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: The most notable new recommendation of the updated hospital-acquired pneumonia/ventilator-associated pneumonia guideline may be its endorsement of limiting the duration of antibiotic therapy to seven days in most cases.

SOURCE: 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 Jul 14. [Epub ahead of print].

The Infectious Diseases Society of America, together with the American Thoracic Society, have updated their guideline dealing with the management of adults with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). The previous guideline also included the management of healthcare-associated pneumonia (HCAP), a concept that was discarded in the development of this guideline because of evidence that the criteria used for the designation of HCAP failed to identify infections with antibiotic-resistant pathogens and led to overuse of broad-spectrum antibiotics.

The following is a brief outline of the guideline recommendations. In the guideline, HAP and VAP are discussed together, while in the outline the two are separated for improved clarity.

HOSPITAL-ACQUIRED PNEUMONIA (HAP)

Definitions

Pneumonia is defined as a new lung infiltrate plus clinical evidence that the infiltrate is of an infectious origin, including the new onset of fever, purulent sputum, leukocytosis, and decline in oxygenation. HAP is defined as a pneumonia that arises more than 48 hours after admission.

Diagnosis

Treatment should be based on the results of microbiologic studies performed on respiratory samples obtained noninvasively, rather than being treated only empirically.

Biomarkers and CPIS in Suspected HAP

The diagnosis of HAP should be made based on clinical criteria alone rather than using procalcitonin, CRP, BAL sTREM-1, or CPIS plus clinical criteria in the decision of whether or not to start antibiotic administration.

Initial (Empiric) Antibiotic Treatment

Empiric treatment regimens should be informed by the local distribution of pathogens associated with HAP and their antimicrobial susceptibilities. Include coverage for Staphylococcus aureus (not necessarily methicillin-resistant S. aureus [MRSA]), P. aeruginosa, and other Gram-negative rods (GNR) in all empiric regimens.

Include an antibiotic active against MRSA only in patients with either a risk factor for MRSA infection (prior intravenous antibiotic use within 90 days, hospitalization in a unit where > 20% of S. aureus isolates are methicillin resistant or in which the prevalence of MRSA is not known), or who are at high risk for mortality (need for ventilatory support due to HAP, septic shock, or markedly elevated procalcitonin without other reasons [e.g., major surgery]).

If empiric coverage for MRSA is indicated, either vancomycin or linezolid is recommended. For patients without risk factors for MRSA infection and not at high risk of mortality (see above), piperacillin-tazobactam, cefepime, levofloxacin, imipenem, or meropenem provides effective empiric coverage for methicillin-susceptible S. aureus (MSSA) infection. (For proven MSSA infection, cefazolin, nafcillin, or oxacillin is recommended.)

For empiric coverage in patients with an increased likelihood of infection with P. aeruginosa or other GNRs (IV antibiotic in previous 90 days or a higher risk of mortality [see above]), or cystic fibrosis or structural lung disease (such as bronchiectasis), administer two anti-pseudomonal antibiotics of different classes. Administer one anti-pseudomonal antibiotic to patients for whom these risk factors are absent.

Avoid use of an aminoglycoside as the sole anti-pseudomonal agent.

Pharmacokinetics/Pharmacodynamics

Optimize antibiotic dosing and administration based on PK/PD data.

Definitive Therapy

P. aeruginosa. For patients with HAP due to P. aeruginosa who are not in septic shock or at a high risk for death, and for whom the results of antibiotic susceptibility testing are known, monotherapy using an antibiotic to which the isolate is susceptible rather than combination therapy is recommended.

For patients with HAP due to P. aeruginosa who are in septic shock or at a high risk for death, and for whom the results of antibiotic susceptibility testing are known, combination therapy using two antibiotics to which the isolate is susceptible rather than monotherapy is suggested. For patients with HAP due to P. aeruginosa, the guideline recommends AGAINST aminoglycoside monotherapy.

ESBL-Producers. For patients with HAP due to extended spectrum beta-lactamase (ESBL)-producing Gram-negative bacilli, the recommendation is that the choice of an antibiotic for definitive (not empiric) therapy be based upon the results of antimicrobial susceptibility testing and patient-specific factors (e.g., allergies and comorbidities that may confer an increased risk of adverse effects).

Acinetobacter. For patients with HAP caused by Acinetobacter species:

If susceptible, treatment with either a carbapenem or ampicillin/sulbactam is suggested.

If susceptible only to colistin, intravenous treatment with a polymyxin (colistin or polymyxin B) is recommended and adjunctive inhaled colistin is suggested; rifampin is not recommended. Tigecycline should not be used.

Carbapenem Resistance. In patients with HAP caused by a carbapenem-resistant GNR susceptible only to polymyxins, an intravenous polymyxin (colistin or polymyxin B) is recommended and adjunctive inhaled colistin is recommended.

Duration, De-escalation of Antibiotic Therapy

The recommended duration of treatment is seven days. De-escalation (e.g., narrowing the coverage spectrum) of empiric therapy, when appropriate, is recommended.

