Azithromycin and doxycycline in the treatment of female patients with acute urethral syndrome caused by Ureaplasma urealyticum: significance of duration of clinical symptoms

One hundred ninety-two female patients with acute urethral syndrome caused by Ureaplasma urealyticum were examined. First, patients were divided into two groups: those with clinical symptoms present for less than 3 weeks before the start of treatment and those with clinical symptoms 3 weeks or longer before the beginning of therapy. The patients were then further divided into groups and randomized to receive azithromycin once daily in a single dose of 1 g or 500 mg once daily for 6 days, or to receive doxycycline 100 mg b.i.d. for 14 days or 100 mg b.i.d. for 7 days (eight study groups in all). Clinical and bacteriological efficacy were evaluated 3 weeks after the end of therapy. In the group of patients with disease symptoms lasting for 3 weeks or longer, eradication and clinical cure rates were significantly higher after the administration of azithromycin at a dose of 1 x 500 mg/6 days than after a single dose of 1 g (p < 0.001).     

Valaciclovir: a review of its long term utility in the management of genital herpes simplex virus and cytomegalovirus infections

Valaciclovir is an aciclovir prodrug used to treat infections caused by herpes simplex virus (HSV) and varicella zoster virus, and for prophylaxis against cytomegalovirus (CMV). Oral valaciclovir provides significantly better oral bioavailability than oral aciclovir itself, contributing to the need for less frequent administration. Several studies have demonstrated the efficacy of long term (> 90 days) therapy with valaciclovir for the suppression of genital HSV disease in otherwise healthy individuals with HSV infection. In 1 randomised, double-blind trial, once daily valaciclovir (1000 mg, 500 mg and 250 mg) produced statistically significant suppression of disease recurrence, as did twice daily valaciclovir 250 mg and aciclovir 400 mg. Valaciclovir dosages of > or = 500 mg daily are recommended for suppression of genital herpes recurrences in immunocompetent individuals. This disease occurs frequently in patients with human immunodeficiency virus (HIV) infection and, in a single randomised double-blind trial, prophylactic valaciclovir (1000 mg once daily or 500 mg twice daily) and aciclovir (400 mg twice daily) were found to be of similar efficacy in the suppression of genital herpes. However, a higher than expected dropout rate indicated that more studies of valaciclovir in patients with HIV are required. In a randomised trial of patients undergoing renal transplant, valaciclovir 2 g 4 times daily for 90 days significantly reduced the incidence and delayed the onset of CMV disease: the incidence in valaciclovir-treated patients who were CMV-seronegative at baseline, and recieived a kidney from a CMV-seropositive donor, was 3% versus 45% for placebo after 90 days of treatment. Acute graft rejection was also reduced in the valaciclovir-treated group. A small study in heart transplant patients compared valaciclovir (2 g 4 times daily) with aciclovir (200 mg 4 times daily) and found a significant reduction in CMV antigenaemia favouring valacilovir at the end of the treatment period. Additional reductions in other indices of CMV in those given valaciclovir compared with aciclovir were also noted. In a preliminary study of prophylaxis for CMV disease in bone marrow transplant recipients valaciclovir (2 g 4 times daily) was superior to aciclovir (800 mg 4 times daily) in terms of time to CMV viraemia or viruria. Although valaciclovir (8 g/day for approximately 30 weeks) reduced the incidence and time to CMV disease compared with aciclovir (3.2 g/day) in patients with advanced HIV disease, valaciclovir was associated with more gastrointestinal complaints and an increased risk of death, leading to premature termination of the study. As yet, no trials comparing the efficacy of valaciclovir with famciclovir (the oral prodrug for penciclovir) in the suppression of recurrent episodes of genital herpes have been published, nor have direct comparisons been made, between valaciclovir with ganciclovir in patients with CMV disease. Valaciclovir is well tolerated at dosages used to suppress recurrent episodes of genital herpes (500 to 1000 mg/day) in immunocompetent and HIV seropositive individuals, with headache being reported most often. However, a potentially fatal thrombotic microangiopathy (TMA)-like syndrome has been reported in some immunocompromised patients receiving high-dose prophylactic valaciclovir therapy (8 g/day) for CMV disease for prolonged periods, and the risk of this syndrome appears to be higher in patients with advanced HIV disease. While the clinical benefits of valaciclovir in some immunocompromised patients may outweigh the risk of TMA, close monitoring for symptoms of TMA is indicated in all immunocompromised patients receiving high-dose valaciclovir. Conclusion: Oral valaciclovir is an effective drug for the suppression of recurrent episodes of genital herpes in immunocompetent and immunocompromised individuals. (ABSTRACT TRUNCATED)     

