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Certain Gram-negative bacteria present serious clinical challenges.1
Carbapenem-resistant Enterobacterales (CRE) (in particular Klebsiella pneumonia carbapenemases, metallo-β-lactamases, and oxacillinase-type carbapenemases), carbapenem-resistant Pseudomonas aeruginosa (CRPA), carbapenem-resistant Acinetobacter baumannii (CRAB), and third-generation cephalosporin-resistant Gram-negative bacteria are resistant to numerous existing treatment options.1 Gram-negative bacteria exhibiting resistance to all fluoroquinolones and all β-lactam categories, including carbapenems, are known as 'difficult-to-treat'.1
In difficult-to-treat Gram-negative infections, delayed treatment means a ~20% increase in the risk of in-hospital mortality.1 To cut wait times, rapid diagnostic tools - such as point-of-care tests and molecular (genotyping) assays - should be used to inform treatment decisions at the earliest possible stage.1
Newer tools and techniques offer higher sensitivity and specificity over standard culture methods and can accelerate the detection of pathogens to guide targeted therapy. However, they are limited by high costs, lack of access in developing countries, and resistance coverage.
Read about traditional bacterial infection identification techniques here.
PLACE YOUR PATIENT
Who is your Gram-negative patient?
Do you know what to look out for?
While diagnostic tools are essential, you can further optimize treatment selection by considering factors like patients' risk of infection and local epidemiology of resistance rates. An emerging approach to improve diagnostic accuracy is resistance typing.1
Resistance typing rapidly determines resistance profiles in bacterial cultures and direct patient samples. There are two main methods:1
| 1. Detecting compounds indicating bacterial growth or degradation of the antibiotic in question | 2. Detecting nucleic acid sequences indicative of resistance genes and their expression |
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Getting this information promptly can reduce indiscriminate antibiotic use. Generally, turnaround times are substantially shorter than with traditional culture methods, too.1
Novel Gram-negative resistance typing techniques (some of which are already available, and others are under development) include:1
| Detecting compounds indicating bacterial growth or degradation of an antibiotic | Detecting nucleic acid sequences indicative of resistance genes and their expression |
|---|---|
|
MALDI-TOF is a form of mass spectrometry with a typical turnaround time of 1-4 hours. However, it can incur significant upfront costs and needs further optimization.
|
Molecular detection systems (nucleic acid amplification-based) can identify multiple different antibiotic resistance mechanisms in 1-3 hours, with sensitivity of 73-100%. Requires a high copy number of the target gene to work.
|
| Colorimetric tests can detect susceptibility and resistance for all antibiotics. Sensitivity and specificity are high (95% and 98-100%, respectively), but some require culture and can be slow. | FISH detects certain types of antibiotic resistance in 60-90 minutes but requires high level of skill and experience from the user. |
| NG-Test® CARBA 5 immunochromatographic test will, once available, quantitatively detect the five most common carbapenemase families in ≤15 minutes. Requires overnight culture. | FISH + time-lapse and automated photography is a method used to detect bacteria and their antibiotic resistance genes from a sample. Take 30-90 minutes. |
| DNA microarray is based on hybridization to detect resistant bacteria in blood or respiratory samples. Takes 2.5-8 hours, with sensitivity of 72.9%, and is currently considered too complex for routine clinical use. |
To get the most out of available diagnostic tools and resistance typing techniques, we'll need to work together. We must integrate rapid identification with the principles of stewardship. Take the first step and form a multidisciplinary team - different perspectives and skill sets can enhance communication, education, and interpretation of diagnostic results, which could go a long way in finding the right therapy for your patients.1
Gram-negative bacteria and nosocomial infections
Bassetti M et al. JAC Antimicrob Resist 2022;4 (5):dlac089.
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