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@Christian Kurts - really fascinating work! What do you think would happen in the case of a high salt diet coupled with increased water intake? Would it still increase corticosterone and promote pyelonephritis?
@Christian Kurts - one approach to reducing UTI risk (which has little evidence to support it) is to acidify the urine - do you have any data on the effect of acidification of the urine on UTI-associated immune responses?
Great idea. We did not try it yet. Perhaps we will
I am sure the corticosterone would still be increased and suppress neutrophils. But we think that flushing Bugs by drinking lots of water is more important. So probably you can repair a high salt diet by drinking a lot. However, this applies only to bacterial infection, not potential adverse cardiovascular effects
In adults urine colony counts are often less than 10*5, don't think such data exist in kids.
@naider shaikh - for the 16S, how did you classify the likelihood of UTI when multiple organisms were identified?
might not 16s broaden our definition of "uropathogen"?
@naider shaikh- interesting data, but if one was to use 16S to clarify whether kids with culture-based “possible UTI” truly have a UTI, it seems like it doesn’t accelerate time to diagnosis (versus if only 16S was performed in a “same day” manner and treatment based on 16S findings)
@Nader Shaikh Thank you for your interesting presentation. Would you think based on your results it is worthwhile for future studies to have a broader look at uropathogens maybe include viruses as those children without a laboratory confirmed UTI did have symptoms and signs of inflammation?
In adults, urine culture more of benefit as far as abx susceptibility, since culture results don't help us that much in dx as empiric rx started before available. Since 30%+ of cultures in symptomatic woman will grow less than 10*5 cfu/ml, even down to 10*1, a "no growth" culture result can be a function of the reporting rules in the laboratory. If one actually quantified to lower colony counts, the correlation with 16s probably higher for the culture group "possible UTI"
Hi Mike. On your question about 16S definitions, we ignored relative abundance <50% for this quick and dirty analysis. Regarding practicality of 16S, yes, you are right right now practical yet.
Dr. Hooton, You ask a difficult question about how 16S might change the gold standard for diagnosis UTI. Right now we do not know whether the taxa uncovered by 16S are truly pathogens. I think over time, when there are more studies of asymptomatic healthy individuals, it will become a bit more clear. So right now we are trying to collect data that eventually may lead to a clearer idea of how to incorporate this data in diagnosis of UTI. I feel that it is like being on a plane where you are trying to design the landing gear as you are up in the air! I think you are right about increased concordance if we used lower cutoff for the urine culture. One issue with this is that many labs don’t identify organisms present if CFU <10,000. The issue of sensitivities is an important one, especially in adult patients where resistance is high. I know some companies are working on 16S panels that also test for presence of genes that confer resistance to frequently used antibiotics.
Dr. de Vroom: How useful is the AUC/MIC ratio clinically if so many with normal dosing are below 125 ratio?
Suzanne de Vroom
Two studies were published that showed delay of treatment of infections when AUC/MIC was not attained, but it is indeed a limitation. We need more studies investigating clinical endpoints and PK/PD ratio’s, such as AUC/MIC. But, right now it is the best evidence we have
How did your patients with altered renal function do clinically in the study?
Suzanne de Vroom
We found no difference in mortality and re-admission to the hospital or days of fever
Suzanne de Vroom
But it was quite hard to differentiate, since many patients received other antibiotics as well or got source control of their infections, that influenced clinical outcome as well.
We unfortunately cannot see all the attendees questions, as the chat default setting is “to panelists”
Numbers in study low of course, but maybe the AUC/MIC ratio that people have used is set too high. I forget the data that supported this ratio as being optimal.
Dr Kuil, I think you are right about the importance of looking for viruses. Seems like a good area to explore