Epidemiology and therapy of Chlamydia trachomatis infections

Chlamydia trachomatis infections are exceedingly prevalent, and can be associated with significant sequelae. The major infections are urethritis, cervicitis, salpingitis, and ocular infection. Chlamydial genital infections present as syndromes, where C. trachomatis is one of the causes of the syndrome. Because specific laboratory diagnosis of a chlamydial infection is often not available, and even if available does not exclude the concurrent presence of other pathogens, therapy should usually be directed at all the major causes of the syndrome. Thus, although C. trachomatis is readily eradicated by tetracyclines, macrolides, sulphonamides, and rifampicin, for most situations tetracyclines are the drugs of choice. Penicillins have some activity when used in multiple-dose therapy, but are not reliable for eradication of chlamydiae. Aminoglycosides, nitroimidazoles, and the newer cephalosporins have minimal or no useful activity. Seven days of tetracycline hydrochloride 500mg 4 times daily or doxycycline 100mg twice daily are the optimum regimens for uncomplicated urethritis, cervicitis (except in pregnancy), and gonorrhoea. These regimens should be extended to 10 days for epididymitis and salpingitis. Additional antimicrobials should be added to the salpingitis regimen. For chlamydial infection during pregnancy, erythromycin 500mg 4 times daily for 1 week or 250mg 4 times daily for 2 weeks should be utilised. Neonatal infection requires 2 to 3 weeks of systemic treatment with erythromycin. Inclusion conjunctivitis responds well to antimicrobials, but improved sanitation has a greater effect than antimicrobial therapy in the management of trachoma.     

Management of cryptococcal meningitis in patients with AIDS

A case of cryptococcal meningitis in a patient with the acquired immunodeficiency syndrome (AIDS) is described, as well as the epidemiology, pathogenesis, clinical manifestations, diagnosis, and therapeutic management of the disease. In July 1987 a 38-year-old white man was admitted to the hospital because of confusion, disorientation, and headache. His medical history was notable for a positive human immunodeficiency virus test. Culture of the cerebrospinal fluid was positive for Cryptococcus neoformans. The patient was started on amphotericin B 16 mg/day (0.3 mg/kg/day) intravenously and flucytosine 2 g every six hours (150 mg/kg/day) orally. Despite premedication with diphenhydramine and acetaminophen, he experienced rigors that were treated with hydrocortisone and meperidine. Three weeks later he was discharged on flucytosine 2 g orally every six hours and amphotericin B 50 mg intravenously every other day. One week later the patient developed fever and chills; blood cultures were positive for methicillin-sensitive Staphylococcus aureus, and his peripheral leucocyte count was 1.8 X 10(3)/cu mm. Flucytosine was discontinued, and he was treated with intravenous nafcillin while remaining on amphotericin B. In October the patient complained of nausea, vomiting, weakness, and agitation. A CSF latex agglutination titer for cryptococcal antigen was 1:32. He was treated with amphotericin B 50 mg daily until symptoms resolved and then continued on amphotericin B 50 mg twice weekly. Cryptococcosis is the most common life-threatening fungal infection among AIDS patients. In contrast to immunocompetent hosts, this population invariably develops disseminated disease, with 85% having meningeal involvement. The most effective therapy for cryptococcal meningitis in patients with AIDS has not been established.(ABSTRACT TRUNCATED AT 250 WORDS)     

