May 2018 (3/3): UTIs, FMT, and inoculum effects

Five days of nitrofurantoin is more effective than one dose of fosfomycin for the treatment of uncomplicated UTI. Nitrofurantoin happens to also be the most reliably effective antibiotic for UTI nationwide (this is including all bacteria causing UTI, which is still heavily weighted toward E.coli), and retrospective data from the VA shows it works just as well as other agents in men, so nitrofurantoin really ought to be our drug of choice unless there's a specific concern for early pyelonephritis, prostatitis, abscess, etc. 29710295

In patients with acute pyelonephritis requiring hospitalization, 7 days of antibiotics is non-inferior to 14 days of antibiotics and is associated with a shorter length of stay. Please don't routinely treat pyelonephritis with extended courses of antibiotics. 29768465

Enterococcus faecium exhibits an inoculum effect against daptomycin in an in vitro model, which can be overcome with higher doses (e.g. 10mg/kg equivalent) of daptomycin. This correlates well with the clinical data published a year or two ago showing that higher doses of daptomycin were associated with better clinical cure and lower mortality in enterococcal BSI. Beta-lactams including ampicillin, ceftaroline, and ertapenem appear to enhance the killing activity of daptomycin against E. faecium. The synergistic effect of combining beta-lactams and daptomycin has also been seen in vitro and in animal models of Staphylococcus aureus infections and is probably mediated by beta-lactam enhancement of daptomycin binding to bacterial cell membranes29760141

This in vitro study demonstrated that two strains of MDR Pseudomonas aeruginosa and Klebsiella pnuemoniae exert an inoculum effect against cefepime and meropenem, but not against ceftazadime-avibactam. Now, obviously this is very preliminary in vitro data, but these findings are interesting for two reasons. One, the presence of an inoculum effect may be an important determinant of the clinical outcome of high-burden infections with MDR gram-negative organisms. There is a precedent for this in gram-positive infections; the presence of an inoculum effect against cefazolin in some strains of MSSA has been associated with cefazolin treatment failures. Two, we see a lot of these MDR gram-negative infections in our critically ill septic ICU patients, and this is also the population for whom we often have to increase antibiotic dosing to achieve optimal serum drug levels because the patient has increased renal clearance and/or drug metabolism. Because the inoculum effect is essentially a problem that comes into play when you have an unfavorable ratio of drug to bugs, it may be an important factor in the ICU patient with a "normal inoculum" infection but slightly subtherapeutic antibiotic levels due to inadequate dosing. 29784837

CSF dialysis (extracorporeal filtration of CSF to remove yeasts) has been proposed as a one-time treatment for cryptococcal meningitis. The authors have demonstrated treatment efficacy in a rabbit model, wherein they were able to reduce the yeast concentration in CSF by 1.6log (about 97%) in a period of 4-6 hours. This is a very interesting idea that will probably be ready for clinical use when we're all just about to retire. 29788431

Long-term followup of patients treated with FMT for C.diff shows great efficacy and patient tolerability. At a mean 22 months of follow-up, 82% of patients had durable cure of their CDI, and 95% of FMT recipients would want the procedure again. Importantly, post-FMT antibiotic exposure was strongly associated with recurrence of CDI, and particularly so if that antibiotic was a cephalosporin, clindamycin, or quinolone (pooled OR for reccurence was 3.8). Eleven percent of FMT recipients reported improvement of a non-C.diff medical condition after FMT, which primarily related to improvements in other GI conditions related to the human microbiome (e.g. Crohns and IBS). However, 33% reported a worsening or new non-C.diff medical problem, the majority of which were new weight gain, and in fact the FMT recipients reported gaining a median 5lb after their treatments. This tracks with prior data (OK, prior case reports) suggesting that obesity may be transmissible via FMT and that lean stool donors should be preferred when possible. 29272401