcomes were changes in absolute HbA1c levels and full-mouth probing depth reported at 3- to 6-month post-treatment. RESULTS: Seventy-two eligible publications evaluating 27 adjuvant treatments were retrieved. The combination of SD and systemic antibiotic metronidazole or SD and antioxidant alpha lipoic acid provided, respectively, 1.4% (95% credible interval [CrI] 0.48; 2.20) and 2.4% (95% CrI 1.50; 3.30) more significant improvement on HbA1c levels, and 0.89 mm (95% CrI 0.23; 1.50) and 0.92 mm (95% CrI 0.02; 0.92) greater periodontal probing depth reductions. Other adjuvant treatments provided added benefit to the periodontal outcomes without discernible effects on HbA1c. CONCLUSIONS: Adjuvant use of metronidazole or alpha lipoic acid was the best adjunct option to provide clinically meaningful HbA1c levels and probing depth reductions. However, no strong recommendation can be drawn due to the scarcity of studies for each adjuvant treatment and the low certainty of the resultant evidence.

Effects of Preoperative Quadruple Therapy for Helicobacter pylori on Bariatric Surgery Metabolic Outcomes.

PURPOSE: To assess the effects of Helicobacter pylori (HP) eradication with an omeprazole, clarithromycin, amoxicillin, and metronidazole (OCAM) regimen on the metabolic profile and weight loss 12 months after bariatric surgery (BS). METHODS: Retrospective analysis of a prospective cohort of patients with morbid obesity undergoing BS. HP presence was tested preoperatively by gastric biopsy and treated with OCAM when positive. Short-term metabolic outcomes and weight loss were evaluated. RESULTS: HP infection was detected in 75 (45.7%) of the 164 patients included. OCAM effectiveness was 90.1%. HP-negative patients had a greater reduction in glucose levels at 3 (-14.6 ± 27.5 mg/dL HP-treated vs -22.0 ± 37.1 mg/dL HP-negative, p=0.045) and 6 months (-13.7 ± 29.4 mg/dL HP-treated vs -26.4 ± 42.6 mg/dL HP-negative, p= 0.021) and greater total weight loss (%TWL) at 6 (28.7 ± 6.7% HP-treated vs 30.45 ± 6.48% HP-negative, p= 0.04) and 12 months (32.21 ± 8.11% HP-treated vs 35.14 ± 8.63% HP-negative, p= 0.023). CONCLUSIONS: Preoperative treatment with OCAM has been associated to poorer glycemic and weight loss outcomes after BS. More research is needed on the influence of OCAM on gut microbiota, and in turn, the effect of the latter on metabolic and weight loss outcomes after BS.

Electro-antibacterial therapy (EAT) to enhance intracellular bacteria clearance in pancreatic cancer cells.

Intratumoral bacteria have been implicated in driving tumor progression, yet effective treatments to modulate the tumor microbiome remain limited. In this study, we investigate the use of electroporation in combination with metronidazole to enhance the clearance of intracellular Fusobacterium nucleatum within pancreatic cancer cells. We explore various parameters, including electric field strength, pulse width, and pulse number to assess the permeability of pancreatic cancer cells infected with F. nucleatum, compared to non-infected cells of the same type. We subsequently quantify the clearance of intracellular bacteria when these pulsing schemes are applied to a suspension of infected pancreatic cancer cells in the presence of metronidazole. Our results reveal distinct differences in cell permeability between infected and non-infected cells, identifying a unique biophysical marker for host cells infected with F. nucleatum. We demonstrate that the combinatorial use of electroporation and metronidazole significantly enhances the delivery of metronidazole into host cells, leading to more effective clearance of intracellular F. nucleatum compared to independent treatments; we term this novel approach Electro-Antibacterial Therapy (EAT). EAT holds promise as an innovative strategy for addressing intratumoral bacteria in pancreatic cancer, other malignancies, and potentially treatment-resistant infections, offering new avenues for therapeutic intervention.

Antibacterial activity of ibezapolstat against antimicrobial-resistant clinical strains of Clostridioides difficile.

