Pathogen-specific treatment is briefly reviewed, including those for MRSA, Pseudomonas
, extended-spectrum beta-lactamase, and carbapenemase-producing organisms. The role of newer ß-lactam/ß-lactamase combinations and older agents (eg, polymyxins) are also briefly addressed, but generally, no specific antimicrobial was shown to be more effective than others. The guidelines now advocate using pharmacokinetic/pharmacodynamic (PK/PD) data to optimize therapy when available, and advise against aminoglycoside monotherapy given poor lung penetration and clinical response, with increased adverse effects.
Regarding duration of therapy, the updated guidelines now recommend treatment for seven days for HAP/VAP, regardless of organism. Prior guidelines also advocated a duration of seven days, but excluded Pseudomonas
spp. and other nonglucose-fermenting, gram-negative organisms due to concerns for increased recurrence with eight versus 15 days of therapy.11
However, an updated meta-analysis did not show an association of recurrence with short-course therapy, and the panel noted that the increased recurrence rate was based only on subgroup analyses from the original Chastre study. It has also been well noted that short-course therapy led to reduction in antimicrobial exposure and MDROs, with no significant change in any clinical outcomes (including mortality) across all subgroups, including infections due to nonglucose-fermenting organisms.11
In addition, the guidelines advocate de-escalation of antibiotics based on clinical experience and rationale. Unfortunately, the quality of evidence supporting the presumed benefits of de-escalation (ie, reducing antimicrobial resistance, side effects, and cost) remains poor. However, when weighing overall potential benefits and possible harms, de-escalation remains a cornerstone of antimicrobial stewardship and a method of reducing broad-spectrum empiric therapy.
Biomarkers and the Clinical Pulmonary Infection Score (CPIS) are discussed in terms of utility for diagnosis and also determining duration of therapy. At this time, it is recommended to use clinical criteria alone to diagnose HAP/VAP. Due to heterogeneous results from the studies reviewed by the panel, it is not recommended to use clinical criteria plus CPIS or clinical criteria plus any of the following biomarkers: procalcitonin (PCT), soluble triggering receptor expressed on myeloid cells, or C-reactive protein. However, PCT may have a role when used in addition to clinical criteria to guide discontinuation of antibiotics. The role of CPIS in addition to clinical criteria to shorten duration of therapy remains controversial. The panel reviewed inconsistent evidence of benefit. One study suggested use of a modified CPIS led to decreased resistance, antimicrobial cost, and superinfections,12
while two other studies, which were not specifically designed to assess the use of CPIS to shorten duration, showed no effect on clinical outcomes.13, 14
Therefore, the panel indicated a preference to use clinical criteria alone to determine duration of therapy for VAP.
Polly Jen, PharmD, BCPSAQ ID, AAHIVP, is a clinical pharmacotherapy specialist in infectious diseases/ antimicrobial stewardship at New York University Langone Medical Center. She received a doctor of pharmacy degree from the Ernst Mario School of Pharmacy at Rutgers University and is a board-certified pharmacotherapy specialist with added qualifications in infectious diseases. Active member of SIDP.
Elizabeth Leung, PharmD, BCPS-AQ ID, is a clinical pharmacy specialist leader in infectious diseases/ antimicrobial stewardship, and co-leads the Antimicrobial Stewardship Program (ASP) at St. Michael's Hospital. Dr. Leung received her doctorate of pharmacy degree from Massachusetts College of Pharmacy and Health Sciences (MCPHS) in Boston, obtained double-specialty residency training (infectious diseases and critical care), and is a board-certified pharmacotherapy specialist with added qualifications in infectious diseases. Active member of SIDP.