The efficacy and safety of two oral moxifloxacin regimens compared to oral clarithromycin in the treatment of community-acquired pneumonia.

An international multi-centre, randomized, prospective, double-blind study compared oral moxifloxacin (200 mg or 400 mg once daily for 10 days) with oral clarithromycin (500 mg, twice daily for 10 days) in the treatment of community-acquired pneumonia (CAP). The clinical success rate in the evaluable population at the primary efficacy assessment, 3-5 days after the end of study treatment, was 93.9% in patients treated with 200 mg moxifloxacin; 94.4%, with 400 mg moxifloxacin; and 94.3%, with clarithromycin. Clinical success rates were maintained at follow-up, 21-28 days after the end of treatment: 90.7% (200 mg moxifloxacin), 92.8% (400 mg moxifloxacin) and 92.2% (clarithromycin). The 95% confidence intervals indicated that all three treatment regimens were equally effective in treating CAP. At follow-up, the 400 mg moxifloxacin dose had a slightly higher observed cure rate than the 200 mg moxifloxacin dose, but this was not statistically significant. The most frequently isolated pathogens were Streptococcus pneumoniae (42%), Haemophilus influenzae (19%), Haemophilus parainfluenzae (10%), Moraxella catarrhalis (6%), Klebsiella pneumoniae (5%) and Staphylococcus aureus (4%). The bacteriological success rate (eradication and presumed eradication) was 72.5% (29/40) for 200 mg moxifloxacin, 78.7% (37/47) for 400 mg moxifloxacin and 70.7% (29/41) for clarithromycin. The adverse event profile was comparable between the three treatment groups. Most adverse events, possibly or probably related to the study drug, were generally mild or moderate in severity and mostly related to the digestive system: diarrhoea, nausea and abdominal pain in 200 mg moxifloxacin patients; diarrhoea, liver function abnormalities and nausea in 400 mg moxifloxacin patients and liver function abnormalities, diarrhoea, nausea and taste perversion in clarithromycin patients. Study drugs were discontinued because of adverse events in 7/229 (3%) patients treated with 200 mg moxifloxacin, 11/224 (5%) with moxifloxacin 400 mg and 11/222 (5%) with clarithromycin. In all assessments, moxifloxacin was at least as effective clinically, and as well tolerated as clarithromycin in the treatment of CAP. Bacteriological success rates in moxifloxacin-treated patients were greater than those of clarithromycin. Moxifloxacin, given once daily, is free of many drug-drug interactions and requires no dosage adjustments in most renal hepatic deficient patients.     

Short-course moxifloxacin therapy for treatment of acute bacterial exacerbations of chronic bronchitis. The Bronchitis Study Group

Chronic bronchitis is common among adults and infectious exacerbations contribute considerably to morbidity and mortality. We aimed to compare the safety and efficacy of moxifloxacin to clarithromycin for the treatment of patients with acute bacterial exacerbations of chronic bronchitis (ABECB) using a prospective, randomized, double-blind, parallel group trial. Between November 21, 1996 and April 7, 1998, 936 patients with acute exacerbations of chronic bronchitis (AECB) were enrolled at 56 centers across the United States of which 491 (52%) had ABECB (i.e. pretherapy pathogen). Patients were randomized to either oral moxifloxacin 400 mg administer once daily, for either 5 or 10 days, or clarithromycin 500 mg bid for 10 days. For the purpose of study blinding, the patients taking moxifloxacin received placebo to maintain uniform dosing. The main outcome measures were bacteriological response at the end of therapy (post-therapy days 0-6) and follow-up (7-17 days post-therapy) visits, as well as overall clinical response, clinical response at the end of therapy and clinical response at follow-up. Two patient populations were analyzed: efficacy-valid (i.e., those with a pretherapy pathogen) and intent-to-treat (i.e., all subjects that took drug). In 420 efficacy valid patients with a pretherapy organism, overall clinical resolution was 89% for 5 days moxifloxacin vs. 91% for 10 day moxifloxacin vs. 91% for 10 day clarithromycin. Bacteriological eradication rates at the end of therapy were 94% and 95% for 5-day moxifloxacin and 10-day moxifloxacin, respectively, and 91% for the clarithromycin group. Eradication rates at follow-up were 89% and 91% for 5-day moxifloxacin and 10-day moxifloxacin respectively, and 85% for the clarithromycin group. Among 926 intent-to-treat patients (312 5-day moxifloxacin, 302 10-day moxifloxacin and 312 clarithromycin), drug-related events were reported for 26%, 30% and 35%, respectively. Moxifloxacin 400 mg once daily, as a 5 or 10 day regimen, was found to be clinically and bacteriologically equivalent to 10 day clarithromycin for the treatment of ABECB. Given its favorable safety and tolerability profile, moxifloxacin administered once daily for 5 days may be as effective and a more convenient treatment than a standard course of clarithromycin for patients with ABECB.     

