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

Clarithromycin as an Adjunct to One-Stage Full-Mouth Ultrasonic Periodontal Debridement in Generalized Aggressive Periodontitis: A Randomized Controlled Clinical Trial.

BACKGROUND: The aim of the present study is to evaluate the periodontal clinical and microbiologic responses and possible adverse effects of clarithromycin (CLM) combined with periodontal mechanical therapy in the treatment of patients with generalized aggressive periodontitis. METHODS: Forty patients were selected and randomly assigned into one of two groups: 1) CLM (n = 20): one-stage full-mouth ultrasonic debridement (FMUD) associated with CLM (500 mg, every 12 hours for 3 days); and 2) placebo (n = 20): FMUD associated with placebo pills. Clinical and microbiologic parameters were evaluated at baseline and 3 and 6 months postoperatively. RESULTS: Both treatments presented statistically significant clinical and microbiologic improvements. However, the CLM group presented lower means of probing depth for pockets ≥7 mm at 6 months (4.0 ± 1.7 mm) compared with the placebo group (4.7 ± 1.3 mm) (P = 0.04). In addition, the CLM group also presented greater reduction of Porphyromonas gingivalis (Pg) DNA counts at 6 months (P = 0.0001). CONCLUSION: Results from this study suggest both treatments are effective; however, adjunct use of CLM to FMUD leads to better reduction of deep pockets and Pg at 6 months compared with FMUD alone.

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

[Paradoxical reactions and responses during antibiotic treatment for Mycobacterium ulcerans infection (Buruli ulcer). Four cases from French Guiana]. / Réponses et réactions paradoxales au cours du traitement médicamenteux de l'infection à Mycobacterium ulcerans (ulcère de Buruli). Quatre observations en Guyane française.

BACKGROUND: In recent years, first-line therapy for Mycobacterium ulcerans infection in French Guiana has consisted of antibiotics active against this organism. Two regimens are used comprising rifampicin associated with clarithromycin or amikacin. PATIENTS AND METHODS: We describe four patients presenting apparent worsening of their lesions during treatment: ulceration of a nodular lesion in a 32-year-old woman and worsening of an ulcerated lesion in three patients aged 16, 27 and 79 years. DISCUSSION: In these 4 patients, we concluded that the symptoms were caused by a paradoxical response or a reaction, a phenomenon already described in tuberculosis and leprosy. Such worsening is transient and must not be misinterpreted as failure to respond to treatment. The most plausible pathophysiological hypothesis involves the re-emergence of potentially necrotizing cellular immunity secondary to the loss of mycolactone, a necrotizing and immunosuppressive toxin produced by M. ulcerans, resulting from the action of the antibiotics.

Cross-sectional microhardness of bovine enamel subjected to three paediatric liquid oral medicines: an in vitro study.

AIM: This study aimed to investigate the in vitro effects of three paediatric liquid oral medicines on bovine dental enamel subsurfaces under pH cycling conditions. METHODS: Bovine enamel blocks were evaluated for surface hardness at baseline for sample selection. 52 intact bovine enamel blocks (16mm(2)) were randomly divided into four groups (n=13) according to the immersion treatments: G1: antibiotic (Klaricid®), G2: antihistamine (Claritin®), G3: antihistamine (Dimetapp®) and G4: control (de-ionised water). The blocks were submitted to pH cycling treatments twice a day for 12 days. The medicines were evaluated for pH, viscosity, and concentration of calcium, phosphate and fluoride. After the treatment period, cross-sectional microhardness (CSMH) measurements of the enamel blocks were taken and the data, expressed in Knoop hardness number (kg/mm(2)) was used to calculate the ΔS. STATISTICS: ANOVA followed by the Tukey test were used for statistical analyses (p<0.05). RESULTS: The antibiotic Klaricid® showed the highest concentration of fluoride, calcium and phosphate. Considering pH and viscosity, the following pattern was observed according to the treatment group: G4>G1>G2>G3 and G1>G2>G3>G4 respectively. Regarding the demineralisation pattern, the following results were observed: G4>G3>G2>G1. Compared to the control, the antibiotic and both the antihistamines provoked less demineralisation of the enamel blocks (p<0.05). CONCLUSIONS: Antibiotic G1 (Klaricid®) presented an in vitro protective effect against acid attacks probably due to its mineral content and viscosity.

Efficacy and safety of clarithromycin in pediatric patients with upper respiratory infections: a systematic review with meta-analysis.

