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“Better never means better for everyone... It always means worse, for some.”
A 73-year-old woman with a history of severe chronic bronchitis, ESRD receiving thrice-weekly hemodialysis and heart failure with a preserved ejection fraction is admitted from home with fevers, cough, vomiting and a right lower lobe consolidation on CXR. In 2016, she had a similar presentation, culminating in 4 days of mechanical ventilation in the ICU. At that time, she grew P. aeruginosa from a tracheal aspirate 3 days into her ICU stay. With her current presentation, she is well-appearing with a CURB-65 score of only 1 without unanticipated bloodwork abnormalities; all of her previous culture data – including MRSA nares – is negative. You wonder what her initial anti-microbial therapy should be?
The last American Thoracic Society/Infectious Disease Society of America [ATS/IDSA] guidelines on community acquired pneumonia [CAP] were published in 2007; it seems hard to remember the world at that time – free from the tweeting of medical information, free from the tweeting of world leaders. Is 2019 better for everyone? Worse? For some?
The 2019 inception of the ATS/IDSA guidelines for CAP reserves a more pragmatic approach than its screed-like predecessor – clearly defining 16 high-yield clinical questions and answering them under the direction of the PICO framework. Critically, the current recommendations make clear that:
“This guideline focuses on patients in the United States who have not recently completed foreign travel…. on adults who do not have an immunocompromising condition, such as inherited or acquired immune deficiency or drug-induced neutropenia, including patients actively receiving cancer chemotherapy, patients infected with HIV with suppressed CD4 counts, and solid organ or bone marrow transplant recipients.”
Accordingly, and as mentioned in the 2016 update on hospital-acquired and ventilator-associated pneumonia, guidelines remain guidelines. They are not sacrosanct; they needn’t be followed without falter in all patients, always; clinical judgement and individual patient characteristics are also guiding principles. In my humble opinion, the only deontological imperative is that you are informed and the current IDSA CAP guidelines are an excellent fund of rational, practical information.
Severe CAP and when to culture
As a number of the recommendations depend, in part, on characterizing ‘severe’ CAP – a definition is in order; severe CAP is carried forward from the 2007 guidelines [see illustration 1]:
With respect to cultures, the guidelines ‘strongly recommend’ blood cultures and lower respiratory tract cultures only when there is severe CAP or if there is concern for MRSA or P. aeruginosa. Additionally, severe CAP is a clinical setting where the authors provide a ‘conditional’ recommendation to perform urinary legionella and streptococcal antigen testing; it is conditional, most likely, because randomized trials have failed to identify a benefit for urinary antigen testing for S. pneumoniae and Legionella. In the guidelines, a ‘conditional’ recommendation means that recommendations were based on low or very low quality of evidence and not believed to represent standards of care. Importantly, though, many of the ‘strong recommendations’ in the guidelines are also based upon low quality evidence.
As the current guidelines restrict themselves to ‘clinically and radiographically-confirmed’ CAP, the question addressed is whether or not procalcitonin can distinguish between bacterial and viral CAP. The question not asked in these guidelines is whether or not procalcitonin can differentiate lower from upper respiratory tract infections. With respect to the former question, the authors give a ‘strong recommendation’ based on ‘moderate evidence’ that procalcitonin cannot reliably distinguish viral from bacterial CAP; thus, treatment should begin based on clinical criteria alone.
On PSI versus CURB-65
The authors recommend using PSI over CURB-65 for determining inpatient versus outpatient therapy for CAP in adults based on published predictive power. Importantly, because neither of these scoring tools were designed to select the level of care within the hospital, it is suggested that neither be used for this purpose. Instead, the authors note that a meta-analysis using the 2007 ATS/IDSA severity score [see illustration 1] that 1 major criterion or at least 3 minor criteria had a sensitivity of 84% for predicting ICU admission. Consequently, 1 major criterion or at least 3 minor criteria define severe CAP. Interestingly, if only 3 minor criteria were used to predict ICU admission, the sensitivity dropped to 56%.
Antibiotics and steroids
The included treatment decision tree [see illustration 2] is meant to aid the reader through the guidelines, but not meant to supplant their reference; some highlights of inpatient management are mentioned herein.
