Metronidazole-Induced Encephalopathy With Probable Crohn Encephalitis: A Case Report.

OBJECTIVES: Metronidazole central nervous system toxicity is a rare finding in patients receiving the medication. We report a peculiar case of metronidazole central nervous system toxicity in which both the underlying condition (Crohn disease) and the drugs used to treat it are potential causes of encephalopathy. METHODS: A 26-year-old female with 6-year history of Crohn's disease for 6 years presented acute-onset encephalopathy. We provide bibliographic evidence to support metronidazole toxicity and potential Crohn disease-associated neurologic involvement. RESULTS: The patient presented dystonia, cerebellar ataxia, and altered mental status. Magnetic resonance imaging of the brain revealed typical findings of metronidazole toxicity and white matter involvement of the centrum semiovale. Immunoelectrophoresis and immunofixation of serum and cerebrospinal fluid proteins were consistent with a systemic inflammatory process. We concluded on an association between drug toxicity and probable Crohn-associated neurologic involvement. Metronidazole was stopped and the patient was placed on vitamin therapy and diazepam to control dystonia. She deteriorated and was transferred to the intensive care unit where she expired. CONCLUSIONS: Acute behavioral changes in a young patient constitute an emergency and differential diagnoses should include infective, inflammatory, metabolic, and toxic causes. Metronidazole is a potential toxic etiology.

Fourteen-day vonoprazan-based bismuth quadruple therapy for H. pylori eradication in an area with high clarithromycin and levofloxacin resistance: a prospective randomized study (VQ-HP trial).

Potassium-competitive acid blockers (P-CABs) provide potent acid inhibition, yet studies on P-CAB-based quadruple therapy for H. pylori eradication are limited. We theorized that integrating bismuth subsalicylate into a quadruple therapy regimen could enhance eradication rates. However, data on the efficacy of vonoprazan bismuth quadruple therapy are notably scarce. Therefore, the aim of this study was to evaluate the efficacy of vonoprazan-based bismuth quadruple therapy in areas with high clarithromycin and levofloxacin resistance. This was a prospective, single-center, randomized trial conducted to compare the efficacy of 7-day and 14-day vonoprazan-based bismuth quadruple therapy for H. pylori eradication between June 1, 2021, and March 31, 2022. Qualified patients were randomly assigned to the 7-day or 14-day regimen (1:1 ratio by computer-generated randomized list as follows: 51 patients for the 7-day regimen and 50 patients for the 14-day regimen). The regimens consisted of vonoprazan (20 mg) twice daily, bismuth subsalicylate (1024 mg) twice daily, metronidazole (400 mg) three times daily, and tetracycline (500 mg) four times daily. CYP3A4/5 genotyping and antibiotic susceptibility tests were also performed. Successful eradication was defined as 13negative C-UBTs 4 weeks after treatment. The primary endpoint was to compare the efficacy of 7-day and 14-day regimens as first-line treatments, which were assessed by intention-to-treat (ITT) and per-protocol (PP) analyses. The secondary endpoints included adverse effects. A total of 337 dyspeptic patients who underwent gastroscopy were included; 105 patients (31.1%) were diagnosed with H. pylori infection, and 101 patients were randomly assigned to each regimen. No dropouts were detected. The antibiotic resistance rate was 33.3% for clarithromycin, 29.4% for metronidazole, and 27.7% for levofloxacin. The CYP3A4 genotype was associated with 100% rapid metabolism. The H. pylori eradication rates for the 7-day and 14-day regimens were 84.4%, 95% CI 74.3-94.2 and 94%, 95% CI 87.4-100, respectively (RR difference 0.25, 95% CI 0.03-0.53, p value = 0.11). Interestingly, the 14-day regimen led to 100% eradication in the clarithromycin-resistant group. Among the patients in the 7-day regimen group, only two exhibited resistance to clarithromycin; unfortunately, neither of them achieved a cure from H. pylori infection. The incidence of adverse events was similar in both treatment groups, occurring in 29.4% (15/51) and 28% (14/50) of patients in the 7-day and 14-day regimens, respectively. No serious adverse reactions were reported. In conclusion, 14 days of vonoprazan-based bismuth quadruple therapy is highly effective for H. pylori eradication in areas with high levels of dual clarithromycin and levofloxacin resistance.