Effectiveness of oral moxifloxacin in standard first-line therapy in community-acquired pneumonia.

Based on recent guidelines for the management of community-acquired pneumonia, this study was designed to evaluate the effectiveness of a new fluoroquinolone compared with standard antimicrobial regimens, in conditions relating as closely as possible to the real world setting. In this study, 564 patients were randomised to either oral moxifloxacin (400 mg o.d.) or to standard oral therapy (amoxicillin 1 g t.i.d. or clarithromycin 500 mg b.i.d. alone or in combination) for up to 14 days using a double-blind procedure. The choice between the three standard regimens was made by the clinician prior to randomisation. Clinical response, quality of life, symptoms, healthcare resources and safety were assessed. In the per-protocol population, clinical success was reported for 201 of 215 (93.5%) and 217 of 231 (93.9%) in the moxifloxacin and standard groups, respectively, at 7-10 days post-therapy. At 28-35 days follow-up, continued clinical cure was observed in 183 of 192 (95.3%) moxifloxacin and 207 of 221 (93.7%) standard groups. Drug-related adverse events were reported in 55 of 274 (20%) moxifloxacin and 86 of 279 (31%) standard patients with diarrhoea >5%. Oral moxifloxacin monotherapy was as effective as, and better tolerated than, optimal antibiotic strategy represented either by mono- or combination therapy (amoxicillin and/or clarithromycin) in community-acquired pneumonia management.     

Treatment of community-acquired pneumonia in outpatients: randomized study of clarithromycin alone versus clarithromycin and cefuroxime.

OBJECTIVE: To evaluate the efficacy of clarithromycin alone in comparison with the combination of clarithromycin and cefuroxime in the treatment of nonhospitalized patients with community-acquired pneumonia (CAP) in a Mediterranean population. METHODS: CAP was defined as the acute onset of fever (>38 degrees C) with pulmonary opacity on chest roentgenogram. The American Thoracic Society (ATS) criteria (1993) were used to decide on patient hospitalization. Ninety subjects, of whom 53 (59%) were men, with a mean age (+/-SD) of 38+/-15 years, were randomized: 45 received clarithromycin 500 mg b.i.d. orally for 14 days (CL group), and 45 received clarithromycin plus cefuroxime 500 mg b.i.d. orally for 7 days (CLCE group). Patients were monitored with clinical, radiological, and laboratory controls at 3 and 21 days. There were no significant differences between the two groups with regard to demographic, clinical, physical and laboratory data. RESULTS: The mean time to defervescence was 2.4+/-1.4 and 2.4+/-1.5 days, respectively. Chest roentgenogram clearance was complete in all cases, without statistically significant differences in the time to resolution between both arms. Side effects were mild (no significant differences between groups): 5 patients in the CL group and 3 in the CLCE group showed gastrointestinal symptoms. Two patients (2.2%), both in the CLCE group, needed hospital admission during follow-up, but all 90 patients showed an excellent outcome. A causative agent was determined in 25 cases (28%). Legionella pneumophila, Streptococcus pneumoniae, and Mycoplasma pneumoniae were the most frequent pathogens. CONCLUSION: Empirical treatment of outpatient CAP with clarithromycin can be considered adequate in the Mediterranean area, independently of the microbiological etiology. ATS criteria for admitting patients with CAP are appropriate in this population.     

