OBJECTIVE: The present study aimed to measure the agreement between BAT and immunoassay in diagnosis of penicillin allergy.
METHOD: BAT was performed using penicillin G (Pen G), penicillin V (Pen V), penicilloyl-polylysine (PPL), minor determinant mix (MDM), amoxicillin (Amx) and ampicillin (Amp) in 25 patients. Immunoassay of total IgE (tIgE) and specific IgE (sIgE) antibodies to Pen G, Pen V, Amx and Amp were quantified. Skin prick test (SPT) using PPL-MDM, Amx, Amp and Clavulanic acid were also performed.
RESULTS: Minimal agreement was observed between BAT and immunoassay (k=0.25). Of two BAT-positive patients, one patient is positive to Amx (59.27%, SI=59) and Amp (82.32%, SI=82) but sIgE-negative to all drug tested. This patient is also SPT-positive to both drugs. Another patient is BAT-positive to Pen G (10.18%, SI=40), Pen V (25.07%, SI=100) and Amp (19.52%, SI=79). In sIgE immunoassay, four patients were sIgE-positive to at least one of the drugs tested. The sIgE level of three patients was between low and moderate and they were BAT-negative. One BAT-positive patient had a high level of sIgE antibodies (3.50-17.5kU/L) along with relatively high specific to total IgE ratio ≥0.002 (0.004-0.007).
CONCLUSIONS: The agreement between BAT and immunoassay is minimal. Performing both tests provides little increase in the sensitivity of allergy diagnosis work-up for immediate reactions to penicillin.
METHODS: We selected randomized controlled trials, assessing efficacy of antibiotics for the treatment of leptospirosis as a case study. A pairwise meta-analysis was conducted using a random effect model, assuming that different studies assessed different but related treatment effects. The analysis was then extended to a network meta-analysis, which consists of direct and indirect evidence in a network of antibiotics trials, using a suite of multivariate meta-analysis routines of STATA (mvmeta command). We also assessed an assumption of 'consistency' that estimates of treatment effects from direct and indirect evidence are in agreement.
RESULTS: Seven randomised controlled trials were identified for this analysis. These RCTs assessed the efficacy of antibiotics such as penicillin, doxycycline and cephalosporin for the treatment of human leptospirosis. These studies made comparisons between antibiotics (i.e. an antibiotic versus alternative antibiotic) in the primary study and a placebo, except for cephalosporin. These studies were sufficient to allow the creation of a network for the network meta-analysis; a closed loop in which three comparator antibiotics were connected to each other through a polygon. The comparison of penicillin versus the placebo has the largest contribution to the entire network (31.8%). The assessment of rank probabilities indicated that penicillin presented the greatest likelihood of improving efficacy among the evaluated antibiotics for treating leptospirosis.
CONCLUSIONS: Findings suggest that network meta-analysis, a meta-analysis comparing multiple treatments, is feasible and should be considered as better precision of effect estimates for decisions when several antibiotic options are available for the treatment of leptospirosis.
METHODS: Nine healthy normotensive subjects participated in this randomized placebo-controlled two-way crossover study examining the effects of 5 days' pretreatment of nafcillin 500 mg or placebo four times daily on the pharmacokinetics of an oral dose of nifedipine 10 mg. Plasma nifedipine concentrations were measured by gas chromatography-mass spectro.
RESULTS: The area under the plasma nifedipine concentration-time curve (AUC0-alpha) in nafcillin-pretreated subjects (80.9 +/- 32.9 micro g l-1 h-1) was significantly decreased compared with subjects who received only nifedipine (216.4 +/- 93.2 micro g l-1 h-1) (P < 0.001). Total plasma clearance of nifedipine (CL/F) was significantly increased with nafcillin pretreatment (138.5 +/- 42.0 l h-1 vs 56.5 +/- 32.0 l h-1) (P < 0.002).
