Vonoprazan-based therapies versus PPI-based therapies in patients with H. pylori infection: Systematic review and meta-analyses of randomized controlled trials.

BACKGROUND: This study aims to evaluate the efficacy and safety of vonoprazan-amoxicillin (VA), vonoprazan-amoxicillin-clarithromycin (VAC), vonoprazan-based bismuth-containing quadruple therapy (VBQT), and PPI-based triple (PAC) or quadruple therapy (PBQT) for H. pylori infection with the consideration of duration of therapy and amoxicillin dose (H: high; L: low). MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for eligible randomized controlled trials (RCTs) up to December 15, 2023. The efficacy outcome was eradication rate, and safety outcomes included the rates of adverse events and treatment discontinuation. RESULTS: Twenty-seven RCTs were included. The pooled eradication rates were 82.8% for VA, 89.1% for VAC, and 91.8% for VBQT, which increased with the higher amoxicillin frequency of administration and extended duration of therapy within each regimen. There were no significant differences in eradication rate when comparing 7-VA versus 7-VAC and 14-VA versus 14-VAC. VA was at least comparable to PAC. The eradication rate did not differ significantly between 10-H-VA or 14-H-VA versus 14-PBQT. 7-L-VAC demonstrated higher eradication rate versus 7-PAC and comparable rate to 14-PAC. 14-VBQT showed higher eradication rates versus 14-PBQT. The adverse events rate was 19.3% for VA, 30.6% for VAC, and 38.4% for VBQT. VA had similar risk of adverse events versus VAC and significantly fewer adverse events compared to PBQT. The treatment discontinuation rate did not differ significantly between treatments. CONCLUSIONS: The eradication rate of VBQT was the highest at above 90% followed by VAC and VA. VA was as effective as VAC and superior to PPI-based therapies with favorable safety, highlighting the potential of VA therapy as a promising alternative to traditional PPI-based therapies. VPZ-based triple or quadruple therapies was more effective than PPI-based therapies. Further studies are needed to establish the optimal treatment regimen especially in the western countries.

Therapeutic efficacy and drug safety comparison of one-week Vonoprazan triple therapy with two-weeks Esomeprazole triple therapy in Helicobacter pylori infection: Findings from a single-centre randomized clinical trial in population of Pakistan.

OBJECTIVE: To compare the therapeutic efficacy and drug safety of Vonoprazan and Esomeprazole triple therapies in Helicobacter pylori infection. METHODS: The randomised clinical trial was conducted from December 2022 to January 2023 at the Department of Pharmacology, Army Medical College, National University of Medical Sciences, Rawalpindi, Pakistan, in collaboration with the Gastroenterology Department of Pak Emirates Military Hospital, Rawalpindi, and comprised patients found positive for Helicobacter pylori by stool antigen test. They were randomly distributed into two groups. The EAL group received twoweek triple therapy with Esomeprazole 20mgand Amoxicillin 1000mg twice daily with Levofloxacin 500mg once daily. The VAL group was prescribed one-week triple therapy with Vonoprazan 20mg and Amoxicillin 1000mg twice daily with Levofloxacin 500mg once daily. Eradication success was evaluated by stool antigen test 4 weeks after starting the treatment. Safety of the therapy was assessed by noting adverse effects at days 3 and 14 of the treatment. Data was analysed using SPSS 27. RESULTS: Of the 122 patients, there were 61(50%) in each of the 2 groups; 30(49.2%) males and 31(50.8%) females with mean age 38.40±12.25 years in group EAL, and 35(57.4%) males and 26(42.6%) females with mean age 40.98±12.13 years in VAL group. In the EAL group, 57(93.4%) patients were found to be free of Helicobacter pylori infection compared to 58(95%) in the VAL group. Nausea 14(23%), bitter taste 41(67.2%), abdominal pain 16(26.2%) and headache 20(32.8%) were the adverse effects that were significantly more common in the EAL group compared to the VAL group B. CONCLUSIONS: Vonoprazan-based triple therapy was found to be more effective with less reported adverse effects and potential benefits of better patient compliance due to shorter therapy duration. Clinical Trial Number: Iranian Registry of Clinical Trials: IRCT20221207056738N1.

Antibiomania: clarithromycin-induced neurotoxicity mimicking autoimmune limbic encephalitis.

