Hospital-Acquired and Ventilator-Associated Pneumonia: Highlights and Pitfalls of the 2016 IDSA / ATS Guidelines

The Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) updated the hospital-acquired and ventilator-associated pneumonia (HAP, VAP) guidelines in 2016. Hospital-acquired pneumonia is defined as pneumonia not associated with mechanical ventilation that develops 48 hours or more after admission to a hospital. Ventilator-associated pneumonia is defined as pneumonia that develops 48 to 72 hours after endotracheal intubation. hospital-acquired pneumonia and ventilator-associated pneumonia account for 22% of all hospital-acquired infections and lead to significant morbidity, mortality, and health care costs. Major differences between the 2005 and 2016 guidelines include removal of health care—associated pneumonia (HCAP), the addition of biomarker (eg, procalci­tonin) usage recommendations for assisting with duration of therapy, and redefinition of duration for most patients from between 8 and 15 days to 7 days. In addition, Grading of Recommendations Assessment, Development and Evaluation methodology was instituted in the new guidelines. In terms of double coverage for Pseudomonas aeruginosa, fewer risk factors to warrant combination were mentioned in the 2016 guidelines. Unit antibiograms, instead of just general local antibiograms, were highlighted as more reliable tools for empiric antibiotic choice because units can vary so drastically within 1 institution. Lastly, new diagnostic recommendations were included in the 2016 guidelines.^1,2

REMOVAL OF HCAP FROM 2016 GUIDELINES

The elimination of HCAP from inclusion in these guidelines was due to 2 main reasons: (1) Many patients presenting from nursing homes or other health care facilities still have community-acquired pneumonia (CAP) with nonresistant pathogens, and (2) these patients are from the community and present to emergency departments, and their management is thus better managed using the CAP guidelines, which we are still anxiously awaiting.

The 2005 guidelines suggested that patients who were exposed to any health care environment (eg, nursing homes, rehab centers) were at risk for multidrug-resistant organisms (MDROs). However, the supporting studies were poorly designed and highly biased (ATS/IDSA 2005).¹ Since then, studies assessing true risk of acquiring MDROs have concluded that patient characteristics (eg, presence of indwelling urinary catheters, recent antibiotic usage in the prior 90 days, previously known Pseudomonas colonization, or prolonged prior hospital admission) likely play a much larger role in predicting MDRO risk.³

MICROBIOLOGIC DIAGNOSIS OF PNEUMONIA

The 2016 IDSA HAP/VAP guidelines place an emphasis on noninvasive respiratory sampling, but it is important to consider these cultures in clinical context, given that the specificity of semiquantitative respiratory cultures is around 50%.^2,4 This is obvious in the guideline setting but not always considered in real practice, where cultures may be obtained as part of a fever work-up but not out of clin­ical concern for HAP/VAP specifically. In clinical practice, we know that many of our critically ill and chronically ill patients may have abnormal chest imaging at baseline for reasons other than pneumonia, making the distinction of respiratory colonization versus true infection more difficult. However, the consideration of other clinical factors such as oxygen requirement changes, hemodynamic instability, and changes in secretions may help a discerning clinician.

USE OF BIOMARKERS

The 2016 guidelines suggest the benefit of using procalci­tonin in addition to clinical criteria to guide duration of therapy (but not to aid in diagnosis of pneumonia).² The major benefits in limiting duration of therapy, when appro­priate, include reduced antibiotic-related adverse effects; sooner reconstitution of gut flora, thereby reducing risk of Clostridium difficile—associated diarrhea and other superin­fections; and cost reduction.

DURATION OF THERAPY

The 2016 guidelines recommend 7 days for both hospital-acquired pneumonia and ventilator-associated pneumonia treatment unless there are complicating factors or slow clinical improvement.² The evidence behind this new duration recommendation came primarily from 2 large systematic reviews assessing patients with HAP/VAP treated with short courses of antibiotics (7-8 days) versus long courses (10-15 days) and found no differences in mortality, recurrent pneumonias, length of stay, or duration of mechanical ventilation.^5,6

For ventilator-associated pneumonia due to nonfermenting gram-negative rods, there was no difference in pneumonia recurrence or mortality. Thus, longer durations based solely on microbiologic species were not supported.

EMPIRIC COVERAGE

The 2016 guidelines highlighted the need to empirically treat all HAP/VAP patients with antibiotics that are active against both Staphylococcus aureus and P aeruginosa. If empiric methicillin-resistant S aureus (MRSA) coverage is necessary, vancomycin or linezolid should be used. Empiric MRSA treatment should be started if MRSA rates are more than 10% to 20% of all S aureus isolates in the specific unit or hospital at which the patient is being treated.² For gram-negative coverage, β-lactams are preferred, although the specific agent of choice depends on local susceptibilities, ideally based on the unit antibiogram. Aminoglycosides should never be used as monotherapy for pneumonia because of increased mortality shown in prior studies.

