Simplified Helicobacter pylori therapy for patients with penicillin allergy: a randomised controlled trial of vonoprazan-tetracycline dual therapy.

BACKGROUND AND AIMS: This study aimed to evaluate the efficacy and safety of vonoprazan and tetracycline (VT) dual therapy as first-line treatment for Helicobacter pylori infection in patients with penicillin allergy. METHODS: In this randomised controlled trial, treatment-naïve adults with H. pylori infection and penicillin allergy were randomised 1:1 to receive either open-label VT dual therapy (vonoprazan 20 mg two times per day+tetracycline 500 mg three times a day) or bismuth quadruple therapy (BQT; lansoprazole 30 mg two times per day+colloidal bismuth 150 mg three times a day+tetracycline 500 mg three times a day+metronidazole 400 mg three times a day) for 14 days. The primary outcome was non-inferiority in eradication rates in the VT dual group compared with the BQT group. Secondary outcomes included assessing adverse effects. RESULTS: 300 patients were randomised. The eradication rates in the VT group and the BQT group were: 92.0% (138/150, 95% CI 86.1% to 95.6%) and 89.3% (134/150, 95% CI 83.0% to 93.6%) in intention-to-treat analysis (difference 2.7%; 95% CI -4.6% to 10.0%; non-inferiority p=0.000); 94.5% (138/146, 95% CI 89.1% to 97.4%) and 93.1% (134/144, 95% CI 87.3% to 96.4%) in modified intention-to-treat analysis (difference 1.5%; 95% CI -4.9% to 8.0%; non-inferiority p=0.001); 95.1% (135/142, 95% CI 89.7% to 97.8%) and 97.7% (128/131, 95% CI 92.9% to 99.4%) in per-protocol analysis (difference 2.6%; 95% CI -2.9% to 8.3%; non-inferiority p=0.000). The treatment-emergent adverse events (TEAEs) were significantly lower in the VT group (14.0% vs 48.0%, p=0.000), with fewer treatment discontinuations due to TEAEs (2.0% vs 8.7%, p=0.010). CONCLUSIONS: VT dual therapy demonstrated efficacy and safety as a first-line treatment for H. pylori infection in the penicillin-allergic population, with comparable efficacy and a lower incidence of TEAEs compared with traditional BQT. TRIAL REGISTRATION NUMBER: ChiCTR2300074693.

Antigiardial and antiamebic activities of fexinidazole and its metabolites: new drug leads for giardiasis and amebiasis.

The intestinal parasites Giardia lamblia and Entamoeba histolytica are major causes of morbidity and mortality associated with diarrheal diseases. Metronidazole is the most common drug used to treat giardiasis and amebiasis. Despite its efficacy, treatment failures in giardiasis occur in up to 5%-40% of cases. Potential resistance of E. histolytica to metronidazole is an increasing concern. Therefore, it is critical to search for more effective drugs to treat giardiasis and amebiasis. We identified antigiardial and antiamebic activities of the rediscovered nitroimidazole compound, fexinidazole, and its sulfone and sulfoxide metabolites. Fexinidazole is equally active against E. histolytica and G. lamblia trophozoites, and both metabolites were 3- to 18-fold more active than the parent drug. Fexinidazole and its metabolites were also active against a metronidazole-resistant strain of G. lamblia. G. lamblia and E. histolytica cell extracts exhibited decreased residual nitroreductase activity when metabolites were used as substrates, indicating nitroreductase may be central to the mechanism of action of fexinidazole. In a cell invasion model, fexinidazole and its metabolites significantly reduced the invasiveness of E. histolytica trophozoites through basement membrane matrix. A q.d. oral dose of fexinidazole and its metabolites at 10 mg/kg for 3 days reduced G. lamblia infection significantly in mice compared to control. The newly discovered antigiardial and antiamebic activities of fexinidazole, combined with its FDA-approval and inclusion in the WHO Model List of Essential Medicines for the treatment of human African trypanosomiasis, offer decreased risk and a shortened development timeline toward clinical use of fexinidazole for treatment of giardiasis or amebiasis.