We describe a 64-year-old woman with relapsing encephalopathy. She initially presented with 5 days of psychomotor agitation, progressing to mania, psychosis and seizures that mimicked autoimmune limbic encephalitis. During her first hospital admission, extensive investigation failed to establish the underlying cause, and she improved with antiseizure medication alone. After a month at home, she relapsed with identical symptoms, and only then did we recognise that both episodes had been provoked by clarithromycin, prescribed for Helicobacter pylori eradication. Clarithromycin-induced neurotoxicity is rarely reported but likely to be under-recognised. It usually manifests within days of starting treatment, with delirium, mania, psychosis or visual hallucinations, sometimes termed 'antibiomania'. Seizures and status epilepticus appear to be less frequent. A full recovery is expected on stopping the medication.

Antibiomania: A Case Report of a Manic Episode Potentially Induced by the Interaction of Clarithromycin and Amoxicillin during H. Pylori Eradication Therapy.

Antibiomanic episodes, or as the DSM-5 refers to them, drug-induced manic episodes, pose a clinical challenge that is still poorly understood. There is insufficient information on the most common clinical presentation, patient profile, or underlying aetiopathogenic mechanisms. We present the clinical case of a 67-year-old woman who, after starting treatment (clarithromycin and amoxicillin) for the eradication of Helicobacter pylori, bacteria presented with a brief manic episode, which resolved after withdrawal of both drugs and with antipsychotic treatment. The possible interaction of both drugs, as GABA antagonists, in the generation of such episodes is discussed, and the clinical importance of such episodes in psychiatric emergency departments and liaison and interconsultation psychiatry, is highlighted.

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.

Pharmacokinetic Interactions Between Tegoprazan and the Combination of Clarithromycin, Amoxicillin and Bismuth in Healthy Chinese Subjects: An Open-Label, Single-Center, Multiple-Dosage, Self-Controlled, Phase I Trial.

BACKGROUND: Tegoprazan is a potassium-competitive acid blocker that inhibits gastric acid and which may be used for eradicating Helicobacter pylori. This study focuses on the pharmacokinetic interaction and safety between tegoprazan and the combination of clarithromycin, amoxicillin and bismuth in healthy Chinese subjects. METHODS: An open-label, three-period, single-center, multiple-dosage, single-sequence, phase I trial was conducted in 22 healthy subjects. In period 1, the subjects took tegoprazan 50 mg twice daily for 7 days, and in period 2 they were administered clarithromycin 500 mg, amoxicillin 1000 mg and bismuth potassium citrate 600 mg twice daily for 7 days (days 14-20). Tegoprazan, clarithromycin, amoxicillin and bismuth potassium citrate were then administered in combination for 7 days (days 21-27) in period 3. Blood samples were collected up to 12 h after the last dose of each period. Safety assessments were performed in each period. RESULTS: The geometric mean ratios (GMRs) [90% confidence interval (CI)] of maximum plasma concentration at steady state (Cmax,ss) and area under the plasma concentration-time curve over the dosing interval (AUCτ) at steady state were 195.93% (175.52-218.71%) and 287.54% (263.28-314.04%) for tegoprazan and 423.23% (382.57-468.22%) and 385.61% (354.62-419.30%) for tegoprazan metabolite M1, respectively. The GMRs (90% CI) of Cmax,ss and AUCτ were 83.69% (77.44-90.45%) and 110.30% (102.74-118.41%) for clarithromycin, 126.25% (114.73-138.93%) and 146.94% (135.33-159.55%) for 14-hydroxyclarithromycin, 75.89% (69.73-82.60%) and 94.34% (87.94-101.20%) for amoxicillin, and 158.43% (125.43-200.11%) and 183.63% (156.42-215.58%) for bismuth, respectively. All reported adverse events were mild. The frequency of adverse events during the coadministration stage was not higher than that during the single- or triple-drug administration stages. CONCLUSION: The plasma exposure of tegoprazan, M1, 14-hydroxyclarithromycin and bismuth was increased after the coadministration of tegoprazan, clarithromycin, amoxicillin and bismuth. The coadministration exhibited favorable safety and tolerability. CLINICAL TRIALS REGISTRATION: CTR20230643.

[Occurrence and environmental risks of antibiotics in surface water of China].