Optimized sequential therapy vs 10- and 14-d concomitant therapy for eradicating Helicobacter pylori: A randomized clinical trial.

BACKGROUND: A cure for Helicobacter pylori (H. pylori) remains a problem of global concern. The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide. Optimizing sequential therapy seems to be one of the most attractive strategies in terms of efficacy, tolerability and cost. The most common sequential therapy consists of a dual therapy [proton-pump inhibitors (PPIs) and amoxicillin] for the first period (5 to 7 d), followed by a triple therapy for the second period (PPI, clarithromycin and metronidazole). PPIs play a key role in maintaining a gastric pH at a level that allows an optimal efficacy of antibiotics, hence the idea of using new generation molecules. AIM: To compare an optimized sequential therapy with the standard non-bismuth quadruple therapies of 10 and 14 d, in terms of efficacy, incidence of adverse effects (AEs) and cost. METHODS: This open-label prospective study randomized 328 patients with confirmed H. pylori infection into three groups (1:1:1): The first group received quadruple therapy consisting of twice-daily (bid) omeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg and metronidazole 500 mg for 10 d (QT-10), the second group received a 14 d quadruple therapy following the same regimen (QT-14), and the third group received an optimized sequential therapy consisting of bid rabeprazole 20 mg plus amoxicillin 1 g for 7 d, followed by bid rabeprazole 20 mg, clarithromycin 500 mg and metronidazole 500 mg for the next 7 d (OST-14). AEs were recorded throughout the study, and the H. pylori eradication rate was determined 4 to 6 wk after the end of treatment, using the 13C urea breath test. RESULTS: In the intention-to-treat and per-protocol analysis, the eradication rate was higher in the OST-14 group compared to the QT-10 group: (93.5%, 85.5% P = 0.04) and (96.2%, 89.5% P = 0.03) respectively. However, there was no statistically significant difference in eradication rates between the OST-14 and QT-14 groups: (93.5%, 91.8% P = 0.34) and (96.2%, 94.4% P = 0.35), respectively. The overall incidence of AEs was significantly lower in the OST-14 group (P = 0.01). Furthermore, OST-14 was the most cost-effective among the three groups. CONCLUSION: The optimized 14-d sequential therapy is a safe and effective alternative. Its eradication rate is comparable to that of the 14-d concomitant therapy while causing fewer AEs and allowing a gain in terms of cost.

Association Between First-time Neurologic Events and Metronidazole Treatment: A Case-time Control Study.

PURPOSE: Metronidazole, a widely used antimicrobial medication, has been linked to neurologic adverse drug reactions. This study investigates the association between metronidazole use and first-time neurologic events. METHODS: We conducted a case-time-control study using data from the Danish National Patient Register and the National Prescription Register in years 2013 to 2021. Patients with a first-time diagnosis of encephalopathy, cerebellar dysfunction, or peripheral neuropathy were included. Conditional logistic regression analyses were performed to estimate the risk of neurologic events associated with metronidazole use. FINDINGS: Out of 476,066 first-time metronidazole prescriptions, the 100-day cumulative incidence of peripheral neuropathy was 0.016%, and 0.002% for cerebellar dysfunction or encephalopathy. In the case-time control study, we identified 17,667 persons with a first-time neurologic event and were included for the analysis. The estimated odds ratio for the combined neurologic events was 0.98 (95% CI, 0.59-1.64, P = 0.95) with no statistically significant association across different subgroups and time windows. IMPLICATIONS: Our findings suggest that metronidazole-induced neurologic events may be rarer than previously described, and we did not find any consistent or statistically significant association between metronidazole exposure. Nonetheless, clinicians should remain vigilant to potential neurologic risks in patients receiving metronidazole, to ensure its safe and effective use.

Clinical Study on the Eradication of Helicobacter pylori by Vonoprazan Combined with Amoxicillin for 10-Day Dual Therapy.