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.

Diagnosis and Treatment of Helicobacter pylori Infection.

The last 5 years have seen major shifts in defining whom to test and how to treat Helicobacter pylori infection. Peptic ulcer has changed from a chronic disease to a one-off condition, and countries with a high incidence of gastric cancer have begun implementing population-wide screening and treatment. A proactive approach to testing and treatment of H. pylori is now recommended, including outreach to family members of individuals diagnosed with active infection as well as high-risk local populations such as immigrants from high-risk countries. Increasing antimicrobial resistance has resulted in an overall decline in treatment success, causing a rethinking of the approach to development of treatment guidelines as well as the need to adopt the principles of antibiotic usage and antimicrobial stewardship. Required changes include abandoning empiric use of clarithromycin, metronidazole, and levofloxacin triple therapies. Here, we discuss these transformations and give guidance regarding testing and use of therapies that are effective when given empirically.

Effectiveness of Helicobacter pylori Treatments According to Antibiotic Resistance.

INTRODUCTION: Antibiotic resistance is one of the main factors that determine the efficacy of treatments to eradicate Helicobacter pylori infection. Our aim was to evaluate the effectiveness of first-line and rescue treatments against H. pylori in Europe according to antibiotics resistance. METHODS: Prospective, multicenter, international registry on the management of H. pylori (European Registry on H. pylori Management). All infected and culture-diagnosed adult patients registered in the Spanish Association of Gastroenterology-Research Electronic Data Capture from 2013 to 2021 were included. RESULTS: A total of 2,852 naive patients with culture results were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 22%, 27%, and 18%, respectively. The most effective treatment, regardless of resistance, were the 3-in-1 single capsule with bismuth, metronidazole, and tetracycline (91%) and the quadruple with bismuth, offering optimal cure rates even in the presence of bacterial resistance to clarithromycin or metronidazole. The concomitant regimen with tinidazole achieved an eradication rate of 99% (90/91) vs 84% (90/107) with metronidazole. Triple schedules, sequential, or concomitant regimen with metronidazole did not achieve optimal results. A total of 1,118 non-naive patients were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 49%, 41%, and 24%, respectively. The 3-in-1 single capsule (87%) and the triple therapy with levofloxacin (85%) were the only ones that provided encouraging results. DISCUSSION: In regions where the antibiotic resistance rate of H. pylori is high, eradication treatment with the 3-in-1 single capsule, the quadruple with bismuth, and concomitant with tinidazole are the best options in naive patients. In non-naive patients, the 3-in-1 single capsule and the triple therapy with levofloxacin provided encouraging results.

Genetic determinants of resistance to antimicrobial therapeutics are rare in publicly available Clostridioides difficile genome sequences.

OBJECTIVES: To determine the frequencies and clonal distributions of putative genetic determinants of resistance to antimicrobials applied for treatment of Clostridioides difficile infection (CDI), as documented in the genomic record. METHODS: We scanned 26 557 C. difficile genome sequences publicly available from the EnteroBase platform for plasmids, point mutations and gene truncations previously reported to reduce susceptibility to vancomycin, fidaxomicin or metronidazole, respectively. We measured the antimicrobial susceptibility of 143 selected C. difficile isolates. RESULTS: The frequency of mutations causing reduced susceptibility to vancomycin and metronidazole, respectively, increased strongly after 2000, peaking at up to 52% of all sequenced C. difficile genomes. However, both mutations declined sharply more recently, reflecting major changes in CDI epidemiology. We detected mutations associated with fidaxomicin resistance in several major genotypes, but found no evidence of international spread of resistant clones. The pCD-METRO plasmid, conferring metronidazole resistance, was detected in a single previously unreported C. difficile isolate, recovered from a hospital patient in Germany in 2008. The pX18-498 plasmid, putatively associated with decreased vancomycin susceptibility, was confined to related, recent isolates from the USA. Phenotype measurements confirmed that most of those genetic features were useful predictors of antibiotic susceptibility, even though ranges of MICs typically overlapped among isolates with and without specific mutations. CONCLUSIONS: Genomic data suggested that resistance to therapeutic antimicrobial drugs is rare in C. difficile. Public antimicrobial resistance marker databases were not equipped to detect most of the genetic determinants relevant to antibiotic therapy of CDI.

