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Better Outcomes From Pneumococcal PneumoniaPneumococcal Pneumonia Outcomes: How Good Is Your Care? FREE TO VIEW

Grant W. Waterer, MD, PhD, FCCP
Author and Funding Information

From the University of Western Australia; and Northwestern University, Chicago, IL.

CORRESPONDENCE TO: Grant W. Waterer, MD, PhD, FCCP, Level 4 MRF Bldg, Royal Perth Hospital, GPO Box X2213, Perth 6847, WA, Australia; e-mail: grant.waterer@uwa.edu.au


FUNDING/SUPPORT: Dr Waterer is funded by the National Health and Medical Research Council of Australia.

FINANCIAL/NONFINANCIAL DISCLOSURES: The author has reported to CHEST that no potential confl icts of interest exist with any companies/organizations whose products or services may be discussed in this article.


Chest. 2014;146(1):6-8. doi:10.1378/chest.14-0171
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Published online

Articles on pneumococcal pneumonia (PP) over the past 2 decades have frequently commented that reported mortality has shown very little, if any, improvement since the 1960s. Making true comparisons across the decades is difficult, however, due to the increasing numbers of elderly patients, the increasing frequency of chronic organ failure in the community, and the large variety of immunocompromised hosts from conditions such as HIV infection, chronic dialysis, and autoimmune diseases and their therapy. Acknowledging the problems of comparing outcomes in different populations, significant attention over the past 2 decades has been given to measuring how “sick” a patient is at entry to the ICU. It is, therefore, now possible to look at outcomes between units or across time intervals and be reasonably sure that you are comparing “apples with apples.”

In this issue of CHEST (see page 22), Gattarello and colleagues1 report their analysis of a matched case-control study of outcomes in PP requiring intensive care between the Community-Acquired Pneumonia en la Unidad de Cuidados Intensivos (CAPUCI) I (2000-2002) and CAPUCI II (2008-2013) trials that were conducted in Europe. What Gattarello and colleagues1 found was that in the later time period, patients with PP were significantly less likely to die in the ICU (OR, 0.82; 95% CI 0.68-0.98), with even more marked improvements in patients with shock (OR, 0.67; 95% CI, 0.50-0.89) or requiring mechanical ventilation (OR, 0.73; 95% CI, 0.55-0.96).

Before considering potential explanations for the observations of Gattarello and colleagues,1 the first question is whether ICU mortality alone is a valid end point. Our increasing ability to keep people alive despite irreversible organ failure from underlying disease means that intensive care can be an extremely expensive way of prolonging the inevitable.2 To survive the ICU only to succumb before ever being discharged from the hospital is also unlikely to be viewed by patients and their families as a good outcome. Partially for these reasons, clinical trials moved to adopt more extended time points such as inpatient, 28-day, or 30-day mortality. Indeed, with increasing evidence of adverse long-term health consequences of pneumonia,3-5 and especially severe pneumonia,6 there is a reasonable argument for considering 12-month or longer end points. While we should, therefore, interpret improvements in ICU survival with caution, it is reassuring that in the analysis presented by Gattarello and colleagues,1 despite greater survival, the overall length of ICU stay was 10 days in both the early and later ICU cohorts.1

The next obvious question is how well were the patients and control subjects matched. Judging by the information presented in Table 1 and 2 of the article, the later time group trended toward being slightly sicker than the control subjects from the earlier time period group (estimated probability of death, 31% vs 24%).

What then explains the impressive drop in ICU mortality for PP in < 1 decade? Well-documented changes in the epidemiology of pneumococcal disease have occurred in recent years with a shift away from the invasive strains covered by the 7-valent conjugate vaccine. However, the starting point of the CAPUCI trials was disease severe enough to require admission to the ICU. Only studying severe pneumonia substantially reduces, although it does not completely remove, a change in pneumococcal virulence as the explanation for the marked drop in ICU mortality.

Between the two time periods of these trials there were significant changes in empirical care of patients with pneumonia, including many publications indicating a likely survival advantage in combining β-lactams with a macrolide, better outcomes being associated with giving the first dose of antibiotics as promptly as possible, and greater attention to early fluid and electrolyte balance,7 which are also key components of clinical care articulated in the Surviving Sepsis Campaign.

In the analysis by Gattarello and colleagues,1 two factors were identified as being the most significant. Use of a macrolide as part of the empirical therapy regimen increased from 66% to 87% between the two trials and, overall, was associated with the greatest reduction in mortality (OR, 0.19; 95% CI, 0.07-0.51). The other significant factor was delivery of the first dose of antibiotics within 3 h, which increased from 27.5% to 70% between the trials and was also associated with a lower pooled mortality (OR, 0.36; 95% CI, 0.15-0.87).

There will remain believers and nonbelievers of significant beneficial effects attributable to macrolides until we have a high-quality, randomized controlled trial with sufficient numbers of critically ill patients (eg, with septic shock and/or respiratory failure requiring mechanical ventilation) to have a mortality rate well above 10%. Personally, I think the weight of evidence in favor of using a combination of antibiotics that includes a macrolide, particularly in patients with bacteremic PP, is overwhelmingly compelling. However, as I indicate at the conclusion of this editorial, a beneficial effect (or not) of macrolides is not where clinicians should be focusing their attention.

