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.
CONCLUSION: Although cefepime-induced thrombocytopenia is rare, clinicians should be alert to this potential adverse effect among critically ill patients.
MATERIALS AND METHODS: Febrile neutropenic patients treated between January 1996 and December 1997 at the pediatric oncology unit of University Hospital, Kuala Lumpur, were prospectively studied. Empirical antibiotic therapy consisted of ceftazidime and amikacin. Those who developed K. pneumoniae bacteremia were identified, and clinical features analyzed. Ceftazidime-resistance was documented via disk-diffusion testing. Production of extended-spectrum beta-lactamase (ESBL) was inferred on the basis of synergy between ceftazidime and amoxicillin-clavulanic acid. The different features between the two groups and variables associated with the development of CRKP bacteremia were analyzed using chi-square and t-tests and calculation of odds ratios. A multivariate analysis was used to identify independent factors for CRKP development.
RESULTS: Ceftazidime-resistance was seen in 51.6% of all K. pneumoniae isolates, and all these isolates were inferred to be ESBL producers. All isolates were sensitive to imipenem. Susceptibility to gentamicin was 90.5%. The mean continuous hospital stay prior to the detection of bacteremia was 13.7 days overall, but significantly longer in the CRKP group (21.9 d) compared to the CSKP group (4.3 d) (P = 0.003). Children with CRKP were more likely to have received antibiotics in the 2 weeks prior to detection of bacteremia (87.5% of cases) than the CSKP group (20.0% of cases) (P = 0.0008). Sepsis-related mortality was higher in those with CRKP (50.0%) than in the CSKP group (13.3%) (P = 0.02). Patients who did not receive CRKP-directed antibiotics within 48 hours of admission were more likely to have a fatal outcome than those who did (P = 0.009). Logistic regression analysis identified use of third-generation cephalosporins 2 weeks prior to presentation and a hospital stay of 2 weeks or more as independent risk factors for development of CRKP.
CONCLUSIONS: More than half of total K. pneumoniae isolated from blood cultures in the unit were ceftazidime-resistant. Children with febrile neutropenia with prolonged hospital stay and recent prior antibiotic exposure are at high risk of developing CRKP bacteremia. Mortality was significantly higher in this group. Early commencement of appropriate antibiotics (e.g., imipenem with or without gentamicin), according to susceptibility study results, may be beneficial in such circumstances.
METHOD: We created an iontophoresis cell; 3% CF was inserted within medullary segment of goat bone and sealed from external saline solution. The cell operated at the following voltages 30, 60 and 90 V and at the following durations 5, 10, 15, 20, 25 and 30 min. Information regarding optimal conditions for its application was then obtained. After which, correlation between voltages and time with CF concentration in the bone was analysed. A bioavailability test was also conducted to observe the optimal rate of CF elution from the graft.
RESULT: The optimal condition for the impregnation process is 3% CF at 90 V for 10 min. Bone graft impregnated with CF at optimal conditions can elute above minimum inhibitory concentration of the CF against MRSA for 21 days.
CONCLUSION: CF iontophoresis was found feasible for allograft impregnation. The technique is simple, inexpensive and reproducible clinically. Iontophoresis offers a novel solution to reduce the rate of perioperative infection in reconstructive surgery involving use of bone graft.
METHODS: PMMA pellets were prepared with three separate concentrations of each of the two antibiotics tested. They were tested to determine the effect of increasing concentration of antibiotics on the biomechanical properties of PMMA and antibiotic activity by measuring the zone of inhibition and broth elution assay.
RESULTS: Ceftaroline PMMA at 3 wt%, three-point bending was 37.17 ± 0.51 N ( p < 0.001) and axial loading was 41.95 N ± 0.51 ( p < 0.001). At 5-wt% vancomycin-PMMA, three-point bending was 41.65 ± 0.79 N ( p = 0.02) and axial loading was 49.49 ± 2.21 N ( p = 0.01). Stiffness of ceftroline-loaded PMMA in low and medium concentration was significantly higher than the vancomycin. The zone of inhibition for ceftaroline was higher than vancomycin. Ceftaroline at 3 wt% eluted up to 6 weeks (0.3 ± 0.1 μg/ml) above the minimum inhibitory concentration (MIC) and vancomycin at 2.5 wt% eluted up to 3 weeks, same as MIC, that is, 0.5 ± 0.0 μg/ml.
CONCLUSIONS: Ceftaroline, loaded at similar concentrations as vancomycin into PMMA, is a more potent alternative based on its more favourable bioactivity and elution properties, while having a lesser effect on the mechanical properties of the cement. The use of 3-wt% ceftaroline as antibiotic laden PMMA against MRSA is recommended. It should be noted that this was an in vitro study and to determine the clinical efficacy would need prospective, controlled and randomized studies.