The Association Between Human Immunodeficiency Virus and Bacterial Vaginosis and Metronidazole Treatment Failure for Trichomonas vaginalis.

BACKGROUND: Trichomonas vaginalis (TV) is a common sexually transmitted infection. High rates of repeated infections have been observed, particularly among women living with human immunodeficiency virus (HIV). Trichomonas vaginalis frequently cooccurs with bacterial vaginosis (BV). The purpose of this study was to determine if coinfections with TV, BV, and HIV could lead to differential treatment failure outcomes. METHODS: Data were pooled from 2 prior randomized control trials comparing 2 g oral single-dose versus 500-mg twice daily oral 7-day dose metronidazole for the treatment of TV in HIV infected and HIV uninfected women. Trichomonas vaginalis rates 1-month postcompletion of treatment were compared by arm, HIV and BV status after removing those who had sexual reexposure, and/or did not complete their treatment. RESULTS: Data for 795 subjects were included in the study, of which 76 (9.6%) experienced treatment failure. In the final multivariable model, which included treatment dose, HIV status, and BV status, odds of treatment failure infection in the 7-day dose group were lower than the odds in the single dose group (odds ratio, 040; 95% confidence interval, 0.23-0.68). Treatment failure was lower in the multidose arm compared with single dose for both HIV-infected (4.0% vs 10.3%; P = 0.0568) and HIV-uninfected (7.3% vs 15.4%; P = 0.0037). Neither HIV nor BV was associated with higher treatment failure. CONCLUSIONS: Human immunodeficiency virus infection and BV status did not significantly alter the rate of repeat infection for either single dose or 7-day dose metronidazole. Among all women, 7-day metronidazole lowered the odds of treatment failure.

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.

Metronidazole and cefazolin vs cefazolin alone for surgical site infection prophylaxis in gynecologic surgery at a comprehensive cancer center.

BACKGROUND: Surgical site infection is one of the most common complications of gynecologic cancer surgery. Current guidelines recommend the administration of cefazolin preoperatively to reduce surgical site infection rates for patients undergoing clean-contaminated surgeries such as hysterectomy. OBJECTIVE: To evaluate the impact of a quality improvement project adding metronidazole to cefazolin for antibiotic prophylaxis on surgical site infection rate for women undergoing gynecologic surgery at a comprehensive cancer center. STUDY DESIGN: This retrospective, single-center cohort study included patients who underwent surgery in the gynecologic oncology department from May 2017 to June 2023. Patients with penicillin allergies and those undergoing concomitant bowel resections and/or joint cases were excluded. The preintervention group patients had surgery from May 2017 to April 2022, and the postintervention group patients had surgery from April 2022 to June 2023. The primary outcome was a 30-day surgical site infection rate. Sensitivity analyses were performed to compare surgical site infection rates on the basis of actual antibiotics received and for those who had a hysterectomy. Factors independently associated with surgical site infection were identified using a multivariable logistic regression model adjusting for confounding variables. RESULTS: Of 3343 patients, 2572 (76.9%) and 771 (23.1%) were in the pre-post intervention groups, respectively. Most patients (74.7%) had a hysterectomy performed. Thirty-four percent of cases were for nononcologic (benign) indications. Preintervention patients were more likely to receive appropriate preoperative antibiotics (95.6% vs 90.7%; P<.001). The overall surgical site infection rate before the intervention was 4.7% compared with 2.6% after (P=.010). The surgical site infection rate for all patients who underwent hysterectomy was 4.9% (preintervention) vs 2.8% (postintervention) (P=.036); a similar trend was seen for benign cases (4.4% vs 2.4%; P=.159). On multivariable analysis, the odds ratio for surgical site infection was 0.49 (95% confidence interval, 0.38-0.63) for the postintervention compared with the preintervention group (P<.001). In a sensitivity analysis (n=3087), the surgical site infection rate was 4.5% for those who received cefazolin alone compared with 2.3% for those who received cefazolin plus metronidazole, with significantly decreased odds of surgical site infection for the cefazolin plus metronidazole group (adjusted odds ratio, 0.40 [95% confidence interval, 0.30-0.53]; P<.001). Among only those who had a hysterectomy performed, the odds of surgical site infection were significantly reduced for those in the postintervention group (adjusted odds ratio, 0.63 [95% confidence interval, 0.47-0.86]; P=.003). CONCLUSION: The addition of metronidazole to cefazolin before gynecologic surgery decreased the surgical site infection rate by half, even after accounting for other known predictors of surgical site infection and differences in practice patterns over time. Providers should consider this combination regimen in women undergoing gynecologic surgery, especially for cases involving hysterectomy.