Sequential IV/PO moxifloxacin treatment of patients with severe community-acquired pneumonia

BACKGROUND: IV/PO moxifloxacin was evaluated in the treatment of hospitalized patients with severe community-acquired pneumonia (CAP). METHODS: Data were pooled from two prospective, randomized studies. In the multinational study, patients received 7-14 days IV/PO moxifloxacin 400 mg QD or IV/ PO amoxicillin clavulanate 1200/625 mg TID +/- IV/PO clarithromycin 500 mg BID. In the North American study, patients received 7-14 days IV/PO moxifloxacin 400 mg QD, IV/ PO alatrofloxacin/trovafloxacin 200 mg QD, or IV/PO levofloxacin 500 mg QD. The primary endpoint was clinical success at the test-to-cure visit. Severe CAP was defined according to the 1993 ATS criteria. RESULTS: In the clinically valid population, clinical success rates were 88% (167/190) for moxifloxacin- and 83% (155/186) for comparator-treated patients (95% CI = -1.9%, 12.2%). Corresponding clinical success rates for the microbiologically valid population were 87% (59/68) and 84% (54/64), respectively (95% CI = 8.6%, 15.0%). A switch from IV to PO therapy was made by day 5 of therapy for 73% of moxifloxacin- vs. 60% of comparator-treated patients (P < 0.01). Clinical success rates were similar in a retrospective analysis using the revised 2001 ATS definition of severe CAP. Mortality rates were 6% (15/241) and 10% (24/238) in the moxifloxacin and comparator treatment groups, respectively. The incidence of drug-related adverse events was similar in both treatment groups. CONCLUSION: Sequential IV/PO moxifloxacin 400 mg QD is as safe and effective as other fluoroquinolones and a beta-lactam/macrolide combination for treating hospitalized patients with severe CAP.     

Cost analyses of community-acquired pneumonia from the hospital perspective

STUDY OBJECTIVES: Community-acquired pneumonia (CAP) is a widespread disease with important implications for health-care systems worldwide. This study investigated direct costs, treatment patterns, and outcomes associated with two patient cohorts hospitalized with CAP. DESIGN: The study design was naturalistic, prospective, and open. PATIENTS: The study enrolled 580 patients. Two hundred sixty-one patients were treated initially with IV moxifloxacin (45%, cohort M); the remaining 319 patients received nonstandardized treatment (cohort S). SETTING: Twenty-two hospitals in Germany. RESULTS: Clinical success rates were similar between treatment groups (cohort M, 242 of 256 patients, 95%; cohort S, 286 of 312 patients, 92%; p = 0.208). Mean +/- SD length of hospital stay was 10.8 +/- 5.2 days, with cohort M having a significantly shorter hospital stay (10.0 +/- 4 days) compared to cohort S (11.5 +/- 6 days; p < 0.001). Median of all direct costs was dollar 1,333 (minimum, dollar 127; maximum, dollar 9,488), with direct costs of dollar 1,250 in cohort M (minimum, dollar 372; maximum, dollar 9,488) and dollar 1,409 in cohort S (minimum, dollar 127; maximum, dollar 9,366) per treated episode of CAP (p = 0.066). CONCLUSIONS: Major determinants of costs were length of hospital stay and ICU admission, whereas costs for staff and hotel were major contributors to direct costs. Initial antibiotic therapy with moxifloxacin resulted in similar clinical efficacy and direct costs compared to nonstandardized therapy; however, patients treated with moxifloxacin benefited with an earlier hospital discharge.     