It also makes sense that giving antibiotics promptly is part of the optimal care of a patient with pneumonia. However, studies focusing purely on quicker delivery of antibiotics have not resulted in better patient outcomes.8 What then explains the apparent disconnect between the observed associations with better patient outcomes and quicker antibiotic delivery, including the analysis by Gattarello and colleagues?1 I think the most likely explanation is that in observational studies, faster antibiotic delivery is a marker of more prompt delivery of a suite of medical interventions including correcting hypovolemia, electrolyte disturbances, and arrhythmias; providing appropriate prophylaxis for venous thromboembolic disease; early recognition and treatment of respiratory failure; and diagnosing and treating coexisting additional medical problems. Focusing purely on one component of a multicomponent approach will never deliver significant improvements in patient outcomes. Although with small subsets it is hard to make definitive comments, it is very interesting that the Kaplan-Meier graphs show mortality dividing very early in the time-to-antibiotic analyses, but not until the second week of treatment in the macrolide analyses. The difference in the survival curves suggests to me that very different causes of preventable mortality may have been influenced.

In the final analysis, I do not think the most important question clinicians should ask is why ICU mortality dropped so markedly for patients with PP in the 6 to 7 years between CAPUCI I and CAPUCI II. In the course of a year, I meet many doctors who consider themselves to be good clinicians, including those treating patients with severe pneumonia. I am quite sure, however, that almost all of them, like me until very recently, had no comparative data to show how their patient outcomes compared with best practice. The most important message from Gattarello and colleagues1 is that the goal posts for best outcomes in severe PP are moving and you cannot rely on historical data to determine if your hospital is performing well. Good clinicians should be making every effort to work with leading centers and/or access the increasingly sophisticated databases that are becoming available in many developed economies to ensure their outcomes are meeting best quality benchmarks. Indeed, I would go so far as to suggest that part of the definition of a “good” clinician must be that they are actively involved in seeking data to determine how their patient outcomes compare. At the very least, the data provided by Gattarello and colleagues1 should be sufficient to determine if you are lagging significantly behind best patient outcomes in PP and may need to rethink your current approaches. Ensuring prompt delivery of a combination of antibiotics, which include a macrolide, would appear to be the most logical starting point if your patient outcomes are not as good as others are achieving.

Acknowledgments

Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript.

Gattarello S, Borgatta B, Solé-Violán J, et al. Decrease in mortality in severe community-acquired pneumococcal pneumonia: impact of improving antibiotic strategies (2000-2013). Chest. 2014;146(1):22-31.
 
Huynh TN, Kleerup EC, Wiley JF, et al. The frequency and cost of treatment perceived to be futile in critical care. JAMA Intern Med. 2013;173(20):1887-1894. [CrossRef] [PubMed]
 
Sandvall B, Rueda AM, Musher DM. Long-term survival following pneumococcal pneumonia. Clin Infect Dis. 2013;56(8):1145-1146. [CrossRef] [PubMed]
 
Waterer GW, Kessler LA, Wunderink RG. Medium-term survival after hospitalization with community-acquired pneumonia. Am J Respir Crit Care Med. 2004;169(8):910-914. [CrossRef] [PubMed]
 
Mortensen EM, Kapoor WN, Chang CC, Fine MJ. Assessment of mortality after long-term follow-up of patients with community-acquired pneumonia. Clin Infect Dis. 2003;37(12):1617-1624. [CrossRef] [PubMed]
 
Karhu J, Ala-Kokko TI, Ylipalosaari P, Ohtonen P, Laurila JJ, Syrjälä H. Hospital and long-term outcomes of ICU-treated severe community- and hospital-acquired, and ventilator-associated pneumonia patients. Acta Anaesthesiol Scand. 2011;55(10):1254-1260. [CrossRef] [PubMed]
 
Waterer GW, Rello J, Wunderink RG. Management of community-acquired pneumonia in adults. Am J Respir Crit Care Med. 2011;183(2):157-164. [CrossRef] [PubMed]
 
Yahav D, Leibovici L, Goldberg E, Bishara J, Paul M. Time to first antibiotic dose for patients hospitalised with community-acquired pneumonia. Int J Antimicrob Agents. 2013;41(5):410-413. [CrossRef] [PubMed]
 

Figures

Tables

References

Gattarello S, Borgatta B, Solé-Violán J, et al. Decrease in mortality in severe community-acquired pneumococcal pneumonia: impact of improving antibiotic strategies (2000-2013). Chest. 2014;146(1):22-31.
 
Huynh TN, Kleerup EC, Wiley JF, et al. The frequency and cost of treatment perceived to be futile in critical care. JAMA Intern Med. 2013;173(20):1887-1894. [CrossRef] [PubMed]
 
Sandvall B, Rueda AM, Musher DM. Long-term survival following pneumococcal pneumonia. Clin Infect Dis. 2013;56(8):1145-1146. [CrossRef] [PubMed]
 
Waterer GW, Kessler LA, Wunderink RG. Medium-term survival after hospitalization with community-acquired pneumonia. Am J Respir Crit Care Med. 2004;169(8):910-914. [CrossRef] [PubMed]
 
Mortensen EM, Kapoor WN, Chang CC, Fine MJ. Assessment of mortality after long-term follow-up of patients with community-acquired pneumonia. Clin Infect Dis. 2003;37(12):1617-1624. [CrossRef] [PubMed]
 
Karhu J, Ala-Kokko TI, Ylipalosaari P, Ohtonen P, Laurila JJ, Syrjälä H. Hospital and long-term outcomes of ICU-treated severe community- and hospital-acquired, and ventilator-associated pneumonia patients. Acta Anaesthesiol Scand. 2011;55(10):1254-1260. [CrossRef] [PubMed]
 
Waterer GW, Rello J, Wunderink RG. Management of community-acquired pneumonia in adults. Am J Respir Crit Care Med. 2011;183(2):157-164. [CrossRef] [PubMed]
 
Yahav D, Leibovici L, Goldberg E, Bishara J, Paul M. Time to first antibiotic dose for patients hospitalised with community-acquired pneumonia. Int J Antimicrob Agents. 2013;41(5):410-413. [CrossRef] [PubMed]
 
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