METHODOLOGY: One hundred and ninety-one episodes of fever and neutropenia in 128 patients from October 1997 to December 1998 were included in a prospective, open-label, single-centre study. Patients were randomly assigned to either treatment group and evaluated as successes or failures according to defined criteria. Daily assessments were made on all patients and all adverse events recorded. Univariate and multivariate analysis of outcomes and a cost analysis were carried out.
RESULTS: There were 176 evaluable patient-episodes with 51.1% in the single-daily ceftriaxone-amikacin group and 48.9% in the ceftazidime-amikacin group. There were 50 positive blood cultures: 12 Gram-positive bacteria, 33 Gram-negative bacteria and five fungi. Pseudomonas aeruginosa (P. aeruginosa) accounted for 14% of total isolates. The overall success rate was 55.5% in the ceftriaxone group compared to 51.2% in the ceftazidime group (P = 0.56). Mean time to defervescence was 4.2 days in the single-daily group and 4.3 days in the thrice-daily group. There were nine infection-related deaths; five in the single-daily ceftriaxone group. The daily cost of the once-daily regime was 42 Malaysian Ringgit less than the thrice-daily regime. There was a low incidence of adverse effects in both groups, although ototoxicity was not evaluable.
CONCLUSIONS: The once-daily regime of ceftriaxone plus amikacin was as effective as the 'standard' combination of thrice-daily ceftazidime and amikacin with no significant adverse effects in either group. The convenience and substantial cost benefit of the once-daily regime will be particularly useful in developing countries with limited health resources and in centres with a low prevalence of P. aeruginosa.
METHODS: We investigated the ocular permeation of topical tazocin after single drop application in normal rabbit eyes by estimating piperacillin and tazobactam concentrations in cornea, aqueous, and vitreous using a validated LC-MS/MS method. Furthermore, we determined the efficacy of repeated dose administration of tazocin against experimentally induced P. aeruginosa keratitis in rabbits in comparison to moxifloxacin. To determine the efficacy, clinical examination, histopathological examination, and estimation of bacterial load and inflammatory cytokines in cornea were done.
RESULTS: Significant corneal concentration of piperacillin and tazobactam was detected in normal rabbit corneas after single dose treatment with tazocin. In rabbits with Pseudomonas-induced keratitis, topical tazocin caused significant clinical and histopathological improvement. This improvement was associated with reduction in corneal bacterial load and inflammatory cytokines. Compared to moxifloxacin 0.5%, tazocin treated group showed greater clinical response which was associated with higher interleukin (IL)-1β, lower tumor necrosis factor (TNF)-α, a comparable level of IL-8, greater reduction in corneal bacterial load, and lesser inflammatory cell infiltration.
CONCLUSION: Tazocin showed good ocular penetration and was effective in treatment of Pseudomonas induced keratitis in rabbits.
METHODS: Demographic data, underlying diseases, procedures and details on polymyxin B therapy were retrospectively analyzed in a cohort of 84 patients who received intravenous polymyxin B in an intensive care unit from 2010 to 2014.
RESULTS: Polymyxin B was used to treat bacteremia (46.4% of cases) and pneumonia (53.6%). Majority of the pathogens isolated were Acinetobacter spp. (96.4%). The mortality rate was 48.8%, of which 82.9% was attributed to polymyxin B treatment failure. The independent predictors of treatment failure were low doses of polymyxin B (p = 0.002), shorter duration of therapy (p = 0.009), not combining with cefoperazone/sulbactam (p = 0.030), female gender (p = 0.004), administered for treatment of bacteremia (p = 0.023) and renal impairment (p = 0.021). Low polymyxin B doses (p = 0.007), not combining with cefoperazone/sulbactam (p = 0.024), female gender (p = 0.048) and renal impairment (p = 0.022) were also significant predictors for in-hospital mortality.
CONCLUSIONS: To the best of our knowledge, this is the first report on the association of inadequate dose of polymyxin B (<15,000 units/kg/day) with poor outcome in critically ill patients. Besides that, further clinical studies are warranted to evaluate the use of cefoperazone/sulbactam as second antibiotic in the combination therapy.
METHODS: A prospective quasi experimental study was conducted by enrolling 450 patients from tertiary care hospital of Lahore, Pakistan, 225 patients in each, control and intervention, arm using non-random convenient sampling. The study parameters included antibiotic indication, choice, dose, frequency, duration and associated costs. This study is registered with Chinese Clinical Trial Registry # ChiCTR-OON-17013246.
RESULTS AND CONCLUSION: After educational intervention, in post-intervention arm, total compliance in terms of correct antibiotic choice, dose, frequency and duration increased from 1.3% to 12.4%. The rate of inappropriate antibiotic choice did not change significantly. After intervention only metronidazole utilization decreased (16%) significantly (p=0.011). Significant reductions were observed in mean duration of antibiotic prophylaxis (17%, p=0.003), average number of prescribed antibiotics (9.1%, p=0.014) and average antibiotic cost (25.7%, p=0.03), with reduction in mean hospitalization cost (p=0.003) and length of stay (p=0.023). Educational intervention was significantly associated (OR; 2.4, p=0.005) with appropriate antibiotic prophylaxis. The benefit of pharmacist intervention, mean antibiotic cost savings to mean cost of pharmacist time, was 4.8:1. Thus, the educational intervention resulted in significant reductions in the duration and average number of antibiotic use having considerable effect on therapy and hospitalization cost.
METHODS USED TO CONDUCT THE REVIEW: This review was conducted in accordance with the Meta-analysis of Observational Studies in Epidemiology (MOOSE) recommendation. Electronic databases including MEDLINE, CINAHL, PubMed, Embase, Cochrane Databases and Cochrane Central Register of Controlled Trials were searched up to March 2017 for relevant trials. The methodological quality of included trials was assessed by using a modified version of the Newcastle-Ottawa Quality Assessment Scale for Case-Control and Cohort Studies. A meta-analysis was conducted using the random-effect model to combine the rate of mortality and length of stay outcomes.
FINDINGS OF THE REVIEW: Nine observational trials involving 2128 patients were considered eligible for inclusion. Although based on low quality evidence, there was a statistically significant difference in favour of the impact of de-escalation on hospital stay but not mortality (MD -5.96 days; 95% CI -8.39 to -3.52).
INTERPRETATIONS AND IMPLICATIONS OF THE FINDINGS: This review highlights the need for more rigorous studies to be carried out before a firm conclusion on the benefit of de-escalation therapy is supported.