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New Trends and Recommendations in the Management of HABP/VABP and Gram-Negative Resistance

Keith S. Kaye, MD, MPH

Chief
Division of Allergy, Immunology and Infectious Diseases
Professor of Medicine
Rutgers Robert Wood Johnson Medical School
New Brunswick, New Jersey


Keith S. Kaye, MD, MPH, has disclosed that he has served as a consultant for Actavis, Allecra, Bayer, Carb-X, Cipla, Clarametyx Biosciences, Contrafect, Cubist, Entasis, Integrated Operations, Melinta, Merck, Nabriva, NS Nanotech, Pratek, QPex, SPERO, Shionogi Inc, UtilityTherapeutics, VenatoRX, and Xellia.


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Released: January 24, 2022

Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP)—a subset of HABP—are among the most challenging infections to manage for various reasons. First, HABP is difficult to diagnose; for example, patients who are mechanically ventilated are quite ill, and several organ systems often are involved in their illnesses, making it hard to determine whether they truly have pneumonia or they have chest x-ray abnormalities for other reasons, such as heart failure.

In addition, once a patient is on a ventilator, they invariably will have colonization in their lungs; therefore, a positive culture of respiratory secretions doesn’t necessarily equal infection. Furthermore, when you start combining the presence of mechanical ventilation with other devices, such as central lines and Foley catheters, and you consider healthcare exposure and prior antimicrobial exposure, the risk for infection due to antimicrobial-resistant pathogens is relatively high. These antimicrobial-resistant pathogens are more challenging to manage than your run-of-the-mill, more susceptible pathogens. Fortunately, we have new guidelines from the Infectious Diseases Society of America (IDSA) on the treatment of HABP/VABP, including some antimicrobial-resistant infections, to help guide management decisions.

Phases of Treatment: Guideline Recommendations
The first phase of treatment for the initial 2-3 days is typically empiric therapy—when you’ve decided that you need to cover a patient for HABP or VABP, but you don’t know which organism is causing the infection. For this therapeutic phase, the IDSA recommends that healthcare professionals consider the most likely pathogen, severity of illness, likely source of infection, and local susceptibility patterns for the most likely pathogen, along with patient-specific risk factors for antimicrobial resistance such as previous organisms identified from the patient, associated antibiotic susceptibility data in the past 6 months, antibiotic exposures within the past 30 days, and the duration of hospitalization and ventilation. Prior microbiologic history is important to consider and sometimes overlooked. For example, if a patient presenting with pneumonia has had a resistant Pseudomonas isolate in the past several months, I would cover for that organism empirically. Prior antibiotic history also is important to consider. If someone received 2 weeks of piperacillin/tazobactam recently and is presenting again with severe pneumonia after a week of stopping this combination, I’m not going to choose piperacillin/tazobactam for empiric therapy. It is important to consider all of these factors when choosing empiric therapy, as beginning effective therapy as quickly as possible—particularly within that first day—can substantially improve outcomes in patients with HABP/VABP. Indeed, it can decrease risk for mortality, duration of hospitalization, and duration of mechanical ventilation.

Specifically for possible gram-negative bacterial infections, when we are considering empiric therapy, we need to decide whether 2 agents are needed to cover the infection. Reasons to use combination therapy include the presence of antimicrobial risk factors and the acute severity of illness. Combination therapy ideally should include agents from different classes, both of which have pseudomonal activity. If single-agent therapy is indicated, often the IDSA guidelines will recommend an antipseudomonal agent such as cefepime or piperacillin/tazobactam.

Following the 2- to 3-day empiric therapy period, culture data often are available (at least in cases of VABP), and therapy probably can be modified. Once culture data and/or other clinical and laboratory data are available, therapy might be able to be narrowed or modified for the remainder of the “consolidative” or “definitive” phase. In fact, if it is determined that the patient didn’t have VABP/HABP, antibiotics might be able to be stopped altogether. If a multidrug or extremely drug resistant pathogen is recovered, you might need to change therapy to provide effective therapy.

Emerging Trend: Shorter Duration of Treatment
A major shift in the treatment of pneumonia is shorter durations of therapy. Indeed, the new guidelines state that “prolonged treatment courses are not necessary against infections by antimicrobial resistant pathogens per se, compared to infections caused by the same bacterial species with a more susceptible phenotype.” Regardless of pathogen, in most cases treatment for 7 days is sufficient. This assumes, of course, that you begin effective therapy early and that your patient is responding.

Rapid Diagnostic Testing
A new player to the HABP/VABP game that has not been widely adopted yet—but that can be very helpful—is rapid diagnostics on respiratory samples. In a patient who is ventilated, the sample typically would be obtained via bronchoalveolar lavage, which can be done either using a bronchoscope or via mini–bronchoalveolar lavage. This approach allows diagnostic testing directly on the specimen, rather than having to wait 1-2 days for the culture to grow. Rapid diagnostic testing can provide information about the organisms present and whether certain resistance determinants also are present. Having this information can inform your early antibiotic therapy decision-making, even on Day 1, which can help healthcare professionals provide effective and optimal therapy earlier.

I think the most valuable aspect of these tests, particularly in the gram-negative world, is that they can tell you whether pathogens that may require empiric combination therapy are present, such as Pseudomonas aeruginosa. These rapid diagnostics are not a panacea, however—they’re not totally helpful in all cases, but they can provide some information rapidly that can be quite informative and useful.

In summary, the new guidelines on the management of gram-negative bacterial infections, combined with the availability of rapid testing to more quickly identify causative pathogens, are important tools to help healthcare professionals identify and treat HABP and VABP.

More on HABP/VABP and Gram-Negative Resistance: Virtual Symposium
To hear more on HABP/VABP and gram-negative resistance, including pathways to early effective therapy and guideline recommendations, join us for an upcoming live virtual symposium. The program will include practical management strategies and perspectives from expert faculty Lilian Abbo, MD; Keith S. Kaye, MD, MPH; and Jason M. Pogue, PharmD.

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