Antibiotics as emerging pollutants are frequently detected in surface water, raising concerns about the associated risk of antibiotic resistance genes (ARGs). Despite the widespread apprehension, there are still research gaps in the occurrence of antibiotic pollution in surface water and the associated ecological risks to aquatic organisms in China. Here, we established a dataset of antibiotic pollution in surface water in China during 2018-2022, which encompassed 3 368 concentration values of 128 antibiotics reported in 124 articles. Our analysis showed that antibiotic concentrations were predominantly in the ng/L-µg/L range, reaching up to 26 µg/L. Notably, sulfonamides (e.g., sulfamethoxazole) and quinolones (e.g., ciprofloxacin) were frequently reported at high concentrations. The pollution degree of antibiotics represented by sulfamethoxazole, ciprofloxacin, roxithromycin, and tetracycline exhibited no significant variation across different years but was lower in summer than that in spring and autumn. Additionally, distinct spatial distribution characteristics of the pollution were observed. According to calculation results of the aquatic ecological risk assessment model and the weighted frequency, we proposed a list of priority antibiotics including clarithromycin, erythromycin, sulfamethoxazole, ofloxacin, and oxytetracycline in surface water. Last but not least, this study points out the deficiencies in current research on the occurrence and ecological risks of antibiotics in surface water of China and provides viable screening strategies and monitoring recommendations in this context.

Efectos de claritromicina sobre el Intervalo QT corregido, en pacientes añosos hospitalizados / Comparative Pharmacodynamic analysis of QT interval prolongation. Induced by Clarithromycin in elderly hospitalized patients

Se estableció los efectos de la claritromicina sobre el intervalo QT corregido (iQTc) en pacientes gerontes, que requirieron hospitalización por infección respiratoria, mediante registro electrocardiográfico al inicio y al final del tratamiento. Se observó en 61% de los casos un aumento del iQTC (0,04 seg en promedio). No obstante las comorbilidades asociadas, ningún caso evolucionó a taquicardia ventricular polimórfica

The effects of clarithromycin on the corrected QT interval (iQTc) in elderly patients, who required hospitalization due to respiratory infection, were established by electrocardiographic recording at the beginning and at the end of the treatment. An increase in iQTC was observed in all cases (0.04 sec on average). Despite the associated comorbidities, no case evolved to polymorphic ventricular tachycardia

Daño hepático agudo inducido por claritromicina. A propósito de un caso / Acute liver injury induced by clarithromycin, case report

Introducción: El daño hepático por fármacos es una lesión secundaria al uso de medicamentos. Posee una baja incidencia, representando la causa más común de muerte por falla hepática aguda. Es importante el diagnóstico y tratamiento precoz para evitar resultados desfavorables. Presentación del caso: Mujer de 73 años, con antecedentes de Hipertensión arterial en tratamiento, colecistectomizada; cursó neumonía adquirida en la comunidad de presentación atípica en tratamiento con claritromicina 500mg/12 horas y al cuarto día de tratamiento presentó ictericia, coluria, hipocolia y astenia. Al examen físico presentó dolor a palpación en hemiabdomen derecho y hepatomegalia. Los exámenes en urgencias mostraron una marcada alteración de las pruebas hepáticas, con leucocitos de 9.020/mm3 y 8% de eosinófilos. Se solicitó ecotomografía abdominal que no evidenció obstrucción de vía biliar. Durante la hospitalización se descartó serología para Virus Hepatitis A, B, C, Epstein Barr, Citomegalovirus y Virus de la Inmunodeficiancia Humana (VIH), junto con un perfil inmunológico no patológico. Se complementó con colangioresonancia que no evidenció obstrucción de la vía biliar, por lo que se indicó biopsia hepática que concluyó "daño hepático secundario a fármacos''. Se suspendió claritromicina, evolucionando favorablemente dándose de alta al séptimo día. Discusión: La claritromicina es un antibiótico usado ampliamente para tratar las infecciones bacterianas, sin embargo, es capaz de inducir daño hepático. El diagnóstico del daño hepático por fármacos es difícil, requiriéndose alto índice de sospecha, en donde las manifestaciones clínicas, la eosinofilia y el descarte de otras patologías son fundamentales para plantear el diagnóstico.