Antimicrobial resistance is emerging in clinical strains of Clostridioides difficile. Ibezapolstat (IBZ) is a DNA polymerase IIIC inhibitor that has completed phase II clinical trials. IBZ has potent in vitro activity against wild-type, susceptible strains but its effect on C. difficile strains with reduced susceptibility to metronidazole (MTZ), vancomycin (VAN), or fidaxomicin (FDX) has not been tested. The primary objective of this study was to test the antibacterial properties of IBZ against multidrug-resistant C. difficile strains. The in vitro activity, bactericidal, and time-kill activity of IBZ versus comparators were evaluated against 100 clinical strains of which 59 had reduced susceptibility to other C. difficile antibiotics. Morphologic changes against a multidrug resistance strain were visualized by light and scanning electron microscopy. The overall IBZ MIC50/90 values (µg/mL) for evaluated C. difficile strains were 4/8, compared with 2/4 for VAN, 0.5/1 for FDX, and 0.25/4 for MTZ. IBZ MIC50/90 values did not differ based on non-susceptibility to antibiotic class or number of classes to which strains were non-susceptible. IBZ bactericidal activity was similar to the minimum inhibitory concentration (MIC) and maintained in wild-type and non-susceptible strains. Time-kill assays against two laboratory wild-type and two clinical non-susceptible strains demonstrated sustained IBZ activity despite reduced killing by comparator antibiotics for IBZ and VAN non-susceptible strains. Microscopy visualized increased cell lengthening and cellular damage in multidrug-resistant strains exposed to IBZ sub-MIC concentrations. This study demonstrated the potent antibacterial activity of IBZ against a large collection of C. difficile strains including multidrug-resistant strains. This study highlights the therapeutic potential of IBZ against multidrug-resistant strains of C. difficile.

Aetiology and use of antibiotics in pregnancy-related infections: results of the WHO Global Maternal Sepsis Study (GLOSS), 1-week inception cohort.

BACKGROUND: Pregnancy-related infections are important contributors to maternal sepsis and mortality. We aimed to describe clinical, microbiological characteristics and use of antibiotics by source of infection and country income, among hospitalized women with suspected or confirmed pregnancy-related infections. METHODS: We used data from WHO Global Maternal Sepsis Study (GLOSS) on maternal infections in hospitalized women, in 52 low-middle- and high-income countries conducted between November 28th and December 4th, 2017, to describe the frequencies and medians of maternal demographic, obstetric, and clinical characteristics and outcomes, methods of infection diagnosis and causative pathogens, of single source pregnancy-related infection, other than breast, and initial use of therapeutic antibiotics. We included 1456 women. RESULTS: We found infections of the genital (n = 745/1456, 51.2%) and the urinary tracts (UTI) (n = 531/1456, 36.5%) to be the most frequent. UTI (n = 339/531, 63.8%) and post-caesarean skin and soft tissue infections (SSTI) (n = 99/180, 55.0%) were the sources with more culture samples taken and microbiological confirmations. Escherichia coli was the major uropathogen (n = 103/118, 87.3%) and Staphylococcus aureus (n = 21/44, 47.7%) was the commonest pathogen in SSTI. For 13.1% (n = 191) of women, antibiotics were not prescribed on the same day of infection suspicion. Cephalosporins (n = 283/531, 53.3%) were the commonest antibiotic class prescribed for UTI, while metronidazole (n = 303/925, 32.8%) was the most prescribed for all other sources. Ceftriaxone with metronidazole was the commonest combination for the genital tract (n = 98/745, 13.2%) and SSTI (n = 22/180, 12.2%). Metronidazole (n = 137/235, 58.3%) was the most prescribed antibiotic in low-income countries while cephalosporins and co-amoxiclav (n = 129/186, 69.4%) were more commonly prescribed in high-income countries. CONCLUSIONS: Differences in antibiotics used across countries could be due to availability, local guidelines, prescribing culture, cost, and access to microbiology laboratory, despite having found similar sources and pathogens as previous studies. Better dissemination of recommendations in line with antimicrobial stewardship programmes might improve antibiotic prescription.