DOUBLE COVERAGE AND MDRO RISK FACTORS

The 2016 guidelines recommend 2 antipseudomonal antibi­otics from different classes if patients have MDRO risk factors or are in a unit where more than 10% of gram-negative isolates are resistant to the preferred agent (usually a β-lactam). MDRO risk factors are different for ventilator-associated pneumonia and hospital-acquired pneumonia; however, prior antibiotic use is significantly associated with acqui­sition of MDRO for both types of pneumonia. Additional factors specific to ventilator-associated pneumonia may predispose patients to MDRO (see the 2016 guidelines for details).²

Regardless, the double coverage suggestion is a weak recommendation, based on low-quality evidence. Therefore, in our opinion, it should be taken with a grain of salt. In fact, to our knowledge, there has never been a study whose results have shown a mortality benefit with addition of a second antipseudomonal agent. The second agent recommended is either a fluoroquinolone or an aminoglycoside because the two are the only non—β-lactam antibiotics currently available for the treatment of pneumonia. Aside from a low quality of evidence used to make this recommendation in the guidelines, many institutions face high rates of quinolone resistance, making the benefit of the addition of fluoroquinolones to β-lactam regimens for patients with HAP/VAP at hospitals with more 30% to 40% gram-negative fluoroquinolone resistance essentially nil but with the higher risk of toxicity and C difficile infection. Combinatorial antibiograms are useful to identify whether quinolones or aminoglycosides remain active for β-lactam—resistant isolates. Although aminoglycosides, particularly amikacin, will likely target many β-lactam–resistant gram-negative strains, higher dosing is warranted for pneumonia. Even with higher dosing, aminoglycosides do not have optimal lung penetration and are not always feasible to initiate in older patients or those with renal dysfunction. However, in patients with concurrent gram-negative bacteremia or in septic shock, it may be prudent to add an aminoglycoside pending susceptibility results. The guidelines do not take into account the clinical stability of the patient.

VENTILATOR-ASSOCIATED TRACHEOBRONCHITIS

The guidelines also include discussion on the lack of high-quality evidence to support treating venti­lator-associated tracheobronchitis and, when weighing the risks associated with antibi­otic usage (resistance, C difficile, etc), recommend against treating venti­lator-associated tracheobronchitis. The only consistently significant benefit in the studies was a possible decrease in mechanical venti­lation days, without benefits in mortality or length of stay.²

In clinical practice, however, it is often difficult for clinicians to distinguish between pneumonia and venti­lator-associated tracheobronchitis. This is particularly the case for patients with abnormal chest imaging at baseline because of chronic lung disease who may also have large oxygen requirements. These patients often get repeat courses of antimicrobials but likely do not experience much benefit.

CONCLUSIONS

The 2016 IDSA/ATS guidelines contain significant improve­ments compared with the 2005 guidelines, as more liter­ature has been published regarding many important concepts. Although the new recommendations highlight the importance of antimicrobial stewardship by de-esca­lation when possible and shorter durations, diagnosis of pneumonia continues to be problematic, particularly in the hospital setting.

Dr. Rosé is the codirector of the Antimicrobial Stewardship Program at Cooper University Hospital in Camden, New Jersey, and an adjunct professor at Cooper Medical School of Rowan University and University of the Sciences.

Dr. Byrne is an infectious disease physician at Cooper University Health Care. She is the director of the antimicrobial stewardship program, as well as the associate infectious diseases fellowship program director and assistant professor of medicine at Cooper Medical School of Rowan University.

References:

1. American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA). Guidelines for the management of adults with hospital-acquired, ventilator associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171:388-416.
2. 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.
3. Gross AE, Van Schooneveld TC, Olsen KM, et al. Epidemiology and predictors of multidrug-resistant community-acquired and health care-associated pneumonia. Antimicrob Agents Chemother. 2014;58:5262-5268.
4. Joseph, Noyal & Sistla, Sarath & Dutta, Tarun & Badhe, Ashok & D, Rasitha & Parija, Subhash. (2010). Role of semi-quantitative and quantitative cultures of endotracheal aspirates in the diagnosis of ventilator-associated pneumonia. Australasian Medical Journal. 3. 627-632. 10.4066/AMJ.2010.344.
5. Dimopoulos G, Poulakou G, Pneumatikos IA, et al. Short-vs long-duration antibiotic regimens for ventilator- associated pneumonia: a systematic review and meta-analysis. Chest. 2013;144:1759-1767.
6. Pugh R, Grant C, Cooke RP, et al. Short-course versus prolonged course antibiotic therapy for hospital-acquired pneumonia in critically ill adults. Cochrane Database Syst Rev. 2015;8:Cd007577.