Vonoprazan holds significant research promise for Helicobacter pylori eradication, with the goal of determining the most effective drug regimen. In this study, H. pylori patients (426) were enrolled and randomized into 3 groups: an EA14 group (20 mg of esomeprazole qid and 1000 mg of amoxicillin tid for 14 days), a VA14 group (20 mg of vonoprazan bid and 750 mg of amoxicillin qid for 14 days), and a VA10 group (20 mg of vonoprazan bid and 1000 mg of amoxicillin tid for 10 days). Key outcomes encompassed the H. pylori eradication rate, patient adverse effects, and compliance. In the EA14, VA14, and VA10 groups, H. pylori eradication rates were 89.4%, 90.1%, and 88.7% in intention-to-treat analysis, and 94.2%, 94.4%, and 94.6% in per-protocol analysis, respectively. Adverse events incidences were 14.8%, 12.7%, and 5.6%, while compliance rates were 88.7%, 90.9%, and 95.8%, respectively. Notably, the VA10 regimen demonstrated comparable H. pylori eradication rates, adverse effect incidences, and compliance levels to the EA14 and VA14 regimens.

Non-antibiotic Treatment Modalities for Bacterial Vaginosis.

Caused by an imbalance in the vaginal microbiome, bacterial vaginosis (BV) is among the most commonly occurring vaginal infections in women of childbearing age. If untreated, BV may have a detrimental impact on the obstetric and gynecological health of an individual. To date, treatment for BV includes a regimen of antibiotics and avoidance of relevant risk factors. Since recurrence and reinfection are frequently observed in patients, pharmaceutical treatment for BV remains ineffective nevertheless. Repeated exposure to antibiotics could precipitate drug-resistant strains. The severity of this problem leads to the emergence of non-antimicrobial therapies. This article aims to provide a review on the types and efficacy of various alternative, non-antimicrobial therapeutic regimens.

Systemic azithromycin versus amoxicillin/metronidazole as an adjunct in the treatment of periodontitis: a systematic review and meta-analysis.

BACKGROUND: The use of systemic azithromycin (AZT) and amoxicillin/metronidazole (AMX/MTZ) as adjuncts provided additional clinical and microbiological benefits over subgingival instrumentation alone. However, the superiority of one antibiotic regimen over another has not been proven. Therefore, the aim of this systematic review and meta-analyses was to evaluate the clinical efficacy and safety of subgingival instrumentation (SI) in conjunction with the systemic use of AZT or AMX/MTZ for the treatment of periodontitis from current published literature. METHODS: Electronic databases were searched to identify randomized controlled trials (RCTs), controlled clinical trials, prospective and retrospective human studies that compared the adjunctive use of systemic AZT to AMX/MTZ with SI in the treatment of periodontitis. The eligibility criteria were defined based on the participant (who had periodontitis), intervention (SI with adjunctive use of systemic AZT), comparison (SI with adjunctive use of systemic AMX/MTZ), outcomes (primary outcome: changes in probing pocket). The risk of bias was assessed using the Cochrane Collaboration's Risk of Bias tool. Data were analysed using a statistical software program. RESULTS: Five studies with 151 participants with periodontitis were included in the present review. Of these, 74 participants received adjunctive AZT, while the remaining participants received AMX/MTZ as an adjunct to SI. The adjunctive use of AZT and AMX/MTZ had comparable changes in probing pocket depths at 1-3 months with no statistically significant difference (mean difference (MD) 0.01; 95% CI -0.20 to 0.22; P = 0.94). The adjunctive use of AZT had significantly fewer number of residual sites with probing pocket depths of ≥5 mm at 1-3 months compared to the adjunctive use of AMX/MTZ (MD -3.41; 95% CI -4.73 to -2.10; P < 0.0001). The prevalence rates of adverse events among participants who received AZT and AMX/MTZ were 9.80% and 14.8%, respectively. The meta-analysis showed that the difference between the two groups was not statistically significant (risk ratio 0.69; 95% CI 0.28 to 1.72; P = 0.43). CONCLUSIONS: Within the limitation of this review, there was no superiority between AZT and AMX/MTZ in terms of mean changes in probing pocket depths, clinical attachment level, bleeding on probing at 1-3 months. AZT seem to be associated with less sites with residual probing pocket depths of ≥5 mm at 1-3 months and fewer adverse events compared with AMX/MTZ. © 2023 Australian Dental Association.

