By Stan Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

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

SYNOPSIS: Discontinuation of empiric antibiotic therapy given for treatment of presumed ventilator-associated pneumonia can be discontinued safely after three days in patients with minimal ventilator requirements.

SOURCE: Klompas M, Li L, Menchaca JT, Gruber S; CDC Prevention Epicenters Program. Ultra short course antibiotics for patients with suspected ventilator-associated pneumonia but minimal and stable ventilator settings. Clin Infect Dis 2016 Dec 29. [Epub ahead of print].

Klompas and colleagues in Boston retrospectively
examined the potential usefulness of simple physiological parameters to guide early discontinuation of empiric antibiotics that had been initiated in adults for presumed ventilator-associated pneumonia (VAP).
For the purposes of this analysis, the diagnosis of suspected VAP required that there had been a culture of respiratory secretions obtained more than three days after initiation of mechanical ventilation and that a new antibiotic was initiated within two days of the culture. They identified 1,290 patients receiving antibiotics for a diagnosis of VAP whose minimum PEEP was 5 cm H2O with FiO2 0.40 for each of at least three days.

Of the 1,290 patients meeting these criteria, 259 had received antibiotics for three days or less, and 1,031 had received them for more than three days. Patients who received three days or less of antibiotics were significantly older, more likely to be in the medical ICU, and to initially have a higher predicted mortality, while those treated for more than three days were more likely to have Staphylococcus aureus or Klebsiella pneumoniae recovered from their respiratory secretions (endotracheal aspirate or bronchoalveolar lavage).

The two groups had a median duration of antibiotic therapy of two days (IQ range, 1-3 days) and nine days (IQ range, 6-12 days), respectively. No significant outcome differences between the short and longer duration antibiotic groups were identified with regard to time to extubation, ventilator death, or hospital death. This was true with both unadjusted analysis and with propensity matching and also was true with restricting the analysis to patients who had both > 25 neutrophils per low power field on Gram stain of respiratory secretions and positive pathogen cultures. Furthermore, the point estimates for each of these three outcomes was better for patients who received three days or less of antibiotic therapy.

COMMENTARY

The diagnosis of VAP is fraught with error, as indicated by a retrospective single-center study that concluded that three-fourths of patients with this diagnosis probably did not truly have VAP. Despite this post-hoc judgement, they received a mean of almost 10 days of antibiotic therapy.1

Nina Singh’s small but important study almost two decades ago used the clinical pulmonary infection score (CPIS) to similarly address the issue of unnecessary continuation of antibiotic administraton.2 In that study, ICU patients with new pulmonary infiltrates and a CPIS 6, but judged by their clinicians to have pneumonia, were randomized to receive antibiotic therapy as determined by their clinician or to receive ciprofloxacin for three days with discontinuation at that time if their CPIS remained 6. There was no significant difference in mortality, but the frequency of superinfection or development of antimicrobial resistance was lower in those whose antibiotics were discontinued at three days compared to those with management by their clinicians. The latter group received antibiotics for a mean of 9.8 days. The only possible interpretations of the results of that study are that either the pneumonia was cured with three days of therapy or that they never had pneumonia — interpretations that also could be applied to the study by Klompas et al reviewed here.

Unfortunately, the CPIS score has been found to have many shortcomings and appears to be little used currently. Another approach is the use of procalcitonin measurements to assist the clinician in making decisions regarding antibiotic discontinuation, and evidence clearly indicates that this is an effective and efficient means of achieving this.3

While clinical judgement remains important, the very evidence contained in studies such as the one reviewed here clearly indicate that, in practice, such judgement frequently is inaccurate. The recently published IDSA/ATS guideline recommends a treatment course of only seven days for VAP4 and this appears to be appropriate for patients who truly have VAP and should be included in clinical pathways. In addition, consideration may be given to incorporating the results of the study by Klompas et al. Thus, patients initiated on empiric antibiotic therapy for VAP but who meet their criteria of minimal ventilator settings for three days may be considered for antibiotic discontinuation. In borderline cases, the use of procalcitonin measurement may assist in this decision.

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. Singh N, Rogers P, Atwood CW, et al. Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription. Am J Respir Crit Care Med 2000;162(2 Pt 1):505-511.
  3. de Jong E, van Oers JA, Beishuizen A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: A randomised, controlled, open-label trial. Lancet Infect Dis 2016;16:819-827.
  4. 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-e111.