LUCIA ROSE, PHARMD

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, procalci&shy;tonin) 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 

, 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.

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).

 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 

colonization, or prolonged prior hospital admission) likely play a much larger role in predicting MDRO risk.

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%.

 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 clin&shy;ical 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.

The 2016 guidelines suggest the benefit of using procalci&shy;tonin in addition to clinical criteria to guide duration of therapy (but not to aid in diagnosis of pneumonia).

 The major benefits in limiting duration of therapy, when appro&shy;priate, include reduced antibiotic-related adverse effects; sooner reconstitution of gut flora, thereby reducing risk of 

associated diarrhea and other superin&shy;fections; and cost reduction.

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.

 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.

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.

The 2016 guidelines highlighted the need to empirically treat all HAP/VAP patients with antibiotics that are active against both 

(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 

isolates in the specific unit or hospital at which the patient is being treated.

 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.

The 2016 guidelines recommend 2 antipseudomonal antibi&shy;otics 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 acqui&shy;sition 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).

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 

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.

The guidelines also include discussion on the lack of high-quality evidence to support treating venti&shy;lator-associated tracheobronchitis and, when weighing the risks associated with antibi&shy;otic usage (resistance, 

, etc), recommend against treating venti&shy;lator-associated tracheobronchitis. The only consistently significant benefit in the studies was a possible decrease in mechanical venti&shy;lation days, without benefits in mortality or length of stay.

In clinical practice, however, it is often difficult for clinicians to distinguish between pneumonia and venti&shy;lator-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.

The 2016 IDSA/ATS guidelines contain significant improve&shy;ments compared with the 2005 guidelines, as more liter&shy;ature has been published regarding many important concepts. Although the new recommendations highlight the importance of antimicrobial stewardship by de-esca&shy;lation 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.

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. 

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. 

Gross AE, Van Schooneveld TC, Olsen KM, et al. Epidemiology and predictors of multidrug-resistant community-acquired and health care-associated pneumonia. 

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. 

Dimopoulos G, Poulakou G, Pneumatikos IA, et al. Short-vs long-duration antibiotic regimens for ventilator- associated pneumonia: a systematic review and meta-analysis. 

Pugh R, Grant C, Cooke RP, et al. Short-course versus prolonged course antibiotic therapy for hospital-acquired pneumonia in critically ill adults. 

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Hospital-acquired and ventilator-associated pneumonia account for 22% of all hospital-acquired infections.

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

The Infectious Diseases Society of America, in addition to organizations such as The Joint Commission and the Centers for Disease Control and Prevention, has emphasized the critical need for antimicrobial stewardship programs (ASPs) across various health care settings in the United States.

 Recommendations published by these organizations provide guidance for methods of conducting ASPs. Members of ASPs often have the necessary knowledge to back up specific recommendations but, when faced with sociobehavioral barriers, may not be equipped with the resources or skills that will alter prescribing habits. In addition, although a great deal of data exist on ways to optimize antibiotic usage, every institution has its own nuanced antibiotic practice patterns that require a tailored approach. Little guidance is available to support ASPs when they encounter difficult situations, such as a “reluctant steward.” As an infectious disease (ID) physician and an ID pharmacist, we aim to provide suggestions to help programs overcome common barriers.

OUTLIER OR RELUCTANT ANTIBIOTIC PRESCRIBERS 

At some point, ASP members will inevitably encounter an outlier antibiotic prescriber. Reasons for outlier prescribing are complex, multifactorial, and not necessarily a result of a knowledge deficit. A systematic review published by Teixeira and colleagues showed that attitudes such as complacency or fear were the 2 most influential intrinsic influencers on antibiotic prescribing. Extrinsic influencers greatly varied, including patient-related factors such as illness, as well as health care—related factors such as time pressure and following policies and guidelines.