Treatment patterns and economic burden of bacterial vaginosis among commercially insured women in the USA.

Aim: Bacterial vaginosis (BV) is a common vaginal dysbiosis associated with adverse clinical sequelae, most notably, increased risk of sexually transmitted infections (STIs). The aims of this study were to estimate the frequency of BV recurrence, treatment patterns, other gynecological (GYN) conditions, and the associated healthcare resource utilization (HCRU) and costs among commercially insured patients in the USA. Patients & methods: Female patients aged 12-49 years with an incident vaginitis diagnosis and ≥1 pharmacy claim for a BV medication (fungal treatment only excluded) were selected from the Merative™ MarketScan commercial database (2017-2020). During a minimum 12-month follow-up, additional treatment courses, treatment patterns, frequency of other GYN conditions, and HCRU and costs were assessed. Generalized linear models were used to identify baseline predictors of total all-cause healthcare costs and number of treatment courses. Results: The study population included 140,826 patients (mean age: 31.5 years) with an incident vaginitis diagnosis and ≥1 BV medication claim. During the follow-up, 64.2% had 1 treatment course, 22.0% had 2, 8.1% had 3, and 5.8% had ≥4; 35.8% had a BV recurrence (≥2 BV medication claims). The most commonly prescribed BV medication was oral metronidazole (73.6%). Approximately 12% (n = 16,619) of patients had a new diagnosis of another GYN condition in the follow-up; 8.2% had a new STI, which were more common among patients with ≥4 treatment courses (12.9%). During follow-up, total all-cause healthcare costs averaged $8987 per patient per year (PPPY) of which $470 was BV-related. BV-related healthcare costs increased from $403 PPPY among those with 1 treatment course to $806 PPPY among those with ≥4 with nearly half the costs attributed to outpatient office visits. Conclusion: BV recurrence among this population represented a substantial clinical and healthcare economic burden warranting improvements in women's healthcare.

A Systematic Review and Meta-analysis of Randomized Clinical Trials on the Prevention and Treatment of Pouchitis after Ileoanal Pouch Anastomosis.

BACKGROUND: This systematic review explored different medications and methods for prevention and treatment of pouchitis after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). METHODS: PubMed, Scopus, and Web of Science were searched for randomized clinical trials that assessed prevention or treatment of pouchitis. The systematic review was reported in line with updated 2020 PRISMA guidelines. Risk of bias in the trials included was assessed using the ROB-2 tool and certainty of evidence was assessed using GRADE. The main outcomes were the incidence of new pouchitis episodes in the preventative studies and resolution or improvement of active pouchitis in the treatment studies. RESULTS: Fifteen randomized trials were included. A meta-analysis of 7 trials on probiotics revealed significantly lower odds of pouchitis with the use of probiotics (RR: 0.26, 95% CI: 0.16-0.42, I2 = 20%, p < 0.001) and similar odds of adverse effects to placebo (RR: 2.43, 95% CI: 0.11-55.9, I2 = 0, p = 0.579). One trial investigated the prophylactic role of allopurinol in preventing pouchitis and found a comparable incidence of pouchitis in the two groups (31% vs 28%; p = 0.73). Seven trials assessed different treatments for active pouchitis. One recorded the resolution of pouchitis in all patients treated with ciprofloxacin versus 67% treated with metronidazole. Both budesonide enema and oral metronidazole were associated with similar significant improvement in pouchitis (58.3% vs 50%, p = 0.67). Rifaximin, adalimumab, fecal microbiota transplantation, and bismuth carbomer foam enema were not effective in treating pouchitis. CONCLUSIONS: Probiotics are effective in preventing pouchitis after IPAA. Antibiotics, including ciprofloxacin and metronidazole, are likely effective in treating active pouchitis.

