Methods: We searched PubMed, Embase and the Cochrane register of trials systematically for studies that examined treatment options for patients with MDR- and XDR-AB infections until April 2016. Network meta-analysis (NMA) was performed to estimate the risk ratio (RR) and 95% CI from both direct and indirect evidence. Primary outcomes were clinical cure and microbiological cure. Secondary outcomes were all-cause mortality and nephrotoxic and non-nephrotoxic adverse events.
Results: A total of 29 studies with 2529 patients (median age 60 years; 65% male; median APACHE II score 19.0) were included. Although there were no statistically significant differences between treatment options, triple therapy with colistin, sulbactam and tigecycline had the highest clinical cure rate. Colistin in combination with sulbactam was associated with a significantly higher microbiological cure rate compared with colistin in combination with tigecycline (RR 1.23; 95% CI 1.03-1.47) and colistin monotherapy (RR 1.21; 95% CI 1.06-1.38). No significant differences in all-cause mortality were noted between treatment options. Tigecycline-based therapy also appeared less effective for achieving a microbiological cure and is not appropriate for treating bloodstream MDR- and XDR-AB infections.
Conclusions: Combination therapy of colistin with sulbactam demonstrates superiority in terms of microbiological cure with a safety profile similar to that of colistin monotherapy. Thus, our findings support the use of this combination as a treatment for MDR- and XDR-AB infections.
METHODS: This was a descriptive cross-sectional study undertaken in the Hospital Universiti Sains Malaysia from April 2011 to March 2012. S. maltophilia isolated from various clinical specimens were included in the study. Antimicrobial susceptibility testing was done using the epsilometer test (E-test) and interpreted according to the guidelines of the Clinical and Laboratory Standards Institute. In the synergy test, the isolates were tested against six different antimicrobial combinations.
RESULTS: In total, 84 S. maltophilia isolates were collected and analysed. According to the E-test, the antimicrobial susceptibility of trimethoprim-sulfamethoxazole (TMP-SMX), tigecycline, and ciprofloxacin was 100%, 91.1%, and 88.9% respectively. The antimicrobial combination of TMP-SMX and ceftazidime showed the highest synergistic effect.
CONCLUSION: TMP-SMX remains the antimicrobial of choice to treat S. maltophilia infection. TMP-SMX and ceftazidime was the most effective combination in vitro.
OBJECTIVE: To study the neuroprotective effect of minocycline via different routes in adult Sprague Dawley rats with brachial plexus injury.
METHODS: The C7 nerve roots of the animals were avulsed via an anterior extravertebral approach. Traction force was used to transect the ventral motor nerve roots at the preganglionic level. Intraperitoneal and intrathecal minocycline (50 mg/kg for the first week and 25 mg/kg for the second week) were administered to promote motor healing. The spinal cord was harvested six weeks after the injury, and structural changes following the avulsion injury and pharmacological intervention were analysed.
RESULTS: Motor neuron death and microglial proliferation were observed after the administration of minocycline via two different routes (intraperitoneal and intrathecal) following traumatic avulsion injury of the ventral nerve root. The administration of intraperitoneal minocycline reduced the microglia count but increased the motor neuron count. Intrathecal minocycline also reduced the microglial count, with a greater reduction than in the intraperitoneal group, but it decreased the motor neuron count.
CONCLUSIONS: Intraperitoneal minocycline increased motor neuron survival by inhibiting microglial proliferation following traumatic avulsion injury of the nerve root. The inhibitory effect was augmented by the use of intrathecal minocycline, in which the targeted drug delivery method increased the bioavailability of the therapeutic agent. However, motor neuron survival was impaired at a higher concentration of minocycline via the intrathecal route due to the more efficient method of drug delivery. Microglial suppression via minocycline can have both beneficial and damaging effects, with a moderate dose being beneficial as regards motor neuron survival but a higher dose proving neurotoxic due to impairment of the glial response and Wallerian degeneration, which is a pre-requisite for regeneration.