含铋剂序贯疗法治疗幽门螺杆菌感染的疗效观察

目的:评价10 d含铋剂序贯疗法与常规序贯疗法及四联疗法对初次根除幽门螺杆菌(H.pylori)失败后补救治疗的疗效。方法:经胃镜下快速尿素酶试验或14C-尿素呼气试验确诊为H.pylori阳性的患者,用标准一线治疗方案进行H.pylori根除治疗,停药4周后行14C-尿素呼气试验,结果仍为阳性者判定为H.pylori根除失败。将初次根除失败的患者随机分为3组,A组:前5 d,雷贝拉唑10 mg、阿莫西林1 g、果胶铋300 mg;后5 d,雷贝拉唑10 mg、克拉霉素0.5 g、奥硝唑0.5 g、果胶铋300 mg。B组:前5 d,雷贝拉唑10 mg、阿莫西林1 g;后5 d,雷贝拉唑10 mg、克拉霉素0.5 g、奥硝唑0.5 g。C组:雷贝拉唑10 mg、果胶铋300 mg、阿莫西林1 g、呋喃唑酮0.1 g,疗程10 d,所有药物均口服,bid。治疗结束4周后复查14C-尿素呼气试验。结果:采用按意向性治疗(intention-to-treat,ITT)分析和按符合方案(per protocol,PP)分析对H.pylori根除率进行评价。A、B、C 3组H.pylori ITT根除率分别为92.3%、74.4%、75.0%,PP根除率分别为94.7%、78.4%、78.9%,2种分析方法均显示A组H.pylori根除率明显高于B、C 2组,差异有统计学意义(P<0.05),而B组与C组间根除率差异无统计学意义(P>0.05)。A组和B组不良反应发生率(5.3%、5.4%)低于C组(21.1%),但差异无统计学意义(P>0.05)。结论:10 d含铋剂序贯疗法可作为H.pylori一线根除治疗失败后安全有效的补救治疗方案。     

Role of sulphydryl-containing agents in the management of recurrent attacks of ulcerative colitis. A new approach.

This double-blind randomised study investigated the role of sulphydryl-containing agents in the management of recurrent attacks of ulcerative colitis. To this end, DL-cysteine (200 mg 4 times daily) and DL-methionine-methyl sulphonium chloride (MMSC, 500 mg 4 times daily) were administered orally. Patients with recurrent attacks of moderate proctosigmoidal ulcerative colitis, despite prophylaxis by oral sulphasalazine (2 g daily), were given prednisolone by mouth, 10 mg four times a day, sulphasalazine by mouth, 500 mg four times a day, and morning and evening retention enema (Predsol 20 mg) alone or with cysteine or MMSC. After 2 weeks of treatment with sulphasalazine and prednisolone, 51% of patients (n = 45) were symptom free. Addition of cysteine (n = 46) or MMSC (n = 47) to this regimen controlled the symptoms within 2 weeks in 85% of patients (p < 0.01). During 12 months of prophylactic treatment, 5% of patients (n = 42) receiving sulphasalazine (2 g daily) and cysteine and 5% of patients (n = 41) taking sulphasalazine (2 g daily) and MMSC relapsed, relative to 27% of cases with sulphasalazine (2 g daily) alone (p < 0.01). These results demonstrate that sulphydryl-containing agents play a key role in the treatment of and protection against ulcerative colitis.     

High eradication rates of Helicobacter pylori with a new sequential treatment

BACKGROUND: Eradication rates of Helicobacter pylori with standard triple therapy are disappointing, and studies from several countries confirm this poor performance. AIM: To assess the eradication rate of a new sequential treatment regimen compared with conventional triple therapy for the eradication of H. pylori infection. METHODS: One thousand and forty-nine dyspeptic patients were studied prospectively. H. pylori-infected patients were randomized to receive 10-day sequential therapy [rabeprazole (40 mg daily) plus amoxicillin (1 g twice daily) for the first 5 days, followed by rabeprazole (20 mg), clarithromycin (500 mg) and tinidazole (500 mg) twice daily for the remaining 5 days] or standard 7-day therapy [corrected] [rabeprazole (20 mg), clarithromycin (500 mg) and amoxicillin (1 g) twice daily]. H. pylori status was assessed by histology, rapid urease test and 13C-urea breath test at baseline and 6 weeks or more after completion of treatment. RESULTS: Higher eradication rates were found with the sequential regimen compared to the standard regimen (intention-to-treat: 92% vs. 74%, P < 0.0001; per protocol: 95% vs. 77%, P < 0.0001). Higher eradication rates were also seen in patients with peptic ulcer disease and non-ulcer dyspepsia. In both treatments, compliance was similar (> 90%), as was the rate of side-effects, which were mild. CONCLUSIONS: This 10-day sequential treatment regimen achieves high eradication rates in peptic ulcer disease and non-ulcer dyspepsia.     