[A case of irreversible metronidazole encephalopathy during liver abscess treatment].

Metronidazole (MNZ) is a widely used drug for protozoan and anaerobic infections. The continuous use of MNZ causes various neurological symptoms, such as cerebellar ataxia, visual disturbance, vestibulocochlear symptoms, gait disturbance, dysarthria, and epileptic seizures of unknown cause, named MNZ-induced encephalopathy (MIE), in rare cases. MIE is a reversible disease that often improves within a few days of MNZ discontinuation, but irreversible neurological symptoms rarely remain. Herein, we report a case of MIE that developed during MNZ administration for a liver abscess, causing prolonged unconsciousness and death even after drug discontinuation. An 85-year-old female patient complained of fever, elevated liver enzymes, and a multifocal abscess in the right hepatic lobe, as seen on computed tomography. Percutaneous transhepatic abscess drainage and antibiotic therapy were initiated. The causative agent of the liver abscess could not be identified, thus meropenem was started, which demonstrated no inflammation improvement, thus oral MNZ was added. The inflammation recurred when MNZ was discontinued, and the patient continued taking MNZ. Vomiting, upper limb tremors, consciousness disturbance, and convulsions appeared on day 46 (total dose of MNZ 73.5mg), and the patient was hospitalized. T2-weighted, diffusion-weighted, and FLAIR head magnetic resonance imaging (MRI) revealed symmetrical abnormal high-signal areas in the cerebellar dentate nucleus, corpus callosum, cerebral white matter, and periventricular areas. MIE was diagnosed based on the patient's course and MRI images, and MNZ was discontinued. The patient continued to suffer from impaired consciousness and convulsions after MNZ discontinuation and died due to aspiration pneumonia. Suggestively, MIE development is related to long-term MNZ administration, poor nutrition, liver disease, underlying diseases (such as advanced cancer), and serious complications. A systematic review of MIE cases revealed that 4.8-5.9% of the patients demonstrated little improvement of symptoms after MNZ discontinuation, and some deaths were reported. Patients with poor prognosis were often suffering from impaired consciousness and convulsions. Furthermore, impaired consciousness was the most common residual symptom. Abnormal signals in characteristic areas, such as the dentate nucleus cerebri and corpus callosum, on head MRI are useful for MIE diagnosis, especially in patients with abnormal findings in the cerebral white matter, which is associated with a poor prognosis. We should pay close attention to the onset of MIE when MNZ is administered.

Can vitamin B6 alleviate the adverse reactions of quadruple anti-Helicobacter pylori regimen? : randomized controlled trial.

BACKGROUND: Vitamin B6 is an essential water-soluble vitamin for humans. It is often used to prevent a variety of neuropathies, relieve vomiting, and relieve symptoms such as hand and foot neuritis. AIM: To evaluate whether vitamin B6 can alleviate the adverse reactions caused by the quadruple anti-Helicobacter pylori treatment regimen containing minocycline and metronidazole. METHODS: In this randomized controlled trial, 280 patients with H. pylori infection were randomly placed into one of two treatment groups-the conventional treatment group and the vitamin B6 supplement treatment group-for 2 weeks. The primary endpoint was the total incidence of adverse reactions up to 2 weeks after treatment initiation. The study was designed according to CONSORT Medicinal Interventions. And it was registered with Chinese Clinical Trial Registry under the number ChiCTR2100053833. RESULTS: In terms of efficacy, vitamin B6 does not affect the efficacy of conventional regimen. In the vitamin B6 supplement treatment group, the incidence of adverse reactions was 56.92%, which was significantly lower than the 74.62% observed in the conventional treatment group. In addition, the severity of adverse reactions was also significantly reduced. The proportion of moderate to severe central nervous system symptoms decreased from 58.7 to 14.63%. And, the proportion of moderate to severe gastrointestinal reactions decreased from 33.33 to 0%. We speculate that the mechanism of vitamin B6 of reducing adverse reaction may be related to the production of GABA in the brain. CONCLUSIONS: Vitamin B6 can alleviate adverse reactions of the quadruple anti-H. pylori regimen containing minocycline and metronidazole.