Introduction: Drug induced liver injury (DILI), is a drug hepatotoxicity, with low incidence. However represents the most common cause of death secondary to acute liver failure. Assertive diagnosis and early treatment is important to avoid adverse results. Case report: A 73-year-old woman, with arterial hypertension and cholecystectomy, who suffered community acquired pneumonia with atypical presentation, was treated with clarithromycin 500 mg twice a day. She manifested jaundice, choluria, hipocholia and fatigue after the fourth day in treatment. Additional, physical examination: at palpation showed right and upper abdominal pain, and hepatomegaly. During the emergency room, laboratory tests showed significant alterations in liver function. Total leukocyte count 9020 with 8% eosinophils. Abdominal ultrasound was negative for biliary obstruction. During hospitalization, markers for autoimmune liver disease were non pathological, and viral serologies (Hepatitis A, B, C viruses, Epstein Barr, Cytomegalovirus and Human immunodeficiency virus) were negative. Biliary obstruction was negative according Magnetic resonance cholangiopancreatography. Liver biopsy showed "drug induced liver injury". Clarithromycin was suspended, and the patient achieved clinical improvement and she was discharge at the 7th day. Discussion: Clarithromycin is an antibiotic widely used for several bacterial infections, capable of induced hepatotoxicity. Diagnosis of DILI is difficult, that requires high index of clinical suspicion. Clinical manifestations, eosinophilia and diferential diagnoses are key for an assertive diagnosis

Intoxicación por carbamazepina con dos dosis de claritromicina: reporte de un caso / Intoxication by carbamazepin with 2 clarithromycin doses: clinical report

La interacción entre carbamazepina y claritromicina ha sido recientemente reportada en la literatura. Reportamos el caso de un niño de 8 años, portador de epilepsia, quien presentó una intoxicación por carbamazepina luego de que se agregara claritromicina al tratamiento. Después de la segunda dosis del antibiótico el paciente se mostró somnoliento y con ataxia cerebelosa, demostrándose una importante elevación del nivel plasmático de carbamazepina. El paciente recobró su condición normal rápidamente, luego de que se suspendiera el antibiótico con la concomitante disminución del nivel plasmático del anticonvulsivante. Se discuten las características de esta interacción de fármacos haciendo resaltar las características del metabolismo de los niños que hace especialmente importante esta situación clínica

Neurotoxoplasmose em pacientes com síndrome de imunodeficiência adquirida: estudo de 33 casos / Central nervous system toxoplasmosis in patients with the acquirred immunodeficiency syndrome: study od 30 cases

Os autores estudaram, retrospectivamente, as manifestações clínicas de 33 pacientes adultos com o diagnóstico de Síndrome de Imunodeficiência Adquirida (SIDA) e neurotoxoplasmose, internados no Serviço de Doenças Infecciosas e Parasitárias do Hospital Universitário Antônio Pedro no período de abril de 1986 a dezembro de 1994, realizando uma correlação com os achados neurorradiológicos e os achados neuropatológicos de 10 pacientes. Dos 33 pacientes estudados, 27 (81,8 por cento) eram do sexo masculino, com predomínio do grupo etário compreendido entre 20 e 40 anos (72,6 por cento). Quanto ao comportamento de risco, observou-se um predomínio da transmissão por via sexual. As manifestações neurológicas mais freqüentes foram: sinais de localização (26 casos - 78,7 por cento); alterações do estado mental (24 casos - 72,7 por cento); cefaléia (20 casos - 60,6 por cento) e crise convulsiva generalizada (18 casos - 54,5 por cento). Quanto aos achados neurorradiológicos, verificou-se que a grande maioria dos pacientes apresentava lesões múltiplas (19 casos - 57,5 por cento) localizadas em hemisférios cerebrais (24 casos - 72,7 por cento) e núcleo da base (16 casos - 48,4 por cento) com captação nodular do contraste (16 casos - 48,4 por cento). Verificou-se ainda que o edema perilesional estava presente em 28 (84,8 por cento) casos e produziu efeito de massa em 16 (48,4 por cento). A instituição do tratamento para neurotoxoplasmose foi acompanhada de resposta parcial em 27 (82,0 por cento) pacientes, resposta completa em dois (6,0 por cento) e ausência de resposta em quatro (12,0 por cento). Na maioria dos casos (20 pacientes - 83,2 por cento), o tempo de sobrevida após o início da terapêutica foi inferior a 12 meses, sendo que em 15 (62,4 por cento) deles foi inferior a seis meses. O estudo histopatológico do Sistema Nervoso Central (SNC) foi realizado em 10 (41,6 por cento) dos 24 pacientes que evoluíram para o óbito. Em todos os casos observou-se alterações morfológicas do SNC. A neurotoxoplasmose ativa foi diagnosticada em cinco (50 por cento) casos, em todos havendo concordância entre o diagnóstico clínico, neurorradiológico e os achados neuropatológicos. Em quatro casos, a neurotoxoplasmose foi considerada a causa primária de morte. Nos cinco pacientes restantes foi constatada a presença de lesões cicatriciais, algumas de aspecto cístico, localizadas em hemisférios cerebrais, núcleos da base e tronco cerebral