I.v. famotidine versus i.v. ranitidine: intragastric pH behavior in surgical intensive care patients

20 patients of a surgical intensive care unit were treated in a randomised double-blind fashion with i.v. famotidine 10 mg and i.v. ranitidine every 6-12 hours for maximally seven days. Both groups were comparable with respect to the grade of risk of stress-induced bleeding. With both H2-blockers (ranitidine and famotidine) the intragastric pH could be increased to 5.0 and more and kept constant at this level over the whole test period. The mean daily doses required were 22.3 mg for famotidine and 154.3 mg for ranitidine. Stress-induced bleeding as well as adverse reactions could not be observed in both treatment groups.     

Emergence of resistance to clarithromycin during treatment of disseminated cutaneous Mycobacterium chelonae infection: case report and literature review.

Results of in vitro susceptibility studies and one clinical trial have led to recommendations of clarithromycin monotherapy for the treatment of disseminated cutaneous Mycobacterium chelonae infections. We describe the case of a 65-year-old woman, immunocompromised by the use of chronic steroid therapy, who developed disseminated cutaneous infection with M. chelonae and failed clarithromycin monotherapy due to the development of drug resistance. In the relapse isolate we document the presence of a single point mutation at position 2058 in the gene coding for 23S rRNA peptidyltransferase regions, a mutation previously implicated in the development of resistance to clarithromycin. Two susceptible control isolates lacked the mutation. Three additional reports in the literature of patients developing recurrent skin lesions with clarithromycin-resistant M. chelonae following initial response to monotherapy are summarized. We demonstrate that clarithromycin monotherapy in patients with disseminated cutaneous infections can lead to clarithromycin resistance and therapeutic failure associated with a single point mutation at position 2058 of 23S rRNA.     

Allogeneic stem cell transplantation (BMT) for AML and MDS following i.v. busulfan and cyclophosphamide (i.v. BuCy)

Pretransplant conditioning therapy with i.v. BuCy followed by allogeneic hematopoietic stem cell transplantation (BMT) was investigated in a phase II trial in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). We gave i.v. Bu at a dose of 0.8 mg/kg every 6h x 16 doses, followed by Cy 60 mg/kg daily for 2 days. Twenty-six AML patients (18 males/eight females) were treated, only eight of whom were in CR1. The rest were either refractory to induction chemotherapy (four patients) or in a more advanced stage of their disease (14 patients). In addition, nine patients with MDS (1M/8F) were treated. Their median age was 41 years (range 21-64). Engraftment to > or =500 neutrophils/microl was reached at 14 days (range 10-29 days) post BMT, and the median time of neutropenia was only 11 days (range 4-28 days). The most common regimen-related toxicity was grade 2-3 nausea. In the post-BMT period (including BMT day +30), two patients died, one each from pulmonary hemorrhage secondary to CMV pneumonia and hepatic veno-occlusive disease (VOD), for an early treatment-related mortality (TRM) of 5.7%. Three patients developed VOD and two of them died. There was no direct regimen-related pulmonary or neurologic toxicity. Overall, the clinical side-effect spectrum was analogous to what would be expected from a high-dose oral Bu-based regimen; there was no unique toxicity experienced with the used solvent system. The disease-free survival in the high-risk subgroup (all patients not in CR1) at 1 and 2 years post transplant was 44% and 31%, respectively. The 13 patients still alive in CR have been followed for a median of 24 months (range 18-32). Pharmacokinetic analysis showed very good interdose reproducibility, and limited interpatient variability in area under the plasma concentration vs time curve, peak concentration, and clearance of Bu after this i.v. formulation. We conclude, that this new i.v. Bu formulation is well tolerated; it has an impressive safety profile, and we suggest that it should be considered as appropriate replacement for oral busulfan in pretransplant conditioning therapy prior to allogeneic BMT for patients with AML or MDS.     