A Randomized Controlled Trial of Topical Analgesia Posthemorrhoidectomy (TAPH Trial).

BACKGROUND: Postoperative pain remains the greatest problem after hemorrhoidectomy. Pain is hypothesized to arise from bacterial infection, sphincter spasm, and local inflammation. OBJECTIVE: This trial was conducted to assess the effects of metronidazole, diltiazem, and lidocaine on posthemorrhoidectomy pain. DESIGN: A double-blinded randomized controlled factorial trial. SETTINGS: This multicenter trial was conducted in Auckland, New Zealand. PATIENTS: A total of 192 participants were randomly assigned (1:1:1:1) into 4 parallel arms. INTERVENTIONS: Participants were randomly assigned into 1 of 4 groups receiving topical treatment with 10% metronidazole, 10% metronidazole + 2% diltiazem, 10% metronidazole + 4% lidocaine, or 10% metronidazole + 2% diltiazem + 4% lidocaine. Participants were instructed to apply treatment to the anal verge 3 times daily for 7 days. MAIN OUTCOME MEASURES: The primary outcome was pain on the visual analog scale on day 4. The secondary outcomes included analgesia usage, pain during bowel movement, and functional recovery index. RESULTS: There was no significant difference in the pain and recovery scores when diltiazem or lidocaine was added to metronidazole (score difference between presence and absence of diltiazem in the formulation: -3.69; 95% CI, -13.3 to 5.94; p = 0.46; between presence and absence of lidocaine: -5.67; 95% CI, -15.5 to 3.80; p = 0.24). The combination of metronidazole + diltiazem + lidocaine did not further reduce pain. Secondary analysis revealed a significant difference between the best (metronidazole + lidocaine) and worst (metronidazole + diltiazem + lidocaine) groups in both pain and functional recovery scores. There were no significant differences in analgesic usage, complications, or return to work between the groups. No clinically important adverse events were reported. The adverse event rate did not change in the intervention groups. LIMITATIONS: Topical metronidazole was used in the control group rather than a pure placebo. CONCLUSIONS: There was no significant difference in pain when topical diltiazem, lidocaine, or both were added to topical metronidazole. See Video Abstract . CLINICALTRIALSGOV IDENTIFIER: NCT04276298. ENSAYO CONTROLADO ALEATORIZADO DE ANALGESIA TPICA POSTERIOR A HEMORROIDECTOMA ENSAYO TAPH: ANTECEDENTES:El dolor postoperatorio sigue siendo el mayor problema tras hemorroidectomía. La hipótesis es que el dolor se debe a infección bacteriana, el espasmo esfínteriano e inflamación local.OBJETIVO:Se realizó un ensayo factorial aleatorizado y controlado para evaluar los efectos del metronidazol, el diltiazem y la lidocaína en el dolor posthemorroidectomía.DISEÑO:Ensayo factorial controlado aleatorizado doble ciego.ESCENARIO:Se realizó un ensayo multicéntrico en Auckland, Nueva Zelanda.PACIENTES:Se aleatorizó a 192 participantes (1:1:1:1) en cuatro brazos paralelos.INTERVENCIONES:Los participantes se asignaron aleatoriamente a uno de los cuatro grupos que recibieron tratamiento tópico con metronidazol al 10% (M), metronidazol al 10% + diltiazem al 2% (MD), metronidazol al 10% + lidocaína al 4% (ML), o metronidazol al 10% + diltiazem al 2% + lidocaína al 4% (MDL). Se indicó a los participantes que lo aplicaran en el margen anal 3 veces al día durante 7 días.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue el dolor en la escala analógica visual en el día 4. Los resultados secundarios incluyeron el uso de analgesia, el dolor al defecar y el índice de recuperación funcional.RESULTADOS:No hubo diferencias significativas en las puntuaciones de dolor y recuperación cuando se añadió diltiazem o lidocaína al metronidazol (diferencia de puntuación entre la presencia y la ausencia de D en la formulación: -3.69; IC del 95%: -13.3; 5.94; p = 0.46; entre la presencia y la ausencia de L: -5.67; IC del 95%: -15.5; 3.80; p = 0.24). La combinación de MDL no redujo más el dolor. El análisis secundario reveló una diferencia significativa entre los grupos mejor (ML) y peor (MDL) tanto en las puntuaciones de dolor como en las de recuperación funcional. No hubo diferencias significativas en el uso de analgésicos, las complicaciones o la reincorporación al trabajo entre los grupos. No se notificaron eventos adversos clínicamente importantes. La tasa de eventosadversos no cambió en los grupos de intervención.LIMITACIONES:Se utilizó metronidazol tópico en el grupo de control, en lugar de un placebo puro.CONCLUSIONES:No hubo diferencias significativas en el dolor cuando se añadió diltiazem tópico o lidocaína, o ambos, al metronidazol tópico. ( Traducción-Dr. Jorge Silva Velazco )Identificador de registro del ensayo clínico:NCT04276298.

