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Antimicrobial Stewardship in HAP / VAP: A Focus on Duration of Therapy

Antimicrobial stewardship programs often focus on antimicrobial de-escalation, while less emphasis is placed on treating for the shortest possible duration. Although both are important stewardship initiatives, there is a paucity of data suggesting that de-escalation directly results in less emergence of resistance. Furthermore, antimicrobial de-escalation has not been found to reduce duration of antibiotic therapy.1 However, reducing overall antibiotic exposure is likely to have an impact on decreasing antimicrobial resistance. By shortening antibiotic duration, overall antibiotic exposure is lessened, reducing selection pressure for multidrug resistant organisms. This finding is supported by studies of ventilator-associated pneumonia (VAP).2,3

Hospital-acquired pneumonia (HAP) and VAP account for significant antibiotic use and together are one of the most common health care–associated infections,4 These infections have a large economic burden and are associated with poor patient outcomes, including prolonged mechanical ventilation and hospital stay.5 A justified concern about the poor outcomes that HAP/ VAP cases represent drives antibiotic use because even suspected-but-unproven cases receive broad-spectrum antibiotic therapy.

Historically, HAP and VAP were treated for 14 to 21 days. Although treating these infections for an extended duration seems logical given their severity and the negative patient outcomes, prolonged courses of antibiotics have not been found to improve outcomes but instead to increase the rate of recurrent infections with multidrug- resistant (MDR) organisms.2,3 In 2005, guidelines by the Infectious Diseases Society of America (IDSA) for the treatment of HAP/VAP recommended treating for either 7 days or 14 days, depending on the causative pathogen. When the causative organism was a non-lactose fermenting gram-negative bacillus (NLFGNB), longer durations were recommended.6

Two well-designed, randomized controlled studies have been conducted to evaluate the equivalence of shorter and longer courses of antibiotic therapy in VAP, both comparing 8 and 15 days. The first study was in 401 patients with microbiologically proven VAP. Patients were randomized to 8 days or 15 days of antibiotics selected at the discretion of the treating clinicians. The rate of recurrence and 28-day mortality were similar in both groups: 18.8% (8 d) versus 17.2% (15 d) and 28.9% (8 d) versus 26% (15 d), respectively, and 8 days was found to be noninferior. A finding of this study was that in patients with NLFGNB VAP, there was a higher rate of infection recurrence in the 8-day group (40.6% vs 25.4%), yet there was no difference in in-hospital mortality: 34.4% and 41.3% for 8 and 15 days, respectively. Not only were clinical outcomes similar between groups, but reducing overall antibiotic exposure resulted in a significant reduction of recurrent MDR pulmonary infections. Recurrent pulmonary infections with an MDR organism occurred less frequently in the shorter-treatment group: 42% and 62% for 8 and 15 days, respectively.7 In the second study, 225 patients with early-onset VAP were randomized to receive 8 or 15 days of a beta-lactam plus an aminoglycoside. This study also did not find a difference in clinical cure between the two treatment durations. Clinical cure was 85.3% in the 8-day group and 84.4% in the 15-day group. Similarly, there was no difference in 21-day mortality, which was 8.6% in the 8-day group and 8.3% in the 15-day group.8 One surprising finding was that the rate of secondary infections was higher in the 8-day treatment group (35.3% vs 19.3%; P <.01).

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