A brief review of moxifloxacin in the treatment of elderly patients with community-acquired pneumonia (CAP)

Community-acquired pneumonia (CAP) remains a common cause of morbidity and a potentially life-threatening illness throughout the world mainly in elderly patients. Initial antibacterial treatment, usually empirical, should be as effective as possible in order to assure rapid clinical resolution and reduce high rates of hospitalization and mortality especially affecting aged patients. New fluoroquinolones with potent activity against the most important respiratory pathogens including Streptococcus pneumoniae, a key pathogen mainly in old patients with CAP, have been recently suggested by several international guidelines as monotherapy for the treatment of most CAP patient categories. Among newer derivatives, moxifloxacin, an advanced generation 8-methoxy quinolone, has demonstrated good clinical and bacteriological efficacy in large, well designed clinical trials both in adults and old patients with CAP, achieving also in aged people efficacy comparable with that of standard treatments. Good pharmacokinetic characteristics such as excellent penetration into respiratory tract tissues and fluids, optimal bioavailability, simplicity of once-daily dosing, and good tolerability, represent potential advantages of moxifloxacin over other therapies. In addition, primarily due to a shorter length of hospital stay, moxifloxacin has been shown to save costs compared with standard therapy.     

Brain-specific expression of an exogenous gene after i.v. administration

The treatment of brain diseases with gene therapy requires the gene to be expressed throughout the central nervous system, and this is possible by using gene targeting technology that delivers the gene across the blood-brain barrier after i.v. administration of a nonviral formulation of the gene. The plasmid DNA is targeted to brain with pegylated immunoliposomes (PILs) using a targeting ligand such as a peptidomimetic mAb, which binds to a transporting receptor on the blood-brain barrier. The present studies adapt the PIL gene targeting technology to the mouse by using the rat 8D3 mAb to the mouse transferrin receptor. Tissue-specific expression in brain and peripheral organs of different exogenous genes (beta-galactosidase, luciferase) is examined at 1-3 days after i.v. injection in adult mice of the exogenous gene packaged in the interior of 8D3-PIL. The expression plasmid is driven either by a broadly expressed promoter, simian virus 40, or by a brain-specific promoter taken from the 5' flanking sequence of the human glial fibrillary acidic protein (GFAP) gene. The transgene is expressed in both brain and peripheral tissues when the simian virus 40 promoter is used, but the expression of the exogenous gene is confined to the brain when the transgene is under the influence of the brain-specific GFAP promoter. Confocal microscopy colocalizes immunoreactive bacterial beta-galactosidase with immunoreactive GFAP in brain astrocytes. These studies indicate that tissue-specific gene expression in brain is possible after the i.v. administration of a nonviral vector with the combined use of gene targeting technology and tissue-specific gene promoters.     

莫西沙星治疗老年社区获得性肺炎的临床对照试验

目的评价莫西沙星在社区获得性肺炎（CAP）老年人群中的疗效和安全性。方法采用前瞻性设计,将100例老年病人随机分为治疗组（52例）和对照组（48例）,治疗组予莫西沙星片0．4g,po,qd,疗程14d。对照组于头孢呋新针2．5g,iv,bid,联用克拉霉素片0．25g,po,bid,疗程14d。或单用克拉霉素片5．0g,po,bid,疗程14d。统计分析治愈率、症状缓解时间、不良反应等。结果疗程结束后,治疗组和对照组治愈率分别为87％和88％,差异无显著意义（P〉0．05）。但在疗程早期（D3、D5）治疗组治愈率高于对照组有显著差异（P〈0．05）。治疗组多种症状（发热、咳嗽、痰液性状改善、胸痛等）缓解时间更短有显著意义（P〈0．01,P〈0.05）。不良反应少,均可耐受。本次试验病原体检出率低（27．9％）。结论莫西沙星治疗老年CAP病人临床疗效肯定,安全,给药方便。     

A multicenter study of grepafloxacin and clarithromycin in the treatment of patients with community-acquired pneumonia.