PURPOSE: Upper respiratory infections (URIs) are one of the most common infectious diseases in children. Macrolides had been considered one of the best options of treatment. Instead of clarithromycin is one of the macrolides most used, meta-analysis about the safety and efficacy of this drug has not been published. MATERIALS AND METHODS: A systematic review with meta-analysis of randomized controlled trials (RCTs) was conducted. Studies in subjects < or = 12 years of age with URIs were included. Central Cochrane Registry, MEDLINE, EMBASE, Lilacs and Artemisa from 1966 to January of 2011 were reviewed. Clinical cure, clinical success, bacteriological eradication, relapse risk and adverse events risks were analyzed. Risks ratios (RR) with 95% confidence intervals (CI 95%) were calculated, using a fixed effects model. RESULTS: 24 studies, from a total of 76 RCTs were included. Clarithromycin was therapeutically equivalent to other antibiotics studied with respect to clinical cure [RR 1.02 (0.98 to 1.06), p NS], clinical success [RR 1.01 (0.99 to 1.03), p NS] and relapse risk [RR 1.34 (0.81 to 2.21), p NS], but was associated with a better bacteriological eradication [RR 1.06 (1.02 to 1.09), p 0.001], and a lower risk for related adverse events [RR 0.77 (0.65 to 0.90), p = 0.001]. CONCLUSIONS: High quality evidence showed that Clarithromycin is a safe and effective alternative for the treatment of URIs in pediatric patients. Is superior to other antibiotics in relation to bacterial eradication. Its equivalence profile related to clinical cure, clinical success and relapse risk, let to consider it as an important alternative.

Clarithromycin-based triple therapy for Helicobacter pylori treatment in peptic ulcer patients.

INTRODUCTION: The scheme proton pump inhibitor/amoxicillin/clarithromycin (PPI/AC) is still the first-line treatment for Helicobacter pylori (H. pylori) infections despite evidence suggesting its failure in up to 20% to 30% of patients. METHODOLOGY: This study involved 493 patients who were prescribed omeprazole (20 mg twice a day) or another proton pump inhibitor in equivalent dosage, amoxicillin (1 g twice a day), and clarithromycin (500 mg twice a day) for seven days. Efficacy was determined by negative urease test and absence of H. pylori on gastric biopsy samples twelve weeks after the end of treatment. Safety was defined according to the adverse effects reported. Mean age of the patients was (± SD) 48.96 ± 13, and demographic and clinical data were recorded for correlation with treatment outcomes. RESULTS: Out of 493 patients, 316 (64.1%) presented duodenal ulcer, 111 (22.5%) gastric ulcer, and 66 (14.4%) simultaneous gastric and duodenal ulcers. Additionally, 267 (54.2%) patients had at least one risk factor for peptic ulcer disease, smoking being the most common (99 [36.5%]). Successful eradication was achieved in 408 patients. The eradication rates per protocol, and according to the intention to treat, were 88.8% and 82.7%, respectively.  Of 164 (35.5%) patients who presented adverse effects, 100 (61%) reported them as mild and only six (3.7%) patients had to discontinue treatment. Previous use of tobacco and non-steroid anti-inflammatory drugs was the only risk factor for treatment failure (P = 0.00). CONCLUSION: PPI/AC is still a valuable and remarkably tolerable option for first-line H. pylori eradication in Brazil.

A randomized clinical trial to determine the efficacy of regimens containing clarithromycin, metronidazole, and amoxicillin among histologic subgroups for Helicobacter pylori eradication in a developing country.

BACKGROUND: Most treatments deemed effective for Helicobacter pylori eradication in developed countries are less effective in developing countries. Regimens containing clarithromycin, metronidazole, and amoxicillin seem efficacious despite antibiotic resistance, and may be a viable option in developing countries. MATERIALS AND METHODS: We evaluated the efficacy of a 14-day regimen with 500 mg clarithromycin b.i.d., 500 mg metronidazole t.i.d., and 500 mg amoxicillin t.i.d. (with and without a proton pump inhibitor), and a 10-day regimen containing 500 mg clarithromycin b.i.d., 1 g amoxicillin b.i.d., and 20 mg omeprazole b.i.d. in Pasto, Colombia, using a randomized, single-blind design stratified by presence of atrophic gastritis. RESULTS: H. pylori was eradicated in 86.8% and 85.3% of the participants randomized to a clarithromycin-metronidazole-amoxicillin and clarithromycin-amoxicillin-omeprazole regimens, respectively (p = .79). Per-protocol analyses indicated greater efficacy for the clarithromycin-metronidazole-amoxicillin regimen (97%) versus the clarithromycin-amoxicillin-omeprazole regimen (86%) (p = .04), particularly for participants with atrophic gastritis (clarithromycin-metronidazole-amoxicillin = 100%, clarithromycin-amoxicillin-omeprazole = 81%; p = .02). Adverse events were mild, but adverse event-related non-compliance was reported more often for regimens containing clarithromycin, metronidazole, and amoxicillin. CONCLUSIONS: Our results suggest that an eradication rate of > 85% can be achieved with 14-day clarithromycin, metronidazole, and amoxicillin and 10-day clarithromycin, amoxicillin, and omeprazole regimens in Pasto, Colombia. The regimens containing clarithromycin, metronidazole, and amoxicillin appear to be superior to the clarithromycin, amoxicillin, and omeprazole regimen for compliant participants and those with atrophic gastritis. Our findings provide treatment options for a population in a developing country with a high prevalence of H. pylori infections and antibiotic resistance.

Furazolidone-based triple therapy for H pylori gastritis in children.