多巴丝肼过量致左侧肢体不随意运动

1例46岁男性患者因帕金森病服用多巴丝肼治疗,最初剂量为125 mg、3次/d,服用1年。因症状进行性加重,自行服用250 mg、4次/d,服用1.5年。之后,患者欲完全控制症状,再次自行将多巴丝肼剂量调整至125 mg/1.5 h(每日剂量达1375 mg)。约3个月后出现发作性左侧肢体不随意运动,停用多巴丝肼后上述症状逐渐减轻。停药第4天起再次给予患者多巴丝肼250 mg、4次/d口服,左侧肢体不自主抽动逐渐减少,1周后肢体抽动症状未发作。随访3个月未发作肢体不随意运动。     

A phase II trial of oral etoposide with mitoxantrone and ifosfamide/mesna consolidated with intravenous etoposide,methylprednisolone, high-dose arabinoside,and cisplatin as salvage therapy for relapsing and/or refractory lymphomas

SummaryPurpose To evaluate the response to oral Etoposide when combined with mesna, ifosfamide, and mitoxantrone in patients with relapsed and/or refractory lymphoma. To evaluate response and its duration after administration of intravenous Etoposide, methylprednisolone, high-dose cytosine arabinoside, and cisplatin (ESHAP) as consolidation therapy after complete or partial responses (CR or PR, respectively) or after crossover therapy for progressive disease.Methods Patients received MINE(o) consisting of mesna, 1.33 g/m² infused over 1 hour daily × 3 followed 4 hours later by oral mesna at 500 mg; ifosfamide, 1.33 g/m² infused over 1 hour daily × 3; mitoxantrone, 8 mg/m² intravenously on day 1, and oral VP-16, 30 mg/m² daily × 13. The ESHAP regimen consisted of intravenous VP-16, 40 mg/m² infused over 2 hours daily × 4; methylprednisolone, 500 mg intravenously daily × 4; cytosine arabinoside, 1.5 g/m² infused over 3 hours on day 4; and cisplatin, 25 mg/m² given as a continuous 24-hour infusion daily × 4. Statistical analysis was performed using the 2-stage design described by Simon. For the oral VP-16 regimen to be of interest, at least 36% patients had to achieve a complete remission.Results The overall response rate achieved with MINE(o) was 40% (15% CR, 25% PR). Seven patients with prior exposure to cytosine arabinoside and cisplatin (AP) received MINE(o) alone of whom only one achieved a response (CR). Thirteen patients without prior exposure to AP received consolidation (2 patients) or crossover (11 patients) therapy with ESHAP. Crossover therapy with ESHAP further improved the response in only two of five patients with partial response to MINE(o) and none of six patients who failed MINE(o). Median response duration for the patients who received MINE(o)/ESHAP was 12 weeks (range, 4–55 weeks).Conclusions Oral VP-16 combined with ifosfamide/mesna and mitoxantrone at the doses and schedules indicated has little activity against relapsed and/or refractory lymphomas. Crossover therapy with ESHAP did not further improve the response rate. The duration of response after MINE(o)/ESHAP was short.     

