The 2016 hospital-acquired and ventilator-associated pneumonia guidelines, sponsored by the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS), and endorsed by the American College of Chest Physicians (CHEST), Society of Critical Care Medicine (SCCM), and the Society for Healthcare Epidemiology, was published recently (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 Sep 1;63[5]:575-82).
This Critical Care Commentary aims to provide the highlights of the new guideline and to motivate readers to read the complete report that best represents the primary intent of the guideline panelists.
Dr. Andre C. Kalil
The new guideline was written using the Grading of Recommendations Assessment, Development, and Evaluation methodology. This was the framework to address all clinical questions referred to as PICOs (patient; intervention; comparator; outcome), which can be explicitly seen in the published guideline. For every PICO question, the wording “we suggest” was used for a weak recommendation (lack of high confidence; further evidence could change it), and “we recommend” was used for a strong recommendation (high confidence; further evidence is unlikely to change it). Also, part of the panel framework was the requirement to disclose any actual, potential, or perceived conflicts of interest for each panelist to be accepted to participate, as well as to remain in the panel for the duration of the process. The cochairs remained free of any financial conflicts during the entire process.
Dr. Mark L. Metersky
Choosing an empiric antibiotic regimen for patients with HAP and VAP requires balancing the potentially competing goals of ensuring that likely infecting pathogens are covered while avoiding excess antibiotic use. In order to guide clinicians on empiric antibiotic therapy, the panel performed a comprehensive review of the potential risk factors for HAP and VAP. For VAP, three factors associated with disease severity (septic shock at time of VAP, ARDS preceding VAP, and acute renal replacement prior to VAP onset) and two epidemiologic factors (prior use of IV antibiotic use within 90 days, and 5 or more days of hospitalization prior to the occurrence of VAP) made the final risk factors list. For HAP, only the prior use of IV antibiotics within 90 days was associated with risk for MDR. However, because of the limitations and small number of studies on HAP only, the panel decided to add risk factors for mortality (ventilator support for HAP and septic shock) as surrogates for MDR risk factors in patients with HAP, as these factors presumably increase the risk of poor outcomes if there is initial inadequate empiric therapy.
In conjunction with the bedside evaluation of risk factors for MDR, the guideline recommends the use of local antibiograms not only to guide empiric therapy but also to decide if antibiotic coverage for MDR is needed. Ideally, the antibiogram should be based on the specific ICU, but if this is not feasible, or the hospital is of small size, an institutional antibiogram can also be helpful. The first benefit of local antibiograms is derived from the knowledge gained regarding the prevalence of each microorganism; for example, if only 3% of all VAP or HAP in a given unit or hospital is caused by Pseudomonas aeruginosa, it is likely that an empiric coverage for this microorganism will neither be necessary nor appropriate for most patients. The second benefit is derived from the knowledge concerning the frequency of MDR microorganisms within the unit or hospital: for example, patients with VAP in units where 10%-20% of Staphylococcus aureus isolates are resistant to methicillin, or greater than 10% of gram-negative isolates are resistant to an agent being considered for monotherapy, should receive antibiotics for MDR infections. With these two critical pieces of information, the clinician will have a higher probability of starting the correct empiric antibiotics, and, consequently, improve the survival outcomes of patients with HAP and VAP.
The choice of the empirical treatment of VAP and HAP becomes a natural derivation of the three main factors discussed above: (1) epidemiologic history of antibiotics’ use and prior hospitalization length, (2) local antibiogram for the prevalence and resistance of microorganisms, and (3) disease severity and risk of mortality by the identification of septic shock, ARDS, and acute renal replacement therapy. For example, if 17% of all VAPs in your unit is from P aeruginosa (which is the national prevalence in patients with VAP), and 8% of these strains are resistant to an agent being considered for gram-negative monotherapy, not prescribing double coverage for P aeruginosa would still result in initial appropriate therapy in 98.6% (derived from 1-[0.17 x 0.08]) of cases. The reason why the panelists chose the threshold of 10% for P aeruginosa, and 10%-20% for S aureus, was based on the national prevalence rates reported by the Centers for Disease Control and Prevention, with the goal of limiting the initial inappropriate antibiotic therapy decision to less than 5% of all cases. We strongly believe that this “epidemiologic/antibiogram/disease severity” approach to select the empiric therapy is both clinically intuitive and essential to improve patients’ outcomes. Further, this approach will substantially reduce the unnecessary use of double antibiotic therapy in patients with VAP or HAP.
This guideline suggests that the use of inhaled antibiotic therapy in conjunction with IV antibiotics may benefit patients with VAP or HAP from MDR microorganisms that are sensitive to only polymyxins or aminoglycosides. The panel also suggested that the use of pharmacokinetic and pharmacodynamics should be used to optimize the administration of antibiotic therapy for all patients with HAP or VAP.
Last, after an extensive review and multiple analyses of all available evidence, the panel concluded that the majority of patients with HAP or VAP should be treated with 7 days of therapy, independent of the microorganism causing the pneumonia. In several meta-analyses performed by the panelists to evaluate all patients with VAP, as well as only patients with VAP caused by nonfermenting gram-negative organisms such as Pseudomonas species, Stenotrophomonas species, and Acinetobacter species, the panel did not find differences between short and long courses of antibiotics regarding mortality, clinical cure, pneumonia recurrence, and mechanical ventilation duration. In recognition of the individual needs of each patient, we made a remark that shorter or longer duration of antibiotics may be indicated, depending upon the rate of improvement of clinical, radiologic, and laboratory parameters. Several adjunctive methods of deescalation were assessed, but only procalcitonin was suggested to aid health care providers to shorten the course of antibiotic therapy.
In conclusion, the authors of this 2016 HAP/VAP IDSA/ATS guideline hope to achieve the ultimate goal of improving the treatment and outcomes of patients with HAP and VAP and reducing unnecessary antibiotic use.
Dr. Kalil is with the department of internal medicine, division of infectious diseases, University of Nebraska Medical Center, Omaha; Dr. Metersky is with the division of pulmonary and critical care medicine, University of Connecticut, Farmington.