Can Metronidazole Cause a Disulfiram-Like Reaction? A Case-Control Study Propensity Matched by Age, Sex, and Ethanol Concentration.

INTRODUCTION: There is controversy over the existence of a metronidazole-induced disulfiram-like reaction. Uncontrolled case reports suggest metronidazole can cause a severe disulfiram-like reaction in combination with ethanol. Criticism of these cases suggest the observed effects appear to be as likely caused by ethanol as by a drug interaction. Controlled experimental data refute these reports, demonstrating metronidazole does not increase acetaldehyde and cannot reliably produce disulfiram-like reactions. The purpose of this study is to retrospectively assess the incidence of clinical effects consistent with a disulfiram-like reaction in a population of patients with confirmed ethanol use who received metronidazole. As alcohol may also be responsible for the effects seen, the incidence of effects is assessed against a control group matched for age, sex, and ethanol concentration. METHODS: A retrospective chart review was performed from December 1, 2010, through December 31, 2020 on emergency department patients with ethanol use confirmed via detectable ethanol concentration who received metronidazole while ethanol was predicted to still be present in the serum. A matched comparator group with the same ethanol concentrations, as well as sex and age, was generated for comparison. The incidence of disulfiram-like reaction symptoms documented in the medical record was compared between groups. RESULTS: Thirty-six patients were included in the study: 18 in the metronidazole group and 18 in the ethanol concentration matched control group. The mean age in both groups was 46 years. The metronidazole group was 50% male, and the mean ethanol concentration was 0.21 g/dL. The control group was 44.4% male. There was significantly less hypertension in the metronidazole group compared to the control group (16.7% vs 61.1%, P $lt; 0.0001). There were no other significant difference in disulfiram-like effects between the two groups. No patients who received metronidazole and had a detectable ethanol concentration had a suspected disulfiram-like reaction documented in the medical record. CONCLUSIONS: This data set further supports the lack of a disulfiram-like reaction when metronidazole is used in patients with recent ethanol use in the acute care setting. Additionally, it highlights that the clinical effects of a disulfiram-like reactions may be present at baseline from ethanol ingestion or underlying disease regardless of metronidazole use. These findings are consistent with well-controlled human and animal data demonstrating no increase in acetaldehyde concentrations or disulfiram-like symptoms when metronidazole is co-administered with ethanol. In patients where metronidazole is indicated as the superior agent, its use should not be avoided due to concern about an interaction with ethanol.

The frequency and duration of side-effects associated with the use of oral metronidazole; A prospective study of VITA trial participants.

BACKGROUND: The tolerability of metronidazole is often perceived as being poor and in particular as being a cause of gastrointestinal side effects, but the frequency, severity and duration of adverse effects (AE) is not well characterised. This study assessed the frequency and type of metronidazole associated AEs in women treated for bacterial vaginosis. METHODS: An exploratory study of participants from the lactic acid gel versus metronidazole for treating bacterial vaginosis (VITA) randomised controlled trial. In this sub-study, women aged ≥16 years, diagnosed with bacterial vaginosis and who received oral MTZ (400 mg twice daily, for 7 days) were followed up prospectively over 2 weeks. Baseline demographic and clinical data, and self-reported data on the incidence, time to onset, and duration of AEs were analysed. RESULTS: 155 women were included, of whom 64% (99/155) reported at least one metronidazole AE, including 47% (72/155) who reported gastrointestinal symptoms (nausea and/or vomiting [52/155], abdominal pain [31/154] or diarrhoea [31/154]) mostly within 3 days of starting treatment and resolving within 5 days of onset. Treatment discontinuation occurred in 8% (12/148) overall and AEs were given as the reason for discontinuing in only 3% (4/148). CONCLUSION: Overall, metronidazole side effects occurred commonly, but resolved within a few days and had a limited impact on treatment completion.

Safety and effectiveness of vonoprazan-based rescue therapy for Helicobacter pylori infection.

