Monthly Archives: July 2022

AMR 2: Management of Antimicrobial resistant gram negatives

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AMR 2: Management of Amp-C Enterobacterales, Carbapenem resistant Acinetobacter baumannii, Stenotrophmonas maltophilia

The second part to the IDSA Guidance paper on the management of antibiotic resistant gram negative bacteria is out. AMR 1 focused on the management of ESBL Enterobacterales, Carbapenem Resistant Enterobacterales and DTR Pseudomonas aeruginosa, click here for my prior review and here for the wonderful tables I made.

AMR 2 is a welcome addition to the IDSA’s guidance paper series. These are living documents that will be edited and changed frequently to keep them as updated as possible. AMR 2 focuses on Amp-C, CRAB and Stenotrophomonas. The initial sections of the document are identical to AMR 1 and focus on empiric management and when to alter empiric therapy. Also, there is a discussion of duration and how resistance does not affect the duration of therapy. Again, click here for my review and AMR 1. Now to the meat of the guidance paper.

Amp-C Enterobacterales: Say goodbye to SPICE or SPICE-M Continue reading

New Antimicrobial approval: cefiderocol (Fetroja).

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BONUS QUESTION: Why is it called Fetroja?

This unique cephalosporin antibiotic utilizes Fe-siderophores to gain access to the cell. Access is between the inner and outer membrane. This explains the weak activity against Gram Positive bacteria (as well as anaerobes). This agent has good in vitro activity against Enterobacteraciae (ESBL and CRE), Pseudomonas, Acinetobacter and Stenotrophomonas.

How cefiderocol works:

The data where presented to the FDA and the agent was approved for complicated UTI. Continue reading

AMR 1: Management of Antimicrobial resistant gram negatives

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AMR 1: Management of Antimicrobial resistant gram negatives. A Focus on Extended-Spectrum β-lactamase Producing Enterobacterales, Carbapenem-Resistant Enterobacterales, and Pseudomonas aeruginosa with Difficult-to-Treat Resistance

Scenario: You are seeing a 63 yo with CKD and admitted with septic shock. The patient is admitted to the ICU and started on piperacillin-tazobactam and vancomycin. Blood and urine cultures return with ESBL Klebsiella pneumoniae (R-ceftriaxone at MIC >2). It is suspected the cause of the septic shock is pyelonephritis. Within 12 hours the pressors are weened, but the patient continues to have fevers. Do you continue piperacillin-tazobactam or do you change to a carbapenem?

This is not an uncommon scenario. I have encountered many patients that are better(-ish) on an antibiotic that either the organism is resistant to or has a resistance gene that makes the antibiotic less then ideal. Until recently it was difficult to find data to help with management decisions and guide therapy in these situations. Faced with the question of pressing on since there is improvement (and risk worsening sepsis) or change to a carbapenem (and face potential expansion of resistance) is there any guidance or data?

Now there is both guidance and data.

The new IDSA Guidance paper, Infectious Diseases Society of America Antimicrobial Resistant Treatment Guidance: Gram-Negative Bacterial Infections.  

The recommendations in this paper are not earth shattering, but they do provide a nice guide for what to do in these vexing situations. The guidance reviews management of AMR in gram negatives, particularly ESBL-Enterobacteriaceae (E. coli, K. pneumoniae, K. oxytoca and P. mirabilis), Carbapenem resistant Enterobacteriaceae and Difficult to Treat (DTR) P aeruginosa. For each organism class there are multiple questions the group attempted to answer and provide some excellent guidance. I have summarized these recommendations in the tables below with some added information.

Empiric therapy: Consider 1) Previous organisms and associated susceptibility data for the last 6 months and 2) Antibiotic exposure in the last 30 days (e.g. if received piperacillin-tazobactam recently consider another class such as a carbapenem)

Duration of therapy: Prolonged treatment courses are not necessary. If the initial antibiotic is found to be inactive, this may change the duration of therapy. As an example, the patient receives 3 days of ceftriaxone, but the E coli is resistant. Days of therapy would start from when an effective therapy was started. Continue reading

(Beta-D-)Glucan Insensitivity

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You are taking care of a patient that is s/p heart transplant that has been complicated by intestinal rupture, abdominal surgery, need for dialysis and prolonged stay in the ICU. The individual has been on piperacillin-tazobactam for more than 10 days due to the abdominal sepsis. Over the past 24 hours the blood pressure has dropped, and the patient has been less responsive.

Should you start anti-fungal therapy?

Is there any other testing that you could do that will alter you to a fungal infection?

Beside sending blood cultures, you wonder about sending a 1,3-Beta-D-Glucan. Would this be the test that tells you a fungal infection is present?

This is not an uncommon scenario or issue or problem we face in medicine (general medicine, critical care, and ID), when to start anti-fungal therapy. Over the past 30 years there has been an increase in the incidence in invasive candidal infections (ICI), especially in the ICU. Unfortunately, outcomes have not changed and in some patient populations may have worsened. Empirical antifungal therapy has failed to demonstrate a survival benefit, even in patients with sepsis that is acquired in the ICU, Candidal colonization and multi-organ failure. Prophylactic antifungal therapy in the surgical setting has been ineffective at reducing mortality in the immune competent. One approach is assessing risk factors (prolong ICU stay, invasive devices, TPN, abdominal surgery in the past 7 days, prior antimicrobial use for >48 hours and renal replacement therapy) and assessing the 1,3-Beta-D-Glucan (BDG). The BDG is a cell wall polysaccharide found in most fungi.  The pooled sensitivity is 74-86% and the pooled specificity is 49-71%, so not a great test. With a low pre-test probability, a BDG <80 pg/ml has a good NPV, but a very low PPV.

This brings us to the recent advanced published study by Bloos et al (1-3)-Beta-D-Glucan guided antifungal therapy in adults with sepsis, Int Care Med 2022. The aim of this study was to test whether BDG-guidance shortens time to antifungal therapy and there by reduces mortality of sepsis in persons at high risk for invasive candida infections (ICI). And an Editorial. Continue reading

Welcome to NUID Blog…So It Goes

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Welcome to the NUID Blog. This site has been set-up as a space to read about new ID related literature, how that literature fits with clinical practice and other ID related resources. This site is designed to be used by Infectious Disease Fellows, Internal Medicine residents, medical students, practicing ID physicians, other practicing physicians and anyone interested in Infectious diseases.

We hope that you enjoy the content, learn something new and return for ID related goodness.

Michael Angarone, DO