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Strategies for Carbapenem-Resistant Acinetobacter
Implementing Guidance Into Practice: Strategies for Carbapenem-Resistant Acinetobacter

Released: December 15, 2025

Keith S. Kaye
Keith S. Kaye, MD, MPH
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Key Takeaways
  • Diagnosis of Acinetobacter pneumonia can be challenging, as presence of the bacteria does not always indicate infection, and cultures should only be sent out if there is reasonable suspicion for infection in order to maintain good antibiotic stewardship.
  • Sulbactam/durlobactam pairs sulbactam with a β-lactamase and carbapenemase inhibitor, durlobactam, thereby providing broad activity against strains of carbapenem-resistant Acinetobacter.
  • However, sulbactam/durlobactam is not readily available in most places outside the US. When it is not available, the recommendation is to use high-dose ampicillin/sulbactam in combination with another active agent.

Antibiotic Stewardship Begins With Diagnosis
Acinetobacter pneumonia is a very difficult disease state to study and treat. One of the key challenges of managing hospital-acquired pneumonia (HAP) and ventilator-acquired pneumonia (VAP) is diagnosis, particularly among patients in the ICU and on a ventilator, because the symptoms are very nonspecific. That is, it is not uncommon to get a fever, to have an abnormal chest x-ray, or to have low oxygen levels. It can be very confusing to determine whether a patient's respiratory status is truly due to pneumonia, or whether it's due to other conditions such as acute respiratory distress syndrome, heart failure, or pulmonary embolus.

Patients who are hospitalized in an intensive care unit, especially those with endotracheal tubes, and those who are mechanically ventilated through a tracheostomy are at increased risk for colonization with pathogenic bacteria. However, a positive culture, particularly in a patient who has a lot of underlying illnesses or who has an endotracheal tube in place, does not always equal infection. Patients may have gram-negative bacteria such as Acinetobacter, Stenotrophomonas, or Pseudomonas, in their sputum, without infection.

The primary thing I would stress is that experts are starting to really champion diagnostic stewardship around HAP and VAP. This means only sending cultures from the respiratory tract when there is true suspicion and just cause to believe that the patient may have pneumonia. For example, if a patient presents with fever and sepsis but their oxygen level is unchanged and they have a clearly infected wound from surgery a few days ago, there’s probably no need to send respiratory cultures for testing. In this case, a respiratory infection is not likely. Unnecessary culturing can lead to unnecessary antibiotic treatment. Ultimately, our goal is to treat infections appropriately and avoid unnecessary antimicrobial therapy.

Treatment Milestones
In terms of treatment developments, I think 1 of the biggest advances has been the approval and availability of sulbactam/durlobactam. Previously, sulbactam was administered as ampicillin/sulbactam, with ampicillin largely just along for the ride, because that was the only formulation in which sulbactam was available. Sulbactam/durlobactam pairs sulbactam with durlobactam, a β-lactamase and carbapenemase inhibitor that restores sulbactam’s activity. As a result, it maintains broad activity against strains of carbapenem-resistant Acinetobacter (CRAB), which are frequently resistant to sulbactam alone, as well as many other antibiotics. Thus, the availability of sulbactam/durlobactam is a major treatment milestone.

Sulbactam/Durlobactam and Combination Therapy
Current guidance has come down very strongly on the recommendation that, regardless of whether or not a CRAB isolate is susceptible to sulbactam in vitro, sulbactam should be used as part of combination therapy. This is the standard approach, although it remains somewhat controversial. The good news is that sulbactam/durlobactam restores sulbactam activity in most sulbactam-resistant CRAB isolates. When using sulbactam/durlobactam, I would recommend combining it with a carbapenem, as was done in the ATTACK trial and as is recommended in guidance from the Infectious Diseases Society of America. This trial specifically used imipenem plus colistin as background therapy with sulbactam/durlobactam, but many places in the United States will use meropenem instead of imipenem—and meropenem is an acceptable alternative to imipenem. Although this was done in the trial partly to cover for polymicrobial infections, there is also evidence of synergistic activity between meropenem and sulbactam/meropenem against Acinetobacter, suggesting the possibility of enhanced efficacy when they are used together.

However, sulbactam/durlobactam is not readily available in most places outside the US. When sulbactam/durlobactam is not available, the recommendation is to use high dose ampicillin/sulbactam in an attempt to increase drug concentrations and squeeze as much activity as possible out of sulbactam. The minimum inhibitory concentration to sulbactam may be elevated, but higher dosing may still provide clinical benefit.

So for CRAB, the options are either sulbactam/durlobactam coupled with a carbapenem or high-dose ampicillin/sulbactam, typically coupled with another agent, such as cefiderocol. Other combination options include tetracycline derivatives, such as minocycline or tigecycline. Polymyxins, like polymyxin B, are also available, but they are limited by their potential for nephrotoxicity and unfavorable pharmacokinetics and pharmacodynamics, particularly in the lungs.

Overall, the major recent developments to the Acinetobacter baumannii calcoaceticus armamentarium include the availability of sulbactam/durlobactam, increasing clinical experience with cefiderocol, and the continued role of ampicillin/sulbactam at higher doses and combined with another active agent when sulbactam/durlobactam is not available. I find that these represent the major shifts emphasized in the most recent guidance.

Your Thoughts
What would you do for a patient whose wound culture is positive for Staphylococcus aureus and is improving with treatment for this infection, but is still ventilated with carbapenem-resistant Acinetobacter from the endotracheal tube? Leave a comment to join the discussion!

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