Nonoperative Treatment of Diverticulitis and Appendicitis: Which Antibiotic Regimen Fails?

INTRODUCTION: Diverticulitis and appendicitis are common emergency general surgical conditions. Both can be treated with antibiotics alone; however, no antibiotic regimen has been identified as superior to others. In this study, we review different antibiotic regimens and their rates of failure. METHODS: Retrospective cohort study of patients treated empirically with antibiotics for diverticulitis or appendicitis from January 1, 2018, to December 31, 2020, at an independent academic hospital in the Midwest. RESULTS: A total of 587 (appendicitis, n = 43; diverticulitis, n = 544) patients were included in the cohort. They were equally male (49%) and female (51%) with a median age of 59 y. Three major antibiotic classes were compared: cephalosporin + metronidazole (C + M), penicillins, and quinolone + metronidazole. Appendicitis patients were more likely to receive C + M for empiric treatment (73%, P < 0.001), while diverticulitis patients were more likely to receive quinolone + metronidazole (45%, P < 0.001). Patients empirically treated with antibiotics for appendicitis were more likely than those treated for diverticulitis to require additional antibiotics or procedure within 90 d (33% versus 13%, respectively; P = 0.005). Empiric treatment with C + M for diverticulitis was more likely to be associated with the need for additional antibiotics or procedures within 90 d than treatment with other regimens (P = 0.003). Choice of antibiotic for empiric treatment did not correlate with death at 90 d for appendicitis or diverticulitis. Diverticulitis patients who were initially treated as inpatients and were prescribed C + M at hospital discharge had a higher rate of death than those who were prescribed the other antibiotics (P = 0.04). CONCLUSIONS: Empiric antibiotic treatment of appendicitis is more likely to be associated with additional antibiotics or procedure when compared with diverticulitis; however, antibiotic choice did not correlate with any of the other outcomes. Empiric treatment with a C + M for diverticulitis was more likely to be correlated with the need for additional antibiotics or procedure within 90 d.

