Perusing the Literature

Inhibitor of the NDM Enzyme

Aspergillomarasmine (AMA) was identified as an inhibitor of the New Delhi Bangla_Sahib_New_Delhi
metallo-betalactamase (NDM) enzyme. This substance, when combined with meropenem, restored antibiotic activity against an NDM lab strain.   AMA is a substance which was already tested in the past in humans.  Concerns about interference with human metalloenzymes proved unfounded; it seems to have negligible toxicity.  Currently, only colistin is active against NDM bacteria.  None of the newer B-lactamase inhibitors (avibactam, MK-7655) inactivates NDMs.
Of note, tigecycline has poor activity against NDM-producers. [1]

Altered Antibiotic PK in Critically Ill Patients Requires Dosing Adjustments

Cefuroxime dosing, like that of other B-lactams, needs to be adjusted upwards in critically ill ICU patients. Especially when CLcr is in the normal range, standard doses are unlikely to achieve levels of T > MIC of 65% or greater.  Hence, pathogens with MICs close to break point or patients with high CLcr may not be adequately covered with intermittent dosing.  Based on PK/PD data, a continuous infusion of high doses may be able to still provide bacterial killing.  As the authors point out, clinical studies to confirm this approach have yet to be performed.[2]

First Case of Ciprofloxacin-Resistant Legionella pneumophila

Bellevue Stratford
Bellevue Stratford – Philadelphia

I guess it had to happen eventually: Bruin et al. report a patient infected with
L. pneumophila serogroup 1 who presented with severe respiratory insufficiency and interstial pneumonia.  The organism MIC – tested at a reference lab – was 2 mg/L.  Sequencing of the gyrA gene revealed a point mutation in the QRDR (quinolone resistance determining region).  It was not clear whether the organism was resistant already prior to ciprofloxacin therapy.[3]


[1] A King  Nature 2014, 510: 503
[2] M Carlier  J Antimicrob Chemother 2014; 69: 2797
[3] J Bruin,  J Antimicrob Chemother 69: 2869, 2014

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