 A prescriber may have many more years of experience compared with the ASP members and has “always done it this way” or perhaps was “burned” once or twice, leading to concern of undertreating or even fear of altering a good track record of favorable outcomes. Providers may be more afraid of the risk of undertreating than the societal or patient risk of receiving unnecessary antibiotics.

 For example, provider X opted not to treat a case of sinusitis 20 years prior that led to a cerebral abscess. Although this provider would ideally remember all the sinusitis cases that did not lead to that poor outcome, it is difficult to forget this single situation and, therefore, their threshold for prescribing antibiotics is lower for this type of infection. Another relevant example is a surgeon with excellent surgical site infection (SSI) outcomes who strongly attributes that it is, in part, because of a practice of using a long duration of postoperative antibiotics. The fear of stopping this practice and having 1 patient develop an SSI is too great, so the surgeon continues this practice. There are many other reasons providers might overprescribe.

It is important to reassure providers that the ASP team is working alongside them to improve patient care and not “policing” antibiotic practice. Communicating about the following themes may be of great benefit: Many antibiotics have lost effectiveness; 

 infection is on the rise; antibiotics alter gut flora, increasing the likelihood of a subsequent multidrug-resistant infection; and most patients who develop an infection will do so regardless of an initially prolonged duration of antibiotics. ASPs need to assume the role of convincing providers that it’s time to change our perception of antibiotics; the risk—benefit balance has become more important than ever.

WHAT DOES THE SOCIOBEHAVIORAL EFFECT HAVE TO DO WITH ANTIBIOTICS? 

Antimicrobial stewardship studies rarely consider sociobehavioral determinants in the evaluation of antibiotic prescribing interventions. Charani et al performed a systematic review and showed that many studies evaluating behavior change on antibiotic prescribing were not of high quality and not scientific. The authors of this review concluded that more research is needed in terms of well-designed interventions that assess prescribing behavior.

 Results from qualitative studies have shown that behavioral determinants significantly affected antibiotic prescribing.

 The DUMAS study findings revealed that a behavioral approach resulted in sustained appropriateness of antibiotic prescribing. This study used a participatory approach based on behavioral theory and maintained prescriber autonomy, essentially allowing prescribers to choose how they wanted to improve their practices and leading to a feeling of ownership.

STRATEGIES TO WORK WITH OUTLIER PRESCRIBERS 

Internal institutional data and published evidence provide leverage to make a change with outlier prescribers. Although educational interventions are important, their use may be limited because results may not be sustained over time, thereby requiring frequent and repeated interventions.

Many prescribers think that they themselves are not the problem or even that their patients are different, warranting longer antibiotic durations and/or broader spectrum agents.

 Regardless of the reasons, the ASP team should remember that providers truly want what is best for their patients; they want good outcomes and happy patients and families. This attitude will help establish a healthy relationship between the ASP and other providers.

Criticizing prescriber practice leads to unsuccessful interventions and mistrust between the ASP and the primary team. It is important to remember that the liability and responsibility of the patient ultimately lie on the primary team, not the ASP. Therefore, statements about this when discussing cases can be helpful in gaining credibility. Reassure the teams that it is ultimately their decision but that you would like to provide guidance for de-escalation or limiting the duration based on the patient’s clinical course and evidence-based practice.

Tread lightly and pick your battles. This gives the team a sense of security and co-ownership when it comes to antibiotic decision making. For example, you might say, “I’m calling to discuss your patient John Smith. It seems that you are treating pneumonia, correct? I realize this patient is very complicated; however, his respiratory cultures have been negative, so perhaps we can de-escalate the vancomycin and continue cefepime. Methicillin-resistant 

 [MRSA] tends to grow very easily. If he had MRSA pneumonia, we would’ve seen growth by now. Also, I’m confirming you are OK with the standard 5-day course of antibiotics, as long as the patient clinically improves.”