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.

Antimicrobial-resistant Helicobacter pylori in Japan: Report of nationwide surveillance for 2018-2020.

BACKGROUND: Antimicrobial therapy is necessary to eradicate Helicobacter pylori infection. The emergence of antimicrobial-resistant bacteria poses a threat to continued treatment with antimicrobial agents. For those who prescribe antimicrobial therapy, it is necessary to constantly monitor the emergence of antimicrobial-resistant bacteria. METHOD: H. pylori clinical isolates were collected in Japan from August 2018 to December 2020 for antimicrobial susceptibility testing. The agar dilution method was used for the determination of the minimum inhibitory concentration (MIC) of clarithromycin (CLR), amoxicillin (AMX), metronidazole (MNZ), and sitafloxacin (STX). RESULTS: MICs for 938 H. pylori isolates were examined. The primary resistance rates of H. pylori clinical isolates for CLR, AMX, MNZ, and STX in Japan were 35.5%, 2.7%, 4.2%, and 27.6%, respectively. The primary resistance rates for CLR, AMX, and MNZ were significantly higher than those of the 2002-2005 isolates. The resistance rate for CLR was significantly higher in females (males: 30.7%, females: 41.5%, p < 0.001) and higher in the ≤29 years age group (54.8%) than in the other age groups, although there were no significant differences (p = 0.104). The MNZ resistance rate was significantly higher in the ≤29 years age group than in the other age groups (p = 0.004). The resistance rate for STX increased with age, but a significant difference was only seen between the 30-49 years age group and the ≥70 years age group (p < 0.001), and the resistance rate was significantly higher in strains isolated in the Kyushu region than in the other regions (p < 0.001). CONCLUSIONS: The primary resistance rates for CLR, AMX, and MNZ of H. pylori clinical isolates in Japan were higher than those of the 2002-2005 isolates. Continuous surveillance is needed to monitor the trends in antimicrobial-resistant H. pylori.

Empirical Therapy Versus Tailored Therapy of Helicobacter pylori in Korea: Results of the K-CREATE Study.

BACKGROUND: The optimal duration of regimens for tailored therapy based on genotypic resistance for clarithromycin has yet to be established. AIM: This study was a nationwide, multicenter, randomized trial comparing empirical therapy with tailored therapy based on genotypic resistance for first-line eradication of Helicobacter pylori. We also compared the eradication rates of 7- and 14-day regimens for each group. PATIENTS AND METHODS: Patients with H. pylori infection were first randomized to receive empirical or tailored therapy. Patients in each group were further randomized into 7- or 14-day regimens. Empirical therapy consisted of a triple therapy (TT) regimen (twice-daily doses of pantoprazole 40 mg, amoxicillin 1 g, and clarithromycin 500 mg) for 7 or 14 days. Tailored therapy consisted of TT of 7 or 14 days in patients without genotypic resistance. Patients with genotypic resistance were treated with bismuth quadruple therapy (BQT) regimens (twice-daily doses of pantoprazole 40 mg, three daily doses of metronidazole 500 mg, and four times daily doses of bismuth 300 mg and tetracycline 500 mg) for 7 or 14 days. A 13C-urea breath test assessed eradication rates. The primary outcome was eradication rates of each group. RESULTS: A total of 593 patients were included in the study. The eradication rates were 65.7% (201/306) in the empirical therapy group and 81.9% (235/287) in the tailored therapy group for intention-to-treat analysis (p < 0.001). In the per-protocol analysis, the eradication rates of the empirical therapy and tailored groups were 70.3% (201/286) and 85.5% (235/274) (p < 0.001), respectively. There was no difference in compliance between the two groups. The rate of adverse events was higher in the tailored group compared to the empirical group (p < 0.001). DISCUSSION: Our study confirmed that tailored therapy based on genotypic resistance was more effective than empirical therapy for H. pylori eradication in Korea. However, no significant difference was found between 7- and 14-day regimens for each group. Future studies are needed to determine the optimal duration of therapy for empirical and tailored therapy regimens.

