ABSTRACT & COMMENTARY
The Concept of Healthcare-Associated Pneumonia Is Not Accurate for Predicting Antibiotic Resistant Pathogens
By Richard R. Watkins, MD, MS, FACP
Division of Infectious Diseases, Akron General Medical Center, Akron, OH; Associate Professor of Internal
Medicine, Northeast Ohio Medical University, Rootstown, OH.
Dr. Watkins reports no financial relationships in this field of study.
This article originally appeared in the March 2014 issue of Infectious Disease Alert. It was edited by Stan Deresinski, MD, FACP, FIDSA, and peer reviewed by Timothy Jenkins, MD. Dr. Deresinki is Clinical Professor of Medicine, Stanford University, Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, and Dr. Jenkins is Assistant Professor of Medicine, University of Colorado, Denver Health Medical Center. Dr. Deresinski does research for the National Institutes of Health, and is an advisory board member and consultant for Merck, and Dr. Jenkins reports no financial relationships relevant to this field of study.
SYNOPSIS: A systematic review and meta-analysis found that the healthcare-associated pneumonia concept was based on low-quality evidence confounded by publication bias and does not accurately identify antibiotic-resistant pathogens.
SOURCE: Chalmers JD, et al. Healthcare-Associated Pneumonia Does Not Accurately Identify Potentially Resistant Pathogens: A Systematic Review and Meta-Analysis. Clin Infect Dis 2014; 58:330-339.
The term healthcare-associated pneumonia (HCAP) was first proposed in the 2005 guidelines from the American Thoracic Society and the Infectious Diseases Society of America.1 It was defined as pneumonia occurring in nursing-home residents, patients hospitalized for 2 or more days in the preceding 3 months, patients receiving home infusion therapy or wound care, and patients attending a hemodialysis center in the preceding 30 days. The concept of HCAP was based on the reasoning that patients with frequent healthcare contacts would initially require broad-spectrum antibiotic therapy because they would be at higher risk for resistant pathogens (and consequently higher mortality) compared to patients without such contacts. However, HCAP has been controversial, with some experts questioning the quality of the studies while others have suggested the HCAP concept varies geographically. Therefore, because of these uncertainties Chalmers and colleagues sought to determine how accurately HCAP identifies patients with resistant pathogens, to evaluate the quality of the HCAP studies and their potential for bias, and to validate or refute the HCAP concept.
The study was a systematic review and meta-analysis of papers published between January 1980 and January 2013. Of the 16,520 publications initially identified, 24 studies that included 22,456 patients were evaluated in the meta-analysis. The entry criteria were: (1) original publications that included a cohort of patients with HCAP compared with a CAP cohort; and (2) reporting of one of the study outcomes (microbiology or clinical). The primary outcome measured was the frequency of potentially resistant organisms in the HCAP group compared to the CAP group. Potentially resistant organisms included methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeroginosa, and Gram-negative Enterobacteriaceae. The secondary outcomes were the frequency of the organisms individually, and the frequency of typical and atypical CAP pathogens. The denominator for the frequency of the pathogens in each group was the total number of patients with HCAP or CAP. Finally, the clinical outcomes measured were intensive care unit admission and mortality.
Of the 24 studies included in the meta-analysis, 4 were rated to be low risk for bias, while 10 were judged to be at high risk. Only 5 used the ATS/IDSA guidelines definition for HCAP, while the others used modified versions such as including immunocompromised patients. There were statistically significant differences in the frequency of pathogens isolated in the HCAP group compared to the CAP group; Streptococcus pneumoniae and the atypical pathogens were less common (P <.05) while S. aureus, MRSA, Enterobacteriaceae and P. aeruginosa were more common (P <.0001). The authors chose to identify a test as being clinically meaningful if it reached a threshold of having a positive likelihood ratio (PLR) >10 or a negative likelihood ratio (NLR) <0.1, or was associated with an area under the receiver operator characteristic curve (AUC) > 0.75. For this study, they were trying to determine whether using the concept of HCAP reached any of these thresholds for being a clinically meaningful distinction. None of the pathogens identified had a PLR > 10 or a NLR < 0.1 nor did HCAP reach the AUC threshold of 0.75 in any of the analyses. Thus, HCAP was not a clinically useful parameter by these statistical criteria. Moreover, limiting the analysis to only prospective studies found no increased risk for ICU admission (n = 4 studies; odds ratio (OR), 0.99; 95% CI, 0.45-2.17; P = .98). The rate of HCAP did vary by region, which was increased in studies from North America (OR, 1.55; 95% CI, 1.35-1.78; P <.0001) but not in Europe (OR, 1.06; 95% CI, 0.56-2.01; P = .90) or Asia (OR, 1.47; 95% CI, 0.92-2.36; P = .10). In the 4 studies that provided adjusted ORs based on age and comorbid illnesses, no significant increase in mortality was associated with HCAP (OR, 1.20; 95% CI, 0.85-1.70; P = .30). Subanalyses found that HCAP performed poorly in European studies (sensitivity 40.0; specificity 75.0), prospective studies (sensitivity 56.3; specificity 70.3), and high-quality studies (sensitivity 51.5; specificity 74.5), none of which reached the AUC threshold of 0.75.
Commentary
The results from this study do not support HCAP being a useful clinical concept. The HCAP definition was poor at discriminating between patients who needed antibiotic coverage for MDR pathogens and those who did not. It is therefore logical to conclude that treating all HCAP cases the same will lead to over treatment in areas of low MDR organism prevalence and under treatment in areas of high prevalence. The authors found a publication bias for small studies which had unusually high frequencies of MDR pathogens. This likely distorts the literature by exaggerating the risks associated with HCAP. Indeed, the excess mortality in HCAP is more likely caused by advanced age and co-morbidities than MDR organisms. Given the risks of broad-spectrum antibiotics (e.g. Clostridium difficile infection, promoting antibiotic resistance) and the lack of high-quality evidence that such therapy improves outcomes in HCAP, a re-examination of this practice seems warranted.
There are some limitations to the study that need to be mentioned. As with all meta-analyses, the conclusions reached are only as valid as the quality of the source studies. Overall the general quality of the studies included in the analysis was poor. Only a few applied strict criteria for classification of the isolates as true pathogens and the higher-quality ones reported lower frequencies of such pathogens. Another limitation was that Enterobacteriaceae were rarely subdivided into extended-spectrum β-lactamase (ESBL) producing organisms which require different antibiotic therapy (i.e. carbapenems) than non-ESBL producers. Finally, the authors could have selected additional clinical measures such as length of stay and re-admission rates that compared HCAP and CAP.
How do the findings from this meta-analysis potentially impact clinical practice? The data make a strong argument for needing to understand the local prevalence of MDR pathogens and creating appropriate treatment algorithms in regions where such prevalence is high. As noted in an accompanying editorial, we also need to elucidate the risk factors for MDR pathogens in individual patients.2 One way could be the utilization of MDR pathogen risk scores which help clinicians objectively quantify the risk for these organisms in order to select appropriate antibiotic therapy. The results from this meta-analysis raise important questions about the validity of the current ATS/IDSA guidelines and support the need for a re-evaluation of the HCAP concept.
References
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American Thoracic Society/Infectious Diseases Society of America. 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.
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Restrepo MI, et al. Healthcare-associated pneumonia: Where do we go next? Clin Infect Dis 2014; 58:340-341.