Serum procalcitonin together with clinical criteria, but not CPIS, is suggested to guide discontinuation of antibiotic therapy.

VENTILATOR-ASSOCIATED PNEUMONIA (VAP)

Definitions

Pneumonia is defined as a new lung infiltrate plus clinical evidence that the infiltrate is of an infectious origin, including the new onset of fever, purulent sputum, leukocytosis, and decline in oxygenation. VAP is defined as a pneumonia that arises more than 48 hours after endotracheal intubation.

Diagnosis

Noninvasive sampling (endotracheal aspirate) with semiquantitative culture is recommended. If, however, invasive quantitative cultures are performed, antibiotics should be withheld if diagnostic criteria (PSB: < 103 CFU/mL; BAL: < 104 CFU/mL; ETA: < 105 CFU/mL) are not met.

Biomarkers and CPIS in Suspected VAP. The diagnosis of VAP should be made based on clinical criteria alone rather than by use of either procalcitonin, CRP, BAL sTREM-1, or CPIS plus clinical criteria in the decision of whether or not to start antibiotic administration.

Initial (Empiric) Antibiotic Treatment

Empiric treatment regimens should be informed by the local distribution of pathogens associated with VAP and their antimicrobial susceptibilities. Include coverage for S. aureus (not necessarily MRSA), P. aeruginosa, and other GNR in all empiric regimens.

Include an antibiotic active against MRSA only in patients with more than one of the following: a risk factor for antimicrobial resistance (IV antibiotic in previous 90 days, septic shock, ARDS preceding VAP, acute renal replacement therapy prior to VAP onset), patients being treated in units where > 10-20% of S. aureus isolates are methicillin resistant, and patients in units where the prevalence of MRSA is not known.

If empiric coverage for MRSA is indicated, either vancomycin or linezolid is recommended. To include MSSA in empiric coverage, piperacillin-tazobactam, cefepime, levofloxacin, imipenem, or meropenem is recommended (for proven MSSA infection, cefazolin, nafcillin, or oxacillin is recommended).

For Empiric Coverage of P. aeruginosa. Administer two anti-pseudomonal antibiotics of different classes only in patients with more than one of the following: IV antibiotic in previous 90 days, patients in units in which > 10% of GNR isolates are resistant to an agent being considered for monotherapy, and patients in an ICU for which local antimicrobial susceptibility rates are not available.

Administer one anti-pseudomonal antibiotic to patients for whom these risk factors are absent.

Avoidance of aminoglycosides and colistin (or polymyxin B) is recommended if alternative agents with adequate anti-GNR activity are available.

Pharmacokinetics/Pharmacodynamics

Optimize antibiotic dosing and administration based on PK/PD data.

Definitive Therapy

For patients with VAP due to GNR that are susceptible only to aminoglycosides or polymyxins (colistin or polymyxin B), administration of both inhaled and systemic antibiotics, rather than systemic antibiotics alone, is recommended.

P. aeruginosa. For patients with VAP due to P. aeruginosa who are not in septic shock or at a high risk for death, and for whom the results of antibiotic susceptibility testing are known, monotherapy using an antibiotic to which the isolate is susceptible rather than combination therapy is recommended.

For patients with VAP due to P. aeruginosa who are in septic shock or at a high risk for death, and for whom the results of antibiotic susceptibility testing are known, combination therapy using two antibiotics to which the isolate is susceptible rather than monotherapy is suggested.

For patients with VAP due to P. aeruginosa, the recommendation is AGAINST aminoglycoside monotherapy.

ESBL-Producers. For patients with VAP due to ESBL-producing Gram-negative bacilli, it is recommended that the choice of an antibiotic for definitive (not empiric) therapy be based upon the results of antimicrobial susceptibility testing and patient-specific factors (e.g., allergies and comorbidities that may confer an increased risk of adverse effects).

Acinetobacter. For patients with VAP caused by Acinetobacter species:

If susceptible, treatment with either a carbapenem or ampicillin/sulbactam is suggested.

If susceptible only to colistin, intravenous treatment with a polymyxin (colistin or polymyxin B) is recommended and adjunctive inhaled colistin is suggested; rifampin is not recommended. Tigecycline should not be used.

Carbapenem Resistance. In patients with VAP caused by a carbapenem-resistant GNR susceptible only to polymyxins, an intravenous polymyxin (colistin or polymyxin B) is recommended and adjunctive inhaled colistin is recommended.

Duration, De-escalation of Antibiotic Therapy

The recommended duration of treatment is seven days. De-escalation (e.g., narrowing the coverage spectrum) of empiric therapy, when appropriate, is recommended.

Serum procalcitonin together with clinical criteria, but not CPIS, is suggested to guide discontinuation of antibiotic therapy.

Ventilator-Associated Tracheitis (VAT)

In patients with VAT, antibiotic therapy is not recommended.