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).

Comparing cefazolin/ metronidazole, piperacillin-tazobactam, or c efoxitin as surgical antibiotic prophylaxis in patients undergoing pancreaticoduodenectomy: A retrospective cohort study.

BACKGROUND: Preoperative antibiotic options for pancreaticoduodenectomy (PD) include cefoxitin (CX), piperacillin-tazobactam (PT), or combined cefazolin and metronidazole (CM). Recent studies suggest the superiority of PT over CX, but evidence for CM is unclear. OBJECTIVE: To explore the impact of preoperative antibiotic selection (CM vs. PT and CX vs. PT) on the development of surgical site infections (SSI). METHODS: Consecutive adult patients at one institution who underwent PD from November 2017 to December 2021 and received either CM, PT, or CX preoperatively, were included. The primary outcome was SSI. Secondary outcomes included postoperative infections and clinically significant postoperative pancreatic fistula (POPF). Logistic regression models were used. RESULTS: Among 127 patients included in the study, PT, CM, and CX were administered in 46 (36.2%), 44 (34.6%), and 37 (29.4%) patients, respectively. There were 32 (27.1%) SSI, 20 (36.1%) infections, and 21 (22.9%) POPF events. PT use was associated with reduced risk of SSI compared to CX (OR: 0.32, 95% CI: 0.11-0.89, p = 0.03), but there was no difference as compared to CM (OR: 0.75, 95% CI: 0.27-2.13, p = 0.59). There were no differences in secondary outcomes. CONCLUSION: PT reduced SSI rates compared to CX but was no different to CM among patients undergoing PD at our center.

Isolation and identification of hoylesella marshii causing pleural infection: a case report.

BACKGROUND: Hoylesella marshii can be isolated from human oral cavities affected by dental pulp and periodontal infections, as well as from the dental plaque of healthy individuals, making it a common bacterium within the oral microbiota. However, its role in causing pleural infections in humans is rare. CASE PRESENTATION: A case of purulent pleural effusion occurred shortly after discharge in an elderly patient who had undergone surgery for gastric cancer. The infection was identified as being caused by an obligate anaerobe through laboratory culture, and was further identified as Hoylesella marshii causing pleural infection through 16 S rRNA gene sequence analysis. Susceptibility testing guided precise treatment with cefoperazone-sulbactam and metronidazole. The patient's clinical symptoms improved rapidly, laboratory test indicators gradually returned to normal, and the patient ultimately recovered. CONCLUSION: Hoylesella marshii can cause pleural infections in humans. Clinical microbiology laboratories should pay special attention to the cultivation of obligate anaerobes when routine aerobic cultures do not show bacterial growth but bacteria are visible on smear staining, and when conventional identification methods fail to identify the bacterium, analysis based on the highly conserved 16 S rRNA gene sequence can accurately and specifically identify the bacterium, guiding clinicians in formulating precise anti-infection strategies.

The co-infection of pulmonary hydatid cyst, lophomoniasis and tuberculosis in a patient with resistant respiratory symptoms; a case report study.