In terms of antibiotic discontinuation recommendations for patients who are not being discharged, it can be beneficial to remind the team that the patient will continue to be monitored and sepsis alerts are now very sensitive; therefore, if the patient develops a new fever or leukocytosis, restarting antibiotics at that point is feasible. In addition, focusing efforts on overall antibiotic prescribing, not just de-escalation, can help the ASP gain creditability. It is comforting for primary teams to know that the ASP may call them to escalate antibiotics or recommend infectious disease physician consultation when the case is outside their scope. Again, these are reminders to the primary team that the ASP aims to assist the team, not police their antibiotics.

In an ideal world, all ASP recommendations would be accepted and patients would be de-escalated consistently. However, we recommend sticking to the low-hanging fruit to increase the chance of acceptance. Certain indications essentially never require antibiotic therapy and can be easy targets for ASPs. Asymptomatic bacteriuria (ASB) is perhaps one of the most important areas to target, because ample data exist to support avoiding antibiotics in most patient populations. The difficulty with ASB involves the “gray zone,” which generally encompasses patients who are nonverbal, are confused, and have neurological deficits. The primary team may defend the decision to start antibiotics by stating that it is difficult to assess for symptoms of urinary tract infection. In most cases, you can recommend a “watch and wait” approach, in which antibiotics are withheld and the patient is watched for 24 to 48 hours. However, to truly target the ASB problem, work with your ED colleagues to stop ordering unnecessary urine tests (including urinalysis and urine cultures).

In the outpatient setting, prescribing for respiratory illnesses represents the most common reason a patient receives an antibiotic inappropriately. Working with the informatics department to obtain reports of outpatients who had coded bronchitis or cold and received antibiotics can be a good tactic if outpatient stewardship is an institutional goal. One effective, low-cost approach to outpatient stewardship is to encourage the use of a commitment poster. A study by Meeker and colleagues showed that if a provider signs a poster describing the commitment to using antibiotics just when they will provide benefit and places it in the patient exam rooms, prescribing for respiratory infections improves.

 This likely reflects the providers’ interest in being consistent with their previous commitments.

Support from clinical leadership (ie, the chief medical officer) and administration are critical in resolving situations that threaten patient safety.

 Establishing these connections will help in scenarios in which the “difficult provider” is not interested in discussing opportunities for practice change. Last, although a written statement from the administration is important, it is insufficient for fostering a valuable relationship. Creating an open dialogue between the ASP and leadership is crucial for optimizing institutional antimicrobial practice. To make a broader change, ASPs need to engage senior colleagues and division heads outside of infectious diseases.

It is important to recognize that some situations are impossible to rectify or will take up too much time to make the time invested worthwhile. Focus on the majority of providers who will accept recommendations and work collaboratively. Pick your battles with those who are unwilling to change their practices, recognizing that if patients are being harmed, leadership may have to step in. Finally, every facility has its own priorities related to optimal antibiotic prescribing. Some institutions may want to focus on optimal treatment of community-acquired pneumonia rather than skin and soft tissue infections. Using prescribing data for action will help identify where stewardship interventions will likely have the most impact.   

Dr. Hicks is the director of the Office of Antibiotic Stewardship in the Division of Healthcare Quality Promotion at the National Center for Emerging and Zoonotic Infectious Diseases, US Centers for Disease Control and Prevention. She is also a captain in the US Public Health Service. Dr. Hicks attended the Philadelphia College of Osteopathic Medicine and completed her internal medicine residency and chief medicine residency at the University of Connecticut and an infectious diseases fellowship at Brown University.  

Dr. Rose received a PharmD at Massachusetts College of Pharmacy & Health Sciences, completed a PGY-1 pharmacy practice residency at UMassMemorial Health Care, and a PGY-2 infectious diseases pharmacotherapy residency at The Brooklyn Hospital Center. She is currently the co-director of the Antimicrobial Stewardship Program at Cooper University Hospital in Camden, New Jersey, and is as an adjunct professor at Cooper Medical School of Rowan University and University of the Sciences. 

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Although challenging, it is not impossible to change some outlier behaviors.

LUCIA ROSE, PHARMD

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