AIM: To evaluate the furazolidone-based triple therapy in children with symptomatic H pylori gastritis. METHODS: A prospective and consecutive open trial was carried out. The study included 38 patients with upper digestive symptoms sufficiently severe to warrant endoscopic investigation. H pylori status was defined based both on histology and on positive (13)C-urea breath test. Drug regimen was a seven-day course of omeprazole, clarithromycin and furazolidone (100 mg, 200 mg if over 30 kg) twice daily. Eradication of H pylori was assessed two months after treatment by histology and (13)C -urea breath test. Further clinical evaluation was performed 7 d, 2 and 6 mo after the treatment. RESULTS: Thirty-eight patients (24 females, 14 males) were included. Their age ranged from 4 to 17.8 (mean 10.9 +/- 3.7) years. On intent-to-treat analysis (n = 38), the eradication rate of H pylori was 73.7% (95% CI, 65.2%-82%) whereas in per-protocol analysis (n = 33) it was 84.8% (95% CI, 78.5%-91%). All the patients with duodenal ulcer (n = 7) were successfully treated (100% vs 56.2% with antral nodularity). Side effects were reported in 26 patients (68.4%), mainly vomiting (14/26) and abdominal pain (n = 13). Successfully treated dyspeptic patients showed improvement in 78.9% of H pylori-negative patients after six months and in 50% of H pylori-positive patients after six months of treatment. CONCLUSION: Triple therapy with furazolidone achieves moderate efficacy in H pylori treatment. The eradication rate seems to be higher in patients with duodenal ulcer.

Rabeprazole containing triple therapy to eradicate Helicobacter pylori infection on the Texas-Mexican border.

BACKGROUND: Antibiotic resistance and duration of therapy influence the success of proton-pump inhibitor-containing Helicobacter pylori eradication therapy. Clarithromycin resistance is associated with treatment failure. AIM: To examine the success of a 7-day rabeprazole-clarithromycin-amoxicillin therapy in the study population. METHODS: Adults from Ciudad Juarez with H. pylori infections identified by culture or histology received rabeprazole 20 mg, clarithromycin 0.5 g and amoxicillin 1 g, each b.d. for 7 days. Outcome was assessed by 13C-urea breath test carried out 4+ weeks after treatment. RESULTS: A total of 111 patients were enrolled and evaluated by urea breath test; 102 completed the full 7 days therapy. Two deviated from protocol, and five stopped because of adverse events. The cure rate (intention-to-treat) was 85% (95% CI: 78-91%); the per-protocol cure rate was 85% (95% CI: 78-91%). Side-effects were not serious and only 6.6% of those with adverse events stopped medication. Only three isolates were clarithromycin-resistant and none was cured. Compliance explained most of the successes. CONCLUSIONS: In the study population a 7-day rabeprazole triple eradication therapy was both effective and well-tolerated. Clarithromycin resistance was uncommon. We observed a slightly better outcome but consistent with results from recent large studies in US populations.

Omeprazole, clarithromycin and furazolidone for the eradication of Helicobacter pylori in patients with duodenal ulcer.

AIM: To evaluate the efficacy of omeprazole plus clarithromycin and furazolidone in Helicobacter pylori eradication and duodenal ulcer healing in Brazilian patients. METHODS: Forty H. pylori-positive patients with duodenal ulcer were randomized to receive 20 mg omeprazole o.m. or b.d. for 1 month plus 500 mg clarithromycin (b.d. ) and 200 mg furazolidone (b.d.) for 1 week. RESULTS: Three months after the end of the treatment the eradication rates were 90% by intention-to-treat analysis, and 97% by per protocol analysis. Mild side-effects were observed in 25 patients, none of whom abandoned the protocol. No difference was observed between the 20 mg and 40 mg omeprazole daily doses. Cure or significant improvement of the symptoms and of the histological alterations were observed after H. pylori eradication. CONCLUSION: Our results demonstrate that clarithromycin and furazolidone in combination with omeprazole are a good alternative for H. pylori eradication in Brazilian patients with duodenal ulcer.

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

Comparative trial of 3 days of azithromycin versus 10 days of clarithromycin in the treatment of children with acute otitis media with effusion.

The authors compared the efficacy, safety and tolerance of azithromycin and clarithromycin in pediatric patients with acute otitis media. A randomized, open clinical trial was performed comparing azithromycin and clarithromycin in children aged 6 months to 12 years of age with acute otitis media with effusion. Patients were allocated to azithromycin at 10 mg/kg once daily for 3 days or to clarithromycin at 15 mg/kg day divided into two equal doses for 10 days. Clinical examinations and tympanometric evaluations were performed at baseline, day 3-5, day 10-14, day 28-30 and day 50-60. Tympanocentesis fluid cultures were collected at enrollment and urine and blood samples were obtained at baseline and day 10-14. Of 100 patients enrolled, 97 were considered evaluable. The most common middle ear pathogens were Streptococcus pneumoniae (60%), Haemophilus influenzae (15%) and Staphylococcus aureus (13%). Fifty patients (100%) treated with azithromycin and 45 (95.7%) patients treated with clarithromycin had a satisfactory clinical response. Rates of persistence of middle ear effusion and possible drug related side effects were comparable. Based on the efficacy and safety results, azithromycin for 3 days and clarithromycin for 10 days are considered to represent an attractive alternative for the treatment of children with acute otitis media.

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