Esomeprazole: a review of its use in the management of acid-related disorders in the US

Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor to be developed as a single optical isomer. It provides better acid control than current racemic proton pump inhibitors and has a favourable pharmacokinetic profile relative to omeprazole. In large well designed 8-week trials in patients with erosive oesophagitis, esomeprazole recipients achieved significantly higher rates of endoscopically confirmed healed oesophagitis than those receiving omeprazole or lansoprazole. Esomeprazole was effective across all baseline grades of oesophagitis; notably, relative to lansoprazole, as the baseline severity of disease increased, the difference in rates of healed oesophagitis also increased in favour of esomeprazole. In two trials, 94% of patients receiving esomeprazole 40mg once daily achieved healed oesophagitis versus 84 to 87% of omeprazole recipients (20mg once daily). In a study in >5000 patients, respective healed oesophagitis rates with once-daily esomeprazole 40mg or lansoprazole 30mg were 92.6 and 88.8%. Resolution of heartburn was also significantly better with esomeprazole than with these racemic proton pump inhibitors. Long-term (up to 12 months) therapy with esomeprazole effectively maintained healed oesophagitis in these patients. Esomeprazole 20 or 40mg once daily for 4 weeks proved effective in patients with symptomatic gastro-oesophageal reflux disease (GORD) without oesophagitis. Eradicating Helicobacter pylori infection is considered pivotal to successfully managing duodenal ulcer disease. Ten days' triple therapy (esomeprazole 40mg once daily, plus twice-daily amoxicillin 1g and clarithromycin 500mg) eradicated H. pylori in 77 to 78% of patients (intention-to-treat) with endoscopically confirmed duodenal ulcer disease. Esomeprazole is generally well tolerated, both as monotherapy and in combination with antimicrobial agents. The tolerability profile is similar to that of other proton pump inhibitors. Few patients discontinued therapy because of treatment-emergent adverse events (<3% of patients) and very few (<1%) drug-related serious adverse events were reported. CONCLUSIONS: Esomeprazole is an effective and well tolerated treatment for managing GORD and for eradicating H. pylori infection in patients with duodenal ulcer disease. In 8-week double-blind trials, esomeprazole effectively healed oesophagitis and resolved symptoms in patients with endoscopically confirmed erosive oesophagitis. Notably, in large (n >1900 patients) double-blind trials, esomeprazole provided significantly better efficacy than omeprazole or lansoprazole in terms of both healing rates and resolution of symptoms. Long-term therapy with esomeprazole effectively maintained healed oesophagitis in these patients. Esomeprazole was also effective in patients with symptomatic GORD. Thus, esomeprazole has emerged as an effective option for first-line therapy in the management of acid-related disorders.     

Antibiotic-resistant H. pylori infection and its treatment

Helicobacter pylori infection causes progressive damage to gastric mucosa and results in serious disease such as peptic ulcer disease, MALT lymphoma, or gastric adenocarcinoma in 20% to 30% of patients. The current approach is to make a firm diagnosis, give combination antibiotic and antisecretory therapy, and confirm that the infection has been cured 4 to 6 weeks later. Antimicrobial resistance is largely responsible for treatment failures. Resistance to metronidazole can frequently be overcome by increasing the dose and duration of treatment with acid suppression. Clarithromycin is the most effective antibiotic against H. pylori but, unfortunately, resistance to it is increasing and can not be overcome by increasing the dose or duration of therapy with clarithromycin. The choice of therapy should be based on local susceptibility patterns. Re-treatment regimens for treatment failure should exclude antibiotics where acquired resistance is expected (i.e., clarithromycin and possibly metronidazole). Where available, treatment failure should prompt endoscopy and culture and susceptibility testing. Overall, higher doses and longer durations of treatment result in the best cure rates. When multiple treatment regimens fail, salvage therapy regimens such as bismuth or furazolidone quadruple therapy (a bismuth and tetracycline HCl 4 times a day along with a proton pump inhibitor twice a day, and either metronidazole 400 or 500 mg three times daily or furazolidone 100 mg three times daily for 14 days) can be used. Newer agents are needed to cope with the increasing prevalence of antibiotic resistance among H. pylori.     

