All right, our next speaker is Nasser Mohamed, who will be speaking about the rise of Acinetobacter gumani, a meta-analysis on the role of intrathecal antimicrobial therapy in reduction of mortality. Good afternoon. I'm Nasser Mohamed. I'm a postdoctoral fellow in the Department of Neurosurgery at Louisiana State University in Shreveport. I'll be talking about the rise of infections due to Acinetobacter gumani in postneurosurgical infections. So in the recent decades, the postneurosurgical infections due to multidrug-resistant organisms have shown a significant rise throughout the world. And this period has already been called as the post-antibiotic era. It was almost more than a decade back when Alexander Fleming accidentally discovered penicillin in his laboratory, and that was the golden era of antibiotics, wherein there was a domination of antibiotics over the microbes, and we could deal with most of these infections. And now there has been a resurgence of resistance, and most of these resistances are becoming multidrug resistances, and this has become a serious problem in the critical care management of postneurosurgical infections. And in particular, the study that I'm speaking about is about the infection because of Acinetobacter gumani. Of course, there are many other multidrug-resistant organisms, like we have Klebsiella, we have tuberculosis. They're also causing a great deal of concern at the present moment. Acinetobacter was actually discovered from the soil. It was a benign organism with low virulence. Almost not much of a thought was given to it until it started acquiring multidrug resistance, and now it's in the foremost concern in the critical care management of patients because of the high rates of mortality because of this infection. And various studies have shown that the mortality because of Acinetobacter gumani can range anywhere between 15 to 72 percent. Some studies showing very high mortality because of this infection. And the emergence has been documented all across the world, and from North America, Argentina, Brazil, China, Taiwan, outbreaks of neurosurgical infections in Taiwan, Hong Kong, and even remote islands like Tahiti also have demonstrated, have shown infections due to Acinetobacter gumani, which are multidrug-resistant. Multidrug resistance is clinically defined as resistance to three or more antibiotics. And of interest, it's also been noted in post-war injury wounds, especially in Iraq. The Iraqi soldiers have been infected with Acinetobacter gumani, and which were actually multidrug-resistant. And it was actually nicknamed as Iraqi bacteria because of this epidemic of infections occurring in these military setup in these particular situations. So it's basically an evolutionary arms race where there is an urgent need to review, evaluate, and find new ways to tackle this difficult problem. Right now, we're dealing with multidrug-resistant, and already there are reports of pan-drug-resistant organisms being reported across. And to have a culture sensitivity report which shows no sensitivity to any of the known antibiotics is definitely a worrying trend, especially in a neurosurgical ICU, and where we just have to probably wait and watch for these patients and support them without having proper antibiotics to support. So this study wanted to look at the intrathecal administration of antibiotics and how it would affect the mortality in this subset of patients who are suffering from Acinetobacter gumani infections. And this was basically intravenous therapy, which was augmented with an intrathecal therapy, and it compared the outcomes, which was the mortality rate, with just intravenous therapy, just patients which received just intravenous therapy. And we tried to review the benefit of these, and the outcome was mortality. And we generated a detailed literature search with an inclusion-exclusion criteria and a statistical methodology which was developed. The guidelines were in accordance with the PRISMA protocol. And the inclusion criteria was basically post-neurosurgical infections, where patients who had undergone neurosurgical procedure and who had subsequently developed a neurosurgical infection due to Acinetobacter gumani. And we conducted a meta-analysis in this review using a random effects model. So out of the total literature review, we could isolate five studies with a total of 126 patients who had post-surgical neurosurgical Acinetobacter gumani infection. And we divided them into two groups. One was the IV group, which received only intravenous therapy, and the other group received both intravenous as well as intrathecal antimicrobial therapy. So there were 75 patients with the only intravenous group and 53 patients belonging to the intravenous and intrathecal group. The mean duration of intravenous therapy was 27 days, and the duration of intramentricular therapy was 21 days. And the dose ranged from 125,000 intrathecine units to 250,000 intrathecine units per day. We could locate 92 studies in the literature which dealt with this subject. But after exclusion of the studies which matched to our criteria, we could isolate only five studies which had both the control group as well as the intervention groups. And each of these studies had a small number of patients, and the purpose of this study was to pool in all the data and to find out a significant association in terms of the benefit with mortality and intravenous therapy. And also, most of these patients actually were operated for traumatic brain injury, subarachnoid hemorrhage, intracerebral hemorrhage, and brain tumors. And some of the studies also had external ventricular drains placed in their patients. And the mortality of all the included studies ranged widely from 27% to as high as 78%. And we performed a random effects model meta-analysis on this, and this is a forest plot that demonstrates the results that we obtained. Here we are seeing the intravenous plus intrathecal group, and here we look at the intravenous group only and the events are the mortality or the deaths that have occurred. And on this side, this is the forest plot that demonstrates the length of the line demonstrates the