Clinical and microbiological efficacy of intra-pocket application of diode laser in grade C periodontitis: a randomized controlled clinical trial.

BACKGROUND: Periodontitis is a microbially induced disease destroying structures anchoring teeth to jaw bones. Although metronidazole in combination with spiramycin is the effective conventional treatment of stage III grade C periodontitis, it has several systemic side effects. Laser therapy is widely used nowadays as an adjunct to scaling and root planing (SRP) to modulate inflammatory host response and eradicate microbes, due to bactericidal and detoxifying effects. Since microbiological analysis is one of the diagnostic methods identifying periodontal risk; our research aimed to investigate the efficacy of intra-pocket application of diode laser (980 nm) versus antibiotic therapy in enhancing clinical and microbiological parameters in stage III grade C periodontitis. METHODS: A randomized controlled clinical trial was conducted on fifty patients with stage III grade C periodontitis, divided equally into two groups. We managed test group by SRP with intra-pocket application of diode laser (980 nm) and the control group by SRP with systemic antibiotic administration (spiramycin and metronidazole). Then, we measured periodontal pocket depth (PPD) and clinical attachment loss (CAL) for both groups, before treatment (baseline), four and twelve weeks after. Moreover, we collected gingival crevicular fluid from both groups at baseline, four and twelve weeks after treatment and analyzed by real-time polymerase chain reaction to detect the relative count of Aggregatibacter actinomycetemcomitans and Porhyromonas gingivalis. RESULTS: Compared to baseline, all assessed clinical and microbiological parameters attested improvement at the end of the study period in each group individually with no significant difference between the two studied groups. Although, at twelve weeks, flare up of bacterial levels was detected with systemic antibiotic administration. CONCLUSION: Laser therapy can be considered as an effective treatment modality in stage III grade C periodontitis, avoiding the systemic antibiotic side effects and solving the recurrence problems due to bacterial resistance by long term usage. TRIAL REGISTRATION: NCT05222737 retrospectively on 03/02/2022, Clinicaltrial.gov.

Tailored therapy guided by genotypic resistance of clarithromycin and levofloxacin detected by polymerase chain reaction in the first-line treatment of Helicobacter pylori infection.

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.

Primary antibiotic resistance of Helicobacter pylori in India over the past two decades: A systematic review.

BACKGROUND: Helicobacter pylori antibiotic resistance has undergone vast changes in the last two decades. No systematic review has been done on the prevalence of antibiotic resistant H. pylori in India in the last two decades. We evaluated the pattern of resistance rates across various regions of India. MATERIALS AND METHODS: A systematic review of the geographical variations in antibiotic resistance pattern of H. pylori was conducted using PubMed, Google Scholar, Web of Science, Science Direct, etc. for articles published between January 1, 2000 and May 30, 2023. Random effects-model-based Cochran's Q test, I2 statistics, and chi-squared tests were used to measure heterogeneity. RESULTS: The overall resistance was highest against metronidazole (77.65%) followed by amoxicillin (37.78%), levofloxacin (32.8%), clarithromycin (35.64%), furazolidone (12.03%), and tetracycline (11.63%). 14.7% of the H. pylori isolates were multi-drug resistant. Under meta-analysis of each antibiotic, high heterogeneity levels were observed having I2 ranges from 86.53% to 97.70% at p < 0.0001. In sub-group analysis, Metronidazole has a stable rate of resistance as compared to other antibiotics. Other antibiotics have had a downtrend in the last 5 years except for levofloxacin, which has had an uptrend in the resistance rate for the past 5 years. Hence, one should avoid using metronidazole for any kind of first-line treatment. CONCLUSIONS: Metronidazole resistance is high in most regions of India except Assam and Mumbai while clarithromycin is found to be ineffective in South India, Gujarat, and Kashmir. As compared to other antibiotics, resistance to amoxicillin is generally low except in certain regions (Hyderabad, Chennai, and the Gangetic belt of North India). Tetracycline and Furazolidone have the least resistance rates and should be part of anti- H. pylori regimens. The resurgence of high single and multidrug resistance to the commonly used drugs suggests the need for newer antibiotics and regular resistance surveillance studies.