STUDY OBJECTIVES: To compare the efficacies of 10-day regimens of grepafloxacin (GFX) (Raxar or Vaxar; Glaxo Wellcome; Greenford, UK), 600 qd, and clarithromycin (CLA) (Klacid, Biaxin, or Klaracid; Abbott Laboratories; Chicago, IL), 500 mg bid, in patients with community-acquired pneumonia (CAP), on the basis of clinical response, including radiographic evidence, and bacteriologic efficacy. DESIGN: Phase IIIb, double-blind, double-dummy, randomized, prospective, parallel-group, comparative study conducted at 58 centers in 11 countries. PATIENTS AND SETTING: Adult patients with signs and symptoms of CAP that was confirmed by radiographic evidence and who did not require parenteral therapy were included in the study. ASSESSMENTS: Patients were assessed before treatment, during treatment, after treatment, and at follow-up (28 to 35 days after treatment completion). Clinical response was evaluated. Blood and sputum samples were cultured for bacterial pathogens, and serology testing was performed to detect atypical pneumonia. RESULTS: A total of 504 patients were enrolled into the trial: 251 were randomly assigned to receive GFX and 253 to receive CLA. In patients able to be clinically evaluated, clinical success rates at follow-up were 147 of 163 patients (90%) in the GFX group and 148 of 167 patients (89%) in the CLA group (95% confidence interval, -6% to 9%). Pretreatment pathogens were confirmed in 131 of 504 patients (26%), either by culture or serology testing, the primary pathogens being Streptococcus pneumoniae (22%), Haemophilus influenzae (17%), Mycoplasma pneumoniae (25%), and Chlamydia pneumoniae (11%). For patients able to be evaluated who had typical pathogens, bacteriologic success was achieved in 92% of the patients in each treatment group. For patients able to be evaluated who had atypical pathogens, 18 of 18 patients (100%) in the GFX and 23 of 26 patients (88%) in the CLA group had a successful clinical outcome. There were similar rates of adverse events in each group, resulting in 相似文献   

Q Fever pneumonia: are clarithromycin and moxifloxacin alternative treatments only?

Medical records of 77 patients with Q fever pneumonia that was serologically confirmed by enzyme-linked immunosorbent assay were studied to compare the clinical efficacy of doxycycline, clarithromycin, and moxifloxacin. The mean times to defervescence were 2.4 days for those receiving doxycycline, 1.9 days for those receiving clarithromycin, and 2.2 days for those receiving moxifloxacin. There were no interruptions of the regimens in any groups because of side effects, and outcome was favorable in all patients with no complications or relapses during follow-up. This efficacy of clarithromycin and moxifloxacin, together with their safety profiles, suggest that these alternative agents in the treatment of Q fever pneumonia could also be used as the first-line therapy.     

Role of fludarabine as monotherapy in the treatment of chronic lymphocytic leukemia