One-week ranitidine bismuth citrate in combinations with metronidazole, amoxycillin and clarithromycin in the treatment of Helicobacter pylori infection: the RBC-MACH study

BACKGROUND: We have previously shown that ranitidine bismuth citrate (RBC)-based triple therapy is comparable to proton pump inhibitor-based triple therapy in eradicating Helicobacter pylori infection. AIM: To test the efficacy of different combinations of antimicrobials with RBC in the treatment of H. pylori infection. METHODS: Dyspeptic patients with H. pylori infection were prospectively randomized to receive one of the following regimens: (i) RBC 400 mg, amoxycillin 1 g, clarithromycin 500 mg [RAC]; (ii) RBC 400 mg, metronidazole 400 mg, clarithromycin 500 mg [RMC]; (iii) RBC 400 mg, metronidazole 400 mg, tetracycline 1 g [RMT] (all given twice daily for 1 week); or (iv) RBC 400 mg plus clarithromycin 500 mg twice daily for 2 weeks [RC-2]. Endoscopy (rapid urease test and culture) and 13C-urea breath test (UBT) were performed before randomization. Four weeks after finishing medication, the 13C-UBT was repeated in all cases and endoscopy was offered to patients with peptic ulcers. RESULTS: Four hundred patients were randomized but in two (one in the RAC group and one in the RMC group) H. pylori infection was not confirmed. Successful eradication of H. pylori (intention-to-treat analysis and 95% CI) of RAC (86% [79-93%]), RMC (90% [84-96%]), RMT (79% [71-87%]) and RC-2 (82% [75-90%]) were comparable, with a trend favouring clarithromycin-containing triple therapy regimens. Among 276 isolates tested for antibiotic sensitivity, primary resistance to metronidazole, clarithromycin and amoxycillin was found in 56%, 2% and 0.4%, respectively. When given RMC or RMT, patients infected by metronidazole-resistant H. pylori had success in eradicating H. pylori similar to patients infected by metronidazole-sensitive H. pylori. CONCLUSION: One-week RBC triple therapy is effective in curing H. pylori infection.     

Rabeprazole-based 3-day and 7-day triple therapy vs. omeprazole-based 7-day triple therapy for the treatment of Helicobacter pylori infection

BACKGROUND: Rabeprazole is a new proton pump inhibitor with more potent acid suppressive and anti-Helicobacter effects. AIM: To compare two different regimens of rabeprazole-based triple therapy vs. 7-day omeprazole-based triple therapy for the eradication of Helicobacter pylori infection. METHOD: Patients with proven H. pylori infection were randomized to receive: (i) 7-day rabeprazole, 10 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily; (ii) 3-day rabeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily; or (iii) 7-day omeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily. Endoscopy (CLO test, histology) was performed before randomization and 6 weeks after drug treatment. RESULTS: One hundred and seventy-three patients were randomized. H. pylori eradication rates (intention-to-treat, n=173/per protocol, n=167) were 88%/91% for 7-day rabeprazole-based therapy, 72%/72% for 3-day rabeprazole-based therapy and 82%/89% for 7-day omeprazole-based therapy, respectively. The per protocol eradication rate was significantly better in the 7-day rabeprazole-based therapy and 7-day omeprazole-based therapy groups when compared to the 3-day rabeprazole-based therapy group (P=0.01 and P=0.04, respectively). Compliance was excellent and all three regimens were well tolerated. CONCLUSIONS: The efficacy of seven-day rabeprazole-based triple therapy is similar to 7-day omeprazole-based triple therapy for the eradication of H. pylori infection.     