BACKGROUND: Vonoprazan (VPZ)-based regimens are an effective first-line therapy for Helicobacter pylori (H. pylori) infection. However, their value as a rescue therapy needs to be explored. AIM: To assess a VPZ-based regimen as H. pylori rescue therapy. METHODS: This prospective, single-center, clinical trial was conducted between January and August 2022. Patients with a history of H. pylori treatment failure were administered 20 mg VPZ twice daily, 750 mg amoxicillin 3 times daily, and 250 mg Saccharomyces boulardii (S. boulardii) twice daily for 14 d (14-d VAS regimen). VPZ and S. boulardii were taken before meals, while amoxicillin was taken after meals. Within 3 d after the end of eradication therapy, all patients were asked to fill in a questionnaire to assess any adverse events they may have experienced. At least 4-6 wk after the end of eradication therapy, eradication success was assessed using a 13C-urea breath test, and factors associated with eradication success were explored. RESULTS: Herein, 103 patients were assessed, and 68 patients were finally included. All included patients had 1-3 previous eradication failures. The overall eradication rates calculated using intention-to-treat and per-protocol analyses were 92.6% (63/68) and 92.3% (60/65), respectively. The eradication rate did not differ with the number of treatment failures (P = 0.433). The rates of clarithromycin, metronidazole, and levofloxacin resistance were 91.3% (21/23), 100.0% (23/23), and 60.9% (14/23), respectively. There were no cases of resistance to tetracycline, amoxicillin, or furazolidone. In 60.9% (14/23) patients, the H. pylori isolate was resistant to all 3 antibiotics (clarithromycin, metronidazole, and levofloxacin); however, eradication was achieved in 92.9% (13/14) patients. All patients showed metronidazole resistance, and had an eradication rate of 91.3% (21/23). The eradication rate was higher among patients without anxiety (96.8%) than among patients with anxiety (60.0%, P = 0.025). No severe adverse events occurred; most adverse events were mild and disappeared without intervention. Good compliance was seen in 95.6% (65/68) patients. Serological examination showed no significant changes in liver and kidney function. CONCLUSION: VAS is a safe and effective rescue therapy, with an acceptable eradication rate (> 90%), regardless of the number of prior treatment failures. Anxiety may be associated with eradication failure.

Efficacy and safety of tazobactam/ceftolozane in combination with metronidazole for intraabdominal infection in a hepato-biliary-pancreatic field in clinical practice.

INTRODUCTION: This single-center study evaluated the efficacy and safety of tazobactam/ceftolozane (TAZ/CTLZ) in combination with metronidazole for intraabdominal infection in a hepato-biliary-pancreatic field in clinical practice. METHODS: This study included 50 patients, including 35 with intraabdominal abscess or peritonitis, 5 with liver abscess, 4 with cholecystitis, and 6 with cholangitis with sepsis. Of the 50 patients, 29 received TAZ/CTLZ and metronidazole after a prior antibacterial therapy failure, including tazobactam/piperacillin, cefmetazole, and levofloxacin. Source control was performed in 36 patients. RESULTS: The clinical response could be evaluated in 49 patients. The clinical cure rate at end-of-therapy was 91.8% (45 of 49 patients) and that at test-of-cure was 89.6% (43 of 48 patients). Of 5 patients in whom clinical response at test-of-cure was a failure, 1 developed infectious disease during chemoradiotherapy for recurrent cancer and 4 after liver resection or pancreatoduodenectomy. Three of the 4 patients were associated with pancreatic juice leakage. Isolated pathogens were eradicated or presumably eradicated in 27 of 31 (87.1%) patients in whom microbiological response at test-of-cure could be evaluated. The response rate for AmpC-producing Enterobacteriaceae was 87.5%. Nausea was observed in two patients. Aspartate and alanine aminotransferase activities were increased in 3 of the 50 (6.0%) patients. The activities improved after the antibiotic discontinuation. CONCLUSIONS: This observational study demonstrated that TAZ/CTLZ in combination with metronidazole has a favorable effect without major drug-related adverse events for intraabdominal infection in the hepato-biliary-pancreatic field in clinical practice although the efficacy of TAZ/CTLZ may decrease in compromised patients.