Fludarabine is a synthetic adenine nucleoside analog that is indicated for first- and second-line treatment of chronic lymphocytic leukemia (CLL). The recommended intravenous (i.v.) dosage regimen is 25 mg/m2 daily for 5 consecutive days, with treatment cycles repeated every 28 days. In treatment-na?ve patients with Binet stage B and C CLL, i.v. fludarabine produces superior responses to established first-line chemotherapies. Fludarabine produces a higher overall remission rate (60-70%) and longer progression-free survival (median approximately 20-30 months) than standard therapy with chlorambucil+/-prednisone and CAP (cyclophosphamide/doxorubicin/prednisone), and a comparable overall remission rate to CHOP (cyclophosphamide/vincristine/prednisone/doxorubicin). Fludarabine demonstrates high efficacy in both intermediate-risk (Rai stage I or II) and high-risk (Rai stage III or IV) patients. Furthermore, fludarabine is equally effective in younger (< or =65 years) and older (>65 years) patients. Fludarabine has significant activity as monotherapy in previously treated CLL, producing objective response rates of up to 94% in typically small-scale, noncomparative studies, with the majority of studies yielding rates of 30-60%. In a phase III multicenter study, the overall remission rate was significantly higher with fludarabine than with CAP (48 versus 27%) among the subset of treatment-refractory patients (n=96). For those patients who are refractory to or have relapsed following conventional chemotherapy (chlorambucil, CAP and CHOP), fludarabine can be considered the treatment of choice for second-line therapy. Moreover, patients with relapsed CLL may benefit from retreatment with fludarabine if they have previously demonstrated sensitivity to the drug. Standard-dose i.v. fludarabine has an established safety profile and comparable tolerability to anthracycline-based regimens (CAP and CHOP) in terms of its myelosuppressive and immunosuppressive effects, and offers the advantage of a markedly lower incidence of gastrointestinal effects (nausea/vomiting) and alopecia.     

Plasma levels and effects of salbutamol after inhaled or i.v. administration in stable asthma

The response and plasma levels of inhaled (0.15 mg.kg-1) and intravenous salbutamol (5 micrograms.kg-1) were studied in 12 patients who had previously been included in a study of acute severe asthma and were now in a stable phase. The maximal value for change (delta) in plasma salbutamol compared with the pretreatment value was higher after i.v. than after inhalation treatment (59 vs 30 nmol.l-1) but the areas under the curve (AUC) during 90 mins after treatment were similar for the two administration routes. The inter-individual differences in peak plasma salbutamol and AUC for delta plasma salbutamol were much greater after inhalation than after i.v. infusion. Immediately after treatment there was a greater increase in pulse rate (mean +17 vs +6 beats.min) and lower serum potassium level (mean -0.3 mmol.l-1) after i.v. than after inhalation treatment. The increase in peak expiratory flow (PEF) measured 90 min after the start of treatment (85 vs 31 l.min-1) and as AUC was significantly higher after inhalation than after i.v. treatment. Six patients had received i.v. treatment in the acute asthma study: in these patients delta PEF immediately after i.v. treatment was significantly lower in the stable situation (+49 vs +115 l.min-1). There was also a significant difference in the effect on the pulse rate immediately after i.v. treatment, with a decrease in the acute asthma and an increase in the stable asthma situation (-5 vs +16 beats.min-1).     

Haemodynamic dose-response effects of i.v. verapamil in coronary artery disease

As an aid to clinical therapeutic decisions, the haemodynamic dose-response effects following intravenous verapamil were evaluated in ten male patients with angiographically confirmed and stable coronary artery disease. Sitting at rest, following a control period with four i.v. boluses of saline, four equivalent boluses of verapamil (logarithmic cumulative dosage; 2, 4, 8 and 16 mg) were administered at four minute intervals; haemodynamic variables were recorded two to four minutes following each i.v. injection. The haemodynamic effects of the drug during upright bicycle exercise were evaluated by comparison of measurements made during a control steady-state exercise period with observations made at the same upright exercise workload (25 to 75 W) immediately following the maximum cumulative dose (16 mg). Following the four i.v. boluses, the plasma verapamil concentrations showed a log-linear increase (r = 0.82; p less than 0.001); the levels achieved (26 +/- 2 to 147 +/- 14 micrograms/l) were within the range at which substantial pharmacodynamic activity has been shown to be present. At rest, compared with control measurements after saline, these plasma concentrations of verapamil were associated with linear decreases in systemic vascular resistance (maximum delta SVR -720 dyne X s X cm-5/m2; p less than 0.01) and blood pressure (maximum delta MBP -8 mmHg; p less than 0.05) and linear increases in cardiac index (maximum delta CI +0.4 l/min/m2; p less than 0.05) and in pulmonary artery occluded pressure (maximum delta PAOP +3 mmHg; p less than 0.05). There was no significant trend of change in the heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oral moxifloxacin vs high-dosage amoxicillin in the treatment of mild-to-moderate, community-acquired, suspected pneumococcal pneumonia in adults