Esomeprazole: a review of its use in the management of acid-related disorders

Esomeprazole (S-isomer of omeprazole), the first single optical isomer proton pump inhibitor, generally provides better acid control than current racemic proton pump inhibitors and has a favourable pharmacokinetic profile relative to omeprazole. In a large well designed 8-week trial in patients (n >5000) with erosive oesophagitis, esomeprazole recipients achieved significantly higher rates of endoscopically confirmed healed oesophagitis than those receiving lansoprazole. Respective healed oesophagitis rates with once-daily esomeprazole 40mg or lansoprazole 30mg were 92.6 and 88.8%. Overall, esomeprazole was also better than omeprazole, although these differences were not always statistically significance. Ninety-two to 94% of esomeprazole recipients (40mg once daily) achieved healed oesophagitis versus 84 to 90% of omeprazole recipients (20mg once daily). Esomeprazole was effective across all baseline grades of oesophagitis; notably, relative to lansoprazole, as baseline severity of disease increased, the difference in rates of healed oesophagitis also increased in favour of esomeprazole. Resolution of heartburn was also significantly better with esomeprazole 40mg than with these racemic proton pump inhibitors. Long-term (up to 12 months) therapy with esomeprazole effectively maintained healing in these patients. Once-daily esomeprazole 20 or 40mg for 4 weeks resolved symptoms in patients with symptomatic gastro-oesophageal reflux disease (GORD) without oesophagitis. Symptoms were effectively managed in the long-term with symptom-driven on-demand esomeprazole (20 or 40mg once daily). Eradicating Helicobacter pylori infection is considered pivotal to successfully managing duodenal ulcer disease. Seven days' treatment (twice-daily esomeprazole 20mg plus amoxicillin 1g and clarithromycin 500mg) eradicated H. pylori in >/=86% of patients (intention-to-treat), a rate that was similar to equivalent omeprazole-based regimens. Esomeprazole is generally well tolerated, both as monotherapy and in combination with antimicrobial agents, with a tolerability profile similar to that of other proton pump inhibitors. Few patients discontinued therapy because of treatment-emergent adverse events (<3% of patients), with very few (<1%) drug-related serious adverse events reported. CONCLUSIONS: Esomeprazole is an effective, well tolerated treatment for managing GORD and for eradicating H. pylori infection in patients with duodenal ulcer disease. In 8-week double-blind trials, esomeprazole healed oesophagitis and resolved symptoms in patients with endoscopically confirmed erosive oesophagitis and overall, provided better efficacy than omeprazole. Notably, in a large (n >5000 patients) double-blind trial, esomeprazole 40mg provided significantly better efficacy than lansoprazole in terms of healing rates and resolution of symptoms. Long-term therapy with esomeprazole maintained healed oesophagitis in these patients. Esomeprazole also proved beneficial in patients with symptomatic GORD without oesophagitis. Thus, esomeprazole has emerged as an option for first-line therapy in the management of acid-related disorders.     

Clinical outcomes and cost minimization with an alternative dosing regimen for meropenem in a community hospital

STUDY OBJECTIVE: To compare outcomes and cost for the traditional United States Food and Drug Administration-approved dosing regimen for meropenem versus an alternative dosing regimen providing similar pharmacodynamic exposure with a lower total daily dose. DESIGN: Retrospective cohort study with a cost-minimization analysis. SETTING: A 417-bed, privately owned community hospital. PATIENTS: One hundred patients who received meropenem 1 g every 8 or 12 hours (traditional dosing regimen) between January 1 and September 30, 2004 (historical controls), and 192 patients who received meropenem 500 mg every 6 or 8 hours (alternative dosing regimen) between October 1, 2004, and September 30, 2005. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical data were collected for all patients. Cost-minimization analysis was performed by using the drug acquisition cost for meropenem. Demographics, sources of infection, distributions of organisms, and Charlson Comorbidity Index scores were similar between patients in the traditionally and alternatively dosed groups. Concomitant therapy, duration of therapy, success rates, lengths of stay, and in-hospital mortality rates were also similar between groups. Median time to the resolution of symptoms was 3 days for traditional dosing and 1.5 days for alternative dosing (p<0.0001). A logistic regression model including the dosing strategy showed that only polymicrobial infections and sepsis were associated with increased failure rates. The median cost for antibiotics was $439.05/patient for traditional dosing and $234.08/patient for alternative dosing (p<0.0001). CONCLUSION: An alternative dosing regimen for meropenem with a lower total daily dose yielded patient outcomes, including success rates and duration of therapy, equivalent to those of the traditional dosing regimen. Alternative dosing decreased total drug exposure, costs for antibiotics, and time to the resolution of infections.     

Hypothyroidism complicated by angina pectoris: therapeutic approaches.