CONCLUSIONS: The results show that nafcillin pretreatment markedly increased the clearance of nifedipine and suggest that nafcillin is a potent inducer of CYP enzyme.
PATIENTS: Patients selected had unequivocal evidence of H. pylori infection based on the urease test, culture and histology and had either peptic ulcer disease or non-ulcer dyspepsia.
DESIGN: The study was a comparative and double-blind study and patients were randomized to receive either amoxycillin 750 mg t.i.d. and metronidazole 500 mg t.i.d. for 12 days or amoxycillin 1000 mg b.i.d. and metronidazole 500 mg b.i.d. for 12 days. Both groups also received famotidine 40 mg for 6 weeks.
MAIN OUTCOME MEASURE: Patients were assessed for successful eradication, defined as absence of bacteria in all tests, at least 4 weeks after completion of antibiotic therapy by repeat gastroscopy.
RESULTS: One hundred and twenty-nine patients were recruited for the study. Two patients defaulted follow-up, two patients were withdrawn from the study and six patients were found to be non-compliant with medications. The eradication rates of the t.i.d. regimen was higher than the b.i.d. regimen (per protocol (PP) analysis: 83.3% (50/60) vs. 76.3% (45/59), P=0.337; intention-to-treat (ITT) analysis: 78.5% (51/65) vs. 75.0% (48/64), P=0.642). Seventy-five patients had pre-treatment cultures checked for metronidazole resistance, 33 (44.0%) were found to be resistant. Acquired resistance occurred in 3/40 (7.5%) patients. Eradication rates of metronidazole-sensitive and metronidazole-resistant patients: t.i.d. regimen - 100% (17/17) and 88.2% (15/17), b.i.d. regimen - 19/21 (90.5%) and 11/15 (73.3%). Side effects were reported in up to 70% of patients but were mild and tolerable in the majority. Two patients were withdrawn from the study because of a fixed drug eruption in one and generalized macular rash in the other.
CONCLUSION: Combination amoxycillin and metronidazole is effective in eradicating H. pylori. There was a tendency for the t.i.d. regimen to be better than the b.i.d. regimen and for metronidazole-resistant infections to be associated with a lower eradication rate but these differences did not reach statistical significance.
DESIGN: Prospective study.
PATIENTS AND METHODS: Patients were followed up endoscopically at 3, 6, 12 and 24 months after successful H. pylori eradication and duodenal ulcer healing. H. pylori status was determined by culture, rapid urease test, Gram's stain of a fresh tissue smear and histological examination of antral biopsies and rapid urease test and histological examination of corpus biopsies.
MAIN OUTCOME MEASURES: Duodenal ulcer healing, H. pylori reinfection.
RESULTS: Thirty-eight patients with duodenal ulcer disease (35 active, 3 healed) had successfully eradicated H. pylori following treatment with omeprazole/amoxycillin (n = 11), omeprazole/amoxycillin/metronidazole (n = 16) and colloidal bismuth subcitrate/ amoxycillin/metronidazole (n = 11). All patients with active duodenal ulcer had healed ulcers at the end of therapy. Thirty-five of 38 patients were seen according to schedule up to 2 years; two patients were seen up to 12 months and one up to 6 months only. Reinfection with H. pylori was not recorded in any of our patients. Shallow duodenal ulcers were noted in three patients at 1-year follow-up, two of whom admitted to taking non-steroidal anti-inflammatory drugs (NSAIDs); H. pylori status was negative in all three. Subsequent follow-up revealed spontaneous healing of the ulcers in all three patients. At 2 years, one patient whose H. pylori status was negative had recurrence of duodenal ulcer. All of the three patients who defaulted subsequent to follow-up were negative for H. pylori and had healed ulcers on follow-up endoscopy at 6 and 12 months.
CONCLUSION: Reinfection rate with H. pylori was zero in a group of South-East Asian patients who had successfully eradicated the infection. Duodenal ulcer relapse was also low (2.9%) in this group of patients at 2 years.