STUDY OBJECTIVES: Comparison of the efficacy and safety of moxifloxacin vs amoxicillin for treatment of mild-to-moderate, suspected pneumococcal community-acquired pneumonia (CAP) in adult patients. DESIGN: Multinational, multicenter, double-blind, randomized study. SETTING: Eighty-two centers in 20 countries (Argentina, Brazil, Chile, Croatia, Czech Republic, Estonia, France, Hong Kong, Hungary, Lithuania, Mexico, Portugal, Russia, Slovenia, South Africa, Spain, Turkey, Ukraine, United Kingdom, and Uruguay). PATIENTS: Four hundred eleven adults (inpatients or outpatients) with suspected pneumococcal CAP. INTERVENTIONS: Randomization 1:1 to moxifloxacin, 400 mg/d, or amoxicillin, 1,000 g tid, for 10 days. RESULTS: Primary efficacy parameter was clinical response, 3 to 5 days after therapy (end of therapy [EOT]) in the per protocol (PP) population (362 patients). The clinical success rate in the PP population was 91.5% (moxifloxacin) and 89.7% (amoxicillin; two-sided 95% confidence interval, -4.2 to 7.8%). The clinical cure rate in patients with proven pneumococcal pneumonia was similar in both treatment groups (87.8%). The bacteriologic success rate in 136 bacteriologically evaluable patients at the EOT was 89.7% (moxifloxacin) and 82.4% (amoxicillin). The bacteriologic success rate against Streptococcus pneumoniae was 89.6% (moxifloxacin) and 84.8% (amoxicillin). The frequency of adverse events was comparable in both treatment groups. Digestive symptoms were the most common drug-related adverse events in both treatment groups. CONCLUSIONS: Moxifloxacin was statistically at least as effective as high-dose amoxicillin for treatment of mild-to-moderate, suspected pneumococcal CAP. Moxifloxacin may be an alternative for empiric CAP treatment, especially in areas where multidrug resistance in S pneumoniae is sufficiently prevalent to preclude routine penicillin.     

The use of i. v. bisphosphonate in pregnancy-associated osteoporosis--case study.

OBJECTIVE: Diagnosis of pregnancy-associated osteoporosis is often delayed and therapeutic interventions insufficient. STUDY DESIGN: A 28-year-old patient (BMI=18.6) with no additional risks for osteoporosis experienced acute lumbosacral pain two months postpartum, while lactating. After conservative therapy, thoracic and lumbar spine were X-rayed: severe pregnancy-associated osteoporosis with vertebral fractures was diagnosed. 2-year treatment with i. v. bisphosphonate ibandronate was initiated (2 mg every 3 months) and calcium and vitamin D supplementation. RESULTS: Rapid improvement was observed. Conclusion: In cases with multiple fractures i. v. bisphosphonate leads to substantial decrease of symptoms and further fractures and significant increase of bone mass density (BMD). CONCLUSION: In severe cases of pregnancy-associated osteoporosis with multiple fractures i. v. biphosphonate therapy leads to a decrease of symptoms and fracture risk and an increase of bone mass density (BMD).     

Safety of i.v. administration of redback spider antivenom

It is unclear what the risk of allergic reactions is with appropriately given dilute i.v. redback spider antivenom (RBSAV). Ninety-five i.v. administrations of RBSAV referred from January 2001 to November 2006 were reviewed. All patients had local pain, 72% radiating pain, 57% diaphoresis and 39% systemic effects. Four patients (4%) had immediate systemic hypersensitivity reactions: none were severe, one was moderate and three mild. In 32 patients followed up for 2 weeks, three (10%) developed serum sickness. RBSAV given i.v. had a low reaction rate.