The association of hypothyroidism and coronary artery disease is not uncommon. The precipitation of angina pectoris, cardiac arrhythmia, and even myocardial infarction may occur in patients when initiating rapid replacement therapy for hypothyroidism. This is particularly true when replacement therapy is instituted in elderly persons or in patients with preexisting coronary artery disease. A starting daily dose of 12.5 to 25 micrograms and increments of 25 micrograms every 2 to 3 weeks is recommended. Close monitoring of cardiac symptoms is essential to avoid side effects. Medical management of angina pectoris includes administration of beta-blockers, nitrates, or at times combination antianginal therapy may be most effective. Persistence of angina in these patients may require coronary angiography with subsequent angioplasty or coronary artery bypass surgery.     

Addition of metronidazole to omeprazole/amoxycillin dual therapy increases the rate of Helicobacter pylori eradication: a double-blind, randomized trial

Aims: To compare the efficacy, safety and tolerability of an omeprazole/amoxycillin (OA) dual therapy Helicobacter pylori eradication regimen with an omeprazole/amoxycillin/metronidazole (OAM) triple therapy regimen. Methods: In this double-blind trial, conducted in 19 hospitals, 119 patients with symptomatic duodenal ulcer disease were randomized to receive either 14 days treatment with omeprazole 40 mg daily, amoxycillin 500 mg t.d.s. and placebo followed by a further 14 days’treatment with omeprazole 20 mg daily (n= 59) or 14 days treatment with omeprazole 40 mg daily, amoxycillin 500 mg t.d.s., and metronidazole 400 mg t.d.s., followed by a further 14 days’treatment with omeprazole 20 mg daily (n= 60). H. pylori status was assessed by ¹³C-urea breath test at entry and at 4 weeks post-treatment. Results: H. pylori infection was eradicated in 46% of the OA treated patients and in 92% of the OAM treated patients, a mean difference of 46% (P < 0.0001, 95% CI for the difference: + 30 to + 62). In only one patient was the duodenal ulcer not endoscopically healed after 4 weeks of treatment (OA 100%; OAM 98% healed). There were no significant differences in speed of symptom relief or improvement in symptoms between the two groups. Both regimens were well tolerated, with 96% of patients completing the course, and only one patient withdrawing due to an adverse event. The only side-effect with a significantly higher incidence in the OAM group was diarrhoea, which occurred in 36% of patients compared to 16% of patients in the OA group (P < 0.05). Conclusions: A regimen consisting of omeprazole 40 mg daily, amoxycillin 500 mg t.d.s. and metronidazole 400 mg t.d.s. for 14 days gives an appreciably higher H. pylori eradication rate than omeprazole and amoxycillin alone, with acceptable tolerability.     

东方胃药联合标准三联疗法与含铋剂四联疗法治疗Hp相关性胃炎及消化性溃疡患者临床疗效对比分析

目的观察东方胃药联合标准三联疗法对幽门螺杆菌H.pylori(Hp)感染的根除率以及合并Hp感染的消化性溃疡的疗效,并与铋剂四联疗法进行对比。方法采用前瞻性随机对照研究,研究对象为伴有Hp感染的慢性胃炎或消化性溃疡的患者。(1)Hp相关性胃炎共123例:东方胃药组(A组,61例)和铋剂四联组(B组,62例)。A组给予东方胃药4粒/次,3次/d,口服,联合标准三联药物:埃索美拉唑20 mg,阿莫西林1 000 mg,克拉霉素500 mg, 2次/d,口服;B组给予枸橼酸铋钾600 mg,联合标准三联药物。两组疗程均为14 d,治疗结束并停药4周复查¹³C尿素呼气试验。(2)合并Hp感染的消化性溃疡共101例:东方胃药组(a组,51例)和铋剂四联组(b组,50例)。a组给予东方胃药4粒/次,3次/d,口服,联合标准三联药物,14 d,第15天起东方胃药4粒/次,3次/d,埃索美拉唑20 mg, 1次/d,口服;b组给予枸橼酸铋钾600 mg联合标准三联药物,14 d,第15天起瑞巴派特100 mg, 3次/d,埃索美拉唑20 mg, 1次/d,口服。两组疗程均为4周,...