BACKGROUND: Lophomonas blattarum is a rare protozoan that causes opportunistic infections, and the co-infection of lophomonas with tuberculosis and human hydatidosis is a serious public problem in the co-endemic areas of developing countries. CASE REPORT: We presented a 58-year-old female with fever, losing weight, and cough with whitish-yellow sputum that started one month ago. Increasing inflammatory markers and hypereosinophilia in laboratory tests, and a cavity with thick, regular walls and undulating air-fluid levels measuring 43 × 30, evident in the upper segment of the right lower lobe (RLL), along with consolidation and the ground glass opacity of the upper segment and posterior basal of the RLL is apparent in CT scan were reported. Then, a bronchoscopy was requested, and the BAL specimen reported a negative fungal and bacterial infection in the samples. Several live and oval flagellated lophomonas protozoa, hydatid cyst protoscoleces (the larval forms of the parasites), and M. tuberculosis were observed in microscopic evaluation. The patient was treated with metronidazole, oral albendazole, and a combination of TB regimen. CONCLUSION: Physicians should always consider the possibility of co-infections of lophomonas with tuberculosis and human hydatidosis and investigate patients with risk factors such as immunodeficiency conditions or treated with immunosuppressive medications.

Management of patient with Fusobacterim nucletum related pleural empyema: intrapleural antibiotic therapy can be considered for salvage therapy.

Pleural empyema can lead to significant morbidity and mortality despite chest drainage and antibiotic treatment, necessitating novel and minimally invasive interventions. Fusobacterium nucleatum is an obligate anaerobe found in the human oral and gut microbiota. Advances in sequencing and puncture techniques have made it common to detect anaerobic bacteria in empyema cases. In this report, we describe the case of a 65-year-old man with hypertension who presented with a left-sided encapsulated pleural effusion. Initial fluid analysis using metagenomic next-generation sequencing (mNGS) revealed the presence of Fusobacterium nucleatum and Aspergillus chevalieri. Unfortunately, the patient experienced worsening pleural effusion despite drainage and antimicrobial therapy. Ultimately, successful treatment was achieved through intrapleural metronidazole therapy in conjunction with systemic antibiotics. The present case showed that intrapleural antibiotic therapy is a promising measure for pleural empyema.

Effects of amoxicillin and metronidazole as an adjunct to scaling and root planing on glycemic control in patients with periodontitis and type 2 diabetes: A short-term randomized controlled trial.

OBJECTIVE: To assess the effects of amoxicillin and metronidazole with scaling and root planing (SRP) on periodontal parameters and glycemic control in patients with severe periodontitis and diabetes mellitus. BACKGROUND: Adjunctive antibiotics use is advantageous for treating periodontitis in patients with severe periodontitis and diabetes. However, the effects of adjunctive antibiotic use on hemoglobin A1c (HbA1c) levels remain unclear. METHODS: This short-term, randomized controlled trial enrolled patients with severe periodontitis and type 2 diabetes. The patients were randomly allocated to SPR only (i.e., control) or SPR + antibiotics (500 mg of amoxicillin and 200 mg of metronidazole, three times daily for 7 days) groups. Periodontal and hematological parameters were assessed at baseline and 3 months after treatment. Inter- and intra-group analyses were performed using Student's t-tests, Mann-Whitney U tests, and the binary logistic regression models. p-values of <.05 were considered statistically significant. RESULTS: This study enrolled 49 patients, with 23 and 26 patients in the SRP-only and SRP + antibiotics groups, respectively. The periodontal parameters improved significantly and similarly in both groups after treatment (p < .05). The SRP + antibiotics group had more sites of improvement than the SRP-only group when the initial probing depth was >6 mm. (698 [78.96%] vs. 545 [73.35%], p = .008). The HbA1c levels decreased in the SRP-only and SRP + antibiotics groups after treatment (0.39% and 0.53%, respectively). The multivariable binary logistic regression model demonstrated that antibiotics administration and a high baseline HbA1c level were associated with a greater reduction in the HbA1c level (odds ratio = 4.551, 95% confidence interval: 1.012-20.463; odds ratio = 7.162, 95% confidence interval: 1.359-37.753, respectively). CONCLUSIONS: SRP and SRP plus systemic antibiotics were beneficial for glycemic control. Adjunctive antibiotic use slightly improved the outcome for patients with severe periodontitis and poorly controlled diabetes.