Because traumatically injured patients with early-onset ventilator-associated pneumonia (VAP) are more likely to be sensitive to narrow-spectrum antibiotics than those with late VAP, empirical treatment of early VAP with narrow-spectrum antibiotics is a reasonable choice, a study has found. The results also concluded that broad-spectrum antibiotics should continue to be standard empirical therapy for late VAP.
“Based on the fact that trauma patients are historically young, healthy males with no prior antibiotic exposure, we would expect that they would not develop an early VAP with multidrug-resistant bacteria,” said Jeffrey R. Simpson, MD, a trauma/critical care surgeon at Research Medical Center, in Kansas City, Mo. “Since the early VAP was likely to be from an aspirated oral flora, we proposed that narrow-spectrum empiric antibiotics would be effective to use in these cases.”
Dr. Simpson was the lead author of the study, which was conducted at the University of California, San Francisco (UCSF) Fresno Community Regional Medical Center. The results were presented at the Society of Critical Care Medicine’s Critical Care Congress (abstract 1109).
Effectiveness of Narrow-Spectrum Antibiotics
The researchers examined the types of bacteria causing VAP in all the patients and determined the effectiveness of antibiotic therapy. “By doing this, we found that early VAPs were more commonly caused by bacteria that are sensitive to narrow-spectrum antibiotics,” Dr. Simpson said. “This justifies the use of narrow-spectrum antibiotics in patients who develop VAP during ventilator days 1 through 4.”
“This study tackles the persistently important question of how best to choose antibiotics for trauma patients with suspected VAP,” commented Michael Klompas, MD, MPH, an infectious disease specialist from Brigham and Women’s Hospital and Harvard Medical School’s Department of Population Medicine, both in Boston. Dr. Klompas was not involved in the study. “The authors focus on whether the pathogens associated with VAP and their antimicrobial spectra vary by duration of hospitalization, and by extension, whether one can safely use narrow-spectrum antibiotics in trauma patients with early VAP—up to four days since hospital admission,” said Dr. Klompas.
Dr. Klompas said the authors suggest that narrow-spectrum antibiotics are more likely to be adequate in trauma patients with early-onset pneumonia, but he noted that 27% of VAPs in the early-onset cohort were not susceptible to narrow-spectrum treatment. Physicians therefore need additional strategies to identify the subset of early VAP patients who may be harboring resistant pathogens, he noted. In addition, physicians need to be prepared to order further diagnostic studies and change treatment if patients do not respond to early therapy, because this might be an indication of an incorrect diagnosis or a resistant pathogen.
According to Dr. Klompas, the broad findings of the study echo those of many similar studies that have noted that, while early-onset VAPs are more likely to be susceptible to more antibiotics than late-onset VAPs, “there is considerable overlap in the microbiology and susceptibility profile of both early- and late-onset pneumonia.” Consequently, time of VAP onset is a reasonable variable to consider when choosing therapy but is not decisive by itself.
Defining VAP
The researchers conducted a retrospective review at a level 1 trauma center of 214 traumatically injured patients with VAP, during 2011 to 2014. VAP was defined by clinical suspicion of pneumonia and respiratory cultures with 105 CFU (colony-forming unit) organisms or greater. Patients were categorized according to early (hospitalization days 1-4) versus late onset (hospitalization day 5 or later) of pneumonia. The primary outcomes were the type and sensitivity of organisms isolated on culture.
Patients were excluded for respiratory cultures with less than 105 CFU (n=23) and mixed flora on final culture (n=22). Early VAP (n=99; 46%) versus late (n=115; 54%) had similar baseline characteristics and comorbidities, although patients in the late group had more severe injuries. Early VAP patients were more likely to be sensitive to narrow-spectrum antibiotics (73% vs. 57%; P=0.02) and less likely to have health care–associated organisms on culture (27% vs. 47%; P=0.003), the study found.
Dr. Simpson said it was surprising to see that even though late VAP increased stays in the ICU and the hospital, it did not affect mortality. “It seems that when examining VAP in the trauma population, VAP tends to be more common but is of less significance to survivorship of the patient,” he said, noting that other studies comparing trauma patients with other ventilated ICU patients have shown this result as well.
Trauma patients represent a unique population and were particularly susceptible to VAP due to depressed levels of consciousness secondary to head trauma, high potential for aspiration, thoracic trauma and the need for insertion of an emergency breathing tube, Dr. Simpson said. “Numerous studies previous to ours have shown that ventilated trauma patients are far more likely to develop pneumonia than other ventilated patients in the ICU. VAP in the ventilated trauma patient is almost a matter of ‘not if, but when,’” Dr. Simpson said. “This high rate of VAP requires diligence on the part of the treating physician and a well-formulated, evidence-driven plan for treatment.”
There are several differences between the characteristics of early and late VAP, Dr. Simpson said. “The early infections are traditionally caused by bacteria that are susceptible to narrow-spectrum antibiotics.” He said typical examples are methicillin-sensitive Staphylococcus aureus, Hemophilus influenzae or simple coliforms. In contrast, he said, late VAP is more likely to be secondary to hospital flora, and thus there is a higher association with multidrug-resistant organisms. Methicillin-resistant S. aureus, Acinetobacter and Pseudomonas aeruginosa are several common pathogens typically found in the late VAP group. As a result, the crude mortality rate is usually higher, and ventilator days and ICU/hospital days are longer in the late VAP group than in the early group.
“Not surprisingly, late VAP patients were more severely injured in our study,” Dr. Simpson said, noting that this is typical in other studies as well. “A common hypothesis for this is that those patients with high injury severity scores, generally in the areas of the head or chest, will require longer periods of mechanical ventilation in order to overcome their illness.”
Prolonged ventilator exposure is an opportunity for multidrug-resistant, hospital-based bacteria to infect these patients. Therefore, VAP that develops on ventilator day 5 or later should be treated with broad-spectrum empirical antibiotics until culture results can be obtained.