By Betty Tran, MD, MSc

Assistant Professor of Medicine, Pulmonary and Critical Care Medicine, Rush University Medical Center, Chicago

Dr. Tran reports no financial relationships relevant to this field of study.

SYNOPSIS: In mechanically ventilated patients with stable ventilator settings for at least three days, very short courses of antibiotics (< 3 days) for suspected ventilator-associated pneumonia were associated with similar outcomes when compared to longer courses (> 3 days).

SOURCE: Klompas M, Li L, Menchaca JT, et al. Ultra-short-course antibiotics for patients with suspected ventilator-associated pneumonia but minimal and stable ventilator settings. Clin Infect Dis 2017;64:870-876.

Given the difficulty in diagnosing ventilator-associated pneumonia (VAP) in the ICU with certainty, many patients who are prescribed antibiotics for suspected VAP do not actually have it.1 Instead of focusing on ways to limit initiation of antibiotics, which is impractical in the setting of non-specific symptoms in critically ill patients, early discontinuation of antibiotics when no longer needed is a more pragmatic approach. Currently, there are few objective strategies that can inform clinical judgment as to when antibiotics can be discontinued without adverse consequences.

In this single-center, retrospective database study between 2006 and 2014, Klompas et al compared outcomes among patients started on empiric antibiotics for suspected VAP with minimal and stable ventilator settings (positive end-expiratory pressure or PEEP < 5 and fraction of inspired oxygen or FiO2 < 40%) who were treated for < 3 days vs. > 3 days. Patients were defined as suspected of having VAP if they exhibited an endotracheal aspirate (ETA) or bronchoalveolar lavage (BAL) on or after day three of mechanical ventilation with initiation of one or more new antibiotics within two days of the culture order date (excluding the first two days of mechanical ventilation). Outcomes assessed included time to extubation alive, ventilator death, time to hospital discharge alive, and hospital death.

Three sensitivity analyses using propensity score matching were performed, including a subset of patients with ICD-9 pneumonia codes entered on or after ventilator day three and within two days of respiratory culture and antibiotic start dates and a subset of patients with > 25 neutrophils per low power field on ETA or BAL Gram stain and positive culture.

Of the 30,336 mechanical ventilation episodes identified, 1,290 patients were suspected of having VAP and had minimal ventilator settings that were stable for at least three days. Of these, 259 were prescribed antibiotics for one to three days, while 1,031 were prescribed > 3 days of antibiotics. Patients prescribed shorter courses of antibiotics tended to be older, more likely be in the medical ICU, exhibit a history of renal failure, and demonstrate higher predicted risk of hospital death on the first day of mechanical ventilation.

Patients in this short-course group were given a median of two days of antibiotics (interquartile range [IQR], 1-3 days) compared to nine days (IQR, 6-12 days) in the long-course group. Subsequent propensity matching eliminated all measured differences between the two groups.

After adjustment for potential confounders, there were no significant differences between the two groups with regard to time to extubation alive, ventilator death, time to hospital discharge alive, or hospital death. In fact, point estimates favored patients treated with shorter courses of antibiotics (i.e., hazard ratios were > 1 for time to extubation alive and time to hospital discharge alive and < 1 for ventilator and hospital death). Similar findings were observed in all three sensitivity analyses.

COMMENTARY

Antibiotic stewardship is an important goal in the ICU, with hopes of improving patient outcomes, reducing microbial resistance, and decreasing the spread of multidrug-resistant organisms.2 However, the predilection to overprescribe antibiotics in the ICU, especially when it comes to predicting VAP, mainly has to do with its nonspecific features, including fever, leukocytosis, increased secretions, and radiographic infiltrates. Once antibiotics are started, even if a pathogenic organism ultimately is not identified, the tendency is to complete a full seven-day course based on Infectious Diseases Society of America/American Thoracic Society guidelines.3

This study raises an interesting question that merits further confirmation in a larger, preferably randomized, controlled trial. It suggests that for patients with suspected VAP, in a subset that have minimal and stable ventilator settings, the cessation of antibiotics after one to three days was not associated with any difference in important outcomes. It is highly possible that this subgroup of patients does not have VAP to begin with. Indeed, a decline in oxygenation, as evidenced by an increase in FiO2 by 20 points or PEEP by 3 cm H2O, is an early requisite in an algorithm proposed for the surveillance of ventilator-associated events, the last tier of which includes possible and probable VAP.4 Alternatively, this group of patients may have mild pneumonia that can be managed effectively with ultra-short courses of antibiotics.

The appeal of using daily ventilator settings as a screening tool to complement clinical judgment in early antibiotic discontinuation is that it is objective, simple, fast, and inexpensive as opposed to other measurements such as procalcitonin testing and the Clinical Pulmonary Infection Score, which are either costly, not widely available (or take time for results to return), and/or are more complicated to calculate or interpret. If these results are confirmed, serial ventilator setting surveillance could be a useful criterion in identifying a group of patients in whom antibiotics can be discontinued earlier.

REFERENCES

  1. Nussenblatt V, Avdic E, Berenholtz S, et al. Ventilator-associated pneumonia: Overdiagnosis and treatment are common in medical and surgical intensive care units. Infect Control Hosp Epidemiol 2014;35:278-284.
  2. Fishman N. Antimicrobial stewardship. Am J Med 2006;119(6 Suppl 1):S53-61.
  3. Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016;63:e61-111.
  4. Magill SS, Klompas M, Balk R, et al. Developing a new, national approach to surveillance for ventilator-associated events: Executive Summary. Clin Infect Dis 2013;57:1742-1746.