Firstly, the addition of targeted anaerobic therapy is largely discouraged, even in those patients ‘suspected of aspiration’ [because everyone aspirates]. Dedicated anaerobic coverage is only ‘conditionally’ recommended in patients in whom either empyema or abscess is suspected; there is no mention of rotten teeth.
Key decision-points for inpatient management of CAP are established upon the presence of MRSA and P. aeruginosa risk factors and upon the severity of CAP [see above]. Notably, and mirroring the 2016 HAP/VAP guideline update, the concept of HCAP is abandoned! What is most strongly emphasized is that hospitals should create their own antibiogram and epidemiologic record – so that local risk factors and prevalence of MRSA and P. aeruginosa may be known. Furthermore, the authors reiterate the data presented in the 2016 HAP/VAP guidelines – that the risk factors underpinning the definition of HCAP were quite poor at predicting resistant pathogens. Additionally, the acceptance of the HCAP paradigm in 2005 has only increased the use of broad-spectrum antibiotics without improving outcome. Accordingly, the authors now highlight the two general risk factors considered predictive enough to warrant empiric MRSA and P. aeruginosa coverage:
1. Previous isolation of the pathogen in a respiratory sample within the last year and
2. Hospitalization and receipt of parenteral antibiotics in the preceding 90 days.
Importantly, respiratory isolation of either MRSA or P. aeruginosa should prompt repeat cultures and empiric coverage for 48 hours of the relevant pathogen, while recent admission and parenteral antibiotics only necessitates empiric MRSA and/or P. aeruginosa coverage if the patient has severe CAP [see illustration 2].
With respect to non-severe, inpatient CAP, and despite the results of the CAP-START trial, the authors do not recommend beta-lactam monotherapy as equivalent to beta-lactam plus macrolide or a respiratory fluroquinolone. CAP-START is referenced, but down-played given that it is a ‘non-inferiority’ trial. Additionally, CAP-START has been criticized because a large proportion of patients [~40%] randomized to beta-lactam monotherapy, also received some macrolide therapy for atypical coverage. The authors also cite a 2016 systematic review showing that combination therapy or fluroquinolone monotherapy generally had a better outcome than solitary beta-lactam therapy for patients admitted with CAP.
Lastly, on steroids, the authors strongly discourage the use of steroids in non-severe CAP and conditionally discourage their use in severe CAP. These recommendations acknowledge the conflicting evidence regarding the benefit of steroids in CAP. They imply that the two meta-analyses which show mortality reduction in severe CAP are balanced against two other meta-analyses that do not demonstrate mortality reduction. In addition, they note that hyperglycemia is a common side-effect and therefore conditionally discourage the use of corticosteroids in severe CAP. However, in refractory shock, the authors endorse the Surviving Sepsis Campaign guidelines.
Overall, the authors should be commended for their strong recommendation on acquiring local knowledge; in effect, challenging all institutions to carry out their own CAP quality improvement projects. It may surprise some medical centres and clinicians that their patients admitted with CAP – and who would have previously been labeled as having HCAP – may have much lower risk of MRSA and P. aeruginosa than previously thought. But this cannot be known until this information is actively sought and documented.
Interestingly, within the text of the guidelines, the authors state that the greatest risk of MRSA or P. aeruginosa is observed when there is previous respiratory tract isolation of the pathogen within the last year; however, this did not carry over to their summary table. One may wonder how to manage a patient with P. aeruginosa in a respiratory tract sputum sample obtained in 2016? What if there has been multiple negative sample since? What if this patient also has severe CAP, severe emphysema and heart failure? Again, when considering the patient in front of you, it rapidly becomes clear that guidelines can only guide; as we all know so well, there is often no absolute.
Please obtain these excellent guidelines for yourself, read them and try your best to apply them to the messiness of real clinical medicine. The information contained above is not meant to replace these guidelines – their breadth is impossible to cover in this short synopsis; this entry is simply meant to encourage engagement and healthy, informed debate.
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How would you manage the patient described at the outset and why? Please comment.
Dr. Kenny is the cofounder and Chief Medical Officer of Flosonics Medical; he also the creator and author of a free hemodynamic curriculum at heart-lung.org