confidence interval, and the area of the square also reflects the amount of patients that were there in each of the study. What the meta-analysis does is it weighs in the studies, individual studies, giving them weightage based on the number of patients in each study. The studies which have low patients are given less weightage as compared to studies which have more weightage, and calculates the odds ratio. And surprisingly, the most significant result that we obtained was we obtained an odds ratio of 1.16, which is a very significant odds ratio for reduction in death rate for patients who received intravenous plus intrathecal therapy. So that would, in other words, translate into almost an 84% lesser odds of dying in patients who have actually received both intravenous and intrathecal therapy compared to those patients who just received intravenous therapy. This is very significant because most of the studies have shown, some of the studies have not shown significant importance, while some studies have shown serious improvement in mortality, in reduction in mortality after intrathecal therapy. But this meta-analysis just showed that there is definitely an overall very significant trend in reduction of mortality with use of intrathecal therapy, especially for acinobacter omani infections in post-neurosurgical patients. And what has happened now is that the discarded, once discarded antibiotics are being brought back into clinical scenario today because of the rise of multidrug resistance. One of the most important antibiotics for treating acinobacter omani infections is cholesterol. And cholesterol is usually a large molecule. It works on the cell membranes, causing damage to the cell membrane, displacing the calcium and phosphate from the cell membrane, destabilizing the cell membrane. And it was actually a highly nephrotoxic antibiotic, which was taken out of clinical practice. But now it is being increasingly used because of the emergence of acinobacter omani. There are many issues about why intrathecal therapy could be so dramatic in terms of reducing the mortality, especially when we're using colistin, because colistin is a large molecule. It doesn't cross the blood-brain barrier as easily as it could. And after intravenous therapy, the CSF concentration might be just less than 5% of the blood concentrations. And pharmacokinetics of the antibiotic plays a very important role as far as the treatment strategy for meningitis and post-neurosurgical infections taken into consideration. So in situations of clinical non-improvement with systemic therapy, it is prudent to get an intrathecal access or intramental access and commence the intrathecal therapy. Traditionally, in cases of post-neurosurgical infections, which do not respond to systemic therapy, people start to give intrathecal therapy as a last resort for it. But with this study, we really want to question whether we would want to begin this intervention upfront. Even in this study, there were eight patients who had actually died despite receiving intravenous and intrathecal therapy. There could be several reasons for their death. The one reason is the timing of the antibiotic. Although the studies do not mention the timing of when the therapy was started, but it could be hypothesized that there could be a delay in starting intrathecal therapy, which could actually impact the overall survival of these patients. And if sensitivity is demonstrated in colistin, then intrathecal therapy should be considered at the earliest. This study is a meta-analysis of retrospective study, which has its own limitations. There's a small number of patients. Of course, the data which is available itself is new and it's upcoming. There are outbreaks occurring. And as such, it is important to realize that what this study is pointing towards is that the reduction of mortality is very significant and should be considered strongly in terms of that. Further questions like optimum intraventricular dosage, duration of the dosage, when it needs to be started, and also the treatment for pan-drug-resistant organisms needs to be given a serious concern right now. So in conclusion, there's a substantial reduction in mortality in patients who receive a combination of intraventricular plus intrathecal therapy versus those that receive only intravenous therapy. And intrathecal therapy should be strongly considered in post-neurosurgical patients who are having multidrug-resistant acinobacter infections. And I would also like to conclude with a statement from Charles Darwin. And I think what we are actually seeing is actually natural selection being played out in the neurocritical ICUs. And it is actually a race, an evolutionary arms race, where the organisms are trying to survive. And the survival being changed with respect to the mortality of disinfections now is more on towards the human side compared to what it was before. So I think the natural selection and the principles of natural selection is what this study actually is drawing our attention to about the process. Thank you. So I've got a quick question for you. So I learned recently that gentamicin has a pH of 3. So I've sort of rethought a little bit using that intrathecally. I'm curious for your thoughts on other antibiotics in terms of intrathecal administration. The gentamicin and amino glycosides do not have a great penetration into the CSF compared to cephalosporins and the carbapenems. And the penetration to CSF is dependent on many factors. The dependent pH depends upon the size of the molecule, depends upon the charge of the molecule. And intrathecal therapy has been utilized in many clinical scenarios whenever there's been a, and several antibiotics have been tried for this particular purpose. Vancomycin has been tried, gentamicin has been tried. And even in cases where there's been no clinical improvement, carbapenems have been tried intrathecally. But as far as gentamicin, I'm not so aware of the details of that particular antibiotic. Fair enough. All right, thank you very much.

Nasser Mohamed

Acinetobacter gumani

post-neurosurgical patients

multidrug-resistant organisms

intrathecal antimicrobial therapy